Inflammatory Markers Interleukin-6 Research Articles

Clinical Correlates Identify ProBDNF and Thrombo-Inflammatory Markers as Key Predictors of Circulating p75NTR Extracellular Domain Levels in Older Adults.

The p75NTR receptor binds all neurotrophins and is mostly known for its role in neuronal survival and apoptosis. Recently, the extracellular domain (ECD) of p75NTR has been reported in plasma, its levels being dysregulated in numerous neurological diseases. However, the factors associated with p75NTR ECD levels remain unknown. We investigated clinical correlates of plasma p75NTR ECD levels in older adults without clinically manifested neurological disorders. Circulating p75NTR levels were measured by enzyme-linked immunosorbent assay in plasma obtained from participants in the BEL-AGE cohort (n = 1,280). Determinants of plasma p75NTR ECD levels were explored using linear and non-linear statistical models. Plasma p75NTR ECD levels were higher in male participants; were positively correlated with circulating concentrations of pro-brain-derived neurotrophic factor, and inflammatory markers interleukin-6 and CD40 Ligand; and were negatively correlated with the platelet activation marker P-selectin. While most individuals had p75NTR levels ranging from 43 to 358 pg/ml, high p75NTR levels reaching up to 9,000 pg/ml were detectable in a subgroup representing 15% of the individuals studied. In this cohort of older adults without clinically manifested neurological disorders, there was no association between plasma p75NTR ECD levels and cognitive performance, as assessed by the Montreal Cognitive Assessment score. The physiological relevance of high p75NTR ECD levels in plasma warrants further investigation. Further research assessing the source of circulating p75NTR is needed for a deeper understanding of the direction of effect, and to investigate whether high p75NTR ECD levels are predictive biomarkers or consequences of neuropathology.

Muscle Mass and Inflammation in Older Adults: Impact of the Metabolic Syndrome

Background: Inflammatory processes are a cause of accelerated loss of muscle mass. Metabolic syndrome (MetS) is a highly prevalent age-related condition, which may promote and be promoted by inflammation. However, whether inflammation in MetS (metaflammation) is associated with lower muscle mass is still unclear. Methods: Complete cross-sectional data on body composition, MetS, and the inflammatory markers interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF), and C-reactive protein (CRP) were available for 1,377 BASE-II participants (51.1% women; 68 ± 4 years old). Appendicular lean mass (ALM) was assessed by dual-energy X-ray absorptiometry. Low muscle mass (low ALM-to-BMI ratio [ALMBMI]) was defined according to the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project. Regression models, adjusted for an increasing number of confounders (sex, age, physical activity, morbidities, diabetes mellitus type II, TSH, albumin, HbA1c, smoking habits, alcohol intake, education, and energy intake/day), were used to calculate the association between low ALMBMI and high inflammation (tertile 3) according to MetS. Results: MetS was present in 36.2% of the study population, and 9% had low ALMBMI. In the whole study population, high CRP (odds ratio [OR]: 2.7 [95% CI: 1.6–4.7; p = 0.001]) and high IL-6 (OR: 2.1 [95% CI: 1.2–1.9; p = 0.005]) were associated with low ALMBMI. In contrast, no significant association was found between TNF, IL-10, or IL-1β with low ALMBMI. When participants were stratified by MetS, results for IL-6 remained significant only in participants with MetS. Conclusions: Among BASE-II participants, low ALMBMI was associated with inflammation. Low-grade inflammation triggered by disease state, especially in the context of MetS, might favor loss of muscle mass, so a better control of MetS might help to prevent sarcopenia. Intervention studies to test whether strategies to prevent MetS might also prevent loss of muscle mass seem to be promising.

The evaluation of cytotoxicity and cytokine IL-6 production of root canal sealers with and without the incorporation of simvastatin: an invitro study

BackgroundFreshly mixed root canal sealers when proximate the periapical tissues, trigger varying degrees of cytotoxicity/inflammatory reactions. Simvastatin, a class of the drug statin, is a widely used cholesterol-lowering agent with additional anti-inflammatory activities. This study assessed the effects of simvastatin on cytotoxicity and the release of IL-6 (Interleukin-6) production when incorporated in zinc oxide eugenol and methacrylate resin-based sealers.MethodsExperimental groups consisted of conventional zinc oxide eugenol and methacrylate based-EndoREZ sealers (ZE & ER respectively) and 0.5 mg/mL simvastatin incorporated sealers (ZES & ERS). L929 mouse fibroblast cells were exposed to freshly mixed experimental sealers and evaluated for cytotoxicity (MTT assay) and inflammation levels (inflammatory marker IL-6 for ELISA) at various time intervals (0h, 24h and 7th day). The values were compared to the cell control (CC; L929 cells alone) and solvent control (SC; L929 cells + DMSO) groups. All the experiments were conducted in triplicates and subjected to statistical analysis using IBM SPSS Statistics software. Non parametric tests were conducted using Kruskal-Wallis and Friedman tests for inter-group and intra-group comparisons respectively. Pairwise comparison was conducted by post hoc Dunn test followed by Bonferroni correction. P values < 0.05 were considered statistically significant.ResultsAll the experimental groups (ZE, ER, ZES, ERS) exhibited varying degree of cytotoxicity and IL-6 expression compared to the control groups CC and SC. The cell viability for ZE and ER decreased on day 7 as compared to 24 h. ZES and ERS had higher viable cells (75.93% & 79.90%) compared to ZE and ER (54.39% & 57.84%) at all time periods. Increased expression of IL-6 was observed in ZE & ER (25.49 pg/mL & 23.14 pg/mL) when compared to simvastatin incorporated ZE & ER (ZES-12.70 pg/mL & ERS-14.68 pg/mL) at all time periods. Highest level of cytotoxicity and inflammation was observed in ZE compared to all the other groups on day 7.ConclusionsAddition of 0.5 mg/mL of simvastatin to the sealers (ZES and ERS) decreased the cytotoxicity in the freshly mixed state and reduces their inflammatory effect.

Do partnership dissolutions and living alone affect systemic chronic inflammation? A cohort study of Danish adults

BackgroundPartnership breakups and living alone are associated with several adverse health outcomes. The aim of this study, carried out in Denmark, is to investigate whether accumulated numbers of divorces/partnership breakups...

The Effect of Outdoor Sports and Green Outdoors on Lung Inflammation

This study aimed to analyze the effect of exercise in open spaces with exposure to pollution and activity in green open areas on lung inflammation. The true experimental method and The Randomized Posttest-Only Control Group Design were used in this study. Twenty-four adult male Wistar white rats weighing 200-250 grams aged 8-9 weeks were randomly divided using simple random sampling technique into four groups, NE (Non-Exercise) as control, NE+Pol (Non Exercise + Pollution Particulate Matter 2.5 &gt;75 ppm, and Carbon Monoxide Meter &lt;100 ppm), Ex (Exercise 5 times/week for four weeks), Ex+Pol (Exercise + pollution). The inflammatory marker Interleukin 6 (IL-6) was analyzed using Western Blotting. To determine the significant differences between groups, one-way ANOVA analysis and Post Hoc test were used. Based on the study results, it can be concluded that there is an effect of exercise in an open space with exposure to pollution on lung inflammation. And other results show that there is no effect of exercise in green open spaces on lung inflammation.

Characterizing Patterns of Nurses' Daily Sleep Health: a Latent Profile Analysis.

Nursing is a demanding occupation characterized by dramatic sleep disruptions. Yet most studies on nurses' sleep treat sleep disturbances as a homogenous construct and do not use daily measures to address recall biases. Using person-centered analyses, we examined heterogeneity in nurses'daily sleep patterns in relation to psychological and physical health. Nurses (N = 392; 92% female, mean age = 39.54years) completed 14 daily sleep diaries to assess sleep duration, efficiency, quality, and nightmare severity, as well as measures of psychological functioning and a blood draw to assess inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP). Using recommended fit indices and a 3-step approach, latent profile analysis was used to identify the best-fitting class solution. The best-fitting solution suggested three classes: (1) "Poor Overall Sleep" (11.2%), (2) "Nightmares Only" (8.4%), (3) "Good Overall Sleep" (80.4%). Compared to nurses in the Good Overall Sleep class, nurses in the Poor Overall Sleep or Nightmares Only classes were more likely to be shift workers and had greater stress, PTSD symptoms, depression, anxiety, and insomnia severity. In multivariate models, every one-unit increase in insomnia severity and IL-6 was associated with a 33% and a 21% increase in the odds of being in the Poor Overall Sleep compared to the Good Overall Sleep class, respectively. Nurses with more severe and diverse sleep disturbances experience worse health and may be in greatest need of sleep-related and other clinical interventions.

Correlation between Selected Inflammatory Biomarkers in Geriatric Anemias − A Case–Control Study

Introduction: Anemia in the geriatric age group is a prevalent disorder, with a complex pathophysiology. In this study, we try to evaluate the correlation between selected inflammatory biomarkers [interleukin 6 (IL-6), C-reactive protein (CRP), and hepcidin (HA)] in geriatric anemia. Materials and methods: Case–control hospital-based study conducted in individual age 60 to 80 years at Chettinad Hospital and Research Institute. One hundred participants are included in this study, where 50 in case group with anemia and 50 in control group without anemia. A one-time blood sample is collected and was evaluated for complete blood count, serum ferritin, vitamin B12, HA, IL-6, and serum CRP. Results: There is a significant association between inflammatory markers IL-6, CRP, HA, and geriatric anemia, which shows statistical significance with P-value &lt;0.001, values in group case are following 6.60 ± 4.42 pg/mL, 3.79 ± 4.25 mg/L, 3.97 ± 2.16 ng/mL, 8.87 ± 1.95, and in control 3.22 ± 2.33 pg/mL, 2.02 ± 3.28 mg/L, 2.77 ± 0.85 ng/mL, and 12.39 ± 1.26. Final diagnosis most common, unexplained anemia with 25 (50.0%), followed by anaemia of chronic disease (ACD) 11 (22.0%) ACD with iron deficiency anaemia (IDA) occur in 6 (12.0%), 5 (10.0%) cases of pure IDA, and 3 (6.0%) megaloblastic anemia. Conclusion: Significant correlation between inflammatory biomarkers in geriatric anemias. Inflammatory biomarkers (CRP, IL-6, HA) will not only help in categorizing geriatric anemia but also eventually leads to specific targeted treatment protocol.

Correlation Analysis of Inflammatory Markers CRP and IL-6 and Postoperative Delirium (POD) in Elderly Patients: A Meta-Analysis of Observational Studies.

Postoperative delirium (POD) is very common in the elderly surgical population, and its occurrence is associated with multiple factors such as preoperative, intraoperative, and postoperative factors, and the increase of serum inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) is considered to be associated with the occurrence of POD, but the results of multiple studies are inconsistent. In this study, we investigated the correlation between inflammatory markers CRP and IL-6 and POD in elderly patients by literature search and meta-analysis. We searched PubMed, Web of Science, the Cochrane library, Embase, Ovid, and Springer Link for cohort studies or case-control studies that investigated the factors involved in the occurrence of POD, used the Newcastle-Ottawa Scale (NOS) to assess the quality of the selected literature, and combined the differences in serum CRP and IL-6 levels between POD and non-POD patients after surgery to evaluate the predictive value of CRP and IL-6 for the occurrence of POD. This research comprised 16 papers for quantitative analysis, with a total of 2967 patients, 758 with POD and 2209 with non-POD. There were 16 cohort studies (100%) and 0 case-control studies (0%) across all the collected literatures; there were 15 prospective cohort studies and 1 retrospective cohort research. A meta-analysis revealed a statistically significant difference in serum IL-6 levels between POD patients after surgery and non-POD patients [MD = 115.68, 95% CI (25.70, 206.66), Z = 2.52, P = 0.012], as well as a statistically significant difference in serum CRP levels [MD = 27.67, 95% CI (12.77, 42.58), Z = 3.64, P = 0.0003]. Discussion. Early after surgery, serum IL-6 and CRP levels were considerably higher in POD patients than in non-POD patients, indicating that early serum inflammatory variables are likely to be predictors of POD. After surgery, the levels of the aforementioned inflammatory factors should be actively monitored to forecast the emergence of delirium, and active treatment should be used to limit the creation and release of the aforementioned inflammatory factors.

Waist-to-height ratio cut-off points to predict obesity in adolescents and associa-tion with inflammatory markers.

Introduction: obesity increases inflammatory molecules and cardiovascular risk even in young populations. New indicators are being investigated, including the waist-to-height ratio (WHtR) to predict obesity and the relationship with inflammatory markers in childhood and adolescence. Objective: to identify the cut-off points of the WHtR to determine obesity and its association with inflammatory markers in adolescents in São Luís, state of Maranhão, Brazil. Methods: this is a cross-sectional study, with 2,209 adolescents aged 18 and 19, belonging to the third phase of the birth cohort entitled "RPS", carried out in 2016. The total area under the ROC curve (AUC) was identified to assess the predictive capacity of WHtR in relation to body fat percentage (%BF), obtained by air displacement plethysmography (ADP). The association of WHtR with inflammatory markers interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and c-reactive protein (CRP) was evaluated. Results: prevalence of obesity by the %BF was 10.3 % in males and 40.4 % in females. The cut-off points for the WHtR were 0.50 for females and 0.51 for males, with an AUC of 0.90 (95 % CI: 0.88-0.92) and 0.93 (95 % CI: 0.90-0.97). There was an association of elevated WHtR with higher levels of IL-6 and CRP (p < 0.05). Conclusion: the predictive capacity of WHtR for obesity was excellent. Elevated values of the WHtR were associated with early inflammatory markers. This study contributed to the identification of cut-off points for simple and low-cost anthropometric indicators.

Clostridium butyricum powders combined with zinc gluconate on inflammatory factors and intestinal microecology in children with infectious diarrhea

Objective: To investigate the clinical value of Clostridium butyricum powders combined with zinc gluconate in the treatment of infectious diarrhea in children, clinical data of 86 children with infectious diarrhea were retrospectively analyzed. Methods: Both groups received routine treatments to reduce symptoms, among which the control group ( n = 40) was given Clostridium butyricum powders, and the experiment group ( n = 46) was given Clostridium butyricum powders and zinc gluconate. Patients in both groups were treated for 5 days. The clinical efficacy, recovery time, safety, serum levels of inflammatory markers (interleukin-6, interleukin-17, C-reactive protein), indicators of the intestinal mucosal function (diamine oxidase, D-lactate) and indicators to intestinal microecology (bifidobacteria, lactobacillus) before and after treatment were compared between the two groups. Results: The clinical efficacy in the experiment group (95.65%) was higher than that in the control group (77.50%, p &lt; 0.05). The time of recovery from symptoms including diarrhea, abdominal pain and vomiting, and to normal body temperature in the experiment group were shorter than those in the control group (all p &lt; .001). After treatment, the serum IL-6, IL-17, CRP levels and DAO, D-lactate levels in both groups were lower than those before treatment, and were lower in the experiment group than in the control group (all p &lt; .001). After treatment, the intestinal bifidobacteria and lactobacillus levels in both groups were higher than those before treatment, and were higher in the experiment group than in the control group (all p &lt; .01). There was no significant difference in the incidence of adverse reactions between the experiment group (8.70%) and the control group (2.50%). Conclusion: In this open-label study, Clostridium butyricum powders combined with zinc gluconate are significantly effective in treating children with infectious diarrhea, which is conducive to relieving early symptoms, downregulating serum inflammatory factor levels, improving intestinal mucosal function, regulating intestinal microecology, and ensuring the safety of patients.

Serum Levels of Inflammatory Markers in Newly Diagnosed Hypothyroid Patients Before and After Levothyroxine Therapy

Introduction: Cytokines have a great significance in autoimmune thyroid disease. They are produced by thyroid follicular cells and have an indispensable role in T-cell and B-cell growth and differentiation. Tumour necrosis factor-alpha (TNF-α) is a cytokine having numerous immunological and metabolic activities and is an important stimulus for Interleukin-6 (IL-6) production. Interleukins play an important role in immune system function. Their deficiency causes autoimmune diseases or immune deficiency. Aim: To assess inflammatory markers IL-6 and TNF- α in hypothyroidism before and after attainment of euthyroid state by levothyroxine therapy and to find the correlation between serum levels of TNF-α and hypothyroid state. Materials and Methods: This quasi-experimental study was conducted at Department of Physiology at University College of Medical Sciences, Delhi, India, from January 2013 to October 2013. Total 30 newly diagnosed hypothyroid patients of the age group 18-45 years formed case group and 30 age and sexmatched subjects formed the control group, were recruited for the study. The patients were given levothyroxine replacement therapy for three months. The inflammatory biomarkers level was evaluated using solid-phase sandwich Enzyme Linked Immunosorbent Assay (ELISA), using kits from Diaclone. Paired and Unpaired t-tests respectively were used for hypothyroid patients in pre-post state and between two groups at baseline. Serum Thyroid Stimulating Hormone (TSH) levels of hypothyroid patients were correlated with serum levels of inflammatory markers using Pearson’s correlation test. Results: There was no statistical difference in age, sex, body mass index and lipid profile in the two groups. Hypothyroidism subjects achieved euthyroidism in three months months after obtaining levothyroxine therapy with the mean TSH levels 26.43±10.244 vs 3.4863±0.1963, mean free T3 levels 0.2980±.09408 vs 1.93±0.5690 and mean free T4 levels 0.2736±0.0973 vs 1.8986±0.2853 in pre-post states respectively. Serum levels of IL-6 and TNF-α were significantly higher (p-value&lt;0.001) in hypothyroid subjects compared to euthyroid controls. A positive correlation between serum levels of IL-6 (r-value= 0.5778, p-value= 0.0008) and TNF-α (r-value= 0.521, p-value= 0.003) with serum TSH levels were found. Conclusion: The study reported a significant effect of levothyroxine therapy in restoring serum levels of raised inflammatory markers among hypothyroid patients. A decrease in low-grade chronic inflammation after treatment showed some clinical importance as chronic inflammation is known to be associated with atherosclerosis and cardiac disease.

Adverse Effects of Chrysene on Human Hepatocytes via Inducement of Oxidative Stress and Dysregulation of Xenobiotic Metabolism

Chrysene is a four-ring polycyclic aromatic hydrocarbon, which has been demonstrated to induce adverse effects through the inducement of oxidative stress. However, the possible mechanisms and potential pathways of chrysene-induced oxidative damages are scarcely investigated. In the present study, oxidative stress and xenobiotic metabolism disorder were investigated in human hepatocytes. Chrysene could cause cell viability reduction and cellular reactive oxygen species accumulation in a dose-dependent manner from 10 to 400 ng/mL. Moreover, the mRNA expression detoxification phases, including phase I and phase II as xenobiotic metabolizing enzymes, along with phase III, were investigated by real-time PCR. The results showed that chrysene upregulated the phase I enzymes cytochrome P-450 1A1, 1A2, and epoxide hydrolase 1, while at the same time downregulated the phase II enzymes glutathione S-transferase alpha 1, NAD(P)H: quinone oxidoreductase 1, and the phase III transporters multiple drug resistant 1 and multidrug resistance-associated protein 2. Furthermore, the inflammatory markers tumor necrosis factor alpha, interleukin-6, interleukin-8, and cyclooxygenase-2 were increased, whereas the antioxidant transcription factor nuclear factor erythroid 2-related factor 2 and its regulated enzymes glutathione peroxidase1, heme oxygenase-1, and superoxide dismutase 2 were decreased. These data suggested that chrysene expressed oxidative stress to hepatocytes, resulting in cytotoxicity and inflammation, which might be due to the damage of the antioxidant system and xenobiotic metabolism.

Hemodialysis Patients with Cardiovascular Disease Reveal Increased Tissue Na+ Deposition

Background: The relationship between Na⁺ balance and cardiovascular disease (CVD) in hemodialysis (HD) patients is not yet fully understood. We hypothesized that HD patients co-diagnosed with CVD show increased tissue Na⁺ accumulation compared to HD patients without CVD. Methods: In our observational study, 52 HD patients were divided into a group with (23 subjects) or without (29 subjects) a positive history of cardiovascular events. We used ²³Na-magnetic resonance imaging (²³Na-MRI) at 3.0 Tesla to quantify Na⁺ content in skin and muscle of both groups directly before and after HD. Additionally, total body fluid distribution was determined by bioimpedance spectroscopy (BIS) and laboratory parameters were assessed. Results: Compared to HD patients without CVD, ²³Na-MRI detected an increased Na⁺ content in skin (21.7 ± 7.3 vs. 30.2 ± 9.8 arbitrary units (a.u.), p < 0.01) and muscle tissue (21.5 ± 3.6 vs. 24.7 ± 6.0 a.u., p < 0.05) in patients with previous CVD events. Simultaneously measured fluid amount by BIS, includingexcess extracellular water (1.8 ± 1.7 vs. 2.2 ± 1.7 L, p = 0.44), was not significantly different between both groups. Tissue Na⁺ accumulation in HD-CVD patients was paralleled by a higher plasma concentration of the inflammation marker interleukin-6 (5.1, IQR 5.8 vs. 8.5, IQR 7.9 pg/mL, p < 0.05). Conclusion: In our cohort, HD patients with CVD showed higher tissue Na⁺ content than HD patients without CVD, while no difference in body water distribution could be detected between both groups. Our findings provide evidence that the history of a cardiovascular event is associated with disturbances in tissue Na⁺ content in HD patients.

Rhubarb Enema Decreases Circulating Trimethylamine N-Oxide Level and Improves Renal Fibrosis Accompanied With Gut Microbiota Change in Chronic Kidney Disease Rats.

Objectives: Trimethylamine N-oxide (TMAO), a metabolic product of gut flora, is increased in chronic kidney disease (CKD) subjects and is recognized as one type of uremic toxins which is associated with poor cardiovascular outcomes and kidney function loss. Previous studies have suggested that rhubarb enema could reduce circulating uremic toxins such as urea, creatinine, and indoxyl sulfate and also regulate the intestinal microbiota. However, whether rhubarb enema retards kidney dysfunction by reducing circulating TMAO and its underlying mechanism, are still unclear. The present study aims to investigate the impact of rhubarb enema on TMAO and its precursors, as well as on the intestinal microbiota in 5/6 nephrectomized (5/6Nx) CKD rats. Design: Rats in the treatment groups were given rhubarb enema after modeling. At the end of the study, blood, feces, and kidney tissues were collected and processed for biochemical analyses, histological and western blot analyses, 16S rRNA sequence and untargeted metabolomic analyses. Results: Rhubarb enema reduced serum TMAO and trimethylamine (TMA) levels, inhibited the expression of inflammatory markers (interleukin-6, tumor necrosis factor α and Interferon-γ) and alleviated tubular atrophy, monocyte infiltration and interstitial fibrosis in 5/6Nx CKD rats. Moreover, rhubarb enema significantly increased the abundance of some symbiotic bacteria and probiotics, while reduced the abundance of some potential pathogens at the genus level. In addition, Spearman’s correlation analysis revealed that lachnospiraceae and romboutsia were positively correlated with TMAO. Conclusion: Rhubarb enema decreases circulating TMAO level and improves renal fibrosis in 5/6Nx CKD rats, which may be related to the regulation of intestinal microbial community.

The effect of intradialytic exercise on inflammatory markers in hemodialysis patients

BackgroundChronic low-grade inflammation is a feature of chronic kidney disease associated with increased risk of multiple morbidities and mortalities. Hemodialysis (HD) patients lead a sedentary life style which may aggravate their inflammatory state and practicing exercise may improve this condition. The aim of this work was to study the effect of intradialytic exercise (IDE) on inflammatory markers in HD patients.ResultsThis prospective cohort study included 40 HD patients, divided into 2 groups: exercise group completed IDE for 3 months and non-exercise group matched in age and sex as controls. At baseline, there was no difference between both groups regarding physical performance assessed using short physical performance battery test (SPBT) or inflammatory markers C-reactive protein (CRP) and interleukin 6 (IL-6) P > 0.05. After 3 months, SPBT significantly improved in exercise group (P < 0.001). Also, both serum CRP and IL-6 levels showed significant decrease in exercise group compared to baseline (P < 0.001), while no similar change was noticed in non-exercise group.ConclusionsRegular intradialytic aerobic exercise program can improve physical function and inflammation in hemodialysis patients. Further studies on larger number of patients are warranted.

Inhalation exposure to silver nanoparticles induces hepatic inflammation and oxidative stress, associated with altered renin-angiotensin system signaling, in Wistar rats.

Silver nanoparticles (AgNPs) have become increasingly popular in the biomedical field over the last few decades due to its proven antibacterial property. Previous scientific studies have reported that one of the major organs responsible for detoxification of AgNPs is the liver. The liver is also the primary organ responsible for secretion of angiotensinogen (AGT), a key signaling molecule involved in the renin-angiotensin system (RAS), which plays an important role in maintaining cardiac output and vascular pressure. The aim of this study was to assess any potential changes in the RAS-associated gene signaling, inflammatory response, and hepatocellular toxicity resulting from AgNP exposure. To do this, 6-week-old, male Wistar rats were exposed to a subacute inhalation exposure of AgNP (200 ppb/days over 4h/days exposure, for 5d) and their livers were analyzed for alterations in RAS components, inflammation, and oxidative stress. Real time qPCR analysis showed that AgNP-exposure resulted in a significant increase in hepatic AGT, angiotensin converting enzyme (ACE)-1, and ACE-2 mRNA expression. Expression of inflammatory markers interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α were also upregulated with AgNP-exposure, compared to controls. Furthermore AgNP-exposure mediated a significant increase in hepatic expression of catalase, and superoxide dismutase, and oxidative stress, as assessed via 8-Oxo-2'-deoxyguanosine staining. Increased oxidative stress was associated with increased monocyte/macrophage-2 staining in the liver of AgNP-exposed rats. Such findings indicate that subacute inhalation exposure to AgNPs mediate increased hepatic RAS signaling, associated with inflammation, macrophage infiltration, and oxidative stress.

Breath and plasma metabolomics to assess inflammation in acute stroke

Inflammation is strongly implicated in both injury and repair processes occurring after stroke. In this exploratory study we assessed the feasibility of repeated sampling of exhaled volatile organic compounds and performed an untargeted metabolomic analysis of plasma collected at multiple time periods after stroke. Metabolic profiles were compared with the time course of the inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6). Serial breath sampling was well-tolerated by all patients and the measurement appears feasible in this group. We found that exhaled decanal tracks CRP and IL-6 levels post-stroke and correlates with several metabolic pathways associated with a post-stroke inflammatory response. This suggests that measurement of breath and blood metabolites could facilitate development of novel therapeutic and diagnostic strategies. Results are discussed in relation to the utility of breath analysis in stroke care, such as in monitoring recovery and complications including stroke associated infection.

Neurological Presentations in Patients with COVID-19 in Cytokine Storm.

Coronavirus disease 2019 (COVID-19) infection causes a wide variety of neurological disorders by affecting both central and peripheral nervous systems. The cytokine storm (CS) has been blamed for the development of severe neurological disorders in COVID-19. However, the relationship between COVID-19 CS and neurological manifestations has not been adequately studied. Thus, we aimed to investigate the neurological presentations in patients with COVID-19 CS. The study population consisted of hospitalized moderate-to-severe COVID-19 patients. It was divided into two groups CS (36 patients, 29.3%) and non-CS (87 patients, 70.7%) based on significant clinical symptoms, elevated inflammatory marker levels, radiological findings, and interleukin-6 levels (IL-6). The three most common neurological symptoms in the CS group were altered level of consciousness, headache, and unsteadiness. Altered level of consciousness was higher in the CS group (69.4%) than the non-CS group (25.3%) (p:0.001). The frequency of headache was comparable in both groups (p:0.186). The number of patients requiring intensive care unit and intubation was higher in the CS group (p:0.005 and p:0.001). The mortality rate in the CS group (38.9%) was higher than the non-CS group (8.0%) (p:0.001). IL-6, CRP, ferritin, neutrophil-lymphocyte ratio, procalcitonin, and D-dimer levels were higher in the CS group (for all p:0.001) while lymphocyte count was lower (p:0.003). The most common neurological presentation in patients with CS was altered level of consciousness. The presence of CS was an independent risk factor for high mortality.

Novel molecular panel for evaluating systemic inflammation and survival in therapy naïve glioma patients

BACKGROUNDInflammation is crucial to tumor progression. A traumatic event at a specific site in the brain activates the signaling molecules, which triggers inflammation as the initial response within the tumor and its surroundings. The educated immune cells and secreted proteins then initiate the inflammatory cascade leading to persistent chronic inflammation. Therefore, estimation of the circulating inflammatory indicators kynurenine (KYN), interleukin-6 (IL-6), tissue-inhibitor of matrix-metalloproteinase-1 and human telomerase reverse transcriptase (hTERT) along with neutrophil-lymphocyte ratio (NLR) has prognostic value.AIMTo assess the utility of chosen inflammatory marker panel in estimating systemic inflammation.METHODSThe chosen markers were quantitatively evaluated in 90 naive, molecularly sub-typed plasma samples of glioma. A correlation between the markers and confounders was assessed to establish their prognostication power. Follow-up on the levels of the indicators was done 3-mo post-surgery. To establish the validity of circulating KYN, it was also screened qualitatively by dot-immune-assay and by immunofluorescence-immunohistochemistry in tumor tissues.RESULTSMedian values of circulating KYN, IL-6, hTERT, tissue-inhibitor of matrix-metalloproteinase-1 and NLR in isocitrate-dehydrogenase-mutant/wildtype and within the astrocytic sub-groups were estimated, which differed from controls, reaching statistical significance (P < 0.0001). All markers negatively correlated with mortality (P < 0.0001). Applying combination-statistics, the panel of KYN, IL-6, hTERT and NLR achieved higher sensitivity and specificity (> 90%) than stand-alone markers, to define survival. The inflammatory panel could discriminate between WHO grades, and isocitrate-dehydrogenase-mutant/wildtype and define differential survival between astrocytic isocitrate-dehydrogenase-mutant/wildtype. Therefore, its assessment for precise disease prognosis is indicated. Association of KYN with NLR, IL-6 and hTERT was significant. Cox-regression described KYN, IL-6, NLR, and hTERT as good prognostic markers, independent of confounders. Multivariate linear-regression analysis confirmed the association of KYN and hTERT with inflammation marker IL-6.There was a concomitant significant decrease in their levels in a 3-mo follow-up.CONCLUSIONThe first evidence-based study of circulating-KYN in molecularly defined gliomas, wherein the tissue expression was found to be concomitant with plasma levels. A non-invasive model for assessing indicators of chronic systemic inflammation is proposed.

Biotic Supplements in Patients With Chronic Kidney Disease: Meta-Analysis of Randomized Controlled Trials

Gut flora imbalance characterizes patients with chronic kidney disease (CKD). Although biotic supplementation has been proposed to lessen inflammation and oxidative stress and, thus, reduce the risk of progressive kidney damage and cardiovascular disease, the effects remain controversial. We conducted a meta-analysis to assess the therapeutic benefits of biotics in CKD. PubMed, Embase, and Cochrane databases were systematically searched for randomized controlled trials that evaluated any biotic (prebiotic, probiotic, synbiotics) supplements in patients with CKD (CKD, stage 3-4 to end-stage renal disease). Primary endpoints included changes in renal function, markers of inflammation, and oxidative stress. Secondary endpoints included changes in levels of uremic toxins and variations in lipid metabolism. Twenty-three eligible studies included 842 participants. In a pooled-analysis, biotics did not change estimated glomerular filtration rate (mean difference [MD] = 0.08, P=.92) or serum albumin (MD=-0.01, P=.86), although prebiotics reduced serum creatinine (standardized mean difference [SMD]=-0.23, P=.009) and blood urea nitrogen (MD=-6.05, P<.00001). Biotics improved total antioxidative capacity (SMD=0.37, P=.007) and malondialdehyde (SMD=-0.96, P=.006) and reduced the inflammatory marker interleukin-6 (SMD=-0.30, P=.01) although not C-reactive protein (SMD=-0.22, P=.20). Biotic intervention reduced some uremic toxins, including p-cresol sulfate (SMD=-2.18, P<.0001) and indoxyl sulfate (MD=-5.14, P=.0009), which decreased in dialysis-dependent patients. Another toxin, indole-3-acetic acid (MD=-0.22, P=.63), did not change. Lipids were unaffected by biotic intervention (total cholesterol: SMD=-0.01, P=.89; high-density lipoprotein: SMD=-0.08, P=.76; low-density lipoprotein: MD=3.54, P=.28; triglyceride: MD=-2.26, P=.58). The results highlight the favorable influence of biotics on circulating markers of creatinine, oxidant stress (malondialdehyde, total antioxidative capacity), inflammation (interleukin-6), and uremic toxins (p-cresol sulfate) in patients with CKD. Biotics did not affect estimated glomerular filtration rate, albumin, indole-3-acetic acid, or lipids in either predialysis or dialysis patients.