The human skin, being our outermost protective barrier, sustains continuous contact with the environment. As such, its cells must be kept in a state of constant alert against external increased oxidative stress and massive environmental insults (e.g. sunlight and UV radiation, air pollution, and mechanical stress). All these insults ultimately result in an impaired redox balance and increased cellular oxidation. One of the pivotal oxidation regulation mechanisms in the skin is the Nrf2–Keap1 pathway, and its activity leads to cutaneous redox maintenance which evidently sustains the principle of hormesis. We suggest that moderate environmental stressors and skin microbiome can provide the necessary continuous stimuli for the activation of the Nrf2 pathway. We also suggest that endogenous neurotransmitters play a major role in this activation.

Aging is a natural process characterized by a decline in organic structure-function and an increase in mortality over time. While many exogenous and endogenous factors contribute to aging, the long-term effects of low environmental temperature have been poorly described. To address this, our study compared 24-month-old male Mill Hill hybrid hooded rats raised at a standard temperature of 22±1°C with age-matched rats that were kept in a cold room (4±1°C) from the age of 6 to 24 months. 3- and 6-month-old rats raised at 22±1°C were included as room temperature controls. We examined two metabolically active organs, interscapular brown adipose tissue (iBAT) and liver. It was found that 24-month-old rats chronically exposed to cold exhibit increased food consumption, which may be attributed to a higher metabolic demand. Chronic exposure of aged rats to low environmental temperature led to an increase in iBAT relative mass, total glutathione (GSH) content, and antioxidant defense (AD) enzyme activity: CuZn superoxide dismutase, Mn superoxide dismutase, catalase, glutathione peroxidase, and thioredoxin reductase. Respirometric analysis further demonstrated an increase in mitochondrial uncoupling in iBAT in 24-month-old rats kept at 4±1°C. Conversely, there was no change of the same parameters in the liver, which maintained consistent AD enzyme activity and GSH content across all experimental groups. Our study confirms that iBAT of aged rats remains responsive to stimulation by low environmental temperature, supporting thermogenic processes through uncoupling and a robust increase in the AD system. These results highlight tissue-specific effects of chronic cold exposure on aged rats underlying acclimation-driven physiological changes.

Breast cancer is one of the most common malignant diseases in women worldwide. Since the involvement of axillary lymph node metastases is related to the poor prognosis of these patients, the objective of our study was to investigate the association between breast tumor size and the presence of axillary lymph node metastases. Our research was performed at the Institute of Oncology of Vojvodina in Sremska Kamenica. The study consisted of 72 women diagnosed with breast cancer aged between 29 and 84 years (average age: 59.04±10.87 years) whose breast tumor was surgically removed at the Institute of Oncology of Vojvodina. Patients who received preoperative chemo- or radiotherapy were excluded from the study. The data concerning breast tumor size and the presence of axillary lymph nodes in these women was obtained from the reports of Department of Pathoanatomical Diagnostics of the Institute of Oncology of Vojvodina. The results of our study indicated to positive, statistically significant moderate correlation between the size of breast tumor and the presence of axillary lymph node metastases (r=0.32, p=0.01). Receiver operating curve (ROC) analysis notified that cut-off value of breast tumor size for the presence of axillary lymph node metastasis was 22.5 mm (AUC=0.70, p=0.01). In our investigation, women with breast tumor size of 22.5 mm or larger were predisposed to the presence of axillary lymph node metastases.

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.