Adipose tissue accumulation is an independent and modifiable risk factor for cardiovascular disease (CVD). The recent CVD European Guidelines strongly recommend regular physical exercise (PE) as a management strategy for prevention and treatment of CVD associated with metabolic disorders and obesity. Although mutations as well as common genetic variants, including theVal66Met polymorphism, are associated with increased body weight, eating and neuropsychiatric disorders, and myocardial infarction, the effect of this polymorphism on adipose tissue accumulation and regulation as well as its relation to obesity/thrombosis remains to be elucidated. Here, we showed that white adipose tissue (WAT) of humanized knock-in BDNFVal66Met (BDNF) mice is characterized by an altered morphology and an enhanced inflammatory profile compared to wild-type BDNF. Four weeks of voluntary PE restored the adipocyte size distribution, counteracted the inflammatory profile of adipose tissue, and prevented the prothrombotic phenotype displayed, per se, by BDNFmice. C3H10T1/2 cells treated with the Pro-BDNFMet peptide well recapitulated the gene alterations observed in BDNFWAT mice. In conclusion, these data indicate the strong impact of lifestyle, in particular of the beneficial effect of PE, on the management of arterial thrombosis and inflammation associated with obesity in relation to the specific BDNF Val66Met mutation.

Accumulating evidence indicates that exercise can enhance brain function and attenuate neurodegeneration. Besides improving neuroplasticity by altering the synaptic structure and function in various brain regions, exercise also modulates multiple systems that are known to regulate neuroinflammation and glial activation. Activated microglia and several pro-inflammatory cytokines play active roles in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. The purpose of this review is to highlight the impacts of exercise on microglial activation. Possible mechanisms involved in exercise-modulated microglial activation are also discussed. Undoubtedly, more studies are needed in order to disclose the detailed mechanisms, but this approach offers therapeutic potential for improving the brain health of millions of aging people where pharmacological intervention has failed.

BACKGROUND: Secretory phospholipases A2 (sPLA2) have functions relevant to asthmatic inflammation, including eicosanoid synthesis and effects on dendritic cells and T cells. The aim of this study was to measure sPLA2 activity in patients with stable and acute asthma and to assess potential associations with body mass index (BMI), and plasma cholesterol and vitamin C concentrations. METHODS: Plasma sPLA2 activity and concentrations of cholesterol and vitamin C were measured in 23 control subjects and 61 subjects with stable asthma (42 mild to moderate, 19 severe). In addition, sPLA2 activity was measured in 36 patients experiencing acute asthma and in 22 of these patients after recovery from the acute attack. RESULTS: sPLA2 activity was not significantly greater in severe (499.9 U; 95% confidence interval (CI) 439.4 to 560.4) compared with mild to moderate asthmatic subjects (464.8; 95% CI 425.3 to 504.3) or control subjects (445.7; 95% CI 392.1 to 499.4), although it was higher in patients with acute asthma (581.6; 95% CI 541.2 to 622.0; p<0.001). Male gender, high plasma cholesterol, increased BMI and atopy were associated with increased sPLA2 activity, while plasma vitamin C was inversely correlated with sPLA2 activity in patients with stable asthma and in control subjects. There were significant interactions between gender and plasma cholesterol and between gender and vitamin C in relation to sPLA2 activity. CONCLUSIONS: Plasma sPLA2 may provide a biological link between asthma, inflammation, increased BMI, lipid metabolism and antioxidants. Interactions among these factors may be pertinent to the pathophysiology and increasing prevalence of both asthma and obesity.

BACKGROUND AND AIMS:High dietary polyphenol intake is associated with reduced all-cause mortality and lower incidence of cardiovascular events. However, the mechanisms involved are not fully understood. The aim of this sub-study of the PREDIMED (Prevention with Mediterranean diet) trial was to analyze the relationship of polyphenol intake measured by total urinary polyphenol excretion (TPE), with circulating inflammatory biomarkers and cardiovascular risk factors in elderly individuals.

MATERIALS AND METHODS:A sub-study of 1139 high-risk participants was carried out within the PREDIMED trial. The subjects were randomly assigned to a low-fat control diet or to two Mediterranean diets, supplemented with either extra-virgin olive oil or nuts. Dietary intake, anthropometrics, clinical and laboratory assessments including inflammatory biomarkers, and urinary TPE were measured at baseline and after one-year intervention.

RESULTS:Participants in the highest tertile of changes in urinary TPE (T3) showed significant lower plasma inflammatory biomarkers [VCAM-1 (-9.47 np/mL), ICAM-1 (-14.71 np/mL), IL-6 (-1.21 pg/mL), TNF-α (-7.05 pg/mL), and MCP-1 (-3.36 pg/mL)] than those in the lowest tertile (T1, P < 0.02; all). A significant inverse correlation existed between urinary TPE and plasma concentration of VCAM-1(r = -0.301; P < 0.001). In addition, systolic and diastolic blood pressure (BP) decreased and plasma HDL-cholesterol increased in parallel with increasing urinary TPE (T3 vs T1)(P < 0.005 and P = 0.004, respectively).

CONCLUSIONS:Increases in polyphenol intake measured as urinary TPE are associated with decreased inflammatory biomarkers, suggesting a dose-dependent anti-inflammatory effect of polyphenols. In addition, high polyphenol intake improves cardiovascular risk factors, mainly BP and the lipid profile. This article is protected by copyright. All rights reserved.

While beneficial properties of physical activity and exercise on human health have been extensively reported in literature, the exact mechanism(s) underpinning impacts of exercise are not well understood. Focusing on metabolic disorders, as the main causes of social and economic burden in current century, exercise exhibited promising effects in prevention, alleviation and retardation of these disorders including, type 2 diabetes (T2D), Alzheimer's disease (AD), major depressive disorder (MDD) and obesity. Recent evidence has unmasked the role of mitochondrial dysfunction and chronic inflammation in pathophysiology of these disorders. Despite of the wealth of research on the etiology of metabolic disorders, intimate connections between these diseases, complex pathophysiology and their comorbidity still remains a challenging dilemma. In addition, although physical activity has improving effects on human health, it is not clear that how exercise is able to exert its modulatory effects on outcomes of metabolic disorders. Among several mechanisms, we assumed the hypothesis that exercise mitigates the production of mitochondrial-induced reactive oxygen species (ROS) and danger associated molecular patterns (DAMPs) as the main triggering factors for inflammasome formation. Since inflammasomes are of highly deleterious molecules relevant to pathogenesis of metabolic disorders, we hypothesized that beneficial effects of exercise may be associated with its ability to enhance the mitochondrial biogenesis and glucose transportation through generation of brain derived neurotrophic factor (BDNF). Also, we proposed that boosting impact of exercise on autophagy process accelerates the elimination of damaged mitochondria and thus, results in considerable decrease in production of ROS and DAMPs and consequently sterile inflammation.

The aim of this study was to identify the role of thioredoxin-interacting protein (TXNIP) and its interaction with antioxidants in the activation of the fructose-induced NOD-like receptor protein 3 (NLRP3) inflammasome in human macrophages. The study was performed with U937 and THP-1 macrophage cell lines. Total reactive oxygen species (ROS) were measured by flow cytometry. Interleukin-1β (IL-1β), IL-18, NLRP3, TXNIP, and caspase-1 protein expression was detected using western blotting. Quantitative real-time polymerase chain reaction was used to detect IL-1β, IL-18, and caspase-1 gene expression. Intracellular shuttling of TXNIP was assessed by immunofluorescent staining with MitoTracker Red. Increased production of ROS and expression of IL-1β, IL-18, and caspase-1 genes and proteins were observed in U937 and THP-1 cells incubated with fructose and were effectively inhibited by quercetin and ascorbic acid. Intracellular shuttling of TXNIP from the nucleus into the mitochondria was detected under stimulation with fructose, which was also attenuated by antioxidants quercetin and ascorbic acid but not butylated hydroxyanisole. Treatment of macrophages with fructose promoted the association between TXNIP and NLRP3 in the cytosol, sequentially resulting in the activation of the NLRP3 inflammasome. This study revealed that intracellular TXNIP protein is a critical regulator of activation of the fructose-induced NLRP3 inflammasome, which can be effectively blocked by the antioxidants quercetin and ascorbic acid.

Curcumin is a widely known natural phytochemical from plant Curcuma longa. In recent years, curcumin has received increasing attention because of its capability to induce apoptosis and inhibit cell proliferation as well as its anti-inflammatory properties in different cancer cells. However, the therapeutic benefits of curcumin are severely hampered due to its particularly low absorption via trans-dermal or oral bioavailability. Phototherapy with visible light is gaining more and more support in dermatological therapy. Red light is part of the visible light spectrum, which is able to deeply penetrate the skin to about 6 mm, and directly affect the fibroblast of the skin dermis. Blue light is UV-free irradiation which is fit for treating chronic inflammation diseases. In this study, we show that curcumin at low concentrations (1.25-3.12μM) has a strong anti-proliferative effect on TNF-α-induced psoriasis-like inflammation when applied in combination with light-emitting-diode devices. The treatment was especially effective when LED blue light at 405 nm was combined with red light at 630 or 660 nm, which markedly amplified the anti-proliferative and apoptosis-inducing effects of curcumin. The experimental results demonstrated that this treatment reduced the viability of human skin keratinocytes, decreased cell proliferation, induced apoptosis, inhibited NF-κB activity and activated caspase-8 and caspase-9 while preserving the cell membrane integrity. Moreover, the combined treatment also down-regulated the phosphorylation level of Akt and ERK. Taken together, our results indicated that the combination of curcumin with LED blue light united red light irradiation can attain a higher efficiency of regulating proliferation and apoptosis in skin keratinocytes.

Background:Cardiovascular disease is the most common cause of mortality in haemodialysis (HD) patients and is highly predicted by markers of chronic inflammation. Regular exercise may have beneficial anti-inflammatory effects, but this is unclear in HD patients. This study assessed the effect of regular intradialytic exercise on soluble inflammatory factors and inflammatory leucocyte phenotypes.

Methods:Twenty-two HD patients from a centre where intradialytic cycling was offered thrice weekly and 16 HD patients receiving usual care volunteered. Exercising patients aimed to cycle for 30 min at rating of perceived exertion of 'somewhat hard'. Baseline characteristics were compared with 16 healthy age-matched individuals. Physical function, soluble inflammatory markers and leucocyte phenotypes were assessed again after 6 months of regular exercise.

Results:Patients were less active than their healthy counterparts and had significant elevations in measures of inflammation [interleukin-6 (IL-6), C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), intermediate and non-classical monocytes; all P < 0.001]. Six months of regular intradialytic exercise improved physical function (sit-to-stand 60). After 6 months, the proportion of intermediate monocytes in the exercising patients reduced compared with non-exercisers (7.58 ± 1.68% to 6.38 ± 1.81% versus 6.86 ± 1.45% to 7.88 ± 1.66%; P < 0.01). Numbers (but not proportion) of regulatory T cells decreased in the non-exercising patients only (P<0.05). Training had no significant effect on circulating IL-6, CRP or TNF-α concentrations.

Conclusions:These findings suggest that regular intradialytic exercise is associated with an anti-inflammatory effect at a circulating cellular level but not in circulating cytokines. This may be protective against the increased risk of cardiovascular disease and mortality that is associated with chronic inflammation and elevated numbers of intermediate monocytes.

Objectives:Lutein/zeaxanthin isomers (L/Zi), the major carotenoids, have demonstrated potent antioxidant and antiinflammation. This study was conducted to clarify the effects of L/Zi on brain transcription and brain-derived neurotrophic factors and synaptic proteins combined with exercise training in rats.

Methods:Wistar rats (age: 8 wks) were allocated into four groups: (i) Control: no treatments (ii) L/Zi: Rats treated with L/Zi (100 mg L/Zi/kg BW); (iii) Exercise: Rats with regular exercise only, (iv) Exercise + L/Zi: Rats with combined treatment of L/Zi (100 mg L/Zi/kg BW) and regular exercise. The exercise practice was carried out on a motor-driven rodent treadmill at 25 m/min, 45 min/day, 5 d/week for 8 wks.

Results:Rats with combined treatment of L/Zi (100 mg L/Zi/kg BW) and regular exercise. The exercise practice was carried out on a motor-driven rodent treadmill at 25 m/min, 45 min/day, 5 d/week for 8 wks. Brain nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase-1(HO-1) levels increased and nuclear factor (NF-κB) reduced in the combined group. In addition, L/Zi supplementation increased cerebral cortex brain-derived neurotrophic factor (BDNF), synapsin I, synaptophysin (SYP) and growth-associated protein-43 (GAP-43) levels both control and exercised rats (<0.001 for all). The highest cerebral cortex BDNF, synapsin I, SYP and GAP-43 levels were detected in the combined group.

Conclusions:These results suggest that regular exercise training with L/Zi may improve brain function by regulating transcription and brain-derived neurotrophic factors and synaptic proteins in rats.

Funding Sources:This study was supported by the Omniactive Health Technologies (NJ, USA) and partially supported by the Turkish Academy of Sciences (Ankara, Turkey).

A chronic inflammatory state is a major characteristic of the aging process, and physical activity is proposed as a key component for healthy aging. Our aim was to evaluate the body composition, hypertension, lipid profile, and inflammatory status of older adults, and these factors' association with physical activity. A total of 116 elderly volunteers were categorized into terciles of quantitative metabolic equivalents of task (MET). Subjects in the first and third terciles were defined as sedentary and active subjects, respectively. Anthropometric and biochemical parameters, hemograms, and inflammatory markers were measured in plasma or peripheral mononuclear blood cells (PBMCs). The active groups exercised more than their sedentary counterparts. The practice of physical activity was accompanied by lower weight, fat mass, body mass index, and diastolic blood pressure when compared to a more sedentary life-style. Physical activity also lowered the haematocrit and total leukocyte, neutrophil, and lymphocyte counts. The practice of exercise induced a decrease in the IL-6 circulating levels and the TLR2 protein levels in PBMCs, while the expression of the anti-inflammatory IL-10 was activated in active subjects. The regular practice of physical activity exerts beneficial effects on body composition and the anti-inflammatory status of old people.

Caloric restriction (CR), in the absence of malnutrition, delays aging and prevents aging-related diseases through multiple mechanisms. A reduction in chronic inflammation is widely observed in experimental models of caloric restriction. The low inflammation status may contribute to the reduced incidence of osteoporosis, Alzheimer's disease, cardiovascular diseases and cancer in the aging subjects. The association of caloric restriction with low inflammation suggests a role of energy accumulation in the origin of the chronic inflammation. This point is enforced by recent advances in obesity research. Abundant literature on obesity suggests that chronic inflammation is a consequence of energy accumulation in the body. The emerging evidence strongly supports that the inflammatory response induces energy expenditure in a feedback manner to fight against energy surplus in obesity. If this feedback system is deficient (Inflammation Resistance), energy expenditure will be reduced and energy accumulation will lead to obesity. In this perspective, we propose that an increase in inflammation in obesity promotes energy expenditure with a goal to get rid of energy surplus. A decrease in inflammation under caloric restriction contributes to energy saving. Inflammation is a mechanism for energy balance in the body. Inflammation resistance will lead to obesity. We will review the recent literature in support of the viewpoints.

AIMS:To determine serum salicylic acid concentrations in non-vegetarians and vegetarians not taking salicylate drugs, and to compare these concentrations with those found in patients taking aspirin, 75 mg daily.

METHODS:Serum samples were obtained from vegetarians (n = 37) and non-vegetarians (n = 39) not taking salicylate drugs. Non-vegetarians and vegetarians were recruited from the community and from a Buddhist monastery, respectively, in Dumfries and Galloway, Scotland. Patients (n = 14) taking aspirin (75 mg daily) were recruited from the Dumfries diabetic clinic. Serum salicylic acid concentrations were determined using a high performance liquid chromatography method with electrochemical detection.

RESULTS:Salicylic acid was detected in every serum sample analysed. Higher serum concentrations of salicylic acid were found in vegetarians than non-vegetarians: median concentrations of 0.11 (range, 0.04-2.47) micromol/litre and 0.07 (range, 0.02-0.20) micromol/litre, respectively; the median of the difference was 0.05 micromol/litre (95% confidence interval for difference, 0.03 to 0.08; p<0.0001). The median serum concentration of salicylic acid in patients taking aspirin (75 mg daily) was 10.03 (range, 0.23-25.40) micromol/litre, which was significantly higher than that found in non-vegetarians and vegetarians. There was overlap in serum salicylic acid concentrations between the vegetarians and patients taking aspirin.

CONCLUSIONS:Salicylic acid, a non-steroidal anti-inflammatory drug, is present in fruits and vegetables and is found in higher concentrations in vegetarians than non-vegetarians. This suggests that a diet rich in fruits and vegetables contributes to the presence of salicylic acid in vivo. There is overlap between the serum concentrations of salicylic acid in vegetarians and patients taking aspirin, 75 mg daily. These findings may explain, in part, the health promoting effects of dietary fruits and vegetables.

We have investigated whether a 1:1 combination of botanical extracts enriched in eitherΔ(9)-tetrahydrocannabinol (Δ(9)-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex, is neuroprotective in Huntington's disease (HD), using an experimental model of this disease generated by unilateral lesions of the striatum with the mitochondrial complex II inhibitor malonate. This toxin damages striatal neurons by mechanisms that primarily involve apoptosis and microglial activation. We monitored the extent of this damage and the possible preservation of the striatal parenchyma by treatment with a Sativex-like combination of phytocannabinoidsusing different histological and biochemical markers. Results were as follows: (i) malonate increased the volume of edema measured by in vivo NMR imaging and the Sativex-like combination of phytocannabinoids partially reduced this increase; (ii) malonate reduced the number of Nissl-stained cells, while enhancing the number of degenerating cells stained with FluoroJade-B, and the Sativex-like combination of phytocannabinoids reversed both effects; (iii) malonate caused a strong glial activation (i.e., reactive microglia labeled with Iba-1, and astrogliosis labeled with GFAP) and the Sativex-like combination of phytocannabinoids attenuated both responses; and (iv) malonate increased the expression of inducible nitric oxide synthase and the neurotrophin IGF-1, and both responses were attenuated after the treatment with the Sativex-like combination of phytocannabinoids. We also wanted to establish whether targets within the endocannabinoid system (i.e., CB(1) and CB(2) receptors) are involved in the beneficial effects induced in this model by the Sativex-like combination of phytocannabinoids. This we did using selective antagonists for both receptor types (i.e., SR141716 and AM630) combined with the Sativex-like phytocannabinoid combination. Our results indicated that the effects of this combination are blocked by these antagonists and hence that they do result from an activation of both CB(1) and CB(2) receptors. In summary, this study provides preclinical evidence in support ofa beneficial effect of the cannabis-based medicine Sativex as a neuroprotective agent capable of delaying signs of disease progression in a proinflammatory model of HD, which adds to previous data obtained in models priming oxidative mechanisms of striatal injury. However, the interest here is that, in contrast with these previous data, we have now obtained evidence that both CB(1) and CB(2) receptors appear to be involved in the effects produced by a Sativex-like phytocannabinoid combination, thus stressing the broad-spectrum properties of Sativex that may combine activity at the CB(1) and/or CB(2) receptors with cannabinoid receptor-independent actions.

BACKGROUND:Peripheral arterial disease (PAD) is a severe atherosclerotic condition frequently accompanied by inflammation and oxidative stress. We hypothesized that vitamin C antioxidant levels might be low in PAD and are related to inflammation and disease severity.

METHODS AND RESULTS:We investigated vitamin C (L-ascorbic acid) levels in 85 PAD patients, 106 hypertensives without PAD, and 113 healthy subjects. Serum L-ascorbic acid concentrations were low among PAD patients (median, 27.8 micromol/L) despite comparable smoking status and dietary intake with the other groups (P<0.0001). Subclinical vitamin C deficiency (<11.4 micromol/L), confirmed by low serum alkaline phosphatase activity, was found in 14% of the PAD patients but not in the other groups. Serum C-reactive protein (CRP) concentrations were significantly higher in PAD patients (P<0.0001) and negatively correlated with L-ascorbic acid levels (r=-0.742, P<0.0001). In stepwise multivariate analysis, low L-ascorbic acid concentration in PAD patients was associated with high CRP level (P=0.0001), smoking (P=0.0009), and shorter absolute claudication distance on a standardized graded treadmill test (P=0.029).

CONCLUSIONS:Vitamin C concentrations are lower in intermittent claudicant patients in association with higher CRP levels and severity of PAD. Future studies attempting to relate vitamin C levels to disease occurrence should include in their analysis an inflammatory marker such as CRP.

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.

The purpose of this study was to evaluate the effects of Spirulina Platensis supplementation on selected blood markers of oxidative stress, muscle damage, inflammation, and performance in trained rats. Rats (250 g - 300 g) were submitted to a strength training program (eight weeks), divided into four groups: control (GT) (trained without supplementation), trained with daily-supplementation of 50 mg/kg (GT50), 150 mg/kg (GT150) and 500 mg/kg (GT500). Training consisted of a jump protocol in PVC-cylinder containing water, with increasing load over experimental weeks. We evaluated the markers of oxidative stress (malondialdehyde - MDA and antioxidant capacity) and inflammation (C-reactive protein) at the end of the training. Among groups submitted to strength training, concentration of C-reactive protein decreased after 8 weeks of intervention in the trained group and GT500. Strength training enhanced plasma MDA concentration of malondialdehyde with supplementation of S. platensis in GT150 and GT500. In plasma analysis, strength training enhanced the percentage of oxidation inhibition, with spirulina supplementation in rates of 150 and 500 mg/kg. Spirulina supplementation for 8 weeks (in a dose-effect manner) improved antioxidant capacity as well as attenuated exercise-induced increases in ROS and inflammation. As a practical application, the use as high doses did not cause a reduction in positive physiological adaptations to exercise training. Additional studies are necessary to test the application of Spirulina Platensis in other contexts, as collective sports (basketball, football, soccer).

Ganoderma lucidum is a popular medicinal mushroom, which has been used in the Traditional Chinese medicine for the prevention or treatment of a variety of diseases. In the present study we evaluated the anti-inflammatory effects of the triterpene extract from G. lucidum (GLT) in LPS-stimulated macrophages. Here we show that GLT markedly suppressed the secretion of inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and inflammatory mediator nitric oxide (NO) and prostaglandin E(2) (PGE(2)) from lipopolysaccharide (LPS)-stimulated murine RAW264.7 cells. GLT also down-regulated LPS-dependent expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in RAW264.7 cells. The anti-inflammatory effects of GLT were mediated by the inhibition of transcription factor NF-kappaB as demonstrated by decreased NF-kappaB-DNA binding activity, and the suppression of p65 phosphorylation in LPS-stimulated macrophages treated with GLT. Moreover, GLT inhibited LPS-dependent AP-1-DNA binding activity and down-regulated expression of AP-1 subunit c-Jun. In addition, GLT suppressed the activity of MAP kinases as observed by the down-regulation of LPS-induced phosphorylation of ERK1/2 and JNK but not p38. In vivo experiments clearly demonstrated that GLT also inhibited the production of TNF-alpha and IL-6 in LPS-induced endotoxemic mice. Apart from its anti-inflammatory activity, GLT suppressed cell proliferation of RAW264.7 cells through cell cycle arrest at G0/G1-G2M, which was mediated by the down-regulation of expression of cell cycle regulatory proteins cyclin D1, CDK4 and cyclin B1, respectively. In conclusion, the anti-inflammatory and anti-proliferative effects of GLT on macrophages are mediated through the inhibition of NF-kappaB and AP-1 signaling pathways.

Exercise could afford multiple beneficial effects on obesity-related metabolic disorders. To address this issue, C57BL/6J mice were used to investigate the effects of 13 weeks of swim training on HFD-induced obesity and related insulin resistance and inflammation. Our results show that swim training can significantly prevent HFD-induced weight gain and increase resting energy expenditure without affecting food intake. The insulin sensitivity was enhanced in the HFD + swim group than in the HFD + sedentary group. Moreover, swim training considerably decreased serum LPS content and downregulates epididymis white adipose tissue (eWAT) expression of the inflammatory mediator Tnf-α, Il-6, and Mcp-1. In summary, 13 weeks of swim training could reverse HFD-induced metabolic disorders including insulin resistance and inflammation.

A patient with newly diagnosed right lung cancer had transientF-fluorodeoxyglucose (FDG)-avid left axillary lymph nodes and intense splenic FDG uptake on positron emission tomography (PET)/computed tomography (CT). History revealed that the patient received a left-sided influenza vaccine 2-3 days before the examination. Although inflammatory FDG uptake in ipsilateral axillary nodes is reported, to our knowledge, this is the first report of visualization of the systemic immune response in the spleen related to the influenza vaccination on FDG-PET/CT. The history, splenic uptake and time course on serial FDG-PET/CT helped to avoid a false-positive interpretation for progressing lung cancer and alteration of the radiation therapy plan.