- Fibrinogen and Neopterin Is Associated with Future Myocardial Infarction and Total Mortality in Patients with Stable Coronary Artery Disease. [Journal Article]
- THThromb Haemost 2018 Feb 19
- Systemic fibrinogen and neopterin are related to inflammation. We investigated the prognostic utility and possible interactions of these biomarkers in stable coronary artery disease (SCAD) patients u...
Systemic fibrinogen and neopterin are related to inflammation. We investigated the prognostic utility and possible interactions of these biomarkers in stable coronary artery disease (SCAD) patients undergoing coronary angiography. We included 3,545 patients with suspected stable angina with a median follow-up of 7.3 and 10.2 years for incident acute myocardial infarction (AMI) and all-cause mortality, respectively. Prospective associations were explored by Cox regression. Potential effect modifications were investigated according to strata of fibrinogen, neopterin or high-sensitivity troponin T (hsTnT) below and above the median, as well as gender and smoking habits. During follow-up, 543 patients experienced an AMI and 769 patients died. In a multivariable model, the hazard ratios (HRs; 95% confidence interval [CI]) per 1 SD increase for fibrinogen in relation to these endpoints were 1.30 (1.20, 1.42;p < 0.001) and 1.22 (1.13, 1.31;p < 0.001), respectively. For neopterin, the HRs (95% CI) were 1.31 (1.23, 1.40;p < 0.001) and 1.24 (1.15, 1.34;p < 0.001), respectively. No significant interaction between fibrinogen and neopterin was observed. The prognostic utility of neopterin for incident AMI was improved in patients with an hsTnT above the median, for total mortality in non-smokers, and for both total mortality and AMI in females. In conclusion, both fibrinogen and neopterin were associated with future AMI and total mortality, but had low discriminatory impact. No interaction was observed between these two biomarkers. The prognostic utility of neopterin was improved in patients with hsTnT levels above the median, and in females and non-smokers.
- Effects of Curcuminoids Plus Piperine on Glycemic, Hepatic and Inflammatory Biomarkers in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind Placebo-Controlled Trial. [Journal Article]
- DRDrug Res (Stuttg) 2018 Feb 19
- CONCLUSIONS: The results of the present trial revealed a beneficial effect of curcuminoids plus piperine supplementation on glycemic and hepatic parameters but not on hs-CRP levels in T2D patients.
- Adverse childhood experiences and adult inflammation: findings from the 1958 British birth cohort. [Journal Article]
- BBBrain Behav Immun 2018 Feb 16
- CONCLUSIONS: ACE were associated in a graded manner with adult inflammation in a British birth cohort. The association was explained by life course socioeconomic and health behavioral factors, in particular. This study highlights the importance of protecting children from ACE and its negative health effects, and in supporting children through education and into skilled, secure work.
- Within-subject associations between inflammation and features of depression: Using the flu vaccine as a mild inflammatory stimulus. [Journal Article]
- BBBrain Behav Immun 2018 Feb 16
- CONCLUSIONS: Minor increases in inflammation were associated with corresponding increases in features of depression, and these associations occurred in the absence of any physical symptoms. The influenza vaccine could be used to probe causal relationships with a high degree of ecological validity, even in high-risk and vulnerable populations, to better understand the role of inflammation in the pathogenesis of depression.
- Attenuation of neuro-inflammation improves survival and neurodegeneration in a mouse model of severe neonatal hyperbilirubinemia. [Journal Article]
- BBBrain Behav Immun 2018 Feb 16
- All pre-term newborns and a high proportion of term newborns develop neonatal jaundice. Neonatal jaundice is usually a benign condition and self-resolves within few days after birth. However, a combi...
All pre-term newborns and a high proportion of term newborns develop neonatal jaundice. Neonatal jaundice is usually a benign condition and self-resolves within few days after birth. However, a combination of unfavorable complications may lead to acute hyperbilirubinemia. Excessive hyperbilirubinemia may be toxic for the developing nervous system leading to severe neurological damage and death by kernicterus. Survivors show irreversible neurological deficits such as motor, sensitive and cognitive abnormalities. Current therapies rely on the use of phototherapy and, in unresponsive cases, exchange transfusion, which is performed only in specialized centers. During bilirubin-induced neurotoxicity different molecular pathways are activated, ranging from oxidative stress to endoplasmic reticulum (ER) stress response and inflammation, but the contribution of each pathway in the development of the disease still requires further investigation. Thus, to increase our understanding of the pathophysiology of bilirubin neurotoxicity, encephalopathy and kernicterus, we pharmacologically modulated neurodegeneration and neuroinflammation in a lethal mouse model of neonatal hyperbilirubinemia. Treatment of mutant mice with minocycline, a second-generation tetracycline with anti-inflammatory and neuroprotective properties, resulted in a dose-dependent rescue of lethality, due to reduction of neurodegeneration and neuroinflammation, without affecting plasma bilirubin levels. In particular, rescued mice showed normal motor-coordination capabilities and behavior, as determined by the accelerating rotarod and open field tests, respectively. From the molecular point of view, rescued mice showed a dose-dependent reduction in apoptosis of cerebellar neurons and improvement of dendritic arborization of Purkinje cells. Moreover, we observed a decrease of bilirubin-induced M1 microglia activation at the sites of damage with a reduction in oxidative and ER stress markers in these cells. Collectively, these data indicate that neurodegeneration and neuro-inflammation are key factors of bilirubin-induced neonatal lethality and neuro-behavioral abnormalities. We propose that the application of pharmacological treatments having anti-inflammatory and neuroprotective effects, to be used in combination with the current treatments, may significantly improve the management of acute neonatal hyperbilirubinemia, protecting from bilirubin-induced neurological damage and death.
- Strawberry extracts efficiently counteract inflammatory stress induced by the endotoxin lipopolysaccharide in Human Dermal Fibroblast. [Journal Article]
- FCFood Chem Toxicol 2018 Feb 16
- A protracted pro-inflammatory state is the common denominator in the development, progression and complication of the common chronic diseases. Dietary antioxidants represent an efficient tool to coun...
A protracted pro-inflammatory state is the common denominator in the development, progression and complication of the common chronic diseases. Dietary antioxidants represent an efficient tool to counteract this inflammatory state. The aim of the present work was to evaluate the effects of strawberry extracts on inflammation evoked by E. Coli lipopolysaccharide in Human Dermal Fibroblast, by measuring reactive oxygen species production, apoptosis rate, antioxidant enzymes activity, mitochondria functionality and also investigating the molecular pathway involved in inflammatory and antioxidant response. The results demonstrated that strawberry pre-treatment reduced intracellular reactive oxygen species levels, apoptotic rate, improved antioxidant defences and mitochondria functionality in lipopolysaccharide -treated cells. Strawberry exerted these protective activities through the inhibition of the NF-kB signalling pathway and the stimulation of the Nrf2 pathway, with a mechanism AMPK-dependent. These results confirm the health benefits of strawberry in the prevention of inflammation and oxidative stress condition in lipopolysaccharide-treated cells.
- Major role for TRPV1 and InsP3R in PAR-2-elicited inflammatory mediator production in differentiated human keratinocytes. [Journal Article]
- JIJ Invest Dermatol 2018 Feb 16
- Proteinase-activated receptor-2 (PAR-2) activation in basal keratinocytes stimulates inflammation via the Ca2+-dependent production of mediators such as interleukin (IL)-1β, tumor necrosis factor (TN...
Proteinase-activated receptor-2 (PAR-2) activation in basal keratinocytes stimulates inflammation via the Ca2+-dependent production of mediators such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and thymic stromal lymphopoietin (TSLP). In this study, we investigated PAR-2 calcium signaling and the consequent production of inflammatory mediators in differentiated human primary keratinocytes (DhPKs). Stimulation with the PAR-2 activating peptide SLIGKV promoted Ca2+store depletion in both undifferentiated human primary keratinocytes (UhPKs) and DhPKs. SLIGKV-evoked Ca2+store depletion did not trigger the store-operated Ca2+entry (SOCE) through ORAI1 in DhPK when compared with UhPK. The inhibition of phospholipase C (PLC) and the concomitant inhibition of transient receptor potential vanilloid 1 (TRPV1) and inositol triphosphate receptor (InsP3R) in DhPKs abrogated the SLIGKV-evoked Ca2+store depletion, NF-κB activity and the production of inflammatory mediators, such as IL-1β, TNF-α and TSLP. Taken together, these results indicate a key role for both InsP3R and TRPV1 in Ca2+internal stores in the PAR-2-evoked Ca2+release and consequent skin inflammation in DhPKs. These findings may provide clues to understanding the pathological role of DhPKs in skin disorders in which PAR-2 is known to be involved, such as atopic dermatitis (AD), Netherton syndrome (NS) and psoriasis.
- Neuroprotective effect of melatonin against lipopolysaccharide-induced depressive-like behavior in mice. [Journal Article]
- PBPhysiol Behav 2018 Feb 16
- Accumulating evidence indicates an interaction between inflammation and depression since increased levels of pro-inflammatory cytokines are associated with depression-related symptoms. Melatonin is a...
Accumulating evidence indicates an interaction between inflammation and depression since increased levels of pro-inflammatory cytokines are associated with depression-related symptoms. Melatonin is a hormone synthesized and secreted by the pineal gland with antioxidant, anti-inflammatory and antidepressant-like effects. In this way, it would be interesting to evaluate the putative antidepressant-like effect of melatonin treatment in an acute inflammation mice model of depression. The present study aimed to investigate the effect of melatonin treatment on lipopolysaccharide (LPS) induced depressive-like behavior, neuroinflammation, oxidative stress and alteration on brain-derived neurotrophic fator (BDNF) levels. Mice were treated with melatonin (10 mg/kg, i.p.) thirty minutes before LPS (0.5 mg/kg, i.p.) injection. Twenty four hours after LPS infusion, mice were submitted to the behavioral tests and, thereafter, biochemical determinations were performed. Melatonin treatment prevented LPS-induced depressive-like behavior in the forced swim and tail suspension tests with no alterations in locomotor activity evaluated in the open field test. Melatonin attenuated LPS-induced increase in tumor necrosis factor-α (TNF-α) and reduction of BDNF levels in the hippocampus. Treatment with melatonin also prevented LPS-induced increase in lipid peroxidation and the reduction of glutathione levels in the hippocampus. In conclusion, the present study suggests that melatonin treatment exerted neuroprotective effects against LPS-induced depressive-like behavior which may be related to reduction of TNF-α release, oxidative stress and modulation of BDNF expression.
- Autofluorescence: A potential pitfall in immunofluorescence-based inflammation grading. [Journal Article]
- JIJ Immunol Methods 2018 Feb 16
- Immunofluorescence (IF) staining of paraffin-embedded tissues is a frequently used method to answer research questions or even detect the abundance of a certain protein for diagnostic use. However, t...
Immunofluorescence (IF) staining of paraffin-embedded tissues is a frequently used method to answer research questions or even detect the abundance of a certain protein for diagnostic use. However, the signal originating from specific antibody-staining might be distorted by autofluorescence (AF) of the assessed tissue. Although the AF phenomenon is well known, its presence is often neglected by insufficient staining controls. In this study, we describe the existence of cellular AF in paraffin-embedded healthy and inflamed human and murine colonic tissues and present ways to reduce AF. The AF signal is detectable at emission spectra from 425 nm-738 nm, upon excitation from 403.6-638.7 nm and appears more pronounced in inflamed tissues. Most signals are located subepithelially in the tissue and in blood vessels. Previous studies have shown that the AF signals are caused by lipofuscin, which accumulates in lamina propria immune cells. In murine small intestine AF signals are present in granules in the Paneth cell zone. For alleviation of the AF signal, sudan black b (SBB) or copper sulfate was used. Incubation of the tissue slices with either one of the substances reduced AF. In conclusion, AF appears as an intrinsic biomarker for colonic inflammation. The dominant existence of AF in immune cells of IBD tissue elucidates the importance of negative controls and the limitation of IF staining for potential diagnostic purposes.
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- Circulating bile acids in healthy adults respond differently to a dietary pattern characterized by whole grains, legumes and fruits and vegetables compared to a diet high in refined grains and added sugars: a randomized, controlled, crossover feeding study. [Journal Article]
- MMetabolism 2018 Feb 16
- CONCLUSIONS: Diets with comparable macronutrient and energy composition, but differing in carbohydrate source, affected fasting plasma bile acids differently. Specifically, a diet characterized by whole grains, legumes, and fruits and vegetables compared to a diet high in refined grains and added sugars led to modest increases in concentrations of TLCA, TCA and GCA, ligands for FXR and TGR5, which may have beneficial effects on glucose homeostasis.