Ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, is linked to neurodegenerative disorders and cold-induced cell death. SLC7A11 (xCT) plays a crucial role in protecting cells against ferroptosis by maintaining intracellular cysteine and glutathione levels. SLC7A11 requires the chaperone protein SLC3A2 for its localization on the plasma membrane to mediate cystine uptake. Arctic ground squirrels (AGS) are known to be protected from cold tissue temperatures and oxidative stress and to resist neuropathology following cerebral ischemia/reperfusion. This study investigated how ferroptosis is influenced by the hibernation season in AGS hippocampus. RNA-Seq, gene expression, and differential gene expression analysis were conducted on hippocampus tissue samples from male and female AGS collected during the summer active season, torpor, and interbout arousal (IBA). Hippocampus was dissected from partially thawed whole brain prior to RNA extraction.  Total RNA samples were used for cDNA library construction and sequencing by BGI Americas Corporation (Cambridge, MA) and analyzed using CLC Genomics Workbench (QIAGEN). Genes were mapped to the Ictidomys tridecemlineatus reference genome and transcript (HiC_Itri_2, GCF_016881025.1). Results show the highest number of differentially expressed genes (4,042) in torpor compared to summer active animals. Notably, SLC7A11 expression was elevated in torpor compared to summer active animals (fold change: 1.80, FDR-p value: 0.0034). Additionally, SLC3A2 was significantly upregulated in torpor compared to IBA (fold change: 1.24; FDR-p value: 0.030). SLC7A11 transports glutamate(out)/cystine(in). Cystine is rapidly converted into cysteine, a limiting reactant for glutathione synthesis, in the presence of NADPH. These findings suggest that SLC7A11 and SLC3A2 may protect AGS from ferroptosis during the hibernation season. This research provides insights into the molecular mechanisms underlying neuroprotection in hibernating AGS and may have implications for understanding and potentially treating neurodegenerative disorders.

Colorectal cancer presents a significant global health challenge, with a high mortality rate. It is the third most commonly diagnosed cancer and is therefore a major cause for concern. The development of colorectal cancer is multifaceted, involving a combination of genetic predispositions and lifestyle factors. The redox and metabolic states may influence the intricate process of colon cancer development. To gain a deeper understanding of the redox-metabolic profiles associated with colon cancer, a human study was conducted. In biopsies from patients with colon cancer, the antioxidant status: copper, zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutamate-cysteine ligase (GCL), thioredoxin (Trx) and lactate metabolism were examined in tumor and unaffected colon tissue (remote 15-20 cm) as well as in adipose tissue: proximal (near the tumour tissue), distal (remote 6 cm) and unaffected (remote over 6 cm). The protein levels of CuZnSOD, MnSOD, GSH-Px, and Trx are increased in the tumor tissue compared to the unaffected colon tissue. In addition, the expression of the lactate dehydrogenase (LDH) A isoform, the total activity of LDH and the lactate concentration are higher in transformed tumor tissue than in normal colon tissue. On the other hand, lactate concentration increases and several AD components (CuZnSOD, MnSOD, CAT, GSH-Px, GCL and Trx) decrease in adipose tissue with tumor proximity. Shifts in redox and lactate metabolism in tumor tissue associated with spatial changes in lactate and antioxidant enzymes gradients in adjacent adipose tissue clearly indicate a local redox metabolic interaction between tumor and tumor-associated adipose tissue in shaping the malignant phenotype in human colorectal cancer.

Multiple sclerosis (MS) is a chronic, immune-mediated inflammatory disease of the central nervous system (CNS). Relapsing-remitting multiple sclerosis (RRMS) is the most common clinical subtype of MS. MS is characterized by demyelination and myelin is mainly composed of lipids. Lipids play many roles in the CNS including signaling, structural support, mediating inflammation, and membrane biogenesis. Omega-3 polyunsaturated fatty acids (PUFA) are central to maintaining health and they are present in a wide array of tissues with broad functions including the active component of phospholipid cell membranes and substrate for molecular signaling pathways. This study aimed to evaluate fatty acids (FA) profiles of patients with RRMS (n=30) compared to healthy people (n=20). Analysis of total lipids was performed from erythrocyte samples. The total lipid extracts from erythrocytes were prepared by adding chloroform/methanol (2:1, v/v) mixture containing butylated hydroxytoluene (0.05% BHT weight/volume). FA methyl esters were prepared by transmethylation with 3N HCl in methanol. FA profiles were determined by gas chromatography (GC). The content of individual FA was expressed as a percentage of the total FA. Results of this study revealed that total saturated fatty acids (SFA) are significantly higher in MS patients compared to controls. While total PUFAs, total n-3 PUFAs, and omega-3 index are statistically lower in MS patients. The n-6/n-3 ratio is significantly higher in MS patients compared to controls. Also, the AA/EPA ratio is significantly lower in the control group compared to MS patients. Conversely, the EPA/AA index is significantly reduced in MS patients. Omega-3 lipids, which have a protective role by preserving the blood-brain barrier, are significantly reduced in the erythrocytes of patients with MS. Increased n-3 PUFA and decreased SFA intake could counteract inflammation, energy storage and utilization imbalance and, overall state in patients with MS.