Immunological outcomes of exercise in older adults

Aging is associated with a dysregulation of the immune system known as immunosenescence. Immunosenescence involves cellular and molecular alterations that impact both innate and adaptive immunity, leading to increased incidences of infectious disease morbidity and mortality as well as heightened rates of other immune disorders such as autoimmunity, cancer, and inflammatory conditions. While current data suggests physical activity may be an effective and logistically easy strategy for counteracting immunosenescence, it is currently underutilized in clinical settings. Long-term, moderate physical activity interventions in geriatric populations appear to be associated with several benefits including reduction in infectious disease risk, increased rates of vaccine efficacy, and improvements in both physical and psychosocial aspects of daily living. Exercise may also represent a viable therapy in patients for whom pharmacological treatment is unavailable, ineffective, or inappropriate. The effects of exercise impact multiple aspects of immune response including T cell phenotype and proliferation, antibody response to vaccination, and cytokine production. However, an underlying mechanism by which exercise affects numerous cell types and responses remains to be identified. Given this evidence, an increase in the use of physical activity programs by the healthcare community may result in improved health of geriatric populations

Echinacea increases arginase activity and has anti-inflammatory properties in RAW 264.7 macrophage cells indicative of alternative macrophage activation

The genus Echinacea is a popular herbal immunomodulator. Recent reports indicate that Echinacea products inhibit nitric oxide (NO) production in activated macrophages. In the present study we determined the inhibitory effects of alcohol extracts and individual fractions of alcohol extracts of Echinacea on NO production, and explored the mechanism underlying the pharmacological anti-inflammatory activity. The alcohol extracts of three medicinal Echinacea species, E. angustifolia, E. pallida and E. purpurea, significantly inhibited NO production by lipopolysaccharide (LPS)-activated the RAW 264.7 macrophage cell line, among them E. pallida was the most active. The Echinacea-mediated decrease in NO production was unlikely due to a direct scavenging of NO because the extracts did not directly inhibit NO released from an NO donor, sodium nitroprusside. An immunoblotting assay demonstrated that the extract of E. pallida inhibited inducible nitric oxide synthase (iNOS) protein expression in LPS-treated macrophages. The enzymes iNOS and arginase metabolize a common substrate, L-arginine, but produce distinct biological effects. While iNOS is involved in inflammatory response and host defense, arginase participates actively in anti-inflammatory activation. Arginase activity of RAW 264.7 cells stimulated with 8- bromo-cAMP was significantly increased by alcohol extracts of all three Echinacea species. The polar fraction containing caffeic acid derivatives enhanced arginase activity, while the lipophilic fraction containing alkamides exhibited a potential of inhibiting NO production and iNOS expression. These results suggest that the anti-inflammatory activity of Echinacea might be due to multiple active metabolites, which work together to switch macrophage activation from classical activation towards alternative activation

Echinacea tennesseensis ethanol tinctures harbor cytokine- and proliferation-enhancing capacities

Background—Members of the genus Echinacea are used medicinally to treat upper respiratory infections such as colds and influenza. The aim of the present investigation was to characterize the phytomedicinal properties of the American federally endangered species Echinacea tennesseensis. Methods—Fifty-percent ethanol tinctures were prepared from roots, stems, leaves, and flowers and tested separately for their ability to influence production of IL-1β, IL-2, IL-10, and TNF-α as well as proliferation by young human adult peripheral blood mononuclear cells (PMBC) in vitro. Tincture aliquots were stored at three different temperatures (4°, −20°C, and −80°C) for 21 h before testing. At one-month post-extraction, tinctures stored at −20°C were tested again for cytokine modulation. Phytochemical analyses were performed using HPLC. Results—Fresh root, leaf, and flower tinctures stimulated PBMC proliferation. Fresh root tinctures alone stimulated IL-1β, IL-10, and TNF-α production. No tinctures modulated IL-2 production. Stem tinctures showed no activity. Storage temperature did not influence any outcomes. Root tinctures maintained their ability to modulate IL-1β, IL-10, and TNF-α production after one month of storage at −20°C. Conclusions—These results suggest E. tennesseensis harbors phytomedicinal properties that vary by plant organ, with roots demonstrating the strongest activities

Alcohol extract of Echinacea pallida reverses stress-delayed wound healing in mice

Healing of open skin wounds begins with an inflammatory response. Restraint stress has been well documented to delay wound closure, partially via glucocorticoid (GC)-mediated immunosuppression of inflammation. Echinacea, a popular herbal immunomodulator, is purported to be beneficial for wound healing. To test the hypothesis, an alcohol extract of E. pallida was administrated orally to mice for 3 days prior to, and 4 days post wounding with a dermal biopsy on the dorsum. Concominantly, mice were exposed to 3 cycles of daily restraint stress prior to, and 4 cycles post wounding. Echinacea accelerated wound closure in the stressed mice, but had no apparent wound healing effect for the non-stressed mice when compared to their respective controls. To test if the positive healing effect is through modulation of GC release, plasma corticosterone concentrations were measured in unwounded mice treated with restraint stress and the herbal extract for 4 days. Plasma GC in restraint stressed mice gavaged with Echinacea was not different from mice treated with restraint only, but was increased compared to the vehicle control. This data suggests that the improved wound healing effect of Echinacea in stressed mice is not mediated through modulation of GC signaling

Enhancement of Innate and Adaptive Immune Functions by Multiple Echinacea Species

Echinacea preparations are commonly used as nonspecific immunomodulatory agents. Alcohol extracts from three widely used Echinacea species, Echinacea angustifolia, Echinacea pallida, and Echinacea purpurea, were investigated for immunomodulating properties. The three Echinacea species demonstrated a broad difference in concentrations of individual lipophilic amides and hydrophilic caffeic acid derivatives. Mice were gavaged once a day (for 7 days) with one of the Echinacea extracts (130 mg/kg) or vehicle and immunized with sheep red blood cells (sRBC) 4 days prior to collection of immune cells for multiple immunological assays. The three herb extracts induced similar, but differential, changes in the percentage of immune cell populations and their biological functions, including increased percentages of CD49+ and CD19+ lymphocytes in spleen and natural killer cell cytotoxicity. Antibody response to sRBC was significantly increased equally by extracts of all three Echinacea species. Concanavalin A-stimulated splenocytes from E. angustifolia- and E. pallida-treated mice demonstrated significantly higher T cell proliferation. In addition, the Echinacea treatment significantly altered the cytokine production by mitogenstimulated splenic cells. The three herbal extracts significantly increased interferon-γ production, but inhibited the release of tumor necrosis factor-α and interleukin (IL)-1β. Only E. angustifolia- and E. pallida-treated mice demonstrated significantly higher production of IL-4 and increased IL-10 production. Taken together, these findings demonstrated that Echinacea is a wide-spectrum immunomodulator that modulates both innate and adaptive immune responses. In particular, E. angustifolia or E. pallida may have more anti-inflammatory potential

Pseudohypericin is necessary for the Light-Activated Inhibition of Prostaglandin E2 pathways by a 4 component system mimicking an Hypericum perforatum fraction

Hypericum perforatum (Hp) has been used medicinally to treat a variety of conditions including mild-to-moderate depression. Recently, several anti-inflammatory activities of Hp have been reported. An ethanol extract of Hp was fractionated with the guidance of an anti-inflammatory bioassay (lipopolysaccharide (LPS)-induced prostaglandin E2 production (PGE2)), and four constituents were identified. When combined together at concentrations detected in the Hp fraction to make a 4 component system, these constituents (0.1 μM chlorogenic acid, 0.08 μM amentoflavone, 0.07 μM quercetin, and 0.03 μM pseudohypericin) explained the majority of the activity of the fraction when activated by light, but only partially explained the activity of this Hp fraction in dark conditions. One of the constituents, light-activated pseudohypericin, was necessary, but not sufficient to explain the reduction in LPS-induced PGE2 of the 4 component system. The Hp fraction and the 4 component system inhibited lipoxygenase and cytosolic phospholipase A2, two enzymes in the PGE2-mediated inflammatory response. The 4 component system inhibited the production of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), and the Hp fraction inhibited the antiinflammatory cytokine interleukin-10 (IL-10). Thus, the Hp fraction and selected constituents from this fraction showed evidence of blocking pro-inflammatory mediators but not enhancing inflammation-suppressing mediators.

Single dose combination nanovaccine provides protection against influenza A virus in young and aged mice

Immunosenescence poses a formidable challenge in designing effective influenza vaccines for aging populations. While approved vaccines against influenza viruses exist, their efficacy in older adults is significantly decreased due to the diminished capabilities of innate and adaptive immune responses. In this work, the ability of a combination nanovaccine containing both recombinant hemagglutinin and nucleoprotein to provide protection against seasonal influenza virus infection was examined in young and aged mice. Vaccine formulations combining two nanoadjuvants, polyanhydride nanoparticles and pentablock copolymer micelles, were shown to enhance protection against challenge compared to each adjuvant alone in young mice. Nanoparticles were shown to enhance in vitro activation of dendritic cells isolated from aged mice, while both nanoadjuvants did not induce proinflammatory cytokine secretion which may be detrimental in aged individuals. In addition, the combination nanovaccine platform was shown to induce demonstrable antibody titers in both young and aged mice that correlated with the maintenance of body weight post-challenge. Collectively, these data demonstrate that the combination nanovaccine platform is a promising technology for influenza vaccines for older adults

Comparison of the Cardiovascular Benefits of Resistance, Aerobic, and Combined Exercise (CardioRACE): Rationale, design, and methods

Background The benefits of aerobic exercise (AE) for cardiovascular disease (CVD) have been well documented. Resistance exercise (RE) has been traditionally examined for its effects on bone density, physical function, or metabolic health, yet few data exist regarding the benefits of RE, independent of and combined with AE, for CVD prevention. This randomized controlled trial, “Comparison of the Cardiovascular Benefits of Resistance, Aerobic, and Combined Exercise (CardioRACE),” is designed to determine the relative benefits of RE, AE, or combined RE plus AE training on CVD risk factors. Methods Participants are 406 inactive men and women (35-70 years) with a body mass index of 25-40 kg/m2 and blood pressure (BP) of 120-139/80-89 mm Hg without taking antihypertensive medications. Participants are randomly assigned to RE only, AE only, combined RE and AE (CE), or a no exercise control group. Participants perform supervised exercise at 50%-80% of their relative maximum intensity for both AE and RE, 3 times a week for 60 minutes per session, for 1 year (all 3 groups are time matched). Results The primary outcome is a composite z score including resting BP, low-density lipoprotein cholesterol (LDL-C), fasting glucose, and percent body fat, which is assessed at baseline, 6 months, and 12 months. Diet and outside physical activity are measured throughout the intervention for 1 year. Conclusion CardioRACE (ClinicalTrials.gov NCT03069092) will fill an important knowledge gap regarding the effects of RE, alone or in addition to the well-documented effects of AE. CardioRACE will help generate more comprehensive and synergistic clinical and public health strategies to prevent CVD

Severe mitral valve insufficiency caused by standard surgical aortic valve implantation and its reparation using suture-less prosthesis

Abstract Background Aortic valve stenosis is the most frequent cardiac valve pathology in the western world. Surgical aortic valve replacement is the gold standard for the treatment of significant degenerative aortic valve diseases. Case presentation This case report highlights an unexpected abnormal iatrogenic shortening of the aorto-mitral continuity and its deformity, during traditional AVR using sutured stented aortic prosthesis as the first choice, which caused significant mitral valve regurgitation. The suture-less prosthesis was a rescue choice to restore the geometry and eliminate the deformation of the aorto-mitral continuity. Conclusions Aortic valve replacement using suture-less prosthesis could be a valuable optional choice for lowering the risk of deformation of the aortic annulus and aorto-mitral continuity. It might provide better outcomes in combined procedures