Oxysterols are oxidized derivatives of cholesterol initially considered as simple metabolic byproducts, nowadays recognized to play significant roles in various biological and pathological processes. In physiology, they are involved in the regulation of cellular processes beyond cholesterol metabolism, influencing cell proliferation, differentiation, apoptosis, and inflammation through various signaling pathways. In medicine, the study of oxysterols holds promise for understanding and treating various diseases, particularly those associated with dysregulated cholesterol metabolism and inflammation. Indeed, some oxysterols have been associated with adverse health effects, including cytotoxicity, pro-inflammatory effects, and potential contributions to the development of chronic diseases. Dysfunctions in oxysterol metabolism have been implicated in the pathogenesis of cardiovascular diseases, neurodegenerative disorders, and certain cancers. Targeting oxysterol pathways could therefore offer novel therapeutic strategies for these conditions. Oxysterols have potential applications in the pharmaceutical and biotechnology industries. Those generated by cholesterol autoxidation can be used as biomarkers for assessing oxidative stress conditions. Additionally, defined oxysterols of enzymatic origin and/or synthetic oxysterol analogs might be developed as antiviral agents. Oxysterols generated through autoxidation processes can serve as markers of lipid oxidation in cholesterol-containing foods and their quantification can help assess the quality and shelf life of food products, and also for ensuring food safety and consumer health. Finally, with regard to skin health and cosmetics industry, prolonged or excessive exposure to and/or formation of certain toxic oxysterols could potentially damage skin cells and disrupt skin barrier function. Therefore, careful formulation and dosage control are essential to ensure the safety of skincare products. Overall, the study of oxysterols spans molecular biology, medicine, and industry, with implications for understanding fundamental biological processes, developing new medical, industrial, and advancing biotechnological applications.

Individual complexes of the mitochondrial oxidative phosphorylation system (OXPHOS) are not linked solely by their function; they also share dependencies at the maintenance/assembly level, where one complex depends on the presence of a different individual complex. Despite the relevance of this ‘interdependence’ behavior for mitochondrial diseases, its true nature remains elusive. To understand the mechanism that can explain this phenomenon, we examined the consequences of the aberration of different OXPHOS complexes in human cells. We demonstrate here that complete disruption of each of the OXPHOS complexes resulted in a perturbation in energy deficiency sensing pathways, including the integrated stress response (ISR) pathway. The secondary decrease of complex I (cI) level was triggered by both complex IV and complex V deficiency, and it was independent of ISR signaling. On the other hand, we identified the unifying mechanism behind cI downregulation in the downregulation of mitochondrial ribosomal proteins and, thus, mitochondrial translation. We conclude that the secondary cI defect is due to mitochondrial protein synthesis attenuation, while the responsible signaling pathways could differ based on the origin of the OXPHOS defect.

The metastasis of breast cancer to the axillary lymph nodes represents a crucial aspect of disease progression and prognostic evaluation. The presence of metastases in the axillary lymph nodes is a key indicator that breast cancer is in an advanced stage, which can influence the therapeutic approach and the patient's prognosis. For this reason, we conducted a study aimed at examining the factors that contribute to the presence of metastases in lymph nodes in our female population. This research represents a prospective study conducted at the Institute of Oncology of Vojvodina in Sremska Kamenica. The study included 72 female participants diagnosed with breast cancer who underwent surgery at the Institute of Oncology of Vojvodina and had not received preoperative chemotherapy or radiation therapy. Initially, anamnestic data were collected from the participants, followed by a pathohistological analysis of the tumor tissue samples, including immunohistochemical analysis. We examined the influence of age, tumor size, activity of estrogen, progesterone, and HER2 receptors (human epidermal growth factor receptor-2)  in tumors, as well as the occurrence of menarche and breastfeeding duration, on the presence of metastases in axillary lymph nodes. The results of binary logistic regression showed that the only significant predictor for the presence of metastases in axillary lymph nodes was tumor size (p=0.01, Wald=6.57, and Exp(B)=1.11), while the other examined predictors were not statistically significant (p>0.05). In our study population, the size of the breast cancer was crucial for the presence of metastases in the axillary lymph nodes.

This research was supported by the Science Fund of the Republic of Serbia, #7750238, Exploring new avenues in breast cancer research: Redox and metabolic reprogramming of cancer and associated adipose tissue - REFRAME.