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Background: Experimental studies suggest that systemic inflammation contributes to the pathophysiology of delirium. The aim of our study was to determine blood-derived inflammatory signatures of post-stroke delirium., Methods: We included 144 ischemic stroke patients. We assessed delirium on a daily basis during the first 7 days of hospitalization. Venous blood was collected at day 3 after the onset of stroke and stimulated ex vivo with lipopolysaccharide (LPS). We measured LPS-induced cytokine concentration (TNFα, IP-10, IL-1β, IL-6, IL-8, IL-10, and IL-12p70) as well as plasma levels of IL-6 and TNFα., Results: Delirium was diagnosed in 21.5% of patients. After correction for monocyte count, patients with delirium had reduced LPS-induced TNFα, IP-10, IL-1β, IL-6, and IL-12 release. The plasma IL-6 level was higher in delirious patients compared to patients without delirium. After adjusting for stroke severity and infections, higher ex vivo TNFα (OR 0.29, 95%CI 0.11-0.72, P = 0.01), IP-10 (OR 0.25, 95%CI 0.08-0.73, P = 0.01), IL-1β (OR 0.42, 95%CI 0.20-0.89, P = 0.02), and IL-12 (OR 0.07, 95%CI 0.01-0.70, P = 0.02) release was associated with the reduced risk of delirium. In multivariate analysis, the higher plasma IL-6 was associated with the increased risk of delirium (OR 1.61, 95%CI 1.00-2.58, P = 0.04)., Conclusions: Reduced ex vivo release of pro-inflammatory cytokines after LPS stimulation and the elevated plasma IL-6 are signatures of post-stroke delirium.

Oxidative stress and inflammation are involved in the development of obesity, type 2 diabetes and vascular complications. Systemic inflammation, as seen in obesity, is associated with high plasmatic levels of pro-inflammatory, pro-atherogenic and pro-thrombotic adipokines. Here we studied the effects of lyophilized cranberries (LCB) on the secretion and expression of PAI-1, IL-6, MCP-1 and leptin in mature 3T3-L1 adipocytes under baseline conditions and excessive inflammatory response elicitation by stimulation with H2O2. Our data demonstrated that LCB significantly reduced the expression and secretion of IL-6, MCP-1 and leptin, as well as suppressed the overexpression of PAI-1 induced by H2O2. Our findings suggested that LCB counteracted the stimulatory effect of H2O2 on secretion and expression of pro-inflammatory adipokines, implying a potential anti-inflammatory effect during the inflammatory process induced via oxidative stress in adipose tissue., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This study was designed to evaluate the anti-inflammatory effects of purple carrot anthocyanins (PCA) with respect to gut inflammation, simulated in a co-culture system consisting of intestinal epithelial Caco-2 cells and RAW264.7 macrophages. The obtained results indicated that PCA extract down-regulates the mRNA expression of proinflammatory interleukins Il-1β (↓91%) and Il-6 (↓69%) as well as inflammatory mediators, such as cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNos), in lipopolysaccharide-activated RAW264.7 cells. The decrease in the generation of prostaglandin E2 (↓48%) and nitric oxide (↓26%) was observed as a result of the inhibition of Cox-2 (↓25%) and iNos (↓12%) mRNA expressions, respectively. Moreover, the PCA reduced mRNA expression (↓40%) and production (↓17%) of IL-8 in intestinal cells. The anti-inflammatory effect of PCA was contributed to the protection of the intestinal barrier, which was disrupted upon the stimulation of macrophages. These findings may provide preliminary justification for the use of PCA in further studies focused on the prevention and therapy supporting the conventional treatment of inflammatory bowel diseases.

Background: Rosa canina L. (rosehip) is used worldwide in traditional medicine as a plant with medicinal properties. However, its anti-obesity effects are not fully explained on a transcriptional level. Methods: In the present work, the 3T3-L preadipocytes were utilized to explore the impact of R. canina fruit extract (RCE) on the cellular and molecular pathways involved in adipocyte hypertrophy. Results: Obtained results showed the ability of RCE to reduce lipid overloads in hypertrophic adipocytes associated with the down-regulation of mRNA expressions of adipogenic transcription factors such as PPARγ, C/EBPα, and SREBP-1c as well as genes involved in lipid biosyntheses such as FAS, LPL, and aP2. Moreover, obesity-associated oxidative stress (antioxidant enzyme activities and ROS generation) and inflammation were ameliorated in RCE-treated hypertrophic adipocytes. The mRNA and protein levels of adipokines such as leptin, resistin, and adiponectin were restored to more favorable levels. Conclusions: Rosa canina fruit might be a valuable source of phytochemicals in preventing obesity and obesity-related metabolic complications. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Lingonberries suppress pro-inflammatory genes expression in adipocytes and macrophages. • Lingonberries counteract the decrease in adiponectin and IL-10 level in adipocytes. • Lingonberries decrease ROS overproduction in TNF-α-induced adipocytes. • Lingonberries affect the expression of antioxidant and oxidant enzymes in adipocytes. Abstract In this study, the lingonberry fruit extract (LGBE) has been investigated for the ability to suppress the inflammatory response and mitigate oxidative stress in activated 3T3-L1 adipocytes and RAW 264.7 macrophages. The obtained results showed that LGBE significantly reduced IL-6, MCP-1 and IL-1β production, and counteracted the decrease in adiponectin and IL-10 expression in TNF-α-induced adipocytes. Moreover, LGBE exhibited a high anti-inflammatory potential in the macrophage cell culture by down-regulation the expression of pro-inflammatory mediators (IL-6, TNF-α, IL-1β, MCP-1, COX-2, iNOS). Furthermore, LGBE decreased intracellular ROS generation in inflamed adipocytes by enhancing expression of antioxidant defense enzymes (SOD, catalase, GPx) and inhibiting an oxidant enzyme (NADPH oxidase 4), which is one of the primary sources of ROS. In conclusion, we have demonstrated that lingonberry fruit may reduce adipose tissue inflammation and support immune cell homeostasis, and thus can be considered a natural tool for inflammation control. [ABSTRACT FROM AUTHOR]

Background and aims The immune response to acute cerebral ischemia plays an important role in the pathophysiology of stroke and could be a therapeutic target. Toll-like receptor 4 (TLR4) is a master regulator of innate immunity. The aim of our study was to determine the association between selected cytokine release after TLR4 activation in blood cells and the outcome after ischemic stroke. Methods We included 156 ischemic stroke patients (median age: 69; 40.4% female). Venous blood was collected at day 3 after the onset of stroke and stimulated ex vivo with lipopolysaccharide (LPS). The LPS-induced level of tumor necrosis factor alpha (TNFα) was used as a proxy of the MyD88-dependent pathway, and interferon-gamma-inducible protein 10 (IP-10) was used as a proxy of the MyD88-independent pathway. The functional outcome was assessed at 3 months after stroke onset. Results TNFα (median: 2.2 vs. 3.5 pg/10 3 monocytes, p  < .01) and IP-10 release (median: 0.3 vs. 0. 6 pg/10 3 monocytes, p  < .01) was reduced in patients with a poor outcome. In a multivariate logistic regression analysis adjusted for age, stroke severity, and pneumonia, low TNFα release was associated with a poor outcome (OR: 4.23, 95%CI: 1.64–10.90, p  = .03). Similarly, low IP-10 release was related to an unfavorable prognosis (adjusted OR: 3.42, 95%CI: 1.49–8.21, p  < .01). Conclusions The reduced release of TNFα and IP-10 after ex vivo blood stimulation with endotoxin is independently associated with poor outcome after stroke. Our results suggest that the inhibition of both the MyD88-dependent pathway and MyD88-independent pathway of TLR4 signaling in blood cells correlates with an unfavorable prognosis in stroke patients. [ABSTRACT FROM AUTHOR]

Endometriosis represents an often painful, estrogen-dependent gynecological disorder, defined by the existence of endometrial glands and stroma exterior to the uterine cavity. The disease provides a wide range of symptoms and affects women's quality of life and reproductive functions. Despite research efforts and extensive investigations, this disease's pathogenesis and molecular basis remain unclear. Conventional endometriosis treatment implies surgical resection, hormonal therapies, and treatment with nonsteroidal anti-inflammatory drugs, but their efficacy is currently limited due to many side effects. Therefore, exploring complementary and alternative therapy strategies, minimizing the current treatments' adverse effects, is needed. Plants are sources of bioactive compounds that demonstrate broad-spectrum health-promoting effects and interact with molecular targets associated with endometriosis, such as cell proliferation, apoptosis, invasiveness, inflammation, oxidative stress, and angiogenesis. Anti-endometriotic properties are exhibited mainly by polyphenols, which can exert a potent phytoestrogen effect, modulating estrogen activity. The available evidence derived from preclinical research and several clinical studies indicates that natural biologically active compounds represent promising candidates for developing novel strategies in endometriosis management. The purpose of this review is to provide a comprehensive overview of polyphenols and their properties valuable for natural treatment strategy by interacting with different cellular and molecular targets involved in endometriosis progression. [ABSTRACT FROM AUTHOR]

Background: The authors of this research study intended to verify whether there are any changes in gene expression in depressed patients without coexisting inflammatory diseases for selected immune-inflammatory factors that are particularly important in autoimmune disease pathogenesis (IL-17, IL-21, IL-23, IL-35, Foxp3). Methods: The study was carried out on a group of 190 patients with depression and 100 healthy volunteers. The severity of depressive symptoms was assessed using the Hamilton Depression Scale. RT-PCR was used to evaluate mRNA expression and ELISA was used to measure protein expression of these genes. Results: The level of gene expression for IL-17, IL-21, IL-23, and IL-35 was substantially higher in the group of patients with depression compared to the control group. The mean mRNA expression of Foxp3 was considerably reduced in patients suffering from depressive disorders. There was a statistically significant correlation between the number of hospitalizations and the expression of specific inflammatory factors. Conclusions: Expression of specific inflammatory genes may be a factor in the etiopathogenesis of depressive disorders. The duration of the disease seems to be more important for the expression of the genes in question than the severity of depression. These cytokines may affect the metabolism of neurotransmitters and neuroendocrine functions in the brain as well as be a marker and a new potential therapeutic target for recurrent depressive disorders. [ABSTRACT FROM AUTHOR]

(1) Background: Activated immune-inflammatory pathways play an important role in the pathogenesis of depression and pathological obesity. Obesity might promote production of cytokine interleukin 17, which plays a significant role in neuro-immune reactions. The study aimed at assessing the relationship between Body Mass Index (BMI) and IL-17 expression, taking into account the clinical psychiatric variables in patients with depression. (2) Methods: A total of 125 participants took part in the study (95 depressed patients, 30 healthy controls). Data concerning the course of depressive disorders and BMI were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Reverse transcription polymerase chain reaction (RT-PCR) was used to assess IL-17 gene expression at the mRNA levels, while enzyme-linked immunosorbent assay (ELISA) was used to assess IL-17 expression at the protein level. (3) Results: Patients with more hospitalizations showed significantly higher IL-17 mRNA expression levels and higher BMI. However, no correlation between BMI and IL-17 expression was found in depressed patients. (4) Conclusions: Our study revealed that BMI does not affect IL-17 expression in patients with depression. However, further studies should be conducted to evaluate the effects of IL-17 inhibition on adipose tissue and vice versa. [ABSTRACT FROM AUTHOR]

Background and aims In animals, peripheral lipopolysaccharide (LPS) injection before cerebral ischemia exacerbates neurological deficit, impairs survival and augments sickness behaviour. The goal of our study was to determine a relationship between plasma LPS, LPS pathway proteins (LPS binding protein (LBP) and sCD14) and outcome in stroke patients. Methods We included 335 patients with ischemic stroke. Plasma LPS activity and levels of LBP and sCD14 were measured within 24 h after stroke onset. The endpoints of this study were (1) 3-month poor functional outcome defined as a modified Rankin Scale score >2; (2) 3-month and 12-month case fatality; (3) delirium during the first 7 days after admission. Results Plasma LPS activity did not correlate with either functional outcome or mortality. The higher levels of LBP and sCD14 predicted 3-month and 12-month case fatality. The adjusted hazard ratio for 12-month case fatality was 1.84 (95% CI: 1.32–2.58, p  < 0.01) for LBP and 1.62 (95% CI: 1.15–2.29, p  < 0.01) for sCD14. On multivariate analysis, higher LPS activity (OR: 1.63, 95% CI: 1.15–2.31, p  = 0.01) and higher LBP (OR: 1.44, 95% CI: 1.04–2.00, p  = 0.03) and sCD14 levels (OR: 1.54, 95% CI: 1.12–2.13, p  = 0.01) were associated with increased risk of delirium. Conclusions In ischemic stroke patients, higher levels of plasma sCD14 and LBP are associated with increased risk of death, whereas, elevated LPS activity and higher levels of LBP and CD14 are associated with post-stroke delirium. [ABSTRACT FROM AUTHOR]

To explore the role of systemic inflammation in post-stroke delirium, we investigated the level of two inflammatory mediators: high mobility group box 1 (HMGB1) and galectin-3 binding protein (Gal-3BP). Of 571 stroke patients, we compared plasma levels of HMGB1 and Gal-3BP in 79 delirious patients with 81 non-delirious patients matched for age and stroke severity. Delirious patients had higher Gal-3BP level (median: 1440 vs 1053 ng/mL, P < 0.01). An elevated level of Gal-3BP was associated with an increased risk of delirium. HMGB1 levels did not differ between groups. Our results suggest that pro-inflammatory monocytes and macrophages might be involved in delirium pathophysiology. [Display omitted] • Systemic inflammation might trigger or exacerbate delirium. • Elevated level of Gal-3BP is associated with higher risk of post-stroke delirium. • Plasma level of HMGB1 is not increased in patients with post-stroke delirium. • Pro-inflammatory monocytes/macrophages can play a role in delirium pathophysiology. [ABSTRACT FROM AUTHOR]