We have previously shown chronic immune activation and enhanced generation of reactive oxygen species in common variable immunodeficiency (CVI). In the present study, we examined levels of glutathione, the dominant intracellular thiol, that play an important protective role against oxidative and inflammatory stress in plasma and in monocytes and lymphocyte subsets in 20 CVI patients and in 16 healthy controls. CD4+ lymphocytes from CVI patients had significantly lower levels of both total and reduced glutathione as well as a lower ratio of reduced to total glutathione compared with healthy controls. This decrease in glutathione levels in CD4+ lymphocytes was most pronounced in the CD45RA+ subset. Plasma levels of total glutathione were also significantly decreased in CVI. In contrast, monocytes from CVI patients exhibited increased levels of both total and reduced glutathione compared with blood donor monocytes. CVI patients had significantly raised serum levels of tumor necrosis factor alpha (TNF alpha) and TNF alpha concentration was strongly associated with glutathione depletion in CD4+ lymphocytes. Furthermore, the lowest levels of both total and reduced glutathione were found in a subgroup of CVI patients characterized by persistent immune activation in vivo, decreased numbers of CD4+ lymphocytes in peripheral blood, and splenomegaly. Finally, supplementation of cell cultures with glutathione-monoethyl ester did significantly enhance interleukin-2 production from peripheral blood mononuclear cells in CVI patients. These glutathione abnormalities in CVI indicate increased oxidative stress, particularly in CD4+ lymphocytes, and intracellular depletion of reduced glutathione of the demonstrated magnitude may have profound implications for CD4+ lymphocyte function and the immunodeficiency in CVI.

OBJECTIVE: This article discusses the role of diet in the management of asthma. Readers will gain an understanding of how evolution of the western diet has contributed to increased asthma prevalence and how dietary modification that includes management of dietary lipids may reduce symptoms of asthma.

DATA SOURCES: Relevant studies published in English were reviewed.

STUDY SELECTION: Medline search to identify peer-reviewed abstracts and journal articles.

RESULTS: Asthma and obesity, which often occur together, have increased in prevalence in recent years. Studies suggest adaption of a western diet has not only contributed to obesity, but that increased intake of specific nutrients can cause changes in the frequency and severity of asthma. Increased asthma prevalence has also been proposed to arise from increased exposure to diesel particles or lack of exposure to infectious agents or endotoxins during childhood, generating a biased Th2 immune response, and increased cytokine and leukotriene production. Antagonists directed against these pro-inflammatory mediators include anticytokines and antileukotrienes. A reduction in the levels of inflammatory mediators associated with asthma has also been seen with dietary interventions, such as the administration of oils containing gamma-linolenic acid and eicosapentaenoic acid.

CONCLUSIONS: Evidence suggests elevated body mass index and dietary patterns, especially intake of dietary lipids, contribute to symptoms of asthma. Dietary modification may help patients manage their asthma as well as contribute to their overall health.

OBJECTIVE:Diabetes mellitus Type 2 is one of the most widespread chronic metabolic diseases. In most cases, this type of diabetes is associated with alterations in levels of some inflammatory cytokines and hormones. Considering anti-inflammatory properties of plant extracts rich in ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E), anti-diabetic properties of these two well-known antioxidant vitamins were investigated through measurement of serum levels of high-sensitivity C-reactive protein (hs-CRP), insulin, leptin, tumor necrosis factor alpha (TNF-α), and serum amyloid A (SAA) in patients with diabetes mellitus type 2.

MATERIALS AND METHODS:Male patients (n=80) were randomly divided into two groups each consisted of 40 subjects. Test groups were supplemented with ascorbic acid (1000 mg/day) or alpha-tocopherol (300 mg/day) orally during four weeks. Before and after treatment, serum biochemical factors of subjects were measured and compared.

RESULTS:Our results showed that both ascorbic acid and alpha-tocopherol could induce significant anti-inflammatory effects by decreasing the level of inflammatory factors such as TNF-α, SAA, and hs-CRP in diabetes mellitus type 2 patients. Effects of alpha-tocopherol and ascorbic acid in decreasing serum leptin level were similar. Ascorbic acid in contrast to alpha-tocopherol diminished fasting insulin and HOMA index but had no effect on LDL serum level.

CONCLUSION:Concerning the obtained results, it is concluded that consumption of supplementary vitamins C and E could decrease induced inflammatory response in patients with diabetes mellitus type 2. It is also possible that vitamin C and vitamin E supplementation can attenuate incidence of some proposed pathological effects of diabetes mellitus.

CONTEXT: Caloric restriction (CR) retards aging in mammals. It has been hypothesized that a reduction in T(3) hormone may increase life span by conserving energy and reducing free-radical production. OBJECTIVE: The objective of the study was to assess the relationship between long-term CR with adequate protein and micronutrient intake on thyroid function in healthy lean weight-stable adult men and women. DESIGN, SETTING, AND PARTICIPANTS: In this study, serum thyroid hormones were evaluated in 28 men and women (mean age, 52 +/- 12 yr) consuming a CR diet for 3-15 yr (6 +/- 3 yr), 28 age- and sex-matched sedentary (WD), and 28 body fat-matched exercising (EX) subjects who were eating Western diets. MAIN OUTCOME MEASURES: Serum total and free T(4), total and free T(3), reverse T(3), and TSH concentrations were the main outcome measures. RESULTS: Energy intake was lower in the CR group (1779 +/- 355 kcal/d) than the WD (2433 +/- 502 kcal/d) and EX (2811 +/- 711 kcal/d) groups (P<0.001). Serum T(3) concentration was lower in the CR group than the WD and EX groups (73.6 +/- 22 vs. 91.0 +/- 13 vs. 94.3 +/- 17 ng/dl, respectively) (P

BACKGROUND:Declines in ovarian function in postmenopausal women may contribute to increase inflammatory cytokines, which can lead to chronic diseases. However, studies have shown that exercise interventions are important to manage inflammatory conditions. Thus, the objective of this study was to analyze the effect of exercise intervention on inflammatory markers among obese and postmenopausal women.

METHODS:70 women composed the sample (Exercise group [EG; n=35] and non-exercise group [nEG; n=35]). IL-6, TNF-α and IL-10 were the inflammatory markers analyzed. Exercise program was 20 weeks long and consisted of aerobic and neuromuscular training. Data about chronic diseases, medication use, dietary intake, body composition and biochemical variables were collected.

RESULTS:EG showed significant reductions in body mass index, waist circumference and body fat percentage, as well as increased lean body mass. EG showed significant reductions in TNF-α and significant interaction between group and intervention time. Reductions in IL-10 were identified only in nEG. Substantial effect of exercise intervention was observed with increased ratio of IL-10/IL-6 and IL-10/TNF-α.

CONCLUSIONS:Combination of aerobic exercise and resistance training was effective in reducing inflammation. Thus, implementation and maintenance of similar exercise programs can contribute to reduce chronic inflammation among obese postmenopausal women.

BACKGROUND:Declines in ovarian function in postmenopausal women may contribute to increase inflammatory cytokines, which can lead to chronic diseases. However, studies have shown that exercise interventions are important to manage inflammatory conditions. Thus, the objective of this study was to analyze the effect of exercise intervention on inflammatory markers among obese and postmenopausal women.

METHODS:70 women composed the sample (Exercise group [EG; n=35] and non-exercise group [nEG; n=35]). IL-6, TNF-α and IL-10 were the inflammatory markers analyzed. Exercise program was 20 weeks long and consisted of aerobic and neuromuscular training. Data about chronic diseases, medication use, dietary intake, body composition and biochemical variables were collected.

RESULTS:EG showed significant reductions in body mass index, waist circumference and body fat percentage, as well as increased lean body mass. EG showed significant reductions in TNF-α and significant interaction between group and intervention time. Reductions in IL-10 were identified only in nEG. Substantial effect of exercise intervention was observed with increased ratio of IL-10/IL-6 and IL-10/TNF-α.

CONCLUSIONS:Combination of aerobic exercise and resistance training was effective in reducing inflammation. Thus, implementation and maintenance of similar exercise programs can contribute to reduce chronic inflammation among obese postmenopausal women.

BACKGROUND AND OBJECTIVES:To evaluate the effect of yoga practice and exercise challenge on Tumour Necrosis Factor alpha (TNF-α), Interleukin-6 (IL-6) levels and lipid profile.

MATERIALS AND METHODS:Two hundred and eighteen subjects participated in the study. One hundred and nine volunteers (51 males and 58 females) in the age group of 20 to 60 years, who practiced yoga regularly for over five years for a period of one hour daily, performed a bout of moderate exercise and a bout of strenuous exercise as per Standardized Shuttle Walk test protocol. Anthropometrically matched, age matched and gender matched subjects, who did not practice yoga (non-yoga group) were chosen as controls (non-yoga, n=109). The non-yoga group also performed similar exercises. The blood samples of both the groups were collected before and after the exercises. TNF-α and IL-6 was analysed before and after the exercise by Sandwich ELISA (Enzyme Linked Immunosorbent Assay).

RESULTS:Resting plasma TNF-α concentration was significantly higher in non-yoga group when compared to yoga group (p<0.05). There was an increase in TNF-α levels in both the groups in response to strenuous exercise. There was no gender difference in TNF-α and IL-6 levels before and after exercise in yoga and non-yoga groups.

CONCLUSION:Regular practice of yoga lowers basal TNF-α and IL-6 levels. It also reduces the extent of increase of TNF-α and IL-6 to a physical challenge of moderate exercise and strenuous exercise. There is no significant gender difference in the TNF-α and IL-6 levels. Regular practice of yoga can protect the individual against inflammatory diseases by favourably altering pro-inflammatory cytokine levels.

The aim of this experimental study was to investigate the effects of low-intensity light-emitting diode (LED) phototherapy on the inflammatory process in the calcaneal tendon of ovariectomized rats (OVX) through the involvement of the inflammatory mediators interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α). Thirty-five female Wistar rats were divided into 4 groups: 3 groups of OVX rats totaling 30 rats (untreated OVX rats [OVX injury group], treated OVX rats [OVX LED group], and control OVX rats; subgroups existed based on the sampling times, which were 3, 7, and 14 days) and 1 group of non-OVX rats (not OVX; n = 5). Tendon injury was induced by trauma using a 208-g mass placed at 20 cm from the right tendon of each animal with energy of 0.70 J. The animals were treated 12 h after tendonitis with LED therapy and every 48 h thereafter until euthanasia (at 3, 7, or 14 days). The tendons were dissected and stored in liquid nitrogen at -196 °C, thawed only at the time of immunoenzymatic testing (ELISA). Groups treated with LED showed a decrease in the number of pro-inflammatory cells, IL-6, and TNF-α (p<0.05), and an increase in IL-10 (p < 0.05) when compared to the not OVX group (p < 0.05). It was concluded that low-intensity LED treatment using the parameters and wavelength of 945 nm in the time periods studied reduced the release of IL-6 and TNF-α and increased the release of IL-10, thereby improving the inflammatory response in OVX rats.

OBJECTIVE:To investigate the effects of short-term forest bathing on human health.

METHODS:Twenty healthy male university students participated as subjects and were randomly divided into two groups of 10. One group was sent on a two-night trip to a broad-leaved evergreen forest, and the other was sent to a city area. Serum cytokine levels reflecting inflammatory and stress response, indicators reflecting oxidative stress, the distribution of leukocyte subsets, and plasma endothelin-1 (ET-1) concentrations were measured before and after the experiment to evaluate the positive health effects of forest environments. A profile of mood states (POMS) evaluation was used to assess changes in mood states.

RESULTS:No significant differences in the baseline values of the indicators were observed between the two groups before the experiment. Subjects exposed to the forest environment showed reduced oxidative stress and pro-inflammatory level, as evidenced by decreased malondialdehyde, interleukin-6, and tumor necrosis factor a levels compared with the urban group. Serum cortisol levels were also lower than in the urban group. Notably, the concentration of plasma ET-1 was much lower in subjects exposed to the forest environment. The POMS evaluation showed that after exposure to the forest environment, subjects had lower scores in the negative subscales, and the score for vigor was increased.

CONCLUSION:Forest bathing is beneficial to human health, perhaps through preventive effects related to several pathological factors.

OBJECTIVE:To probe into effect of electroacupuncture on intestinal permeability in the patient with acute pancreatitis and the mechanism.

METHODS:Sixty-eight cases of acute pancreatitis were randomly divided into a treatment group and a control group. The control group and the treatment group were treated with anti-infection, inhibiting secretion of pancreas, improving microcirculation and protective agent of gastric mucosa, with electroacupuncture at Zusanli (ST 36), Shangjuxu (ST 37), Gongsun (SP 4), Taichong (LR 3) and Xuanzhong (GB 39) added, twice daily for 3 days, in the treatment group. Their clinical therapeutic effects and changes of endothelin (ET), nitric oxide (NO), tumor necrosis factor (TNF-alpha) and lactulose/mannose ratio (L/M) before and after treatment were compared.

RESULTS:The total effective rate of 86.7% in the treatment group was better than 76.3% in the control group (P<0.05). After treatment, ET, NO, TNF-alpha contents and L/M all were higher than those before treatment, with those in the treatment group being significantly lower than those in the control group (P<0.05).

CONCLUSION:Electroacupuncture can significantly decrease permeability of intestinal mucosa in the patient with acute pancreatitis, reduce accumulation of endogenous inflammatory mediators (ET, TNF-alpha) and vascular active substance (NO) in intestinal mucosa, so as to alleviate necrosis of intestinal epithelial cells and protect the barrier of gastro-intestinal mucosa.

Sepsis is associated with high morbidity and mortality. This study was to investigate the protective effects of electroacupuncture (EA) pretreatment with different waveforms on septic brain injury in rats and its mechanism. Male Sprague-Dawley rats were pretreated by EA with different waveforms (continuous wave, dilatational wave, or intermittent wave) at Baihui (GV20) and Tsusanli (ST36) acupoints for 30min, and underwent cecal ligation and puncture (CLP) or sham operation. The results showed that EA pretreatment with different waveforms improved survival rate, attenuated encephaledema, brain injury, neuronal apoptosis and cognitive dysfunction, and preserved blood-brain barrier (BBB). EA pretreatment decreased the production of tumor necrosis factor(TNF)-α, interleukin(IL)-6, malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD) and catalase (CAT) in serum and hippocampus at 48h after sham or CLP operation. Additionally, EA pretreatment downregulated the expressions of toll-like receptor-4 (TLR-4), nuclear factor-kappa B (NF-κB) and ionized calcium binding adaptor molecule 1(Iba 1). The effect of dilatational wave was the most significant, followed by intermittent wave, and continuous wave was relatively poor. In conclusion, our results demonstrate that EA pretreatment with three waveforms alleviates sepsis-inducedbrain injury by inhibition of microglial activation and attenuation of inflammation, oxidative stress and apoptosis. These findings suggest that EA pretreatment with dilatational wave at Baihui and Tsusanli acupoints might be a promising therapeutic strategy for relieving septic brain injury.

BACKGROUND:Poria cocos Wolf, a medicinal fungus, is widely used in traditional medicines in East Asian countries owing to its various therapeutic potentials. Although several studies have demonstrated the anti-inflammatory activity of this fungus, its underlying mechanisms have not yet been clearly defined.

METHODS:In the present study, we have demonstrated the anti-inflammatory effects of ethanol extract of P. cocos (EEPC) in lipopolysaccaride (LPS)-stimulated RAW 264.7 macrophages. As inflammatory parameters, the productions of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-1β and tumor necrosis factor (TNF)-α were evaluated. We also examined the EEPC's effect on the nuclear factor-kappaB (NF-κB) signaling pathway.

RESULTS:Our results indicated that EEPC exhibits a potent inhibitory effect on NO production and inhibits PGE2 release in LPS-induced macrophages without affecting cell viability. EEPC also significantly attenuated LPS-induced secretion of inflammatory cytokines IL-1β and TNF-α. Additionally, LPS-induced expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, IL-1β, and TNF-α was decreased by pre-treatment with EEPC at the transcriptional level. Moreover, EEPC clearly inhibited LPS-induced nuclear translocation of NF-κB p65 subunits, which correlated with EEPC's inhibitory effects on inhibitor kappaB (IκB) degradation. Moreover, EEPC clearly suppressed the LPS-induced DNA-binding activity of NF-κB, as well as the nuclear translocation of the NF-κB p65, which correlated with EEPC's inhibitory effects on inhibitor kappaB (IκB) degradation.

CONCLUSIONS:Taken together, our data indicates that EEPC targets the inflammatory response of macrophages via inhibition of iNOS, COX-2, IL-1β, and TNF-α through inactivation of the NF-κB signaling pathway, supporting the pharmacological basis of P. cocos as a traditional herbal medicine for treatment of inflammation and its associated disorders.

BACKGROUND:Exercise may help to mitigate symptoms of depression by reducing inflammation; however, little is known about the influence of exercise intensity on depressed mood.

METHODS:In the present study, sixty-one university students were assigned to six weeks of high-intensity interval training (HIT), moderate continuous training (MCT), or no exercise (CON) during their academic term. We measured changes in depression, anxiety and perceived stress along with pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and C-reactive protein (CRP).

RESULTS:Depression increased for CON, demonstrating how quickly mental health can decline for students during their academic term. In contrast, MCT decreased depression and pro-inflammatory cytokine TNF-α levels. Although HIT decreased depressive symptoms, it also increased perceived stress, TNF-α and IL-6 relative to MCT. This may be due to the higher level of physical stress evoked by the more strenuous exercise protocol.

CONCLUSIONS:Taken together, the results suggest that moderate-intensity exercise may be an optimal intensity of exercise for the promotion of mental health by decreasing TNF-α. This is critical for informing the use of exercise as medicine for mental health.

OBJECTIVE:This study examined the effects of exercise training (ExT) upon concentration of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) in the gastrocnemius of rats with heart failure (HF) induced by left coronary artery ligation.

METHODS:Adult male Wistar rats submitted to myocardial infarction (MI) or sham surgery were randomly allocated into one of four experimental groups: trained HF (Tr-HF), sedentary HF (Sed-HF), trained sham (Tr-Sham) and sedentary sham (Sed-Sham). ExT protocol was performed on treadmill for a period of 8 weeks (60m/days, 5×/week, 16m/min), which started 6 weeks after MI. Cardiac hemodynamic evaluations of left ventricular end-diastolic pressure (LVEDP) and morphometric cardiac were used to characterize HF. The hemodynamic variables were recorded and gastrocnemius muscle was collected. TNF-α, IL-6 and IL-10 proteinlevels were determined by multiplex bead array.

RESULTS:Sed-HF group presented increase of TNF-α level when compared with the Sed-Sham group (mean difference, MD 1.3; 95% confidence interval, CI -0.04 to 2.5). ExT reduced by 59% TNF-α level in Tr-HF group (MD -1.7; 95% CI -2.9 to -0.3) and increased IL-10 (MD 15; 95% CI 11-26) when compared with the Sed-HF group. Thus, the gastrocnemius muscle IL-10/TNF-α ratio was increased in Tr-HF rats (MD 15; 95% CI -8 to 47) when compared with the Sed-HF rats.

CONCLUSION:These results demonstrate that ExT not only attenuates TNF-α level but also improves the IL-10 cytokine level in skeletal muscle of HF rats.

Ganoderma lucidum, an oriental medical mushroom, has been used in Asia for the prevention and treatment of a variety of diseases, including cancer. We have previously demonstrated that G. lucidum inhibits growth and induces cell cycle arrest at G0/G1 phase through the inhibition of Akt/NF-kappaB signaling in estrogen-independent human breast cancer cells. However, the molecular mechanism(s) responsible for the inhibitory effects of G. lucidum on the proliferation of estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231) breast cancer cells remain to be elucidated. Here, we show that G. lucidum inhibited the proliferation of breast cancer MCF-7 and MDA-MB-231 cells by the modulation of the estrogen receptor (ER) and NF-kappaB signaling. Thus, G. lucidum down-regulated the expression of ERalpha in MCF-7 cells but did not effect the expression of ERbeta in MCF-7 and MDA-MB-231 cells. In addition, G. lucidum inhibited estrogen-dependent as well as constitutive transactivation activity of ER through estrogen response element (ERE) in a reporter gene assay. G. lucidum decreased TNF-alpha-induced (MCF-7) as well as constitutive (MDA-MB-231) activity of NF-kappaB. The inhibition of ER and NF-kappaB pathways resulted in the down-regulation of expression of c-myc, finally suppressing proliferation of estrogen-dependent as well as estrogen-independent cancer cells. Collectively, these results suggest that G. lucidum inhibits proliferation of human breast cancer cells and contain biologically active compounds with specificity against estrogen receptor and NF-kappaB signaling, and implicate G. lucidum as a suitable herb for chemoprevention and chemotherapy of breast cancer.

To study the effects of gentamicin in combination with ascorbic acid on septic arthritis, mice were infected with Staphylococcus aureus (S. aureus) and treated with gentamicin, which was given at 5 mg/kg after 24 h of infection, followed by ascorbic acid, given at 20 mg/kg body weight after 2 h of gentamicin treatment. Mice were sacrificed at 3, 9, 15 days post-infection (dpi). Combined treatment of infected mice with gentamicin and ascorbic acid eradicated the bacteria from the blood, spleen and synovial tissue and showed a significant gross reduction in arthritis, reduced serum levels of tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). S. aureus-infected mice have demonstrated the disturbed antioxidant status measured in terms of cellular antioxidants like reduced glutathione and antioxidant enzymes such as superoxide dismutase (SOD) and catalase. The same were ameliorated when the animals were co-treated with gentamicin along with ascorbic acid.

Background:Grape seed proanthocyanidin extract (GSPE) has been extensively reported to possess a wide range of beneficial properties in multiple tissue damage. Previous studies have shown that exhaustive exercise-induced fatigue associates with oxidative stress injury, inflammatory response, and mitochondrial dysfunction.

Objective:The aim of this study is to investigate the anti-fatigue effects of GSPE in mice and explore its possible underlying mechanism.

Design:The mouse model of exhaustive exercise-induced fatigue was established by using the forced swimming test, and GSPE was orally treated for successive 28 days at 0, 1, 50 and 100 mg/kg/day of body weight, designated the control, GSPE-L, GSPE-M and GSPE-H groups, respectively.

Results:The presented results showed that treatment of GSPE at a dose of 50 and 100 mg/kg/day of body weight significantly relieved exhaustive exercise-induced fatigue, indicated by increasing the forced swimming time. In addition, treatment of GSPE significantly improved the creatine phosphokinase and lactic dehydrogenase, as well as lactic acid level in exhaustive swimming. For underlying mechanisms, treatment of GSPE had anti-fatigue effects by promoting antioxidant ability and resisting oxidative effect, as represented by increased total antioxidative capability levels, enhanced superoxide dismutase and catalase activities, and ameliorated malondialdehyde levels. Furthermore, treatment of GSPE significantly inhibited the activity of tumor necrosis factor-α and interleukin-1β, which suggested that its protective effects on exhaustive exercise-induced fatigue may be attributed to inhibition of inflammatory response. Last but not the least, treatment of GSPE significantly improved succinate dehydrogenase and Na+-K+-ATPase levels to enhance mitochondrial function during exhaustive swimming-induced fatigue.

Conclusions:These results proved that treatment of GSPE possessed the beneficial properties of anti-inflammatory, antioxidant, and mitochondrial protection to improve exhaustive exercise, which suggested that GSPE could be used as an effective functional food to delay fatigue.

Highly active antiretroviral therapy (HAART) has significantly improved the prognosis of HIV-1-infected patients but is associated with significant side effects such as diabetes, atherosclerosis, and cardiovascular complications. Oxidative stress can disrupt endothelial homeostasis by dysregulating the balance between pro- and antiatherogenic factors. We hypothesized that chronic exposure to HAART results in endothelial oxidative stress and activation of mononuclear cell recruitment, an early event in atherosclerosis. We studied the effects of HAART drug combinations, consisting of zidovudine, a nucleoside reverse transcriptase inhibitor; efavirenz, a nonnucleoside reverse transcriptase inhibitor; and either of the two protease inhibitors (PIs), indinavir or nelfinavir, on human aortic endothelial cells (HAECs) by monitoring the following parameters: (1) generation of reactive oxygen species (ROS), (2) mono-nuclear cell (Jurkat or U-937) adhesion, and (3) expression of cell adhesion molecules (CAMs). HAART exposure increased ROS formation in HAECs. Exposure to PIs alone and in HAART combinations increased mononuclear cell adhesion to HAECs in a concentration-dependent manner. Mononuclear cell adhesion to HAART-exposed HAECs was significantly enhanced following acute (24-h) exposure to the inflammatory cytokines, tumor necrosis factor (TNF)-alpha or interleukin (IL)-1beta and was suppressed by the antioxidants N-ace-tylcysteine and glutathione. Exposure to HAART increased intercellular adhesion molecule-1 (ICAM-1) gene expression and concomitant exposure to TNF-alpha further increased ICAM-1, vascular cell adhesion molecule-1 (VCAM-1), and endothelial-leukocyte adhesion molecule cell surface protein levels. These studies indicate that chronic HAART exposure increases oxidative stress in endothelial cells and induces mononuclear cell recruitment, which may eventually precipitate the cardiovascular diseases observed in HIV-1+ individuals on antiretroviral therapy.

Hericium erinaceus (HE) is an edible mushroom that has been shown to exhibit anticancer and anti-inflammatory activities. We investigated the antiangiogenic and antioxidant potentials of ethanol extracts of HE in human endothelial (EA.hy926) cells upon tumor necrosis factor-α- (TNF-α-) stimulation (10 ng/mL). The underlying molecular mechanisms behind the pharmacological efficacies were elucidated. We found that noncytotoxic concentrations of HE (50-200 μg/mL) significantly inhibited TNF-α-induced migration/invasion and capillary-like tube formation of endothelial cells. HE treatment suppressed TNF-α-induced activity and/or overexpression of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). Furthermore, HE downregulated TNF-α-induced nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) followed by suppression of I-κB (inhibitor-κB) degradation. Data from fluorescence microscopy illustrated that increased intracellular ROS production upon TNF-α-stimulation was remarkably inhibited by HE pretreatment in a dose-dependent manner. Notably, HE triggered antioxidant gene expressions of heme oxygenase-1 (HO-1), γ-glutamylcysteine synthetase (γ-GCLC), and glutathione levels, which may contribute to inhibition of ROS. Increased antioxidant status was associated with upregulated nuclear translocation and transcriptional activation of NF-E2 related factor-2 (Nrf2) in HE treated cells.Our findings conclude that antiangiogenic and anti-inflammatory activities of H. erinaceus may contribute to its anticancer property through modulation of MMP-9/NF-κB and Nrf2-antioxidant signaling pathways.

OBJECTIVE:To evaluate the effects of acute and daily consumption of high-oleic peanuts (HOP) on inflammation and glucose homeostasis in overweight/obese men.

METHODS:In a 4-week randomized clinical trial, males with body mass index of 29.8± 2.3 kg/m(2) and aged 18-50 years were assigned to the groups: control (CT, n = 22); conventional peanuts (CVP, n = 22); or HOP (n = 21). They followed a hypocaloric-diet with or without 56 g/day of CVP or HOP. Main outcomes were changes in fasting blood biomarkers and postprandial insulin, glucose, tumor necrosis factor-alfa (TNF-α), and interleukin-10 (IL-10) responses after acute peanut intake.

RESULTS:At baseline, HOP showed significantly lower postprandial responses of glucose, insulin, and TNF-α than CVP and CT. Changes in fasting blood biomarkers did not differ between groups after the 4-week intervention. However, within groups, total cholesterol decreased in CT, and all groups reduced High-density lipoprotein (HDL-c). Triglycerides were reduced in HOP and CVP. IL-10 increased significantly in all groups while only the CT and CVP showed increased TNF-α after intervention.

CONCLUSION:Acute high-oleic peanut consumption leads to stronger moderation of postprandial glucose, insulin, and TNF-α concentrations than CVP and control meal intake. Whether daily intake of high-oleic peanuts has additional benefits to CVP remains uncertain.