BACKGROUND:Grape seed extract (GSE) is a natural supplement known for its various health benefits, including anti-inflammatory effect. This study aimed to evaluate the effects of GSE supplementation on inflammatory markers, neuropeptide Y, anthropometric measurements, and appetite in obese or overweight individuals.

METHODS AND MATERIALS:A randomized, double-blind clinical trial was performed on 40 obese or overweight subjects who were randomly assigned to receive GSE (300 mg/day) or placebo for a period of 12-weeks. Both groups were under a restricted calorie diet (RCD)(~250 kcal lower than the estimated energy requirement). Anthropometric measurements, biochemical biomarkers and dietary intakes were determined during the study period.

RESULTS:The reductions of body weight, body mass index, waist circumference, and waist to hip ratio were significantly higher in the GSE group compared to the placebo group (P = 0.045, 0.033, 0.029, and 0.021, respectively). Lower levels of neuropeptide Y, tumor necrosis factor alpha, and high sensitivity C-reactive protein were observed in the GSE group in comparison with the placebo group (P = 0.041, 0.001, and 0.034, respectively).

CONCLUSION:GSE supplement with a RCD has favorable effects in reducing anthropometric measurements and inflammatory markers in obese or overweight individuals, and may play an effective role in the treatment of obesity.

IMPORTANCE:Psychological and health-restorative benefits of mind-body therapies have been investigated, but their impact on the immune system remain less defined.

OBJECTIVE:To conduct the first comprehensive review of available controlled trial evidence to evaluate the effects of mind-body therapies on the immune system, focusing on markers of inflammation and anti-viral related immune responses.

METHODS:Data sources included MEDLINE, CINAHL, SPORTDiscus, and PsycINFO through September 1, 2013. Randomized controlled trials published in English evaluating at least four weeks of Tai Chi, Qi Gong, meditation, or Yoga that reported immune outcome measures were selected. Studies were synthesized separately by inflammatory (n = 18), anti-viral related immunity (n = 7), and enumerative (n = 14) outcomes measures. We performed random-effects meta-analyses using standardized mean difference when appropriate.

RESULTS:Thirty-four studies published in 39 articles (total 2, 219 participants) met inclusion criteria. For inflammatory measures, after 7 to 16 weeks of mind-body intervention, there was a moderate effect on reduction of C-reactive protein (effect size [ES], 0.58; 95% confidence interval [CI], 0.04 to 1.12), a small but not statistically significant reduction of interleukin-6 (ES, 0.35; 95% CI, -0.04 to 0.75), and negligible effect on tumor necrosis factor-α (ES, 0.21; 95% CI, -0.15 to 0.58). For anti-viral related immune and enumerative measures, there were negligible effects on CD4 counts (ES, 0.15; 95% CI, -0.04 to 0.34) and natural killer cell counts (ES, 0.12, 95% CI -0.21 to 0.45). Some evidence indicated mind-body therapies increase immune responses to vaccination.

CONCLUSIONS:Mind-body therapies reduce markers of inflammation and influence virus-specific immune responses to vaccination despite minimal evidence suggesting effects on resting anti-viral or enumerative measures. These immunomodulatory effects, albeit incomplete, warrant further methodologically rigorous studies to determine the clinical implications of these findings for inflammatory and infectious disease outcomes.

IMPORTANCE:Psychological and health-restorative benefits of mind-body therapies have been investigated, but their impact on the immune system remain less defined.

OBJECTIVE:To conduct the first comprehensive review of available controlled trial evidence to evaluate the effects of mind-body therapies on the immune system, focusing on markers of inflammation and anti-viral related immune responses.

METHODS:Data sources included MEDLINE, CINAHL, SPORTDiscus, and PsycINFO through September 1, 2013. Randomized controlled trials published in English evaluating at least four weeks of Tai Chi, Qi Gong, meditation, or Yoga that reported immune outcome measures were selected. Studies were synthesized separately by inflammatory (n = 18), anti-viral related immunity (n = 7), and enumerative (n = 14) outcomes measures. We performed random-effects meta-analyses using standardized mean difference when appropriate.

RESULTS:Thirty-four studies published in 39 articles (total 2, 219 participants) met inclusion criteria. For inflammatory measures, after 7 to 16 weeks of mind-body intervention, there was a moderate effect on reduction of C-reactive protein (effect size [ES], 0.58; 95% confidence interval [CI], 0.04 to 1.12), a small but not statistically significant reduction of interleukin-6 (ES, 0.35; 95% CI, -0.04 to 0.75), and negligible effect on tumor necrosis factor-α (ES, 0.21; 95% CI, -0.15 to 0.58). For anti-viral related immune and enumerative measures, there were negligible effects on CD4 counts (ES, 0.15; 95% CI, -0.04 to 0.34) and natural killer cell counts (ES, 0.12, 95% CI -0.21 to 0.45). Some evidence indicated mind-body therapies increase immune responses to vaccination.

CONCLUSIONS:Mind-body therapies reduce markers of inflammation and influence virus-specific immune responses to vaccination despite minimal evidence suggesting effects on resting anti-viral or enumerative measures. These immunomodulatory effects, albeit incomplete, warrant further methodologically rigorous studies to determine the clinical implications of these findings for inflammatory and infectious disease outcomes.

PURPOSE:The purpose of this study was to examine the effects of oral cryotherapy on oral mucositis, reactive oxygen series, inflammatory cytokines, and oral comfort in patients undergoing chemotherapy for gynecologic cancers.

METHODS:Participants were randomly assigned to the experimental group (n=25, receiving oral cryotherapy during chemotherapy) and the control group (n=25, receiving the usual care consisting of 0.9% normal saline gargles three times before meals). Oral mucositis was assessed using the oral assessment guide, while oral comfort was assessed using the oral perception guide. Reactive oxygen series was measured as total oxidant stress, and the level of two inflammatory markers, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), were examined. The data were analyzed using t-test, chi-square test, Fisher's exact test, Mann-Whitney U-test, and repeated measures analysis of variance.

RESULTS:There was a significant difference in the oral mucositis score, reactive oxygen series score, TNF-α level, and oral comfort score between the two groups, and there were significant changes over time and in the group-by-time interactions. There was a significant difference in the IL-6 score between the two groups, but there were no significant changes over time or in the group-by-time interactions.

CONCLUSION:The study results revealed that oral cryotherapy was more effective than the usual care regime of normal saline gargles for reducing oral mucositis, reactive oxygen series, and inflammatory cytokines and for improving oral comfort in gynecologic cancer patients undergoing chemotherapy.

This study was designed to determine whether kefir accentuates the positive health benefits assessed by measures in fitness, body composition, or both, as a measure of cardiovascular disease risk as well as the biomarker C-reactive protein (CRP). Sixty-seven adult males and females aged 18 to 24 yr were assigned to 1 of 4 groups: (1) endurance training + control beverage, (2) endurance training +kefir beverage,(3) active control + control beverage, or (4) active control + kefir beverage. The exercise groups completed 15 wk of structured endurancetraining while the active control groups maintained their usual exercise routine. Additionally, each group was assigned to either a kefir or a calorie/macronutrient matched placebo beverage that was consumed twice per week. No significant interactions were found among groups with respect to outcome variables with the exception of serum CRP. The endurance training was effective in improving 1.5-mile (2.41 km) times and kefir supplementation may have been a factor in attenuating the increase in CRP that was observed over the course of the intervention period. This preliminary study suggests that kefir may be involved in improving the risk profile for cardiovascular disease as defined by CRP.

Purpose . This study examined the effects of tai chi (TC) on biobehavioral factors associated with cardiovascular disease (CVD) risk in women. Design . A randomized trial used a wait-list control group, pretest-posttest design. Data were collected immediately before, immediately after, and 2 months following the intervention. Setting . The study was community based in central Virginia. Subjects . Women aged 35 to 50 years at increased risk for CVD. Intervention . The 8-week intervention built on prior work and was designed to impact biobehavioral factors associated with CVD risk in women. Measures . Biological measures included fasting glucose, insulin, and lipids as well as C-reactive protein and cytokines. Behavioral measures included fatigue, perceived stress, depressive symptoms, social support, mindfulness, self-compassion, and spiritual thoughts and behaviors. Analysis . A mixed effects linear model was used to test for differences between groups across time. Results . In 63 women, TC was shown to decrease fatigue (∂ [difference in group means] = 9.38, p = .001) and granulocyte colony stimulating factor (∂ = 12.61, p = .052). Consistent with the study model and intervention design, significant changes observed 2 months post intervention indicated that TC may help down-regulate proinflammatory cytokines associated with underlying CVD risk, including interferon gamma (∂ = 149.90, p = .002), tumor necrosis factor (∂ = 16.78, p = .002), interleukin (IL) 8 (∂ = 6.47, p = .026), and IL-4 (∂ = 2.13, p = .001), and may increase mindfulness (∂ = .54, p = .021), spiritual thoughts and behaviors (∂= 8.30, p = .009), and self-compassion (∂ = .44, p = .045). Conclusion . This study contributes important insights into the potential benefits and mechanisms of TC and, with further research, may ultimately lead to effective strategies for reducing CVD risk in women earlier in the CVD trajectory.

Ultraviolet (UV) eye irradiation denatures the cells of the intestine. This study examined the action of UVA and UVB on dextran sodium sulfate (DSS)-induced ulcerative colitis. We produced a mouse model of ulcerative colitis by administering DSS for 5 days and irradiated the eye with UVB or UVA for each day of the DSS treatment period. DSS-induced ulcerative colitis was deteriorated by the UVB eye irradiation. Conversely, the symptoms improved with UVA eye irradiation. The levels of adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), urocortin 2, interleukin (IL)-18, IL-6 and histamine in the blood increased after the UVB eye irradiation of DSS-treated mice (UVB/DSS-treated mice). In contrast, theβ-endorphin level in the blood of the UVA/DSS-treated mice increased and the levels of urocortin 2, tumor necrosis factor (TNF)-α and histamine decreased. Furthermore, in the colon, the expression of melanocortin-2 receptors (MC2R) increased in the UVB/DSS-treated mice, while the expression of μ-opioid receptors increased in the UVA/DSS-treated mice. When an ACTH inhibitor was administered, UVB eye irradiation caused the deterioration of DSS-treated ulcerative colitis, while the effect of UV eye irradiation disappeared with a μ-opioid receptor antagonist. These results suggested that UV eye irradiation plays an important role in DSS-induced ulcerative colitis.

The health benefits of exercise and physical activity (PA) have been well researched and it is widely accepted that PA is crucial for maintaining health. One of the mechanisms by which exercise and PA exert their beneficial effects is through peripheral immune system adaptations. To date, very few studies have looked at the regulation of neuroimmune reactions in response to PA. We studied the effect of voluntary wheel running (VWR) on pro- and anti-inflammatory cytokine levels, patterns of glial cell activation and expression of immune receptors in the brains of female C57BL/6 mice. By using homozygous monocyte chemoattractant protein (MCP)-1 null mice, we investigated the role of this key immunoregulatory cytokine in mediating VWR-induced neuroinflammatory responses. We demonstrated that, compared to their sedentary counterparts, C57BL/6 mice exposed for seven weeks to VWR had increased levels of pro- and anti-inflammatory cytokines, markers of glial cell activation and a trend towards increased expression of toll-like receptor (TLR) 4 in the brain. Measurements of serum cytokines revealed that the alterations in brain cytokine levels could not be explained by the effects of PA on peripheral cytokine levels. We propose that the modified neuroimmune status observed in the VWR group represents an activated immune system, as opposed to a less activated immune system in the sedentary group. Since MCP-1 knockout mice displayed differing patterns of pro- and anti-inflammatory brain cytokine expression and glial activation when compared to their wild-type counterparts, we concluded that the effects of VWR on neuroimmune reactions may be modulated by MCP-1. These identified immunomodulatory effects of PA in the brain could contribute to the observed positive relationship between physically active lifestyles and a reduced risk for a number of neurodegenerative diseases that possess a significant neuroinflammatory component.

A broad range of mind-body therapies (MBTs) are used by the public today, and a growing body of clinical and basic sciences research has resulted in evidence-based integration of many MBTs into clinical practice. Basic sciences research has identified some of the physiological correlates of MBT practices, leading to a better understanding of the processes by which emotional, cognitive and psychosocial factors can influence health outcomes and well-being. In particular, results from functional genomics and neuroimaging describe some of the processes involved in the mind-body connection and how these can influence health outcomes. Functional genomic and neurophysiological correlates of MBTs are reviewed, detailing studies showing changes in sympathetic nervous system activation of gene transcription factors involved in immune function and inflammation, electroencephalographic and neuroimaging studies on MBT practices, and persistent changes in neural function and morphology associated with these practices. While the broad diversity of study designs and MBTs studied presents a patchwork of results requiring further validation through replication and longitudinal studies, clear themes emerge for MBTs as immunomodulatory, with effects on leukocyte transcription and function related to inflammatory and innate immune responses, and neuromodulatory, with effects on brain function and morphology relevant for attention, learning, and emotion regulation. By detailing the potential mechanisms of action by which MBTs may influence health outcomes, the data generated by these studies have contributed significantly towards a better understanding of the biological mechanisms underlying MBTs.

A broad range of mind-body therapies (MBTs) are used by the public today, and a growing body of clinical and basic sciences research has resulted in evidence-based integration of many MBTs into clinical practice. Basic sciences research has identified some of the physiological correlates of MBT practices, leading to a better understanding of the processes by which emotional, cognitive and psychosocial factors can influence health outcomes and well-being. In particular, results from functional genomics and neuroimaging describe some of the processes involved in the mind-body connection and how these can influence health outcomes. Functional genomic and neurophysiological correlates of MBTs are reviewed, detailing studies showing changes in sympathetic nervous system activation of gene transcription factors involved in immune function and inflammation, electroencephalographic and neuroimaging studies on MBT practices, and persistent changes in neural function and morphology associated with these practices. While the broad diversity of study designs and MBTs studied presents a patchwork of results requiring further validation through replication and longitudinal studies, clear themes emerge for MBTs as immunomodulatory, with effects on leukocyte transcription and function related to inflammatory and innate immune responses, and neuromodulatory, with effects on brain function and morphology relevant for attention, learning, and emotion regulation. By detailing the potential mechanisms of action by which MBTs may influence health outcomes, the data generated by these studies have contributed significantly towards a better understanding of the biological mechanisms underlying MBTs.

:Playing various musical instruments is the cause of an additional load that affects the condition of dentition and of all organs and body systems at large. Each group of instruments is known to exert a specific impact on the health of the musicians including the undesirable influence on the state of thir oral cavity, such as a change of occlusion and irritation of oral mucosa. Taken together, these effects contribute to the development of periodontal disease, one of the most common dental disorders.

AIM:The objective of the present study was to evaluate the effectiveness of ozone therapy conducted with the use of the generator producing ozone under effect of ultraviolet radiation for the treatment of periodontitis in musicians-instrumentalists.

MATERIAL AND METHODS:The study included 42 musicians presenting with the diagnosis of periodontitis who were divided into two groups depending on the severity of the disease. Group 1 was comprised of the subjects with mild periodontitis while group 2 consisted of the musicians having periodontitis of moderate severity. All the participants in the study remained under observation over 6 months during which they were treated by ozone therapy. The results of the treatment were estimated immediately after the onset of therapy as well as within the next 3 and 6 months. The variance analysis with the use of Student's t-test was employed for the statistical treatment of the data obtained.

RESULTS:The study has demonstrate that ozone therapy resulted in the reduction of inflammation and normalization of local blood circulation in the periodontal tissues; moreover, it extended and lengthened the periods of remission and stabilization of the process of recovery.

CONCLUSION:The results of the study are of primary importance for the maintenance of oral cavity health in musicians-instrumentalists which is indispensable for the maintenance of their successful professional activity.

BACKGROUND:An individual's level of physical activity is one of a set of lifestyle or behavioral factors that can affect immune function and health.

METHODS:The purpose of this review is to summarize the current knowledge in this research field and to review the recent developments in exercise immunology.

RESULTS:Most studies showed that regular exercise training increases immune competence and reduces the risk of infection compared to a sedentary lifestyle. In contrast, acute prolonged bouts of exercise and periods of intensified training are followed by a temporary increase in the risk of infection. This differential regulation can also be found in changes of several humoral and cellular immune parameters. In patients with persistent systemic inflammation, a typical feature of cardiovascular and metabolic diseases, regular exercise training lowers levels of pro-inflammatory cytokines. It is supposed that these effects are mediated by a modification of metabolic signals and innate immune regulation, the release of anti-inflammatory cytokines from muscle, the release of stress hormones, and a process known as browning of adipose tissue.

CONCLUSION:The effect of physical activity on the immune system depends strongly on the mode and intensity of exercise or training. Thereby, considerable knowledge has accumulated concerning the significance of exercise as an important lifestyle factor for prevention and therapy of several chronic diseases.

BACKGROUND:Oxidative stress and inflammation are involved in the pathogenesis of paracetamol-induced renal damage. This study examines the relationship between 8-iso-prostaglandin F2α (8-iso-PGF2α) and platelet activation as well as the relative contribution of the pro-inflammatory markers interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) in enhanced 8-iso-PGF2α biosynthesis, as a complementary onset during analgesic nephropathy induced by chronic treatment with paracetamol. The protective effects of vitamin C on the aforementioned settings are also investigated.

METHODS:Analgesic nephropathy was induced in Wistar rats. Renal function markers and the activity of antioxidant enzymes were determined spectrophotometrically. Immunoassays were used to measure the pro-inflammatory markers and the markers of lipid peroxidation and platelet activation.

RESULTS:The chronic treatment with paracetamol led to renal dysfunction, represented by the elevation of plasma urea and creatinine and the decline in the enzymatic antioxidant status, but did not cause a significant increase in TNF-α and IL-1β. The paracetamol-induced lipid peroxidation and enhanced production of 8-iso-PGF2α was not sufficient to cause changes in platelet activation represented by the level of 11-dehydro thromboxane B2.

CONCLUSIONS:Our results suggest that oxidative stress cannot circumvent the need of stimulation by circulatory cytokines in order to induce inflammatory response and changes in platelet activation during analgesic nephropathy. Vitamin C proved to be beneficial in restoring the renal function markers to normal, increasing the renal enzymatic antioxidant potential, inhibiting lipid peroxidation, and lowering cytokine production and 11-dehydro thromboxane B2 excretion. The observed effects of vitamin C offer support for its potential use as protective treatment in cases of chronic paracetamol overdose.

UNLABELLED:In an increasingly ageing population, the incidence of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease are rising. While the aetiologies of these disorders are different, a number of common mechanisms that underlie their neurodegenerative components have been elucidated; namely neuroinflammation, excitotoxicity, mitochondrial dysfunction and reduced trophic support. Current therapies focus on treatment of the symptoms and attempt to delay the progression of these diseases but there is currently no cure. Modulation of the endogenous cannabinoid system is emerging as a potentially viable option in the treatment of neurodegeneration. Endocannabinoid signalling has been found to be altered in many neurodegenerative disorders. To this end, pharmacological manipulation of the endogenous cannabinoid system, as well as application of phytocannabinoids and synthetic cannabinoids have been investigated. Signalling from the CB1 and CB2 receptors are known to be involved in the regulation of Ca(2+) homeostasis, mitochondrial function, trophic support and inflammatory status, respectively, while other receptors gated by cannabinoids such as PPARγ, are gaining interest in their anti-inflammatory properties. Through multiple lines of evidence, this evolutionarily conserved neurosignalling system has shown neuroprotective capabilities and is therefore a potential target for neurodegenerative disorders. This review details the mechanisms of neurodegeneration and highlights the beneficial effects of cannabinoid treatment.

LINKED ARTICLES:This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit undefined

. Inflammation is associated with strenuous exercise and methylsulfonylmethane (MSM) has been shown to have anti-inflammatory properties.. Physically active men were supplemented with either placebo or MSM (3 grams per day) for 28 days before performing 100 repetitions of eccentric knee extension exercise.andtesting consisted of evaluating cytokine production in blood (whole blood and isolated peripheral blood mononuclear cells (PBMCs)) exposed to lipopolysaccharide (LPS), before and through 72 hours after exercise, whiletesting included the evaluation of cytokines before and through 72 hours after exercise.. LPS stimulation of whole blood after MSM supplementation resulted in decreased induction of IL-1, with no effect on IL-6, TNF-, or IL-8. After exercise, there was a reduced response to LPS in the placebo, but MSM resulted in robust release of IL-6 and TNF-. A small decrease in resting levels of proinflammatory cytokines was noted with MSM, while an acute postexercise increase in IL-10 was observed with MSM.. Strenuous exercise causes a robust inflammatory reaction that precludes the cells from efficiently responding to additional stimuli. MSM appears to dampen the release of inflammatory molecules in response to exercise, resulting in a less incendiary environment, allowing cells to still have the capacity to mount an appropriate response to an additional stimulus after exercise.

Ozone therapy is an effective medical treatment for various diseases. A previous study has demonstrated its reno-protective effect in chronic kidney disease (CKD), but the mechanism involved is not completely known. This study produced the 5/6 nephrectomized CKD rat model and investigated whether the reno-protective effect of ozone therapy was achieved by its anti-inflammatory property through the modulation of the NLRP3 inflammasome. The results showed that ozone therapy at a low concentration improved renal function and ameliorated renal morphological injury in 5/6 nephrectomized rats. The expression of NLRP3, ASC, and caspase-1-p10 in the kidney of these rats was simultaneously lowered by ozone therapy. Moreover, renal inflammation caused by IL-1β was significantly alleviated by ozone therapy. The Pearson correlation analysis indicated that the protein level of IL-1β was positively correlated with renal injury scores. Taken together, these results indicated that ozone therapy might reduce sterile renal inflammation and slow down CKD progression through the modulation of the NLRP3 inflammasome in 5/6 nephrectomized rats.

Chronic inflammation is involved in the pathogenesis of insulin resistance, atherosclerosis, neurodegeneration, and tumour growth. Regular exercise offers protection against type 2 diabetes, cardiovascular diseases, colon cancer, breast cancer, and dementia. Evidence suggests that the protective effect of exercise may to some extent be ascribed to the antiinflammatory effect of regular exercise. Here we suggest that exercise may exert its anti-inflammatory effect via a reduction in visceral fat mass and/or by induction of an anti-inflammatory environment with each bout of exercise. According to our theory, such effects may in part be mediated via muscle-derived peptides, so-called"myokines". Contracting skeletal muscles release myokines with endocrine effects, mediating direct anti-inflammatory effects, and/or specific effects on visceral fat. Other myokines work locally within the muscle and exert their effects on signalling pathways involved in fat oxidation and glucose uptake. By mediating anti-inflammatory effects in the muscle itself, myokines may also counteract TNF-driven insulin resistance. In conclusion, exercise-induced myokines appear to be involved in mediating both systemic as well as local anti-inflammatory effects.

A higher level of physical activity (PA) is associated with decreased risk of mortality, dementia, and depression, yet the mechanisms involved are not well understood, and little evidence exists for Mexican Americans. With data from the Sacramento Area Latino Study on Aging (1998-2007), we used Cox proportional hazards regression to separately evaluate associations of baseline PA level with mortality, dementia/cognitive impairment without dementia (CIND), and depressive symptoms, and we estimated the mediating effects of inflammatory markers in additive hazard models. A low level of PA (<35 metabolic equivalent of task-hours/week) was associated with increased mortality (hazard ratio (HR) = 1.50, 95% confidence interval (CI): 1.20, 1.88), dementia/CIND (HR = 1.37, 95% CI: 0.96, 1.96), and depressive symptoms (HR = 1.23, 95% CI: 1.00, 1.52). A low PA level added 512 (95% CI: -34, 1,058) cases of dementia/CIND per 100,000 person-years at risk (direct effect), while, through a mediating path, interleukin 6 (IL-6) added another 49 (95% CI: 5, 94) cases, or 9% of the total effect. For mortality, 8%-10% of the PA total effect was mediated through IL-6, tumor necrosis factorα (TNF-α), or TNF-α receptors. None of the inflammatory markers mediated the association between PA and depressive symptoms. Our results suggest that antiinflammation (especially as assessed by IL-6 and TNF-α levels) may partly explain how PA protects against dementia/CIND and mortality.

The aim of the current study was to test the hypothesis that forest bathing would be beneficial for elderly patients with chronic heart failure (CHF) as an adjunctive therapy. Two groups of participants with CHF were simultaneously sent to the forest or an urban control area for a four-day trip, respectively. Subjects exposed to the forest site showed a significant reduction of brain natriuretic peptide (BNP) in comparison to that of the city group and their own baseline levels. The values for the cardiovascular disease related pathological factors, including endothelin-1 (ET-1), and constituents of the renin-angiotensin system (RAS), including renin, angiotensinogen (AGT), angiotensin II (ANGII), and ANGII receptor type 1 or 2 (AT1 or AT2) in subjects exposed to the forest environment were lower than those in the urban control group. Obviously, a decreased level of inflammatory cytokines and improved antioxidant function was observed in the forest group rather than in the city group. The assessment of the profile of mood states (POMS) indicated that the negative emotional mood state was alleviated after forest bathing. As anticipated, a better air quality in the forest site was observed according to the detection of PM2.5 (particulate matter<2.5μm) and negative ions. These results provided direct evidence that forest bathing has a beneficial effect on CHF patients, and thus may pave the way for potential development of forest bathing as an effective adjunctive therapy on cardiovascular disorders.

Although many cardiovascular (CVD) medications, such as antithrombotics, statins, and antihypertensives, have been identified to treat atherosclerosis, at most, many of these therapeutic agents only delay its progression. A growing body of evidence suggests physical exercise could be implemented as a non-pharmacologic treatment due to its pro-metabolic, multisystemic, and anti-inflammatory benefits. Specifically, it has been discovered that certain anti-inflammatory peptides, metabolites, and RNA species (collectively termed"exerkines") are released in response to exercise that could facilitate these benefits and could serve as potential therapeutic targets for atherosclerosis. However, much of the relationship between exercise and these exerkines remains unanswered, and there are several challenges in the discovery and validation of these exerkines. This review primarily highlights major anti-inflammatory exerkines that could serve as potential therapeutic targets for atherosclerosis. To provide some context and comparison for the therapeutic potential of exerkines, the anti-inflammatory, multisystemic benefits of exercise, the basic mechanisms of atherosclerosis, and the limited efficacies of current anti-inflammatory therapeutics for atherosclerosis are briefly summarized. Finally, key challenges and future directions for exploiting these exerkines in the treatment of atherosclerosis are discussed.