Among the most important traditional medicinal fungi, Ganoderma lucidum has been used as a therapeutic agent for the treatment of numerous diseases, including cancer, in Oriental countries. The aim of this study is to investigate the anti-inflammatory, anticancer and anti-metastatic activities of Ganoderma lucidum extracts in melanoma and triple-negative breast cancer cells. Ganoderma lucidum extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS) and pretreatment with Ganoderma lucidum extract at different concentrations. Our study demonstrates, for the first time, how Ganoderma lucidum extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly, Ganoderma lucidum extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of Ganoderma lucidum extract for the therapeutic management of melanoma and human triple-negative breast cancer.

INTRODUCTION:Cannabidiol (CBD) containing products are available in a plethora of flavors including oral, sublingual, and inhalable forms. Immunotoxicological effects of CBD containing liquids were assessed by hypothesizing that CBD regulates oxidative stress and lipopolysaccharide (LPS) induced inflammatory responses in macrophages, epithelial cells, and fibroblasts.

METHODS:Epithelial cells (BEAS-2B and NHBE), macrophages (U937), and lung fibroblast cells (HFL-1) were treated with varying CBD concentrations or exposed to CBD aerosols and reactive oxygen species (ROS), and the inflammatory mediators, were measured. Furthermore, monocytes and epithelial cells were stimulated with LPS in combination with CBD or dexamethasone to understand the anti-inflammatory effects of CBD.

RESULTS:CBD showed differential effects on IL-8 and MCP-1, and acellular and cellular ROS levels. CBD significantly attenuated LPS-induced NF-κB activity and IL-8 and MCP-1 release from macrophages. Cytokine array data depicted a differential cytokine response due to CBD. Inflammatory mediators, IL-8, serpin E1, CXCL1, IL-6, MIF, IFN-γ, MCP-1, RANTES, and TNF-α were induced, whereas MCP-1/CCL2, CCL5, eotaxin, IL-1ra, and IL-2 were reduced. CBD and dexamethasone treatments reduced the IL-8 level induced by LPS when the cells were treated individually, but showed antagonistic effects when used in combination via MCPIP (monocytic chemotactic protein-induced protein).

CONCLUSION:CBD differentially regulated basal pro-inflammatory response and attenuated both LPS-induced cytokine release and NF-κB activity in monocytes, similar to dexamethasone. Thus, CBD has a differential inflammatory response and acts as an anti-inflammatory agent in pro-inflammatory conditions but acts as an antagonist with steroids, overriding the anti-inflammatory potential of steroids when used in combination.

BACKGROUND: The aim of this study was to examine the impact of elemental diet on mucosal inflammation in Crohn's disease (CD), mainly by cytokine measurements.

METHODS: Twenty-eight consecutive patients with active CD were treated with an elemental diet (Elental) for 4 weeks. The mucosal biopsies were obtained from the terminal ileum and large bowel before and after treatment. As a control group, mucosal biopsies were obtained from 20 patients without inflammation. Mucosal cytokine concentrations were measured by enzyme-linked immunosorbent assay.

RESULTS: After treatment, clinical remission was achieved in 20 patients (71%). Endoscopic healing and improvement rates were 44% and 76% in the terminal ileum and 39% and 78% in the large bowel, respectively. Histologic healing and improvement rates were 19% and 54% in the terminal ileum and 20% and 55% in the large bowel, respectively. Before treatment, the mucosal concentrations of interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1ra), IL-6, IL-8, and tumor necrosis factor-alpha in the ileum and large bowel were significantly higher than in controls. These cytokine concentrations decreased to the levels of control after treatment. IL-1ra/IL-1beta ratio in the ileum and large bowel was significantly lower than in controls before treatment. The ratio increased to the level of controls after treatment. The endoscopic and histologic healing of the mucosal inflammation was associated with a decline of the mucosal cytokines and an increase of the IL-1ra/IL-1beta ratio.

CONCLUSIONS: The elemental diet (Elental) reduced mucosal cytokine production and corrected an imbalance between proinflammatory and anti-inflammatory cytokines in CD.

Background Low-grade inflammation, largely mediated by monocyte-derived macrophages, contributes to atherosclerosis. Sedentary behavior is associated with atherosclerosis and cardiovascular diseases (CVD). We examined whether reducing sedentary behavior and improving walking time improves monocyte inflammatory phenotype in subjects with increased cardiovascular risk.

Methods and Results Across 2 waves, 16 individuals with increased cardiovascular risk performed a 16-week intervention study (age 64±6 years, body mass index 29.9±4.3 kg/m), using a device with vibration feedback to promote physical activity. Before and after intervention, we objectively examined physical activity (ActivPAL), cytokine production capacity after ex vivo stimulation in peripheral blood mononuclear cells, metabolism of peripheral blood mononuclear cells, circulating cytokine concentrations, and monocyte immunophenotype. Overall, no significant increase in walking time was found (1.9±0.7 to 2.2±1.2 h/day,=0.07). However, strong, inverse correlations were observed between the change in walking time and the change in production of interleukin (IL)-1β, IL-6, IL-8, and IL-10 after lipopolysaccharide stimulation (=-0.655, -0.844, -0.672, and -0.781, respectively, all<0.05). After intervention optimization based on feedback from wave 1, participants in wave 2 (n=8) showed an increase in walking time (2.2±0.8 to 3.0±1.3 h/day,=0.001) and attenuated cytokine production of IL-6, IL-8, and IL-10 (all<0.05). Glycolysis (=0.08) and maximal OXPHOS (=0.04) of peripheral blood mononuclear cells decreased after intervention. Lower IL-6 concentrations (=0.06) and monocyte percentages (<0.05), but no changes in monocyte subsets were found.

Conclusions Successfully improving walking time shifts innate immune function towards a less proinflammatory state, characterized by a lower capacity to produce inflammatory cytokines, in individuals with increased cardiovascular risk. Clinical Trial Registration Information URL: undefined Unique identifier: NTR6387.

A triathlon, which consists of swimming, bicycling, and running, is a high-intensity and long-term form of exercise that can cause injuries such as muscular damage, inflammation, oxidative stress, and energy imbalance. Probiotics are thought to play an important role in disease incidence, health promotion, and nutrient metabolism, but only a few studies have focused on physiological adaptations to exercise in sports science. Previous studies indicated that Lactobacillus supplementation could improve oxidative stress and inflammatory responses. We investigate the effects of Lactobacillus plantarum PS128 supplementation on triathletes for possible physiological adaptation. The triathletes were assigned to one of two groups with different exercise intensity stimulations with different time-points to investigate the effects of body compositions, inflammation, oxidative stress, performance, fatigue, and injury-related biochemical indices. L. plantarum PS128 supplementation, combined with training, can significantly alleviate oxidative stress (such as creatine kinase, Thioredoxin, and Myeloperoxidase indices) after a triathlon (p<0.05). This effect is possibly regulated by a 6⁻13% decrease of indicated pro-inflammation (TNF-α, IL-6, and IL-8) cytokines (p<0.05) and 55% increase of anti-inflammation (IL-10) cytokines (p<0.05) after intensive exercise stimulation. In addition, L. plantarum PS128 can also substantially increase 24⁻69% of plasma-branched amino acids (p<0.05) and elevate exercise performance, as compared to the placebo group (p<0.05). In conclusion, L. plantarum PS128 may be a potential ergogenic aid for better training management, physiological adaptations to exercise, and health promotion.

Psychological factors have been shown to influence the process of wound healing. This study examined the effect of Mindfulness-Based Stress Reduction (MBSR) on the speed of wound healing. The local production of pro-inflammatory cytokines and growth factors was studied as potential underlying mechanism. Forty-nine adults were randomly allocated to a waiting-list control group (n = 26) or an 8-week MBSR group (n = 23). Pre- and post-intervention/waiting period assessment for both groups consisted of questionnaires. Standardized skin wounds were induced on the forearm using a suction blister method. Primary outcomes were skin permeability and reduction in wound size monitored once a day at day 3, 4, 5, 6, 7, and 10 after injury. Secondary outcomes were cytokines and growth factors and were measured in wound exudates obtained at 3, 6, and 22 h after wounding. Although there was no overall condition effect on skin permeability or wound size, post hoc analyses indicated that larger increases in mindfulness were related to greater reductions in skin permeability 3 and 4 days after wound induction. In addition, MBSR was associated with lower levels of interleukin (IL)-8 and placental growth factor in the wound fluid 22 h after wound induction. These outcomes suggest that increasing mindfulness by MBSR might have beneficial effects on early stages of wound healing. Trial Registration NTR3652, http://www.trialregister.nl.

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.

BACKGROUND:Self-report measures indicate that Yoga practices are perceived to reduce stress; however, molecular mechanisms through which YB affects stress are just beginning to be understood. While invasive sampling such as blood has been widely used to measure biological indicators such as pro-inflammatory biomarkers, the use of saliva to measure changes in various biomolecules has been increasingly recognized. As Yoga practice stimulates salivary secretion, and saliva is considered a source of biomarkers, changes in salivary cytokines before and after Yogic breathing exercise as specified in an ancient Tamil script, Thirumanthiram, were examined using a Cytokine Multiplex to compare to Attention Control (AC) group.

METHODS:Twenty healthy volunteers were randomized into two groups stratified by gender (N = 10 per YB and AC groups); The YB group performed two YB exercises, each for ten minutes, for a total of twenty minutes in a single session as directed by a trained Yoga instructor. The AC group read a text of their choice for 20 min. Saliva was collected immediately after YB training at 0, 5,10, 15 and 20 min and analyzed by Multiplex enzyme linked immunosorbent assay (ELISA).

RESULTS:The levels of interleukin (IL)-1β, IL-8, and monocyte chemotactic protein -1 (MCP-1) were significantly reduced in YB group when compared to AC group. The level of reduction of IL-8 was significant at all time points tested, whereas IL-1β showed reduction at 15 and 20 min time points (p < 0.05), and MCP-1 level was marginally different at 5-20 min. There were no significant differences between YB and AC groups in the salivary levels of IL-1RA, IL-6, IL-10, IL-17, IP-10, MIP-1b, and TNF-α.

CONCLUSIONS:These data are the first to demonstrate the feasibility of detecting salivary cytokines using multiplex assay in response to a Yoga practice. This study was registered in Clinical Trials.gov # NCT02108769.