Abnormalities in lipid homeostasis have been associated with many human diseases, and the interrelation between lipotoxicity and cellular dysfunction has received significant attention in the past two decades. Ceramides (Cers) are bioactive lipid molecules that serve as precursors of all complex sphingolipids. Besides their function as structural components in cell and mitochondrial membranes, Cers play a significant role as key mediators in cell metabolism and are involved in numerous cellular processes, such as proliferation, differentiation, inflammation, and induction of apoptosis. The accumulation of various ceramides in tissues causes metabolic and cellular disturbances. Recent studies suggest that Cer lipotoxicity has an important role in obesity, metabolic syndrome, type 2 diabetes, atherosclerosis, and cardiovascular diseases (CVDs). In humans, elevated plasma ceramide levels are associated with insulin resistance and impaired cardiovascular and metabolic health. In this review, we summarize the role of ceramides as key mediators of lipotoxicity in obesity, diabetes, cardiovascular diseases, and inflammation and their potential as a promising diagnostic tool.

Rheumatoid arthritis (RA) is one of the most common chronic autoimmune diseases which global prevalence is approximately 0.3–2%. Numerous studies provide evidence that the elevated levels of reactive oxygen species (ROS) contribute to the pathogenesis and progression of RA. In response to redox imbalance, several intrinsic antioxidant defence mechanisms are activated to counteract oxidative stress and scavenge ROS. The aim of the present study is to analyse whether the levels of lactoferrin and thioredoxin, two proteins which are part of the antioxidant defence of the body, are associated with fibrinogen and other acute phase proteins such as CRP and ferritin in RA. Serum lactoferrin, thioredoxin, ferritin, and CRP levels were measured using ELISA. Significant positive correlations of lactoferrin and thioredoxin with fibrinogen were observed in RA patients, r = 0.394, p < 0.0001 and r = 0.410, p = 0.002, respectively. These positive correlations were also observed in females, r = 0.375, p < 0.0001 and r = 0.447, p = 0.001, in the subgroup of patients with DAS28 < 5.1, r = 0.689, p < 0.0001 and r = 0.604, p = 0.001 and in the subgroup of patients with normal CRP, r = 0.488, p < 0.0001 and r = 0.414, p = 0.005, respectively. These findings help clarify the pathogenetic interplay between oxidative stress, inflammation, and coagulation in RA and indicate the need for further studies to elucidate the potential of lactoferrin and thioredoxin as biomarkers that capture pathological disease changes.

Background: Thioredoxin (Trx) and lactoferrin (Lf) are multifunctional proteins that are part of the body's antioxidant defence and counteract oxidative tissue damage. Our study aims to investigate Trx and LF levels in the serum of rheumatoid arthritis (RA) patients and establish the association of these proteins with the rheumatoid factor (RF) and other disease markers. Methods: The study included 114 patients with RA and 42 healthy subjects. Serum concentrations of Trx 1, LF, RF, anti-cyclic citrullinated peptide (anti-CCP) antibodies, Creactive protein (CRP), and IL-6 were determined using commercially available ELISA kits. Results: Serum thioredoxin 1 levels in RA were significantly higher compared to the control group, 36.4 (29.6-40.2), ng/mL versus 19.0 (16.3-26.8), ng/mL, p<0.0001. Serum lactoferrin levels were elevated in RA compared to the control group. However, the difference was not statistically significant, 579.6 (312.8-947.5) ng/mL versus 519.0 (262.5-928.0) ng/mL. We found substantial negative Trx 1 and LF correlations with rheumatoid factor in RA (r=-0.254, p=0.05 and r=-0.238, p=0.014, respectively). The correlations of thioredoxin and lactoferrin with other disease markers, such as anti-CCP antibodies, DAS28, erythrocyte sedimentation rate (ESR), CRP, and IL6 were not statistically significant. A strong positive correlation between Trx 1 and LF was observed in the study group of RA patients (r=0.519, p<0.0001) but not in the control group. Conclusions: Thioredoxin and lactoferrin were associated with rheumatoid factor but not with anti-CCP antibodies and systemic disease activity; therefore, the two proteins may serve as new biomarkers for assessing pathological changes and monitoring disease severity and progression in RA.