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.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease with articular and systemic manifestations, and one of the most common is anemia. This study aims to investigate whether the levels of the soluble receptors sRAGE, sRANKL, and OPG are affected by the distribution of RA patients in subgroups according to soluble transferrin receptor/log ferritin (sTfR-F index) and hemoglobin (Hb) levels and to examine their correlation with indicators of iron metabolism, disease activity, and autoimmune and inflammatory changes. The levels of sRANKL and sRAGE were significantly higher in the subgroup of anemia of chronic disease combined with iron deficiency anemia (ACD/IDA) compared to the ACD group: p < 0.0001 and p < 0.0001. The level of OPG tended to decrease in ACD/IDA (p = 0.053). sRAGE was positively correlated with prohepcidin, RF and anti-CCP antibodies, sRANKL, CRP, and IL-6 only in the ACD group. A negative correlation was found between sRAGE, sRANKL, and serum iron only in the ACD/IDA group. sRANKL was positively correlated with OPG, prohepcidin, CRP, IL-6, RF, anti-CCP antibodies, and DAS28 only in the ACD group. Positive correlations were observed between OPG and ferritin, sTfR, CRP, IL-6, RF, and DAS28, and a negative correlation was observed with serum iron only in the ACD group. Therefore, the investigated soluble receptors may serve as reliable biomarkers involved in the pathogenesis of RA and may contribute to the identification of patients at risk of developing combined anemia.