Multiple roles have been indicated for reactive oxygen species (ROS) in the immune system in recent years. ROS have been extensively studied due to their ability to damage DNA and other subcellular structures. Noticeably, they have been identified as a pivotal second messenger for T-cell receptor signaling and T-cell activation and participate in antigen cross-presentation and chemotaxis. As an agent with direct toxic effects on cells, ROS lead to the initiation of the autoimmune response. Moreover, ROS levels are regulated by antioxidant systems, which include enzymatic and nonenzymatic antioxidants. Enzymatic antioxidants include superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Nonenzymatic antioxidants contain vitamins C, A, and E, glutathione, and thioredoxin. Particularly, cellular antioxidant systems have important functions in maintaining the redox system homeostasis. This review will discuss the significant roles of ROS generation and antioxidant systems under normal conditions, in the immune system, and pathogenesis of multiple sclerosis.

Autophagy is a cellular degradation process that plays a crucial role in maintaining metabolic homeostasis under conditions of stress or nutrient deprivation. This process involves sequestering, breaking down, and recycling intracellular components such as proteins, organelles, and cytoplasmic materials. Autophagy also serves as a mechanism for eliminating pathogens and engulfing apoptotic cells. In the absence of stress, baseline autophagy activity is essential for degrading damaged cellular components and recycling nutrients to maintain cellular vitality. The relationship between autophagy and cancer is well-established; however, the biphasic nature of autophagy, acting as either a tumor growth inhibitor or promoter, has raised concerns regarding the regulation of tumorigenesis without inadvertently activating harmful aspects of autophagy. Consequently, elucidating the mechanisms by which autophagy contributes to cancer pathogenesis and the factors determining its pro- or anti-tumor effects is vital for devising effective therapeutic strategies. Furthermore, precision medicine approaches that tailor interventions to individual patients may enhance the efficacy of autophagy-related cancer treatments. To this end, interventions aimed at modulating the fate of tumor cells by controlling or inducing autophagy substrates necessitate meticulous monitoring of these mediators’ functions within the tumor microenvironment to make informed decisions regarding their activation or inactivation. This review provides an updated perspective on the roles of autophagy in cancer, and discusses the potential challenges associated with autophagy-related cancer treatment. The article also highlights currently available strategies and identifies questions that require further investigation in the future.

Hussein Baharlooi, Maryam Azimi, Zahra Salehi, Maryam Izad. IJSC 2020;13:13-23. https://doi.org/10.15283/ijsc19108

Background and Aims: Synbiotics found to be beneficial in breast cancer survivors (BCSs) through its antioxidant properties. The aim of this study was to assess the effects of synbiotic supplementation on edema volume and some oxidative markers among obese and overweight patients with BCRL. Method: This randomized double-blind, placebo-controlled trial was conducted on 88 overweight and obese BCSs aged 18–65 years. All the subjects were given a specified low-calorie diet (LCD) and were randomly assigned into two groups to intake 10⁹ CFU/day synbiotic supplement (n = 44) or placebo (n = 44) for 10 wk. Edema volume and serum total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD) concentration were measured at baseline and after the 10-wk intervention. Results: Ten-wk supplementation with synbiotics leads to a significant reduction in serum MDA levels (P = 0.001) and an increase in serum SOD concentration (P = 0.007) compared to placebo. No significant changes were observed in serum GPx, TAC, and edema volume between groups. Conclusion: Our findings reveal that 10-wk synbiotic supplementation along with a LCD program-reduced serum MDA levels and elevate the activity of SOD in overweight and obese patients with BCRL. However, its effect on serum GPx, TAC, and edema volume was not significant.

Abnormal angiogenesis leads to tumor progression and metastasis in colorectal cancer (CRC). This study aimed to elucidate the association between angiogenesis-related genes, including VEGF-A, ANGPT-1, and ANGPT-2 with both metastatic and microsatellite alterations at selected tetranucleotide repeats (EMAST) subtypes of CRC. We conducted a thorough assessment of the ANGPT-1, ANGPT-2, and VEGF-A gene expression utilizing publicly available RNA sequencing and microarray datasets. Then, the experimental validation was performed in 122 CRC patients, considering their disease metastasis and EMAST^+/− profile by using reverse transcription polymerase chain reaction (RT-PCR). Subsequently, a competing endogenous RNA (ceRNA) network associated with these angiogenesis-related genes was constructed and analyzed. The expression level of VEGF-A and ANGPT-2 genes were significantly higher in tumor tissues as compared with normal adjacent tissues (P-value < 0.001). Nevertheless, ANGPT-1 had a significantly lower expression in tumor samples than in normal colon tissue (P-value < 0.01). We identified a significantly increased VEGF-A (P-value = 0.002) and decreased ANGPT-1 (P-value = 0.04) expression in EMAST⁺ colorectal tumors. Regarding metastasis, a significantly increased VEGF-A and ANGPT-2 expression (P-value = 0.001) and decreased ANGPT-1 expression (P-value < 0.05) were established in metastatic CRC patients. Remarkably, co-expression analysis also showed a strong correlation between ANGPT-2 and VEGF-A gene expressions. The ceRNA network was constructed by ANGPT-1, ANGPT-2, VEGF-A, and experimentally validated miRNAs (hsa-miR-190a-3p, hsa-miR-374c-5p, hsa-miR-452-5p, and hsa-miR-889-3p), lncRNAs (AFAP1-AS1, KCNQ1OT1 and MALAT1), and TFs (Sp1, E2F1, and STAT3). Network analysis revealed that colorectal cancer is amongst the 82 significant pathways. We demonstrated a significant differential expression of VEGF-A and ANGPT-1 in colorectal cancer patients exhibiting the EMAST⁺ phenotype. This finding provides novel insights into the molecular pathogenesis of colorectal cancer, specifically in EMAST subtypes. Yet, the generalization of in silico findings to EMAST⁺ colorectal cancer warrants future experimental investigations. In the end, this study proposes that the EMAST biomarker could serve as an additional perspective on CMS4 biology which is well-defined by activated angiogenesis and worse overall survival.