Antioxidants & Redox Signaling

Recent studies by Ball et al (Ball et al., 2022) and Zhang et al (Zhang et al., 2023) have provided evidence for the direct binding of thioredoxin1 (TRX1) to a component of inflammasome complex NLRP-1. This interaction suggests a potential role for TRX1 in the regulation of the NLR family pyrin domain containing 1 (NLRP-1) inflammasome. Furthermore, the NLRP-3 inflammasome is known to bind TRX1 and its inhibitor, thioredoxin-binding protein-2/thioredoxin-interacting protein/vitamin D3 upregulated protein-1 (TBP2/TXNP1/VDUP-1)...

SIGNIFICANCE: NADH represents the reduced form of NAD+, and together they constitute the two forms of the Nicotinamide adenine dinucleotide whose balance is named as the NAD+/NADH ratio. NAD+/NADH ratio is mainly involved in redox reactions since both the molecules are responsible for carrying electrons to maintain redox homeostasis. NADH acts as a reducing agent and one of the most known processes exploiting NADH function is energy metabolism. The two main pathways generating energy and involving NADH are Glycolysis and Oxidative phosphorylation, occurring in cell cytosol and in the mitochondrial matrix, respectively...

Preclinical and clinical research in the past two decades has redefined the mechanism of action of some chemotherapeutics that are able to activate the immune system against cancer when cell death is perceived by the immune cells. This immunogenic cell death (ICD) activates antigen-presenting cells (APCs) and T cells to induce immune-mediated tumor clearance. One of the key requirements to achieve this effect is the externalization of the danger-associated molecular patterns (DAMPs), molecules released or exposed by cancer cells during ICD that increase the visibility of the cancer cells by the immune system...

AIM: This research was aimed at investigating the effects of HIF-1α-mediated DNA methylation enzymes (TET2 and DNMT3a) under hypoxic conditions on S100A6 transcription, thereby promoting the growth and metastasis of lung cancer cells. METHODS: The expression of HIF-1α or S100A6 in lung cancer cells was interfered with under normoxic and hypoxic conditions, and the cell proliferative, migratory, and invasive properties were assessed. The mechanism of HIF-1α-regulated TET2 and DNMT3 effects on S100A6 transcription under hypoxic conditions was further investigated...

SIGNIFICANCE: Peroxisome proliferator-activated receptors (PPARs) have a moderately preserved amino-terminal domain, an extremely preserved DNA-binding domain, an integral hinge region, and a distinct ligand-binding domain that are frequently encountered with the other nuclear receptors. PPAR-β/δ is among the three nuclear receptor superfamily members in the PPAR group. RECENT ADVANCES: Emerging studies provide an insight on natural compounds that have gained increasing attention as potential anticancer agents due to their ability to target multiple pathways involved in cancer development and progression...

Renal transplantation is an effective treatment for severe chronic kidney diseases. However, young patients often face a scarcity of kidneys from donors of similar age, resulting in the transplantation of older organs which increase the risk of graft rejection and several complications compared to older individuals who receive kidneys from donors of similar age or younger. This paper focuses on studying different senescence biomarkers in donors and patients who received kidneys from various age ranges complying with the STROBE requirements...

SIGNIFICANCE: Physiological levels of reactive oxygen and nitrogen species (ROS/RNS) function as fundamental messengers for many cellular and developmental processes in the cardiovascular system. ROS/RNS involved in cardiac redox-signaling originate from diverse sources, and their levels are tightly controlled by key endogenous antioxidant systems that counteract their accumulation. However, dysregulated redox-stress resulting from inefficient removal of ROS/RNS leads to inflammation, mitochondrial dysfunction, and cell death, contributing to the development and progression of cardiovascular disease (CVD)...

Nitrosative stress is a feature of Alzheimer's disease, however the underlying cause(s) driving nitrosative stress and the impact of nitric oxide (NO) on neuronal function in Alzheimer's disease is still largely unknown. We analysed neuronal nitric oxide synthase (nNOS) protein levels in post mortem tissue and induced pluripotent stem cell (iPSC) derived neurons from Alzheimer's patients and controls by immunohistochemistry and western blots. Furthermore, we assessed the impact of modulating nNOS function or NO levels on neuronal glutamatergic signalling using calcium imaging...

SIGNIFICANCE: Platelets are the smallest cells in circulation (measuring 2 microns in diameter). Platelet activation is necessary for thrombus formation and relies on calcium mobilisation from the endoplasmic reticulum (ER). Platelet activation leads to mobilization of ER resident proteins to the platelet surface; these are essential for the function of platelet receptors and intercellular interactions. RECENT ADVANCES: ER homeostasis is maintained by an appropriate redox balance, regulated calcium stores and normal protein folding...

AIM: Mitochondrial homeostasis is essential for maintaining redox balance. Besides canonical autophagy, Rab9-dependent alternative mitophagy is a crucial mechanism in metabolic cardiomyopathy. Here, we aim to investigate the role of alternative mitophagy and Beclin 1 haploinsufficiency (Beclin 1+/-) in high-fat diet (HFD)-induced metabolic cardiomyopathy. RESULTS: 24-week HFD impaired glucose tolerance and cardiomyocyte contraction in WT mice, both of which were rescued in Beclin 1+/- mice...

SIGNIFICANCE: Currently, a large amount of evidence of beneficial effects of diets enriched with polyphenols on various aspects of health has been accumulated. These phytochemicals have a geroprotective potential slowing down the pathological processes associated with aging and ensuring longevity. In this study, a comprehensive analysis was conducted to determine the adherence of individual polyphenols to geroprotector criteria. Data from experimental models, clinical trials, and epidemiological studies were analyzed...

SIGNIFICANCE: Neutrophils are crucial components of the innate immune system that combat invading pathogens and maintain homeostasis. Nitric oxide (NO•) exerts regulatory influence on neutrophil rolling, adhesion, oxidative burst, chemotaxis, phagocytosis, cytoneme, apoptosis, and NETosis by diverse mechanisms in autocrine and paracrine manner. RECENT ADVANCES: Recent research has identified the critical role of NO• in the proliferation of neutrophil progenitors, differentiation, survival, and other functions...

AIMS: Hepatic fibrosis is the pathological change during chronic liver diseases (CLD) that turns into cirrhosis if not reversed timely. Allogenic Mesenchymal Stem Cell (MSC) therapy is an alternative to liver transplantation for CLD. However, poor engraftment of the transplanted MSCs limits their therapeutic efficacy. MSCs express chemokine receptors that regulate their physiology. We observed several-fold increased expressions of Cxcl3 and decreased expression of Mmp13 in the fibrotic liver...

SIGNIFICANCE: Metabolic syndrome (MetS) has become a major global public health problem and there is an urgent need to elucidate its pathogenesis and find more effective targets and modalities for intervention. RECENT ADVANCES: Oxidative stress and inflammation are two of the major causes of MetS-related symptoms such as insulin resistance and obesity. Nuclear factor erythroid 2 related factor 2 (Nrf2) is one of the important systems responding to oxidative stress and inflammation...

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No abstract text is available yet for this article.

SIGNIFICANCE: Stringent regulation of protein homeostasis pathways, under both physiological and pathological conditions, is necessary for the maintenance of proteome fidelity. However, when challenged by endogenous or exogenous stressors these proteostasis pathways can become dysregulated with detrimental consequences for protein fate, cell survival and overall organism health. There are numerous somatic pathologies associated with a loss of proteostatic regulation including neurodegenerative disorders, type 2 diabetes and some cancers...

AIMS: Radiotherapy inevitably causes radiation damage to the salivary glands (SGs) in patients with head and neck cancers (HNCs). Excessive reactive oxygen species (ROS) levels and imbalanced mitochondrial homeostasis are serious consequences of ionizing radiation in SGs; however, there are few mitochondria-targeting therapeutic approaches. Glycyrrhizin is the main extract of licorice root and exhibits antioxidant activity to relieve mitochondrial damage in certain oxidative stress conditions...

SIGNIFICANCE: Aging is a complex process associated with an increased risk of many diseases, including thrombosis. The current review summarizes age-related prothrombotic mechanisms in clinical settings of thromboembolism, focusing on the role of fibrin structure and function modified by oxidative stress. RECENT ADVANCES: Aging affects blood coagulation and fibrinolysis via multiple mechanisms, including enhanced oxidative stress, with an imbalance in the oxidant/antioxidant mechanisms, leading to loss of function and accumulation of oxidized proteins, including fibrinogen...

AIMS: Scavenger receptor class B type I (SRBI) promotes cell cholesterol efflux and the clearance of plasma cholesterol. Thus, SRBI deficiency causes abnormal cholesterol metabolism and hyperlipidemia. Studies have suggested that ferroptosis is involved in lipotoxicity; however, whether SRBI deficiency could induce ferroptosis remains to be investigated. RESULTS: We knocked down or knocked out SRBI in renal HK-2 cells and C57BL/6 mice to determine the expression levels of ferroptosis-related regulators...