Lipoprotein(a) is linked to atherothrombosis and aortic valve stenosis independent of C-reactive protein.

AIMS: Recent evidence suggest that the lipoprotein(a)-associated risk of atherosclerotic cardiovascular disease (ASCVD) may be observed only in individuals with low-grade systemic inflammation. It was hypothesized that high lipoprotein(a) is a main driver for the risk of ASCVD, myocardial infarction, and aortic valve stenosis irrespective of C-reactive protein levels. METHODS AND RESULTS: A total of 68 090 individuals from the Copenhagen General Population Study, a prospective cohort study, were included. During a median follow-up of 8.1 years, 5104 individuals developed ASCVD, 2432 myocardial infarction, and 1220 aortic valve stenosis. The risk of ASCVD, myocardial infarction, and aortic valve stenosis increased with higher values of both lipoprotein(a) and C-reactive protein. For individuals with lipoprotein(a) in the 91st-100th percentiles (≥70 mg/dl, ≥147 nmol/l) vs. the 1st-33rd percentiles (≤6 mg/dl, ≤9 nmol/l), the multivariable-adjusted hazard ratio for ASCVD was 1.61 (95% confidence interval 1.43-1.81) for those with C-reactive protein <2 mg/l and 1.57 (1.36-1.82) for those with C-reactive protein ≥2 mg/l (P for interaction = 0.87). The corresponding values were 2.08 (1.76-2.45) and 1.65 (1.34-2.04) for myocardial infarction, and 2.01 (1.59-2.55) and 1.73 (1.31-2.27) for aortic valve stenosis, respectively (P for interaction = 0.15 and = 0.18). The highest absolute 10-year risks were found in men aged 70-79 years with lipoprotein(a) levels in the 91st-100th percentiles and C-reactive protein ≥2 mg/l, with 34% for ASCVD, 19% for myocardial infarction, and 13% for aortic valve stenosis. The corresponding values in women were 20%, 10%, and 8%, respectively. CONCLUSION: High lipoprotein(a) was a main driver for the risk of ASCVD, myocardial infarction, and aortic valve stenosis independent of C-reactive protein levels.

Systemic low-grade inflammation and depressive symptomology at chronic phase of ischemic stroke: The chain mediating role of fibrinogen and neutrophil counts.

BACKGROUND: Post-stroke depression (PSD) is the most common psychological consequence of stroke. Increased inflammatory markers resulting from ischemic stroke may played an important role in the pathogenesis of depressive symptomology. The present study was conducted to further elucidate the relationship between stroke severity, systemic low-grade inflammation and chronic phase post-stroke depressive symptomology (CP-PSDS). METHODS: A total of 897 stroke patients were consecutively recruited in this multicenter prospective cohort study and followed up for 1 year. The analytical sample consisted of 436 patients with ischemic stroke (23.4% female, median age = 57 years) from this cohort. Serum concentrations of inflammatory markers were measured in all 436 patients with ischemic stroke, from fasting morning venous blood samples on admission. Stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) on admission and post-stroke depressive symptomology (PSDS) was evaluated by 17-item Hamilton Rating Scale for Depression (HRSD). RESULTS: In the fully adjusted models, we observed that 1) NIHSS (Model 2: ß = 0.200, 95%CI, 0.057 ∼ 0.332), fibrinogen (Model 2: ß = 0.828, 95%CI, 0.269 ∼ 1.435), white blood cell counts (WBC, model 2: ß = 0.354, 95%CI, 0.122 ∼ 0.577) and neutrophil counts (Model 2: ß = 0.401, 95%CI, 0.126 ∼ 0.655) can independently predict the CP-PSDS after ischemic stroke onset; 2) fibrinogen (Indirect effect = 0.027, 95%CI, 0.007 ∼ 0.063, 13.4% mediated), WBC (Indirect effect = 0.024, 95%CI, 0.005 ∼ 0.058, 11.8% mediated) and neutrophil counts (Indirect effect = 0.030, 95%CI, 0.006 ∼ 0.069, 14.8% mediated) could partially mediate the association between stroke severity and CP-PSDS, and 3) stroke severity might cause CP-PSDS partly through the chain-mediating role of both fibrinogen and neutrophil counts (chain mediated effect = 0.003, 95%CI, 0.000 ∼ 0.011, p = 0.025, 1.6% mediated). CONCLUSIONS: Findings revealed that fibrinogen, WBC and neutrophil counts may be independent predictors of CP-PSDS and partial mediators of the relationship between stroke severity and CP-PSDS among patients with ischemic stroke. In addition, the chain mediating effect of fibrinogen and neutrophil counts might play an important role in the occurrence of CP-PSDS. However, no inflammatory markers were associated with CP-PSDS in females.

The impact of type 2 diabetes duration on serum asymmetric dimethylarginine and C-reactive protein concentration in Bosnian patients.

Objective. The present study assessed the impact of type 2 diabetes mellitus (T2DM) duration on the serum asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP) concentration in Bosnian patients. Methods. Participants for this cross-sectional study were randomly selected from the Family Medicine Clinic (Sarajevo, Bosnia and Herzegovina). Serum ADMA concentration was determined by ELISA. Serum high-sensitivity (hs-CRP) was determined by particle-enhanced immunonephelometry. ANOVA test followed by Scheffe post-hoc test or Kruskal-Wallis test followed by Man-Whitney test were used for statistical analysis. Results. The study included 38 patients in up to 10 years diabetes duration (≤10 years T2DM) group, 22 patients in greater than 10 years diabetes duration (>10 years T2DM) group, and 60 controls. Serum ADMA concentration in the >10 years T2DM group (1.81±0.15 µmol/L) was significantly higher compared to serum ADMA concentration in the ≤10 years T2DM group (1.38±0.41 µmol/L; p<0.001) and in controls (0.62±0.15 µmol/L; p<0.001). A significant difference in serum ADMA concentration was found between the <10 years T2DM group and the controls (p<0.001). The serum CRP concentration in the >10 years T2DM group [5.95 (4.20-9.12) mg/L] was significantly higher compared to serum CRP concentration in the <10 years T2DM group [2.35 (1.40-4.30) mg/L; p<0.001] and controls [0.85 (0.50-1.30) mg/L; p<0.001]. Significant difference in serum CRP concentration was observed between the <10 years T2DM group and controls (p<0.001). Conclusions. The present study showed an increase in the serum ADMA and CRP concentrations with the advancement of T2DM. These results suggest that ADMA and CRP may serve as indicators of endothelial dysfunction and chronic low-grade inflammation progression in patients with T2DM. Larger prospective studies are required to confirm the observed findings.

The relation between systemic inflammation and incident cancer in patients with stable cardiovascular disease: a cohort study.

AIMS: Low-grade inflammation, measured by elevated plasma concentrations of high-sensitive C-reactive protein (CRP), is a risk factor for cardiovascular disease (CVD). There is evidence that low-grade inflammation is also related to a higher risk of cancer. The present prospective cohort study evaluates the relation between low-grade systemic inflammation and risk of cancer in patients with stable CVD. METHODS AND RESULTS: In total, 7178 patients with stable CVD and plasma CRP levels ≤10 mg/L were included. Data were linked to the Dutch national cancer registry. Cox regression models were fitted to study the relation between CRP and incident CVD and cancer. After a median follow-up time of 8.3 years (interquartile range 4.6-12.3) 1072 incident cancer diagnoses were observed. C-reactive protein concentration was related to total cancer [hazard ratio (HR) 1.35; 95% confidence interval (CI) 1.10-1.65] comparing last quintile to first quintile of CRP. Especially lung cancer, independent of histopathological subtype, was related to CRP (HR 3.39; 95% CI 2.02-5.69 comparing last to first quintile of CRP). Incidence of epithelial neoplasms and especially squamous cell neoplasms were related to CRP concentration, irrespective of anatomical location. Sensitivity analyses after excluding patients with a cancer diagnosis within 1, 2, and 5 years of follow-up showed similar results. No effect modification was observed by smoking status or time since smoking cessation (P-values for interaction > 0.05). CONCLUSION: Chronic systemic low-grade inflammation, measured by CRP levels ≤10 mg/L, is a risk factor for incident cancer, markedly lung cancer, in patients with stable CVD. The relation between inflammation and incident cancer is seen in former and current smokers and is uncertain in never smokers.

Systemic low-grade inflammation and subsequent depressive symptoms: Is there a mediating role of physical activity?

OBJECTIVE: Systemic low-grade inflammation has been associated with the onset of depression, but the exact mechanisms underlying this relationship remain elusive. This study examined whether physical activity (PA) explained the association between elevated serum levels of inflammatory markers and subsequent depressive symptoms. DESIGN: Prospective cohort design. METHOD: The sample consisted of 3809 non-depressed men and women (aged 50+) recruited from the English Longitudinal Study of Ageing (ELSA). Serum levels of inflammatory markers (C-reactive protein (CRP), fibrinogen) and covariates (age, sex, education, wealth, body mass index, smoking, cholesterol, triglycerides) were measured at baseline (wave 4, 2008/09). Self-reported weekly moderate/vigorous (high) PA versus no weekly moderate/vigorous (low) PA was examined at a four-year follow-up (wave 6, 2012/13), using a single-item question. Depressive symptoms were assessed at baseline, four years (wave 6, 2012/13) and six years post baseline (wave 7, 2014/15), using the 8-item version of the Centre for Epidemiological Studies Depression Scale (CES-D). RESULTS: Participants with higher baseline concentrations of inflammatory markers were significantly more likely to report low PA levels four years later (CRP: OR: 1.25; 95% CI, 1.05-1.48; fibrinogen: OR: 1.18; 95% CI, 1.05-1.39). Moreover, low PA was associated with higher odds of elevated depressive symptoms at follow-up (OR: 1.59; 95% CI, 1.15-2.19). Mediation analyses revealed that low PA explained a total of 36.71% of the relationship between high CRP and elevated depressive symptoms, and 33.26% between higher levels of fibrinogen and elevated depressive symptoms six years later. No direct association was found between systemic low-grade inflammation and future depressive symptoms. CONCLUSION: These results suggest that low PA is a significant partial mediator of the relationship between systemic low-grade inflammation and subsequent elevated depressive symptoms in a nationally representative cohort of older adults.

Fried Soybean Oil Causes Systemic Low-Grade Inflammation by Disrupting the Balance of Gut Microbiota in Mice.

Previous reports have mainly investigated the long-term effects (>30 d), such as gut microbiota dysbiosis and systemic low-grade inflammation, in mice fed fried oil. However, short-term intake of deep-fried oil is more likely to occur in daily life, and such studies are lacking. This study aimed to investigate the short-term effects of fried oil intake on systemic low-grade inflammation. Male Kunming mice were fed non-fried soybean oil or low (25%), medium (50%), or high (100%)-fried oil at 4.4 g/kg for 6 d. Serum and fecal samples were collected on day 7. In all groups fed fried oil, the serum levels of tumor necrosis factor (TNF-α) were significantly elevated 2-4-fold. Among the gut microbiota, the abundance of Alloprevotella significantly decreased by up to 76%, while Lactobacilli significantly increased by up to 385%. The fecal valeric acid content was significantly increased and positively correlated with TNF-α levels. Both valeric acid and TNF-α levels were positively correlated with the abundance of Lactobacilli and negatively correlated with that of Alloprevotella. In summary, a short-term ingestion of even low doses of fried oil alters the gut microbiota Alloprevotella and Lactobacilli and increases fecal valeric acid content, which correlates with increased serum TNF-α levels.

Water Extract of Chrysanthemum indicum L. Flower Inhibits Capsaicin-Induced Systemic Low-Grade Inflammation by Modulating Gut Microbiota and Short-Chain Fatty Acids.

Systemic low-grade inflammation induced by unhealthy diet has become a common health concern as it contributes to immune imbalance and induces chronic diseases, yet effective preventions and interventions are currently unavailable. The Chrysanthemum indicum L. flower (CIF) is a common herb with a strong anti-inflammatory effect in drug-induced models, based on the theory of "medicine and food homology". However, its effects and mechanisms in reducing food-induced systemic low-grade inflammation (FSLI) remain unclear. This study showed that CIF can reduce FSLI and represents a new strategy to intervene in chronic inflammatory diseases. In this study, we administered capsaicin to mice by gavage to establish a FSLI model. Then, three doses of CIF (7, 14, 28 g·kg-1·day-1) were tested as the intervention. Capsaicin was found to increase serum TNF-α levels, demonstrating a successful model induction. After a high dose of CIF intervention, serum levels of TNF-α and LPS were reduced by 62.8% and 77.44%. In addition, CIF increased the α diversity and number of OTUs in the gut microbiota, restored the abundance of Lactobacillus and increased the total content of SCFAs in the feces. In summary, CIF inhibits FSLI by modulating the gut microbiota, increasing SCFAs levels and inhibiting excessive LPS translocation into the blood. Our findings provided a theoretical support for using CIF in FSLI intervention.

Are serum hsCRP and IL-6 prognostic markers in somatic symptom disorder and related disorders? An exploratory analysis in a prospective cohort study.

OBJECTIVE: To investigate the roles of hsCRP and IL-6 as prognostic markers for treatment outcome in SSRD. METHODS: In this prospective cohort study, 237 consecutive outpatients diagnosed with SSRD at the Clinical Centre of Excellence for Body Mind and Health, the Netherlands were assessed. At intake, venepuncture was performed for serum hsCRP and IL-6. Baseline scores for PHQ-9, GAD7, physical symptom score (PSQ-51) and BPI questionnaires were obtained. Patients were followed up at the end of their usual treatment programme, which lasted approximately 12 months. RESULTS: Higher baseline hsCRP was associated with high physical symptom scores (PSQ-51), but not BPI, GAD-7 and PHQ-9 questionnaire scores at end of treatment. No association was identified between baseline IL-6 and follow-up symptom questionnaire scores after treatment. Adjustment for age, gender and somatic comorbidity showed no significant change in the association. CONCLUSION: This exploratory analysis provides some evidence that in patients with SSRD, high baseline serum hsCRP may predict poorer treatment outcomes in physical symptoms but not depression, anxiety or pain symptoms. Baseline serum hsCRP may therefore be a useful factor in identifying SSRD patients who are at risk of a persistent high physical symptom burden.

Four clinical profiles of adult outpatients with somatic Symptom Disorders and Related Disorders (SSRD). A latent class analysis.

OBJECTIVE: To obtain more insight into the patterns of co-occurring symptoms, biomarkers and predictors in Somatic Symptom Disorders and Related Disorders (SSRD) and to identify subgroups with profiles that might allow for personalised treatment. METHODS: Cross-sectional study design with Latent class analysis (LCA) to determine different subgroups in a cohort of 239 outpatients with SSRD in 3 steps: 1) building a latent class model; 2) assigning subjects to the latent classes that suited them best based on their posterior probability; 3) investigating the associations between these classes and personal characteristics such as age, gender, somatic comorbidity and general health perception. RESULTS: Four classes with clinically relevant profiles were found. One with trauma plus elevated inflammation biomarkers, high somatic symptom levels, pain and comorbid depression and anxiety. One with pain plus elevated biomarkers, depression and anxiety. One with low IL-6 and hsCRP, mostly linked to Illness Anxiety. And one with high pain and high elevated biomarkers, but less probability of other factors, that occurred mostly in men. General health perception was lower in classes with elevated inflammation biomarkers. CONCLUSIONS: The findings of this first study exploring latent classes in an SSRD sample corroborate the current DSM-5 SSD subclassification for pain and Illness Anxiety Disorder. There is scope to extend the current DSM-5 classification with a subclassification of SSD with trauma, and a subclassification with elevated IL6 or hsCRP, as relevant for developing new personalised treatments addressing trauma or SLI in SSRD. Further research is needed to explore this.

The chain mediating role of C-reactive protein and triglyceride-glucose index between lung function and cognitive function in a systemic low-grade inflammation state.

OBJECTIVES: This study examined whether serum C-reactive protein (CRP) level and triglyceride-glucose index (TyG) explained the association between lung function and subsequent cognitive function in middle-aged and older adults with a systemic low-grade inflammation state. DESIGN: A prospective cohort study. SETTING AND PARTICIPANTS: The sample consisted of 1, 742 participants recruited from the English Longitudinal Study of Ageing (ELSA). METHODS: Lung function and covariates were measured at baseline (wave 4, 2008/09). Serum CRP level and TyG were examined at a four-year follow-up (wave 6, 2012/13). Cognitive function was assessed at eight years post baseline (wave 8, 2016/17) in the main interview. The mediation was initially assessed using multivariate linear regression models. Indirect effects were assessed using the structural equation modeling and the bootstrap method. RESULTS: We observed that serum CRP level and TyG significantly mediated the relationships between lung function (forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC)) and cognitive function (immediate recall and delay recall). Moreover, serum CRP level mediated the association between lung function (FEV1 and FVC) and TyG. Our finding also suggested that FEV1 (1.19% mediated) and FVC (1.72% mediated) might influence cognitive function partly through the chain mediating role of both serum CRP level and TyG. CONCLUSIONS AND IMPLICATIONS: The present study revealed that serum CRP level and TyG play a chain mediating role in the relationship between lung function at baseline and subsequent cognitive impairment in a nationally representative cohort of middle-aged and older adults with a systemic low-grade inflammation state.

Long-Term Effects of Ambient Particulate and Gaseous Pollutants on Serum High-Sensitivity C-Reactive Protein Levels: A Cross-Sectional Study Using KoGES-HEXA Data.

Ambient air pollutants reportedly increase inflammatory responses associated with multiple chronic diseases. We investigated the effects of long-term exposure to ambient air pollution on high-sensitivity C-reactive protein (hs-CRP) using data from 60,581 participants enrolled in the Korean Genome and Epidemiology Study-Health Examinees Study between 2012 and 2017. Community Multiscale Air Quality System with surface data assimilation was used to estimate the participants' exposure to criteria air pollutants based on geocoded residential addresses. Long-term exposure was defined as the 2-year moving average concentrations of PM10, PM2.5, SO2, NO2, and O3. Multivariable linear and logistic regression models were utilized to estimate the percent changes in hs-CRP and odds ratios of systemic low-grade inflammation (hs-CRP > 3 mg/L) per interquartile range increment in air pollutants. We identified positive associations between hs-CRP and PM10 (% changes: 3.75 [95% CI 2.68, 4.82]), PM2.5 (3.68, [2.57, 4.81]), SO2 (1.79, [1.10, 2.48]), and NO2 (3.31, [2.12, 4.52]), while negative association was demonstrated for O3 (-3.81, [-4.96, -2.65]). Elevated risks of low-grade inflammation were associated with PM10 (odds ratio: 1.07 [95% CI 1.01, 1.13]), PM2.5 (1.08 [1.02, 1.14]), and SO2 (1.05 [1.01, 1.08]). The odds ratios reported indicated that the exposures might be risk factors for inflammatory conditions; however, they did not reflect strong associations. Our findings suggest that exposure to air pollutants may play a role in the inflammation process.

Physical Fitness Attenuates the Impact of Higher Body Mass and Adiposity on Inflammation in Women With Systemic Lupus Erythematosus.

Aims: Higher body mass and adiposity represent independent contributors to the systemic low-grade inflammatory state often observed in patients with systemic lupus erythematosus (SLE). This study assessed the role of physical fitness in the association of body mass and adiposity with inflammation in women with SLE. Methods: A total of 77 women with SLE were included in this cross-sectional study. We obtained body mass index, waist-to-height ratio, and body fat percentage as indicators of body mass and adiposity. Inflammation was assessed through Serum levels of C-reactive protein, interleukin 6, and leptin. Cardiorespiratory fitness was assessed with the 6-minute walk test, range of motion with the back-scratch test, and muscular strength with handgrip dynamometry. Results: Cardiorespiratory fitness attenuated the association of both body mass index and body fat percentage with interleukin 6 (all, P<0.05). Range of motion attenuated the association of body mass index with interleukin 6 (P<0.05) and the association of body fat percentage with C-reactive protein (P<0.05). These interactions indicated that higher fitness was associated with a lower increase in inflammation per unit increase of body mass or adiposity. Muscular strength showed a non-significant trend to attenuate the association of body fat percentage with interleukin 6 (P=0.057) but potentiated the association of body fat percentage with leptin (P<0.05). Conclusion: These findings suggest that higher levels of cardiorespiratory fitness and range of motion might attenuate the impact of higher body mass and adiposity on inflammation in women with SLE. The role of muscular strength requires further investigation.

Assessment of cytokines, microRNA and patient related outcome measures in conversion disorder/functional neurological disorder (CD/FND): The CANDO clinical feasibility study.

BACKGROUND: Conversion disorder/functional neurological disorder (CD/FND) occurs often in neurological settings and can lead to long-term distress, disability and demand on health care services. Systemic low-grade inflammation might play a role, however, the pathogenic mechanism is still unknown. AIM: 1) To explore the feasibility to establish and assess a cohort of CD/FND with motor symptoms, involving persons with lived experience (PPI). 2) To generate proof of concept regarding a possible role for cytokines, microRNA, cortisol levels and neurocognitive symptoms in patients with motor CD/FND. METHOD: Feasibility study. RESULTS: The study showed active involvement of patients despite high clinical illness burden and disability, neurocognitive symptoms, childhood adverse experiences (ACE) and current life events. The study provided valuable knowledge regarding the feasibility of conducting a study in these patients that will inform future study phases. In the sample there were elevated levels of IL6, IL12, IL17A, IFNg, TNFa and VEGF-a, suggesting systemic low-grade inflammation. Also, microRNAs involved in inflammation and vascular inflammation were correlated with TNFa and VEGFa respectively, suggesting proof of concept for an epigenetic mechanism. Owing to the COVID-19 outbreak, the patient sample was limited to 15 patients. CONCLUSION: It is a novelty that this study is conducted in the clinical setting. This innovative, translational study explores stress-related SLI in CD/FND patients and the feasibility of a larger project aiming to develop new treatments for this vulnerable population. Given the positive findings, there is scope to conduct further research into the mechanism of disease in CD/FND.

(-)-Epicatechin metabolites promote vascular health through epigenetic reprogramming of endothelial-immune cell signaling and reversing systemic low-grade inflammation.

Ingestion of (-)-epicatechin flavanols reverses endothelial dysfunction by increasing flow mediated dilation and by reducing vascular inflammation and oxidative stress, monocyte-endothelial cell adhesion and transendothelial monocyte migration in vitro and in vivo. This involves multiple changes in gene expression and epigenetic DNA methylation by poorly understood mechanisms. By in silico docking and molecular modeling we demonstrate favorable binding of different glucuronidated, sulfated or methylated (-)-epicatechin metabolites to different DNA methyltransferases (DNMT1/DNMT3A). In favor of this model, genome-wide DNA methylation profiling of endothelial cells treated with TNF and different (-)-epicatechin metabolites revealed specific DNA methylation changes in gene networks controlling cell adhesion-extravasation endothelial hyperpermeability as well as gamma-aminobutyric acid, renin-angiotensin and nitric oxide hypertension pathways. Remarkably, blood epigenetic profiles of an 8 weeks intervention with monomeric and oligomeric flavanols (MOF) including (-)-epicatechin in male smokers revealed individual epigenetic gene changes targeting similar pathways as the in vitro exposure experiments in endothelial cells. Furthermore, epigenetic changes following MOF diet intervention oppose atherosclerosis associated epigenetic changes. In line with biological data, the individual epigenetic response to a MOF diet is associated with different vascular health parameters (glutathione peroxidase 1 and endothelin-1 expression, acetylcholine-mediated microvascular response), in part involving systemic shifts in blood immune cell types which reduce the neutrophil-lymphocyte ratio (NLR). Altogether, our study suggests that different (-)-epicatechin metabolites promote vascular health in part via epigenetic reprogramming of endothelial-immune cell signaling and reversing systemic low-grade inflammation.

A Cross-Sectional Study of the Gut Microbiota Composition in Moscow Long-Livers.

The aim was to assess the gut microbiota of long-livers from Moscow. This study included two groups of patients who signed their consent to participate. The group of long-livers (LL) included 20 participants aged 97-100 years (4 men and 16 women). The second group included 22 participants aged 60-76 years (6 men) without clinical manifestations of chronic diseases (healthy elderly). Gut microbiota was studied by 16S rRNA sequencing. Long-livers underwent a complex geriatric assessment as well as expanded blood biochemistry. Gut microbiota composition in the cohorts was also compared with microbiome in long-livers from Japan and Italy. Russian long-livers' microbiome contained more beneficial bacteria than healthy elderly including Ruminococcaceae, Christensenellaceae, Lactobacillaceae families. Conditional pathogens like Veillonellaceae, Mogibacteriaceae, Alcaligenaceae, Peptococcaceae, Peptostreptococcaceae were more abundant in the healthy elderly. Compared with Italian and Japanese microbiome LL, the Russian LL appeared to be more similar to the Italian cohort. Bifidobacterium/Coprococcus and Faecalibacterium/Coprococcus balances were associated with femoral and carotid intima-media thickness, respectively. Bifidobacterium/Coriobacteriaceae balance was assessed with the folic acid level and Faecalibacterium/Coriobacteriaceae_u the with Mini Nutritional Assessment score. Long-livers' microbiome appeared to be unexpectedly balanced. The high representation of beneficial bacteria in long-livers may prevent them from low-grade inflammation and thus protect them from the development of atherosclerosis and other aging-associated conditions.

The Association Between Vascular Inflammation and Depressive Disorder. Causality, Biomarkers and Targeted Treatment.

Diabetes, obesity, atherosclerosis, and myocardial infarction are frequently co-morbid with major depressive disorder. In the current review, it is argued that vascular inflammation is a factor that is common to all disorders and that an endothelial dysfunction of the blood-brain barrier could be involved in the induction of depression symptoms. Biomarkers for vascular inflammation include a high plasma level of C-reactive protein, soluble cell-adhesion molecules, von Willebrand factor, aldosterone, and proinflammatory cytokines like interleukin-6 or tumor necrosis factor α. A further possible biomarker is flow-mediated dilation of the brachial artery. Treatment of vascular inflammation is expected to prevent or to reduce symptoms of depression. Several tentative treatments for this form of depression can be envisioned: eicosapentaenoic acid (EPA), valproate, Vagus-nerve stimulation, nicotinic α7 agonists, and agonists of the cannabinoid CB2-receptor.

IL-6 and hsCRP in Somatic Symptom Disorders and related disorders.

Interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) are biomarkers of systemic low-grade inflammation (SLI) in depression and anxiety. The question if SLI in those conditions is related to comorbid chronic medical conditions has not been resolved. DSM-5 Somatic symptom disorders and related disorders (SSRD) are conditions with serious distress related to physical symptoms as main criterion. They can occur in patients with medically unexplained symptoms (MUS) and in patients with known comorbid chronic medical conditions. Often, comorbid depression and anxiety are present. SSRDs offer the opportunity to explore the role of SLI in relation to mental distress, including trauma, MUS, chronic medical conditions and comorbid mental disorder. AIM: We hypothesized that increased IL-6 and hsCRP may be directly linked to SLI in SSRD, and that comorbid chronic medical conditions, childhood trauma, current stress and comorbid depression and anxiety may be risk factors that account for some of the variance of SLI in SSRD. METHODS: We explored these relationships in a large sample of 241 consecutive outpatients with SSRD. RESULTS: Mean hsCRP level was 3.66 â€‹mg/l, and mean IL-6 level was 3.58 â€‹pg/ml. IL-6 and hsCRP levels were associated with each other: τ â€‹= â€‹0.249, p â€‹< â€‹.001; a medium size correlation. Comorbid chronic medical conditions, adverse childhood events other than sexual trauma, and current stress levels were not associated with IL-6 or hsCRP levels. CONCLUSION: IL-6 and hsCRP are elevated in SSRD, indicating SLI in SSRD independently of comorbid chronic medical conditions. In clinical research, elevated IL-6 and hsCRP can be used as biomarkers of SLI and can indicate risk for childhood sexual abuse in SSRD. Elevated hsCRP may be a biomarker indicating risk for comorbid depression or high pain levels in SSRD as well.

Induction of Chronic Subclinical Systemic Inflammation in Sprague-Dawley Rats Stimulated by Intermittent Bolus Injection of Lipopolysaccharide.

Chronic subclinical systemic inflammation has a key role in stimulating several chronic conditions associated with cardiovascular diseases, cancer, rheumatoid arthritis, diabetes, and neurodegenerative diseases. Hence, developing in vivo models of chronic subclinical systemic inflammation are essential to the study of the pathophysiology and to measure the immunomodulatory agents involved. Male Sprague-Dawley rats were subjected to intraperitoneal, intermittent injection with saline, or lipopolysaccharide (LPS) (0.5, 1, 2 mg/kg) thrice a week for 30 days. Hematological, biochemical, and inflammatory mediators were measured at different timepoints and at the end of the study. The hearts, lungs, kidneys, and livers were harvested for histological evaluation. Significant elevation in peripheral blood leukocyte includes neutrophils, monocytes, and lymphocytes, as well as the neutrophils-to-lymphocyte ratio. The pro-inflammatory mediator levels [C-reactive protein, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß, and IL-8] along with the biochemical profile (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatine kinase, creatinine, and urea) were increased significantly (P < 0.05) and increased the expression of monocyte chemoattractant protein-1 and TNF-ß. The histopathological changes of heart, lung, kidney, and liver tissues revealed degeneration, cellular infiltration of leukocyte in the inflammatory foci and interstitial space, edema, early signs of fibrosis, apoptosis, and necrosis. In conclusion, these results indicate that intermittent exposure to LPS produces chronic subclinical systemic inflammation in multiple organs leading to chronic conditions and supports this model to be a useful preclinical tool for developing immunotherapeutic agents that could prevent, or reduce, chronic inflammatory diseases associated with, or without, bacterial translocation.

Antimicrobial Emulsifier-Glycerol Monolaurate Induces Metabolic Syndrome, Gut Microbiota Dysbiosis, and Systemic Low-Grade Inflammation in Low-Fat Diet Fed Mice.

SCOPE: Glycerol monolaurate (GML) is widely consumed worldwide in the food industry and is considered safe, but for chronic diseases, supporting scientific data remain sparse. This study investigates whether dietary GML induces metabolic syndrome, gut microbiota dysbiosis, and systemic low-grade inflammation. METHODS AND RESULTS: GML-induced occurrence of metabolic syndrome, gut microbiota alterations, and systemic low-grade inflammation are investigated. The results demonstrate that GML induced metabolic syndrome by significantly increasing the body weight, weight gain, food intake, body fat, fat droplet size and percentage of epididymal fat, serum triglycerides (TG), LDL, and atherogenic index, and decreasing the body muscle ratio, liver weight, and HDL, compared to the control (CON) group. Meanwhile, GML significantly changed the ß-diversity and composition of gut microbiota and upregulated the circulating levels of serum LPS, IL-1ß, IL-6, and TNF-α. Importantly, GML significantly decreased Akkermansia muciniphila and Lupinus luteus, and increased Bacteroides acidifaciens, Escherichia coli and the microbial DNA abundance of the ten predicated metabolism pathways involved in carbohydrate, amino acid, and lipid metabolism. CONCLUSION: Our results indicate that relatively low-dose GML consumption promotes metabolic syndrome, gut microbiota dysbiosis, and systemic low-grade inflammation, thereby calling for a reassessment of GML usage.