Plasma Levels Of Inflammatory Markers Research Articles

Systemic inflammation is associated with myocardial fibrosis in patients with obstructive hypertrophic cardiomyopathy.

Chronic low-grade inflammation, often observed in hypertrophic cardiomyopathy (HCM), promotes adverse ventricular remodelling. This study aimed to investigate the relationship between inflammatory markers and myocardial fibrosis (MF) in patients with HCM. This study included 102 patients with complete baseline data who underwent septal myectomy. Myocardial samples were stained with Masson's trichrome and analysed to determine myocardial collagen content and MF levels. Plasma levels of inflammatory markers were measured using standard laboratory procedures. Univariate and multivariate logistic regression analyses were performed to explore the relationship between the inflammatory markers and MF. Among the 102 participants included in the analysis, the mean age was 48.9years, with 69 [67.6%] being men. The overall MF ranged from 2.5% to 40.7% (mean=15.2±8.1%, median=13.0%, IQR=9.9%-18.4%). Participants were divided into two groups based on a median MF of 13%. The high MF group had a larger left atrial diameter and left ventricular ejection fraction. Levels of interleukin (IL)-2, tumour necrosis factor (TNF)-α and interferon (IFN)-α were significantly higher in patients with high MF compared to those with low MF (2.3 vs. 4.0pg/mL, 3.1 vs. 3.9pg/mL, 4.2 vs.4.7pg/mL, respectively; all P<0.05). In multivariate models adjusted for age, sex and other clinical features, IL-2, IL-5 and TNF-α, were correlated with increased interstitial MF [odds ratio (OR): 1.54, 95% confidence interval (CI): 1.10-2.14; OR: 1.42, 95% CI: 1.02-1.98; OR: 1.33, 95% CI: 1.04-1.70]. After additional adjustment for imaging indicators, IL-2 and TNF-α remained significant (OR: 1.49, 95% CI: 1.06-2.09, P=0.021; OR:1.35, 95% CI: 1.01-1.80, P=0.044). The correlation analysis between inflammation and replacement fibrosis assessed by CMR in 97 patients revealed that 72 (74.2%) showed late gadolinium enhancement (LGE). No significant correlation was found between inflammatory markers and the presence or extent of LGE. Higher levels of IL-2 and TNF-α were associated with increased histopathological interstitial MF in patients with HCM. Given the gradual progression of MF in HCM, initiating anti-inflammatory treatment in the early stages may delay its progression.

Inflammation biomarkers and neurobehavioral performance in rural adolescents.

Systemic inflammation has been associated with lower neurobehavioral performance in diverse populations, yet the evidence in adolescents remains lacking. Cytokines can alter neural network activity to induce neurocognitive changes. This work seeks to investigate the association between inflammation and neurobehavior in adolescents living in a rural region of Ecuador. We examined 535 adolescents in rural communities of Ecuador (ESPINA study), 508 of which had neurobehavioral assessments (NEPSY-II) and circulating plasma levels of inflammatory markers (CRP, IL-6, TNF-⍺, sICAM-1, sVCAM-1, SAA, and sCD14). Associations between inflammatory biomarker concentrations and neurobehavioral scores were examined using adjusted bivariate semi-parametric models with generalized estimating equations. A partial least square regression approach was used to create composite variables from multiple inflammation biomarkers and model their association with cognitive outcomes. Higher sCD14 and TNF-α concentrations were significantly associated with lower social perception scores, by -0.47 units (95% CI: -0.80, -0.13) and -0.42 (-0.72, -0.12) for every 50% increase in inflammatory marker concentration, respectively. Similarly, every 50% increase in the inflammation summary score was associated with a significantly lower Social Perception score by -0.11 units (-0.19, -0.03). A unit increase in inflammatory composites of seven markers were associated with lower scores in language (-0.11 units, p=0.04), visuospatial processing (-0.15, p= 0.09), and social perception (-0.22, p=0.005) domains. Higher levels of inflammation were associated with lower neurobehavioral performance in adolescents, especially with social perception. In addition, using a robust analytic method to examine an association between a composite inflammatory variable integrating seven markers led to additional findings, including the domains of language and visuospatial processing. A longitudinal follow-up of such investigations could unveil potential changes in inflammation-neurobehavior performance links through developmental stages and intervention opportunities.

Adherence to the Healthy Nordic Food Index is associated with reduced plasma levels of inflammatory markers in patients with heterozygous familial hypercholesterolemia

Background and aimsFamilial hypercholesterolemia (FH) is an inherited disease associated with hypercholesterolemia, and dietary treatment is part of the treatment. We aimed to assess the dietary pattern in relation to the Healthy Nordic Food Index (HNFI) in adults with and without heterozygous FH (HeFH), and to examine the associations between dietary quality and biomarkers related to cardiovascular disease in adults with HeFH. MethodsWe included 205 adults (≥18 years) with HeFH who received follow-up at the Lipid Clinic in Oslo and compared them to controls (n=228). Dietary intake was assessed using a food frequency questionnaire and dietary quality was assessed using the HNFI. Blood samples were analysed for levels of blood lipids, plasma fatty acids (FAs), and markers of inflammation and platelet activation. ResultsThe HeFH patients (median 60 years; 50.2% female; 25.9% in secondary prevention) had lower intake of total and saturated fat compared to controls (32.6 energy percent (E%) vs. 34.9E%, and 9.6 E% vs 12.0 E%, respectively; p<0.001 for both). In the HeFH patients, increasing dietary quality was associated with increased plasma levels of the n-3 polyunsaturated FAs (PUFAs) eicosapentaenoic acid and docosahexaenoic acid, and the n-6 PUFA linoleic acid, and lower plasma levels of the inflammatory cytokines Tumor Necrosis Factor and interleukin-6, and of the platelet-derived inflammatory cytokines Platelet Factor 4 and Neutrophil-Activating Peptide-2. ConclusionNorwegian patients with HeFH followed up at a Lipid Clinic eat healthier than controls. Adherence to a healthy dietary pattern is associated with higher plasma levels of n-3 and n-6 PUFA, and lower levels of inflammatory markers, including platelet markers. This may suggest that adherence to an overall healthy dietary pattern might be beneficial for HeFH patients independent of the cholesterol-lowering effect of the diet.

Metabolic Dysfunction-Associated Steatotic Liver Disease: The Associations between Inflammatory Markers, TLR4, and Cytokines IL-17A/F, and Their Connections to the Degree of Steatosis and the Risk of Fibrosis.

Background: The pathogenesis of MASLD (metabolic dysfunction-associated steatotic liver disease) is driven by environmental, genetic, metabolic, immune, and inflammatory factors. IL-17 and TLR4 determine hepatic steatosis, inflammation, and finally fibrosis. Objectives: To explore the associations between the plasma levels of inflammatory markers, TLR4, and the cytokines IL17A/F, as well as their connections with the degree of hepatic steatosis and the risk of hepatic fibrosis (defined by the FIB-4 score) in MASLD patients. Methods: The study cohort included 80 patients diagnosed with MASLD. The IL-17A/F and TLR4 serum concentrations were determined using the ELISA method. Results: We found a significant difference in the CAR levels (C-reactive protein to albumin ratio) when comparing MASLD patients with severe steatosis to those with mild/moderate steatosis (Student's t test, t (71) = 2.32, p = 0.023). The PIV (pan-immune inflammatory value) was positively correlated with the SII (systemic immune inflammation index), (r = 0.86, p < 0.0001) and the CAR (r = 0.41, p = 0.033) in MASLD patients with severe steatosis. In contrast, increased values of the LMR (lymphocyte to monocyte ratio) were significantly associated, with decreased levels of the SII (ρ = -0.38, p = 0.045). We also found a positive correlation between the CAR and the SII (r = 0.41, p = 0.028). In patients with mild/moderate steatosis, a significant positive correlation was observed between the SII and IL17A (r = 0.36, p = 0.010), the PIV and the CAR (r = 0.29, p = 0.011), the PIV and the SII (r = 0.87, p < 0.0001) and the PIV and IL17A (r = 0.3, p = 0.036). A negative correlation was observed between the LMR and the SII (r = -0.55, p < 0.0001) and the CAR and IL17F (r = -0.37, p = 0.011). Regarding the inflammatory markers, the PIV (336.4 vs. 228.63, p = 0.0107), and the SII (438.47 vs. 585.39, p = 0.0238) had significantly lower levels in patients with an intermediate-high risk of hepatic fibrosis as compared with the patients with a low risk of hepatic fibrosis. The PNI (prognostic nutritional index) (47.16 vs. 42.41, p = 0.0392) had significantly different levels in patients with the likelihood of hepatic fibrosis than those with a low risk of hepatic fibrosis. Conclusions: Regarding the inflammatory markers, the PIV and the SII hold promise as biomarkers for discriminating between MASLD patients with an intermediate-high risk and those with a low risk of hepatic fibrosis. Our findings underscore the role of IL-17A and its potential relationship with inflammatory markers in MASLD pathogenesis and the progression to hepatic fibrosis.

O70 INVOLVEMENT OF MICRORNAs-146a-5P, -155-5P, AND -29b-5P IN CARDIAC REMODELLING AND DYSFUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS

Background: MicroRNAs have been implicated in the pathogenesis of cardiovascular disease. However, the contribution of microRNAs remain poorly understood in the context of hypertensive cardiac pathology. Aim: We investigated the role of miR-146a-5p, -155-5p, and -29b-5p in the development of cardiac hypertrophy and dysfunction in male and female spontaneously hypertensive rats (SHR). Methods: Seven (7)-month-old SHR (n=7 male, n=10 female), and age- and sex-matched normotensive Wistar Kyoto rats (WKY, n=7 male, n=9 female) were used for the study. Cardiac geometry and function were determined from echocardiography. Plasma levels of inflammatory markers were measured by ELISA. Collagen fraction area was determined from histological sections of the left ventricle (LV). MicroRNA, and mRNA expression of target genes was determined in the LV by RT-qPCR. Group differences were ascertained from 2-way ANOVA. Associations were determined from pearson's correlation. Results: In SHR, normalised heart and LV masses, LVPWTd, RWT, E, A, E/e’, and collagen fraction area were significantly greater compared to WKY. MidFS, e’, and a’ were significantly lower in SHR versus WKY. Female rats exhibited significantly greater LV mRNA expression of Lox1, Col1a/Col3a ratio, and plasma levels of CRP, IL-6, and TNF-α compared to males. MiR-29b-5p showed similar expression levels across experimental groups. MiR-146a-5p was upregulated in SHR and exhibited positive associations with BP, normalised heart and LV masses, RWT, collagen fraction area, and E/e’ ratio, but negative associations with e’. Conversely, miR-155-5p was downregulated in females and only positively associated with absolute heart, LV, kidney masses, and stroke volume. Conclusion: Upregulation of miR-146a-5p was associated with indices of concentric LVH, diastolic dysfunction, reactive fibrosis, and may be involved in the hypertensive-induced LV remodelling; whereas, changes in expression of miR-155-5p may be involved with a cardiac phenotype related to sexual dimorphism.

Systemic inflammatory markers in ageing, Alzheimer's disease and other dementias.

Systemic inflammation with alterations in inflammatory markers is involved in aging and Alzheimer's disease. However, few studies have investigated the longitudinal trajectories of systemic inflammatory markers during aging and Alzheimer's disease, and specific markers contributing to Alzheimer's disease remain undetermined. In this study, a longitudinal cohort (cohort 1: n = 290; controls, 136; preclinical Alzheimer's disease, 154) and a cross-sectional cohort (cohort 2: n = 351; controls, 62; Alzheimer's disease, 63; vascular dementia, 58; Parkinson's disease dementia, 56; behavioural variant frontotemporal dementia, 57; dementia with Lewy bodies, 55) were included. Plasma levels of inflammatory markers were measured every 2 years during a 10-year follow-up in the longitudinal cohort and once in the cross-sectional cohort. The study demonstrated that the inflammatory markers significantly altered during both aging and the development of Alzheimer's disease. However, only complement C3, interleukin-1β, and interleukin-6 exhibited significant changes in participants with preclinical Alzheimer's disease, and their longitudinal changes were significantly associated with the development of Alzheimer's disease compared to controls over the 10-year follow-up. In the cross-sectional cohort, complement C3 demonstrates specificity to Alzheimer's disease, while interleukin-1β and interleukin-6 were also altered in other dementias. The study provides a new perspective on the involvement of inflammatory markers in the aging process and the development of Alzheimer's disease, implying that regulating inflammation may have a pivotal role in promoting successful aging and in the prevention and treatment of Alzheimer's disease.

Decoding the intestinal response to heat stress in Gymnocypris eckloni: Insights from a thorough analysis of microbiome and transcriptome

The Qinghai-Tibetan Plateau has exhibited heightened sensitivity to global warming than any other region. G. ekloni, an endemic fish of the Qinghai-Tibetan Plateau, holds ecological significance and is a key highland cold-water species in Chinese aquaculture. However, the warming of its habitat poses a significant threat to its survival. The intestine serves as the primary line of external immune defense. There are no reports available on alterations in the intestine of G. eckloni in response to varying levels of heat stress. In this study, G. ekloni was categorized into the optimum temperature culture group (CO, control group), the 22 °C heat stress culture group (HT-22) and the 28 °C heat stress culture group (HT-28).The adaptability of G. ekloni intestine to varying levels of heat stress was investigated through a comprehensive analysis involving tissue sections, blood biochemical indexes, sequencing of 16S and RNA-Seq. Tissue sections showed severe intestinal damage in the HT-28, characterized by mucosal layer necrosis, swelling of thrush cells, and erosion of villi. In the HT-28 group, the significantly increased plasma levels of inflammatory markers (DAO, LPS, IL-1β, IL-6, and TNF-α) also corroborated the substantial impairment of intestinal barrier function. Meanwhile, the RNA-Seq analysis revealed a significant upregulation of most genes in the HIF-1 signaling pathway. This suggests that the HIF-1 signaling pathway likely plays a crucial role in safeguarding the intestinal tract from injuries caused by extreme temperature stress.Intriguingly, there was very little change in the intestinal histological structure and no significant changes in biochemical indicators of stress and inflammation in the blood in the HT-22 group, and 16S amplification sequencing also revealed a greater abundance of intestinal microbial species in the HT-22 group. Through co-analysis with the up-regulated DEGs in HT-22, it was determined that the augmentation of intestinal flora taxa in the HT-22 group positively contributing to enhancing intestinal immunity and stabilizing intestinal barrier. This comprehensive histomorphological and multi-omics study showcased the resilience of G. ekloni intestine to environmental warming. The findings offer fundamental data for future research on the artificial culture of highland economic fishes, and their environmental adaptations.

Adherence to the American Cancer Society guidelines on nutrition and physical activity for cancer survivors and biomarkers of inflammation among breast cancer survivors.

This study investigated whether adherence to the overall lifestyle recommendations in the American Cancer Society (ACS) guidelines on nutrition and physical activity for cancer survivors was associated with inflammation in breast cancer survivors. The study included 409 women who had undergone breast cancer surgery at least 1 year before enrollment. A generalized linear model was used to estimate the least square means and 95% confidence intervals of plasma levels of inflammatory markers according to lifestyle factors defined in terms of adherence to the ACS guidelines. Higher overall adherence scores were associated with lower levels of high-sensitivity C-reactive protein (hs-CRP) (p for trend=0.015) and higher levels of adiponectin (p for trend=0.009). Similar significant associations of hs-CRP (p for trend= 0.004) and adiponectin (p for trend=0.010) levels were observed with the score for the body mass index (BMI) component of the adherence score. A higher diet component score was associated with a higher adiponectin level (p for trend=0.020), but there was no significant association for the physical activity component score. The present study's findings suggest that maintaining a healthy lifestyle according to the ACS guidelines was associated with beneficial effects on inflammatory marker levels, especially hs-CRP and adiponectin, among breast cancer survivors. Among the 3 components of lifestyle guidelines, the BMI component exhibited the most similar tendency to the overall adherence score in relation to inflammatory indicators. Further prospective and intervention studies are needed to investigate longitudinal associations between lifestyle factors and inflammatory markers among breast cancer survivors.

Effects of a single phosphate-enriched test meal on inflammasome activity and postprandial inflammatory markers in healthy subjects.

The consumption of highly processed food is often associated with a high intake of inorganic phosphate. Hyperphosphatemia is accompanied by an inflammatory status in patients with chronic kidney disease. However, the immune response to high phosphorus intake in healthy individuals is largely unknown. Therefore, the aim of the present study was to evaluate the effect of a single phosphate-enriched meal on inflammasome activity and plasma levels of inflammatory markers. The analysis included 28 participants who received a single dose of either 700mg phosphorus or a placebo with a test meal. At baseline, 4 and 8h post-meal, plasma interleukin (IL)-6, IL-1β, IL-10, c-reactive protein (CRP), soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (sgp130) levels were determined. At baseline and 4h post-meal, peripheral blood mononuclear cells were isolated to assess inflammasome activity. Subsequently, the effect of phosphate with or without glucose on IL-6 and IL-1β gene expression and secretion in U937 monocytes was examined. While both groups showed a marked postprandial increase in IL-6 plasma levels, neither plasma levels of IL-6, IL-1β, CRP, IL-10, sIL-6R, and sgp130 nor inflammasome activity were affected by phosphate compared to placebo. In U937 cells, there was also no effect of phosphate on IL-6 expression, but the addition of glucose increased it. Phosphate, however, reduced the IL-1β secretion of these cells. Postprandial inflammatory markers were not affected by dietary phosphate. However, IL-6 plasma levels were markedly increased post-meal, which appears to be a metabolic rather than a pro-inflammatory phenomenon. ClinicalTrials.gov, NCT03771924, date of registration: 11th December 2018, retrospectively registered.

Design and Rationale of Cytokine Filtration in Lung Transplantation (GLUSorb): Protocol for a Multicenter Clinical Randomized Controlled Trial.

Lung transplantation (LTx) is the only treatment option for end-stage lung disease. Despite improvements, primary graft dysfunction (PGD) remains the leading cause of early mortality and precipitates chronic lung allograft dysfunction, the main factor in late mortality after LTx. PGD develops within the first 72 hours and impairs the oxygenation capacity of the lung, measured as partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2). Increasing the PaO2/FiO2 ratio is thus critical and has an impact on survival. There is a general lack of effective treatments for PGD. When a transplanted lung is not accepted by the immune system in the recipient, a systemic inflammatory response starts where cytokines play a critical role in initiating, amplifying, and maintaining the inflammation leading to PGD. Cytokine filtration can remove these cytokines from the circulation, thus reducing inflammation. In a proof-of-concept preclinical porcine model of LTx, cytokine filtration improved oxygenation and decreased PGD. In a feasibility study, we successfully treated patients undergoing LTx with cytokine filtration (ClinicalTrials.gov; NCT05242289). The purpose of this clinical trial is to demonstrate the superiority of cytokine filtration in improving LTx outcome, based on its effects on oxygenation ratio, plasma levels of inflammatory markers, PGD incidence and severity, lung function, kidney function, survival, and quality of life compared with standard treatment with no cytokine filtration. This study is a Swedish national interventional randomized controlled trial involving 116 patients. Its primary objective is to investigate the potential benefits of cytokine filtration when used in conjunction with LTx. Specifically, this study aims to determine whether the application of cytokine filtration, administered for a duration of 12 hours within the initial 24 hours following a LTx procedure, can lead to improved patient outcomes. This study seeks to assess various aspects of patient recovery and overall health to ascertain the potential positive impact of this intervention on the posttransplantation course. The process of patient recruitment for this study is scheduled to commence subsequent to a site initiation visit, which was slated to take place on August 28, 2023. The primary outcome measure that will be assessed in this research endeavor is the oxygenation ratio, a metric denoted as the highest PaO2/FiO2 ratio achieved by patients within a 72-hour timeframe following their LTx procedure. We propose that cytokine filtration could enhance the overall outcomes of LTx. Our hypothesis suggests potential improvements in LTx outcome and patient care. ClinicalTrials.gov NCT05526950; https://www.clinicaltrials.gov/study/NCT05526950. PRR1-10.2196/52553.

Choroid plexus volume is increased in mood disorders and associates with circulating inflammatory cytokines

Depressed patients exhibit altered levels of immune-inflammatory markers both in the peripheral blood and in the cerebrospinal fluid (CSF) and inflammatory processes have been widely implicated in the pathophysiology of mood disorders. The Choroid Plexus (ChP), located at the base of each of the four brain ventricles, regulates the exchange of substances between the blood and CSF and several evidence supported a key role for ChP as a neuro-immunological interface between the brain and circulating immune cells. Given the role of ChP as a regulatory gate between periphery, CSF spaces and the brain, we compared ChP volumes in patients with bipolar disorder (BP) or major depressive disorder (MDD) and healthy controls, exploring their association with history of illness and levels of circulating cytokines. Plasma levels of inflammatory markers and MRI scans were acquired for 73 MDD, 79 BD and 72 age- and sex-matched healthy controls (HC). Patients with either BD or MDD had higher ChP volumes than HC. With increasing age, the bilateral ChP volume was larger in patients, an effect driven by the duration of illness; while only minor effects were observed in HC. Right ChP volumes were proportional to higher levels of circulating cytokines in the clinical groups, including IFN-γ, IL-13 and IL-17. Specific effects in the two diagnostic groups were observed when considering the left ChP, with positive association with IL-1ra, IL-13, IL-17, and CCL3 in BD, and negative associations with IL-2, IL-4, IL-1ra, and IFN-γ in MDD. These results suggest that ChP could represent a reliable and easy-to-assess biomarker to evaluate the brain effects of inflammatory status in mood disorders, contributing to personalized diagnosis and tailored treatment strategies.

Soluble P2X7 Receptor Plasma Levels in Obese Subjects before and after Weight Loss via Bariatric Surgery

Obesity is a systemic disease frequently associated with important complications such as type 2 diabetes and cardiovascular diseases. It has also been proven that obesity is a disease associated with chronic low-grade systemic inflammation and that weight loss improves this low-grade chronic inflammatory condition. The P2X7 purinergic receptor (P2X7R), belonging to the family of the receptors for extracellular ATP, is a main player in inflammation, activating inflammasome and pro-inflammatory cytokine production. In this study, we evaluated the plasma levels of soluble P2X7R (sP2X7R) measured in a group of obese patients before and one year after bariatric surgery. Furthermore, we evaluated the relation of sP2X7R to inflammatory marker plasma levels. We enrolled 15 obese patients who underwent laparoscopic sleeve gastrectomy, evaluating anthropometric parameters (weight, height, BMI and waist circumference) before and after surgery. Moreover, we measured the plasma levels of inflammatory markers (CRP, TNFα and IL-6) before and after weight loss via bariatric surgery. The results of our study show that one year after bariatric surgery, obese patients significantly decrease body weight with a significant decrease in CRP, TNF-alfa and IL-6 plasma levels. Similarly, after weight loss, obese subjects showed a significant reduction in sP2X7R plasma levels. Moreover, before surgery, plasma levels of sP2X7R were inversely related with those of CRP, TNF-alfa and IL-6. Given the role of P2X7R in inflammation, we hypothesized that, in obese subjects, sP2X7R could represent a possible marker of chronic low-grade inflammation, hypothesizing a possible role as a mediator of obesity complications.

Primary apical periodontitis correlates to elevated levels of interleukin-8 in a Swedish population: A report from the PAROKRANK study.

To explore associations between root filled teeth, primary and secondary apical periodontitis, and levels of inflammatory markers in blood from patients with a first myocardial infarction and matched controls. Between May 2010 and February 2014, 805 patients with a first myocardial infarction and 805 controls, matched for sex, age, and postal code area, were recruited to the multicentre case-control study PAROKRANK (periodontitis and its relation to coronary artery disease). All participants underwent a physical and oral examination, as well as blood sampling. Using panoramic radiography, root filled teeth, primary apical periodontitis, and secondary apical periodontitis were assessed by three independent observers. Blood samples were analysed with enzyme-linked immunosorbent assay method for the following inflammatory markers: interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-12p70, tumour necrosis factor-α, and high-sensitivity C-reactive protein (hsCRP). Additionally, white blood cell count and plasma-fibrinogen were analysed. Associations between endodontic variables and the levels of inflammatory markers were statistically analysed with Mann-Whitney U-test and Spearman correlation, adjusted for confounding effects of baseline factors (sex, age, myocardial infarction, current smoking, diabetes, family history of cardiovascular disease, education, marital status, and periodontal disease). Mean age of the cohort was 62 years, and 81% were males. Root fillings were present in 8.4% of the 39 978 examined teeth and were associated with higher levels of hsCRP, fibrinogen, and leukocyte count, but lower levels of IL-2 and IL-12p70. After adjusting for confounders, root filled teeth remained associated with higher levels of fibrinogen, but lower levels of IL-1β, IL-2, IL-6, and IL-12p70. Primary apical periodontitis was found in 1.2% of non-root filled teeth and associated with higher levels of IL-8 (correlation 0.06, p = .025). Secondary apical periodontitis was found in 29.6% of root filled teeth but did not relate to the levels of any of the inflammatory markers. This study supports the notion that inflammation at the periapex is more than a local process and that systemic influences cannot be disregarded. Whether the observed alterations in plasma levels of inflammatory markers have any dismal effects on systemic health is presently unknown but, considering the present results, in demand of further investigation.

Association of Soluble Markers of Inflammation With Peri-coronary Artery Inflammation in People With and Without HIV Infection and Without Cardiovascular Disease.

Inflammation is linked to elevated cardiovascular disease (CVD) risk in people with HIV (PWH) on antiretroviral therapy (ART). Fat attenuation index (FAI) is a measure of peri-coronary inflammation that independently predicts CVD risk in HIV-uninfected persons. Whether FAI is associated with soluble inflammatory markers is unknown. Plasma levels of inflammatory markers were measured in 58 PWH and 16 controls without current symptoms or prior known CVD who underwent coronary computed tomography angiography and had FAI measurements. A cross-sectional analysis was performed, and associations of markers with FAI values of the right coronary artery (RCA) and left anterior descending artery (LAD) were assessed using multivariable regression models adjusted for the potential confounders age, sex, race, low-density lipoprotein cholesterol, body mass index, and use of lipid-lowering medication. Several inflammatory markers had significant associations with RCA or LAD FAI in adjusted models, including sCD14, sCD163, TNFR-I, and TNFR-II, CCL5, CX3CL1, IP-10. The associations between indices of systemic and peri-coronary inflammation are novel and suggest that these systemic markers and FAI together are promising noninvasive biomarkers that can be applied to assess asymptomatic CVD in people with and without HIV; they also may be useful tools to evaluate effects of anti-inflammatory interventions.

Bacterial gut microbiome differences in adults with ADHD and in children with ADHD on psychostimulant medication

Recent evidence suggests that there is a link between neurodevelopmental disorders, such as attention-deficit hyperactivity disorder (ADHD), and the gut microbiome. However, most studies to date have had low sample sizes, have not investigated the impact of psychostimulant medication, and have not adjusted for potential confounders, including body mass index, stool consistency and diet. To this end, we conducted the largest, to our knowledge, fecal shotgun metagenomic sequencing study in ADHD, with 147 well-characterized adult and child patients. For a subset of individuals, plasma levels of inflammatory markers and short-chain fatty acids were also measured. In adult ADHD patients (n = 84), compared to controls (n = 52), we found a significant difference in beta diversity both regarding bacterial strains (taxonomic) and bacterial genes (functional). In children with ADHD (n = 63), we found that those on psychostimulant medication (n = 33 on medication vs. n = 30 not on medication) had (i) significantly different taxonomic beta diversity, (ii) lower functional and taxonomic evenness, (iii) lower abundance of the strain Bacteroides stercoris CL09T03C01 and bacterial genes encoding an enzyme in vitamin B12 synthesis, and (iv) higher plasma levels of vascular inflammatory markers sICAM-1 and sVCAM-1. Our study continues to support a role for the gut microbiome in neurodevelopmental disorders and provides additional insights into the effects of psychostimulant medication. However, additional studies are needed to replicate these findings and examine causal relationships with the disorder.

Antimicrobial prophylaxis in patients undergoing endoscopic mucosal resection for 10- to 20-mm colorectal polyps: A randomized prospective study

Endoscopic mucosal resection (EMR) is frequently used for the removal of colorectal neoplasms. However, the use of prophylactic antibiotics in patients undergoing EMR is debatable. The aim of this randomized controlled trial was to assess whether antimicrobial prophylaxis is crucial in the perioperative period of EMR, especially for 10- to 20-mm lesions in this setting. Two hundred and sixty-four patients were randomized equally into 2 groups, the antibiotic (cefixime) group and the control group. The occurrence of adverse events was examined at 1 to 3 days after EMR. Plasma levels of inflammatory markers were analyzed at pre-operation, 1 day post-operation and 3 days post-operation. Blood samples collected at 1 day post-operation were used for culture. A total of 264 and 268 polyps were removed by EMR in the antibiotic group and the control group, respectively. There were 5 cases of fever, with 2 in the antibiotic group and 3 in the control group. In the antibiotic group, 12 patients had abdominal pain and 10 suffered bleeding, whereas in the control group, abdominal pain and bleeding were observed in 10 and 11 patients, respectively. There were no significant differences in the proportion of patients with fever or the incidences of postoperative complications between the groups. No significant differences between the groups were reported in plasma levels of white blood cell count, erythrocyte sedimentation rate, C-reactive protein or procalcitonin at pre-operation or post-operation. No patients provided positive blood cultures. The use the prophylactic antibiotics for EMR procedures in the perioperative period is no longer required when the lesions are 10 to 20 mm in size.

Associations of body mass index and weight change with circulating levels of high-sensitivity C-reactive protein, proinflammatory cytokines, and adiponectin among breast cancer survivors.

This study examined the associations of body mass index (BMI) and weight change with inflammatory markers among breast cancer survivors in Korea. A total of 495 women were included who had been diagnosed with primary breast cancer and survived for at least 6 months since the surgery. Information on the body weight and height of the participants was collected both at the study enrollment and diagnosis. The plasma levels of inflammatory markers were measured, including high-sensitivity C-reactive protein, interleukin (IL)-6, IL-8, tumor necrosis factor-α, and adiponectin. A summary z-score was calculated by summing up the z-scores of each biomarker. The least-square means and 95% confidence intervals (CIs) were calculated using a generalized linear model and odds ratios (ORs) and 95% CIs for the elevated levels of inflammatory markers with a multivariate logistic regression model. Participants with a BMI ≥27.5kg/m2 at the study enrollment and at diagnosis were significantly associated with elevated summary z-scores compared to those with a BMI<23kg/m2 ; the ORs (95% CIs) were 5.42 (2.15-13.71) for current BMI and 3.66 (1.68-7.98) for BMI at diagnosis, respectively. Additionally, a weight loss>5% since diagnosis was associated with a lower prevalence of high summary z-scores; the OR (95% CI) was .20 (.08-.52) compared to a stable weight. A high BMI at diagnosis and current BMI with a greater degree were associated with unfavorable levels of inflammatory markers among breast cancer survivors. Additionally, weight loss since diagnosis was inversely associated with these markers.

The Curcumin Supplementation with Piperine Can Influence the Acute Elevation of Exercise-Induced Cytokines: Double-Blind Crossover Study.

Simple SummaryInflammation is an immune response to harmful stimuli, such as pathogens and damaged cells. Intense exercise can induce a local and systemic inflammatory response as well. We believe that exercise-induced inflammatory responses are essential for muscle repair and regeneration. However, uncontrolled acute inflammation in athletes during the training process and competition could reduce the level of performance. In this study, we investigate the effects of curcumin and piperine on the exercise-induced inflammatory response.Background: to evaluate the effects of one week of supplementation with curcumin combined with piperine on physical performance, immune system cell counts, muscle damage, and plasma levels of inflammatory markers after a treadmill running training session. Methods: This study is a double-blind, crossover-balanced clinical trial with a three-week intervention. Sixteen male runners with a mean age of 36 ± 9 years and VO2 max of 60.6 ± 9.03 mL.kg −1 min −1 were recruited and randomly divided into 2 groups: the first group (CPG) was supplemented daily for 7 days with 500 mg of curcumin + 20 mg piperine, and the second group (PG) was supplemented with 540 mg of cellulose. After the 7th day of supplementation, the volunteers participated in the experimental running protocol, where blood samples were collected before, after, and one hour after exercise for analysis of the number of leukocytes, creatine kinase, and cytokine concentration (IL-2, TNF-α, IFN, IL-6, and IL-10) using flow cytometry. This process was repeated, reversing the supplementation offered to the groups. Results: curcumin and piperine supplementation could not change the physical performance, immune cell counts, and muscle damage; however, the aerobic fatiguing exercise protocol inhibited the elevation of the plasmatic levels of some cytokines. The running exercise protocol could elevate the circulating levels of IL-2 (from 49.7 to 59.3 pg/mL), TNF-α (from 48.5 to 51.5 pg/mL), INF (from 128.8 to 165.0 pg/mL), IL-6 (from 63.1 to 77.3 pg/mL), and IL-10 (from 48.9 to 59.6 pg/mL) 1 h after the end of the running protocol. However, the curcumin and piperine supplementation could inhibit this elevation. Conclusions: curcumin and piperine supplementation had no effect on physical performance, immune cell counts, or muscle damage; however, the supplementation could modulate the kinetics of IL-2, TNF-α, INF, IL-6, and IL-10 1 h after the end of exercise.

Combination Therapy of Alpha-Lipoic Acid, Gliclazide and Ramipril Protects Against Development of Diabetic Cardiomyopathy via Inhibition of TGF-β/Smad Pathway.

Background: Diabetic cardiomyopathy (DCM) is a major long-term complication of diabetes mellitus, accounting for over 20% of annual mortality rate of diabetic patients globally. Although several existing anti-diabetic drugs have improved glycemic status in diabetic patients, prevalence of DCM is still high. This study investigates cardiac effect of alpha-lipoic acid (ALA) supplementation of anti-diabetic therapy in experimental DCM. Methods: Following 12 h of overnight fasting, 44 male Sprague Dawley rats were randomly assigned to two groups of healthy control (n = 7) and diabetic (n = 37) groups, and fasting blood glucose was measured. Type 2 diabetes mellitus (T2DM) was induced in diabetic group by intraperitoneal (i.p.) administration of nicotinamide (110 mg/kg) and streptozotocin (55 mg/kg). After confirmation of T2DM on day 3, diabetic rats received monotherapies with ALA (60 mg/kg; n = 7), gliclazide (15 mg/kg; n = 7), ramipril (10 mg/kg; n = 7) or combination of the three drugs (n = 7) for 6 weeks while untreated diabetic rats received distilled water and were used as diabetic control (n = 9). Rats were then sacrificed, and blood, pancreas and heart tissues were harvested for analyses using standard methods. Results: T2DM induction caused pancreatic islet destruction, hyperglycemia, weight loss, high relative heart weight, and development of DCM, which was characterized by myocardial degeneration and vacuolation, cardiac fibrosis, elevated cardiac damage markers (plasma and cardiac creatine kinase-myocardial band, brain natriuretic peptide and cardiac troponin I). Triple combination therapy of ALA, gliclazide and ramipril preserved islet structure, maintained body weight and blood glucose level, and prevented DCM development compared to diabetic control (p < 0.001). In addition, the combination therapy markedly reduced plasma levels of inflammatory markers (IL-1β, IL-6 and TNF-α), plasma and cardiac tissue malondialdehyde, triglycerides and total cholesterol while significantly increasing cardiac glutathione and superoxide dismutase activity and high-density lipoprotein-cholesterol compared to diabetic control (p < 0.001). Mechanistically, induction of T2DM upregulated cardiac expression of TGF-β1, phosphorylated Smad2 and Smad3 proteins, which were downregulated following triple combination therapy (p < 0.001). Conclusion: Triple combination therapy of ALA, gliclazide and ramipril prevented DCM development by inhibiting TGF-β1/Smad pathway. Our findings can be extrapolated to the human heart, which would provide effective additional pharmacological therapy against DCM in T2DM patients.

Associations of Sleep Insufficiency and Chronotype with Inflammatory Cytokines in College Students.

PurposeSleep insufficiency and circadian rhythm disturbances in college students have become prominent. Current findings show that sleep insufficiency is closely related to inflammation. Studies on the correlation between chronotype and inflammatory factors are still lacking. Therefore, this research intended to examine the relationships between sleep duration, chronotype and inflammatory cytokines in young adults, and to estimate the correlation between chronotype and inflammatory cytokines stratified by sleep duration.Patients and MethodsWe conducted a cross-sectional study in April and May 2019. Participants were recruited from two colleges located in central China. The Pittsburgh Sleep Quality Index (PSQI) and the Morning and Evening Questionnaire-5 (MEQ-5) were administered to assess sleep duration and chronotype. Sleep duration less than 7 hours was defined as insufficient sleep. Fasting venous blood was collected to measure plasma levels of inflammatory markers including IL-1β, IL-6, TNF-α and IL-10.ResultsA total of 723 participants were included in this study, with a mean age of 18.68 years (standard deviation=0.99). After adjusting for confounding factors, the results of generalized linear model showed that sleep insufficiency was positively correlated with IL-1β, TNF-α and IL-10; and evening-types (E-types) were positively associated with the levels of IL-1β and IL-6 (p<0.05). Compared to the control group (sleep sufficiency and M-types), there were positive interaction effects of sleep insufficiency and neutral-types (N-types) on the levels of IL-1β, IL-6, TNF-α and IL-10 (p<0.05). The hierarchical regression model showed that N-types and E-types were positively correlated to the levels of IL-1β, IL-6, TNF-α and IL-10 among college students with sleep insufficiency (p<0.05).ConclusionThe levels of inflammatory markers were higher among college students with sleep insufficiency and E-types. N-types and E-types were positively correlated with IL-1β, IL-6, TNF-α and IL-10 among college students with sleep insufficiency.