Investigation of the Associations of Novel Inflammatory Biomarkers—Systemic Inflammatory Index (SII) and Systemic Inflammatory Response Index (SIRI)—With the Severity of Coronary Artery Disease and Acute Coronary Syndrome Occurrence

Atherosclerosis, the underlying cause of coronary artery disease (CAD), has a significant inflammatory component. White blood cell count is an affordable and accessible way to assess the systemic immune response, as it comprises many subgroups with distinct and complex functions. Considering their multidirectional effect on atherosclerosis, new biomarkers integrating various leukocyte subgroups, the Systemic Inflammatory Index (SII) and the Systemic Inflammatory Response Index (SIRI), were recently devised to describe the balance between inflammation and immune reaction. This research aimed to evaluate the relationship of the intensity of inflammation measured by these biomarkers with the severity of CAD assessed with coronary angiography and with the diagnosis of acute coronary syndrome (ACS) or stable CAD in 699 patients. SIRI, but not SII, was associated with the diagnosis, having the highest values for patients with ACS (STEMI), significantly higher than in patients with stable CAD (p < 0.01). The highest SII and SIRI values were observed in patients with three-vessel CAD. SII and SIRI require further in-depth and well-designed research to evaluate their potential in a clinical setting.     

Metabolic Syndrome and β-Oxidation of Long-Chain Fatty Acids in the Brain,Heart, and Kidney Mitochondria

We present evidence that metabolic syndrome (MetS) represents the postreproductive stage of the human postembryonic ontogenesis. Accordingly, the genes governing this stage experience relatively weak evolutionary selection pressure, thus representing the metabolic phenotype of distant ancestors with β-oxidation of long-chain fatty acids (FAs) as the primary energy source. Mitochondria oxidize at high-rate FAs only when succinate, glutamate, or pyruvate are present. The heart and brain mitochondria work at a wide range of functional loads and possess an intrinsic inhibition of complex II to prevent oxidative stress at periods of low functional activity. Kidney mitochondria constantly work at a high rate and lack inhibition of complex II. We suggest that in people with MetS, oxidative stress is the central mechanism of the heart and brain pathologies. Oxidative stress is a secondary pathogenetic mechanism in the kidney, while the primary mechanisms are kidney hypoxia caused by persistent hyperglycemia and hypertension. Current evidence suggests that most of the nongenetic pathologies associated with MetS originate from the inconsistencies between the metabolic phenotype acquired after the transition to the postreproductive stage and excessive consumption of food rich in carbohydrates and a sedentary lifestyle.     

Characterization of Lipids in Saliva,Tears and Minor Salivary Glands of Sjögren’s Syndrome Patients Using an HPLC/MS-Based Approach

The diagnostic work-up of primary Sjögren’s syndrome (pSS) includes quantifying saliva and tear production, evaluation of autoantibodies in serum and histopathological analysis of minor salivary glands. Thus, the potential for further utilizing these fluids and tissues in the quest to find better diagnostic and therapeutic tools should be fully explored. Ten samples of saliva and tears from female patients diagnosed with pSS and ten samples of saliva and tears from healthy females were included for lipidomic analysis of tears and whole saliva using high-performance liquid chromatography coupled to time-of-flight mass spectrometry. In addition, lipidomic analysis was performed on minor salivary gland biopsies from three pSS and three non-SS females. We found significant differences in the lipidomic profiles of saliva and tears in pSS patients compared to healthy controls. Moreover, there were differences in individual lipid species in stimulated saliva that were comparable to those of glandular biopsies, representing an intriguing avenue for further research. We believe a comprehensive elucidation of the changes in lipid composition in saliva, tears and minor salivary glands in pSS patients may be the key to detecting pSS-related dry mouth and dry eyes at an early stage. The identified differences may illuminate the path towards future innovative diagnostic methodologies and treatment modalities for alleviating pSS-related sicca symptoms.     

Association of CDKN2BAS Polymorphism rs4977574 with Coronary Heart Disease: A Case-Control Study and a Meta-Analysis

The goal of our study was to explore the significant association between a non-protein coding single nucleotide polymorphism (SNP) rs4977574 of CDKN2BAS gene and coronary heart disease (CHD). A total of 590 CHD cases and 482 non-CHD controls were involved in the present association study. A strong association of rs4977574 with CHD was observed in females (genotype: p = 0.002; allele: p = 0.002, odd ratio (OR) = 1.57, 95% confidential interval (CI) = 1.18–2.08). Moreover, rs4977574 was more likely to be a risk variant of CHD under the recessive model in females (χ² = 10.29, p = 0.003, OR = 2.14, 95% CI = 1.31–2.77). A breakdown analysis by age had shown that there was an 87% increased risk of CHD for females younger than 65 years (genotype: χ² = 14.64, degrees of freedom (df) = 2, p = 0.0002; allele: χ² = 11.31, df = 1, p = 0.0008, OR = 1.87, 95% CI = 1.30–2.70). Similar observation was also found in males younger than 65 years (genotype: χ² = 8.63, df = 2, p = 0.04; allele: χ² = 7.55, df = 1, p = 0.006, OR = 1.45, 95% CI = 1.11–1.90). p values were adjusted by age, sex, smoking, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). Meta-analysis of 23 studies among 36,452 cases and 39,781 controls showed a strong association between rs4977574 and the risk of CHD (p < 0.0001, OR = 1.27, 95% CI = 1.22–1.31).