Serum PCSK9 Correlates with PTX3 and Apolipoproteins B, A1, and C3 Concentrations in Patients with Type 2 Diabetes

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in the regulation of LDL metabolism. There is evidence that circulating PCSK9 is a cardiovascular risk factor. In this study, we determined factors associated with circulating PCSK9 in a group of patients with type 2 diabetes mellitus (DM2). Material included 116 consecutive patients with DM2 from outpatient diabetes clinic. Circulating PCSK9, PTX3, apolipoprotein (apo) B100, apo B48, and apo C3 levels were determined by ELISA, apo A1 by immunoturbidimetry. The mean (sd) age of patients was 59.1 (11.1) years, the mean (sd) values of serum PCSK9 were 255.4 (106.97) ng/ml. Circulating PCSK9 correlated negatively with age ( r = − 0.21 , p < 0.05 ) and HbA1c ( r = − 0.21 , p < 0.05 ) and positively with BMI ( r = 0.21 , p < 0.05 ), total cholesterol ( r = 0.59 ), LDL-cholesterol ( r = 0.50 ), triglyceride ( r = 0.35 ), apo B100 ( r = 0.43 ), apo A1 ( r = 0.43 ) ( p < 0.001 for all), apo C3 ( r = 0.29 , p < 0.01 ), and apo B48 ( r = 0.25 , p < 0.01 ) concentration and FLI ( r = 0.26 , p < 0.01 ). Strong correlation between PTX3 and PCSK9 levels was observed ( r = 0.47 , p < 0.001 ). Multiple stepwise backward regression analysis with PCSK9 as dependent variable revealed that PTX3, apo B100, apo A1, apo B48, and BMI were significantly positive and the presence of NAFLD and HbA1c negatively associated with PCSK9 concentrations. These variables together explain 57% of PCSK9 variability; the strongest relationship was observed between PCSK9 and PTX3 and apo B100. Our results indicate that circulating PCSK9 is significantly associated with inflammation marker PTX3 as well as atherogenic lipids and apolipoproteins C3, B100, and B48, which might be of value in understanding interactions between development of atherosclerosis and inflammatory state in DM2 patients.

The Pattern of Neuroinflammatory miRNAs, C-Reactive Protein, and Alanine Aminotransferase During Hospitalization In Recovered or Not-Recovered COVID-19 Patients

Background: Our aim was to investigate the expression of miRNAs, C-reactive protein as a blood inflammation marker, and alanine aminotransferase as a tissue inflammation marker in recovered and not-recovered COVID-19 patients. Methods: This cross-sectional project was done in three medical center of Iran from December to March, 2021. Generally, a total of 20 confirmed cases of COVID-19 with grade III and 20 healthy subjects were enrolled in the study. Then, the neuroinflammatory expression of miRNAs (miR-199, miR-203, and miR-181), C-reactive protein, and alanine aminotransferase were investigated during hospitalization from week 0 to week 2. Results: In not-recovered COVID-19 subjects, the expression of miR-199, miR-203, and miR-181 were decreased and the levels of C-reactive protein and alanine aminotransferase were increased during hospitalization. Conversely, in recovered COVID-19 subjects, the relative expression of miR-199, miR-203, and miR-181 were increased and the levels of C-reactive protein and alanine aminotransferase were decreased during hospitalization. Conclusions: The expression pattern of neuroinflammatory miRNAs is depends on whether the COVID-19 patient is recovering or deteriorating. Their expression is down-regulated in not-recovered COVID-19 patients and up-regulated in recovered COVID-19 patients.

Association Between Levels of Depression Symptoms and Moderately Increased Levels of the Inflammation Marker Albuminuria Is Explained by Age and Comorbidity.

Background: The study aimed to examine whether there are associations between levels of depression symptoms and levels of the inflammation marker albuminuria. Materials and methods: The 8303 participants in this cross-sectional study were subjects from the second survey of the Trøndelag Health Study (HUNT, Norway). Depression symptoms were assessed by the Hospital Anxiety and Depression Scale (HADS). Logistic regression analysis was performed to estimate the odds ratio (OR) for moderately increased albuminuria (ACR > 3.0 mg/mmol) according to different HADS subgroups and -scores.Results: Unadjusted ORs for moderately increased albuminuria were significantly increased in those with HADS > 8 (OR 1.27, 95% CI 1.05-1.54, p=0.013) and HADS > 11 (OR 1.59, 95% CI 1.19-2.14, p=0.002). However, after adjusting for age and sex, only HADS > 11 was significantly associated with ACR > 3.0 mg/mmol (OR 1.46, 95% CI 1.08-1.98, p=0.014), and after multivariable adjustments for cardiovascular risk factors and comorbidity, there were no significant associations. Conclusion: The positive and significant association between moderately increased albuminuria and symptoms of depression found in unadjusted analyses weakened and disappeared after adjustments. Although individuals with depressive symptoms had albuminuria more often than individuals without such symptoms, albuminuria may reflect other comorbidity and inflammation conditions than depression.

PRO-INFLAMMATORY CYTOKINES IL-4 AND IL-13 IN CHILDREN WITH "SECRETOR" AND "NON-SECRETOR" STATUS OF H ANTIGEN DURING FOOD ALLERGY

Analysis of peculiarities of production of inflammatory cytokines IL-4 and IL-13 in children with approved diagnosis "food allergy" with "secretor" and "non-secretor" H-antigen status was carried out. "Non-secretor" children were shown to have 1.7 times higher content of a Th2 inflammation marker, IL-4, in blood serum than children with "secretor" status. IL-13 content was also elevated, although not so significantly. In children with "non-secretor" status, higher level of pro-inflammatory cytokines correlated with more severe progression of allergic inflammation, which makes determination of H antigen in the saliva of children and their mothers a promising non-invasive prognostic marker of progression of allergic inflammation in children with food allergy.

Investigating the inflammation marker neutrophil-to-lymphocyte ratio in Danish blood donors with restless legs syndrome

Background Restless Legs Syndrome (RLS) is a neurological sensorimotor disorder that occurs in the evening and night, thereby impacting quality of sleep in sufferers. The pathophysiology of RLS is poorly understood but inflammation has been proposed as possibly being involved. The neutrophil-to-lymphocyte ratio (NLR) can be used as an inflammation marker but results from small studies have been inconclusive in determining whether NLR is associated with RLS. We aimed to assess whether an association between NLR and RLS exists in a large cohort of healthy individuals. Methods Neutrophils and lymphocytes were measured in blood samples of 13,055 individuals from the Danish Blood Donor Study, all of whom completed the validated Cambridge-Hopkins RLS-questionnaire for RLS assessment. Results In the sample, 661 individuals were determined as current RLS cases (5.1%). A higher proportion of individuals with RLS were females (62.5% vs 47.5%; P<0.001) and RLS cases were older than controls (P<0.001), but no differences in body mass index (BMI), smoking or alcohol consumption were found between the two groups. An increased NLR was observed in RLS cases compared to controls (median NLR: 1.80 vs 1.72; P = 0.033). In an unadjusted logistic regression model, increased NLR was associated with RLS (OR = 1.10 per NLR unit increase [95%CI:1.01–1.20]; P = 0.032); however, the association was not significant in multivariate models adjusting for sex and age (P = 0.094) or sex, age, alcohol consumption, smoking status and BMI (P = 0.107). Conclusion We found no association between RLS and NLR among Danish blood donors after adjusting for sex, age, alcohol consumption, smoking status and BMI. Further studies are needed to determine whether inflammation is a risk factor for RLS.

Elevated fecal and serum calprotectin in COVID-19 are not consistent with gastrointestinal symptoms

Intestinal epithelial cell damage caused by SARS-CoV-2 infection was thought to be associated with gastrointestinal symptoms and decreased fecal consistency. The association of the gastrointestinal symptoms with the COVID-19-mediated inflammatory response triggered by the gastrointestinal immune system was investigated in this paper. Intestinal inflammation marker fecal calprotectin along with serum calprotectin and other inflammatory markers were measured in COVID-19 cases with and without GI manifestations as well as healthy individuals. Analyses were performed to compare COVID-19 patient subgroups and healthy controls and examine the relationship between fecal and serum calprotectin levels with gastrointestinal symptoms and disease severity. COVID-19 patients (n = 70) were found to have markedly elevated median levels of fecal (124.3 vs. 25.0 µg/g; P < 0/0001) and serum calprotectin (3500 vs. 1060 ng/mL; P < 0/0001) compared with uninfected controls. Fecal and serum calprotectin levels were not significantly different between COVID-19 patients who displayed GI symptoms and those who did not. Compared with other acute phase markers, both fecal and serum calprotectin were superior in identifying COVID-19 patients who progressed to severe illness. Although the progression of COVID-19 disease is marked by an elevation of fecal and serum calprotectin, gastrointestinal symptoms or diarrhea were not correlated with calprotectin increase level.

Eleven genomic loci affect plasma levels of chronic inflammation marker soluble urokinase-type plasminogen activator receptor

Soluble urokinase-type plasminogen activator receptor (suPAR) is a chronic inflammation marker associated with the development of a range of diseases, including cancer and cardiovascular disease. The genetics of suPAR remain unexplored but may shed light on the biology of the marker and its connection to outcomes. We report a heritability estimate of 60% for the variation in suPAR and performed a genome-wide association meta-analysis on suPAR levels measured in Iceland (N = 35,559) and in Denmark (N = 12,177). We identified 13 independently genome-wide significant sequence variants associated with suPAR across 11 distinct loci. Associated variants were found in and around genes encoding uPAR (PLAUR), its ligand uPA (PLAU), the kidney-disease-associated gene PLA2R1 as well as genes with relations to glycosylation, glycoprotein biosynthesis, and the immune response. These findings provide new insight into the causes of variation in suPAR plasma levels, which may clarify suPAR’s potential role in associated diseases, as well as the underlying mechanisms that give suPAR its prognostic value as a unique marker of chronic inflammation.