Cardiovascular diseases (CVDs) are characterized by high morbidity and mortality rates, imposing substantial epidemiological and economic burdens worldwide. Among the multifaceted mechanisms implicated in CVDs, autophagy and ferroptosis, two intimately linked cellular processes, emerge as pivotal pathophysiological contributors. Autophagy, as an evolutionary conserved process that mediates the degradation

Our previous study revealed that mice exposed to 1-nitropyrene (1-NP) develop pulmonary fibrosis and senescent alveolar cells. However, the impacts of chronic 1-NP on chronic obstructive pulmonary disease (COPD) and the underlying mechanism are unclear. Our research suggested that chronic 1-NP evoked alveolar structure damage, inflammatory cell infiltration, and pulmonary function decline in mice.

Plants and animals/humans have evolved sophisticated innate immune systems to cope with microbial attack. Innate immunity implies the presence of membrane-located and intracellular receptors to recognize compounds released by damage or by invading pathogens. After detection the receptor molecules initiate intracellular defense signaling, resulting in cell death and/or production of defense molecules

Selenium (Se) deficiency, affecting hundreds of millions of individuals worldwide, is linked to increased incidence of colorectal cancer (CRC), yet tumors paradoxically accumulate Se to evade ferroptosis and promote metastasis. Therefore, understanding the prognostic impact of Se status at diagnosis is crucial to consider and enable personalized interventions.

Extracellular traps (NETs) released by neutrophils during inflammation play a role in clearing infection but also contribute to disease pathology. NETs consist of a DNA backbone containing histones, anti-microbial granule proteins, such as myeloperoxidase (MPO), and other proteins. MPO remains enzymatically active and generates hypochlorous acid (HOCl) to kill pathogens. However, HOCl also readily

Peripheral arterial disease (PAD) is prevalent among the elderly, and therapeutic neovascularization is a research hotspot in PAD treatment. Supplementing nicotinamide adenine dinucleotide (NAD+) precursors is an important approach for promoting neovascularization, but clinical trials in the elderly PAD patients have shown limited success. This study aims to find effective ways to boost NAD+ levels

Pharmacological ascorbate (P-AscH, high-dose, intravenous, vitamin C), is a pro-drug that generates hydrogen peroxide (H2O2) and is being investigated as a neoadjuvant treatment for pancreatic adenocarcinoma (PDAC). In a randomized, phase II clinical trial, P-AscH demonstrated encouraging results in terms of efficacy and safety. However, some patients do not respond to P-AscH suggesting that resistance

Age-related cognitive decline and neurodegenerative diseases, such as Alzheimer's disease, represent major global health challenges, particularly with an aging population. Mitochondrial dysfunction appears to play a central role in the pathophysiology of these conditions by driving redox dysregulation and impairing cellular energy metabolism. Despite extensive research, effective therapeutic options

Reactive oxygen species (ROS), regulators of cellular behaviors ranging from signaling to cell death, have complex production and control mechanisms to maintain a dynamic redox balance under physiological conditions. Redox imbalance is frequently observed in tumor cells, where ROS within tolerable limits promote oncogenic transformation, while excessive ROS induce a range of regulated cell death (RCD)

We live in a world increasingly dominated by plastic, leading to the generation of microplastic particles that pose significant global health concerns. Microplastics can enter the body via ingestion, inhalation, and direct contact, accumulating in various tissues and potentially causing harm. Despite this, the specific cellular mechanisms and signaling pathways involved remain poorly understood. Macrophages

Excessive reactive oxygen species (ROS) are closely associated with the initiation and progression of cancers. As the most abundant intracellular antioxidant, glutathione (GSH) plays a critical role in regulating cellular ROS levels, modulating physiological processes, and is intricately linked to tumor progression and drug resistance. However, the underlying mechanisms remain not fully elucidated

We established an LC-MS/MS method for detecting uric acid oxidation metabolites to evaluate reactive oxygen and nitrogen species, as uric acid gives specific products. Parabanic acid was identified during attempts to detect hydroxyl radical–specific products in the Fenton reaction. As parabanic acid is a singlet oxygen–specific product of uric acid, this indicates the Fenton system, which is known

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by diverse clinical presentations, often associated with dysregulated oxidative stress mechanisms leading to heightened production of reactive oxygen species (ROS) in the brain. Due to its multifactorial etiology, effective therapeutic approaches for ASD remain challenging to ascertain. This work engineers Prussian

Hypobaric hypoxia in plateau environments inevitably disrupts metabolic homeostasis and contributes to high-altitude diseases. Vascular endothelial cells play a crucial role in maintaining vascular homeostasis. However, it remains unclear whether hypoxia-mediated changes in energy metabolism compromise vascular system stability and function. Through integrated transcriptomic and targeted metabolomic

Subarachnoid hemorrhage (SAH) represents a stroke subtype that can lead to prolonged cognitive deficits as well as death or disability. Prior investigation has suggested that CoQ10 analogs can mitigate oxidative stress and inflammation and promote mitochondrial biogenesis in the context of brain injury and neurodegenerative disorders. However, the precise mechanisms underlying early brain injury (EBI)

Infertility is a significant public health concern, affecting one in six couples globally, with male-factor infertility representing half of all cases. Obesity is an important health problem and is increasingly linked to poor reproductive outcomes as it induces metabolic disturbances and dyslipidemia, both of which impair male fertility. Dyslipidemia, characterized by abnormal lipid profiles, is associated

Acute respiratory distress syndrome (ARDS) following cardiopulmonary bypass (CPB) is driven by oxidative stress during lung ischemia-reperfusion injury (LIRI). Mitochondrial-derived peptide MOTS-c has emerged as a regulator of mitochondrial-nuclear communication, yet its role in CPB-induced ARDS remains unclear. Here, we identify MOTS-c as a critical mediator of endothelial protection against LIRI

Intestinal ischemia/reperfusion (II/R) is a common and grave clinical event, with high morbidity and mortality which can cause cerebral dysfunctions. There are no ideal prevention and treatment measures yet. The present study aimed to determine whether muscle-derived factors can alleviate gut-associated cerebral dysfunctions (GACD) following II/R. We measured the tibialis anterior muscle thickness

With increasing age, skeletal muscle gradually loses mass and strength, and the risk of falls and fractures escalates among elderly individuals. Inflammation is closely related to age-related muscle atrophy and is the potential target for treating muscular atrophy. Here, biomimetic curcumin nanoparticles (M12MNCs) are prepared via encapsulating curcumin in the skeletal muscle cell membranes modified

In inherited neuromuscular disease, Duchenne muscular dystrophy (DMD), glucocorticoids significantly slow disease progression yet impart side effects severe enough to preclude use in a significant proportion of patients. Extending our findings that acute treatment with FDA approved multiple sclerosis drug, dimethyl fumarate (DMF), rescues muscle pathology in juvenile mdx mice, we aimed to conduct tiered

The mitochondrial chaperone TRAP1 exerts protective functions under diverse stress conditions. It induces metabolic rewiring and safeguards cancer cells from oxidative insults, thereby contributing to neoplastic progression.

Cytosolic thioredoxin (Trx) is a critical redox protein that converts protein disulfides to thiols via catalytic activity of thioredoxin reductase-1 (TrxR1) and NADPH. Thioredoxin-2 (Trx2) is a mitochondria-localized isoform. It is generally believed that Trx and Trx2 perform similar functions within the cytosol and mitochondria respectively. Here, we demonstrate that cytosolic Trx shuttles into mitochondria

Pancreatic ductal adenocarcinoma (PDAC) is still a highly aggressive and fatal disease. The molecular mechanisms for PDAC progression are still not fully understood. Here, we demonstrated the overexpression of MYOF in PDAC in multiple sample sets, which is significantly associated with poor outcome of PDAC patients. MYOF knockout suppresses PDAC progression in vitro and in vivo. MYOF knockout exerts

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease, encompassing a spectrum from simple steatosis to steatohepatitis (MASH), cirrhosis, and hepatocellular carcinoma. As part of metabolic syndrome, MASLD/MASH is characterized by inflammation, oxidative stress, and fibrosis, highlighting the need for targeted therapies. The dysregulation of Janus kinase/signal

Mitochondrial dysfunction is the key pathological mechanism of cognitive decline, and homocysteine (Hcy) plays a vital role in modulating mitochondrial homeostasis. However, the regulating mechanism and intervention targets of Hcy-induced mitochondrial damage involved in brain impairment remain unclear. Herein, it is found that elevated Hcy levels lead to the increasement of METTL4 expression and augmentation

Ascorbyl tetraisopalmitate (AT), a vitamin C derivative, exhibits better stability and transdermal absorption than vitamin C and shows potential for skin whitening and wound healing. However, their low water solubility and specific storage requirements limit their application. To overcome these limitations, in this study, we aimed to develop AT-loaded ferrocene polymer nanoparticles (AT@FNPs) using

Acute liver failure (ALF) represents a critical clinical syndrome marked by massive hepatocyte death and severe functional deterioration. While metabolic dysregulation is a recognized hallmark, the pathophysiological implications of iron metabolism disturbance in ALF progression remain poorly understood, which may unveil novel therapeutic targets. Using clinical samples and preclinical murine models

Pseudomonas aeruginosa, a leading cause of hospital-acquired infections, triggers host defenses, including oxidant release by phagocytes. Targeting bacterial antioxidants could reduce pathogen infectivity. This study investigates LsfA, a 1-Cys peroxiredoxin (Prx), member of the Prx6 subfamily, involved in P. aeruginosa virulence. LsfA efficiently reduced various peroxides (106-107 M−1s−1), while exhibiting

Mitochondria are essential regulators of bone health, controlling cell differentiation, cellular energy production, immune function, osteogenesis, and osteoclast activity. Their dysfunction is linked to orthopedic disorders such as osteoporosis, osteoarthritis, and osteomyelitis, contributing to impaired bone homeostasis and increased fracture risk. While mitochondrial research has been more advanced

Fibrillin 1 gene (Fbn1) mutations cause Marfan syndrome (MFS), triggering life-threatening aortic complications and multi-organ effects. MFS is increasingly linked to neurovascular complications, amplified by aortic surgery risks. However, the impact of MFS on the brain remains unclear, including the roles of sex, aging, and their contribution to cerebral injury. This study examines brain alterations

The ubiquitin-like protein NEDD8/Rub1 is initially translated as a precursor and undergoes maturation before becoming functional, a process mediated by the ubiquitin hydrolase UCHL3/Yuh1. Across studied organisms, the mature form of NEDD8/Rub1 modifies cullins, the central subunits of CRLs. NEDD8/Rub1 modification typically enhances CRL-mediated ubiquitination of key cellular regulators, leading to

Low oxygen availability (hypoxia) is a prominent but poorly understood feature in multiple sclerosis (MS). Whether hypoxia causes or drives MS pathology and symptoms or whether it is a consequence of other pathological events, such as inflammation and vascular dysfunction, is unknown.

Ferroptosis is one of the most critical biological consequences of glutathione depletion. Excessive oxidative stress, indicated by an elevated oxidized glutathione (GSSG)/reduced glutathione (GSH) ratio, is recognized as a key driver of ferroptosis. However, in glutathione depletion-induced ferroptosis, a marked decrease in total glutathione levels (including both GSH and GSSG) is frequently observed

The essential trace element selenium (Se) plays a significant role in redox homeostasis, while Se is very reactive and has a potent toxicity. Understanding the molecular machinery that supports Se metabolism is important for the both physiological and pathophysiological context. Incorporated Se is translated/transformed in the liver into selenoprotein P (SeP; encoded by Selenop), an extracellular Se

Myokine dysregulation and mitochondrial dysfunction are implicated in the pathogenesis of sarcopenia in chronic obstructive pulmonary disease. The objective of this study is to explore the role of myokines and mitochondrial dysfunction in sarcopenia in chronic obstructive pulmonary disease.

The prevalence of autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by impairments in social communication and restricted/repetitive behavioral patterns, has increased significantly over the past few decades. The etiology of ASD involves a highly complex interplay of genetic, neurobiological, and environmental factors, contributing to significant heterogeneity in its clinical

Most microbial cells on earth predominantly exist in non-proliferating, dormant conditions, such as the stationary state. The stationary phase is a crucial stage during the cellular lifespan, which requires homeostatic rewiring for long-term viability and rapid responses to environmental changes. Here, we show that entry to the stationary phase in yeast is accompanied by increased cytosolic and mitochondrial

Oxidative stress serves as a fundamental mechanism contributing to ionizing radiation-induced damage, which has significant implications for tissue injury. Cysteine dioxygenase type 1 (CDO1) catalyzes the rate-limiting step for cysteine oxidation pathway, thereby playing a crucial role in regulating cellular cysteine availability. However, the regulation of CDO1 activity and cysteine oxidation under

Redox regulators are emerging as critical mediators of lung tumorigenesis. NRF2 and its negative regulator KEAP1 are commonly mutated in human lung cancers, leading to NRF2 accumulation and constitutive expression of NRF2 target genes, many of which are at the interface between antioxidant function and anabolic processes that support cellular proliferation. Nrf2 activation promotes lung tumor initiation

Drug resistance in colorectal cancer (CRC) poses a major challenge for cancer therapy and stands as the primary cause of cancer-related mortality. The N6-methyladenosine (m6A) modification has emerged as a pivotal regulator in cancer biology, yet the precise m6A regulators that propel CRC progression and chemoresistance remain elusive. Our study established a significant correlation between m6A regulatory

Impaired mitophagy underlies the pathophysiology of acute liver failure (ALF) and is closely associated with tissue damage and dysfunction. A novel mitophagy inducer, TJ0113, was used for treatment during ALF pathogenesis. In this study, we used a novel mitophagy inducer, TJ0113, to investigate the effects and mechanisms of TAA-induced ALF mice. The results showed that TJ0113 could enhance mitophagy

Myc hyperactivation coordinately regulates numerous metabolic processes to drive lymphomagenesis. Here, we elucidate the temporal and functional relationships between the medley of pathways, factors, and mechanisms that cooperate to control redox homeostasis in Myc-overexpressing B cell lymphomas. We find that Myc overexpression rapidly stimulates the oxidative pentose phosphate pathway (oxPPP), nucleotide

Colorectal cancer (CRC) exhibits significant diversity and heterogeneity, posing a requirement for novel therapeutic targets. Polysulfides are associated with CRC progression and immune evasion, but the underlying mechanisms are not fully understood. Sulfide: quinone oxidoreductase (SQR), a mitochondrial flavoprotein, catalyzes hydrogen sulfide (H2S) oxidation and polysulfides production. Herein, we

Ectopic fat deposition in skeletal muscle (SKM) due to obesity leads to biochemical and morphological alterations that deteriorate SKM quality and performance. Here, we show that impaired MPST-derived hydrogen sulfide (H2S) signaling contributes to obesity-related SKM dysfunction. Muscle tissues from obese db/db mice exhibit reduced MPST expression, correlating with decreased protein persulfidation

Particulate matter (PM) poses a significant risk to human health; however, it remains uncertain which size fraction is especially harmful and what mechanisms are involved. We investigated the varying effects of particle size on specific organ systems using a custom mouse exposure system and synthetic PM (SPM). Whole-body exposure of mice showed that micrometer-sized fine SPM (2–4 μm) accumulated in

LMNA mutation related Emery-Dreifuss muscular dystrophy (LMNA-related EDMD), is a rare genetic disorder often involving life‐threatening cardiac complications. However, the molecular links between LMNA mutations and their related EDMD cardiac phenotypes have remained unclear. Here, using EDMD patient-specific and genome-edited induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), we link

Microbial infections have been a widely studied area of disease research since historical times, yet they are a cause of severe illness and deaths worldwide. Furthermore, infections by pathogens are not just restricted to humans; instead, a diverse range of hosts, including plants, livestock, marine organisms and fish, cause significant economic losses and pose threats to humans through their transmission

Ischemic retinopathies, including proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP), are characterized by abnormal retinal neovascularization and can lead to blindness in children and adults. Current treatments, such as intravitreal anti-VEGF injections, face limitations due to high treatment burden and variable efficacy, as multiple signaling pathways, beyond VEGF, contribute

This study investigated the protective effects of taurine against cellular senescence and hepatokine secretion in a mouse model of carbon tetrachloride (CCl4)-induced chronic liver injury. Oral taurine administration by tap water containing 3 % taurine significantly attenuated liver damage, as evidenced by reduced serum AST, ALT level and hepatic lipid peroxidation. Importantly, hepatic taurine level

Acrolein (ACR) is an endogenous reactive unsaturated aldehyde that can be detoxified by the aldo-keto reductase (AKR) enzyme system. While it has been shown that accumulation of ACR is associated with several health problems, including inflammation, oxidative stress, and cardiovascular disease the study aimed to analyze whether an endogenous accumulation of ACR is causal for vascular dysfunction in

Metabolic dysfunction-associated fatty liver disease (MAFLD), a condition that stems from hepatic lipid accumulation in the absence of liver damage and overt inflammation, has become the most common hepatic disorder worldwide. Hydrogen sulfide (H2S), a gasotrasmitter, endogenously generated mainly by cystathionine-γ lyase (CTH), cystathionine-β synthase (CBS) and 3-mercaptopyruvate sulfurtransferase

The hypothesis of a significant shift from oxidative phosphorylation (OXPHOS) to glycolysis in a number of solid tumors has been dominant for many years. Recently, however, evidence has begun to accumulate that OXPHOS is the major mode of energy production in many neoplasias, especially those that have undergone chemo- or radiotherapy, and especially in chemoresistant malignancies. In the present work

Actin is an extraordinarily complex protein whose functions are essential to cell motility, division, contraction, signaling, transport, tissular structures, DNA repair, and many more cellular activities critical to life for both animals and plants. It is one of the most abundant and conserved proteins and it exists in either a soluble, globular (monomeric, G-actin) or an insoluble, self-assembled

Inhibiting ferroptosis represents a promising strategy to combat ferroptosis-related diseases. Here we show that 428, a selenide-containing noscapine derivative, effectively inhibits ferroptosis in various cell lines by enhancing the stability and activity of GPX4. TRIM41 was identified as a novel E3 ubiquitin ligase of GPX4 and 428 was demonstrated to bind to the selenocysteine residue Sec46 of GPX4

Inflammation and oxidative stress are involved in Proliferative Retinopathies (PR). Müller glial cells (MGCs) and microglia play pivotal roles in pathological neovascularization (NV) and neurodegeneration in PR. Nitro-fatty acids are important electrophilic signaling mediators with anti-inflammatory and antioxidant properties. Herein, our goal was to evaluate the cytoprotective effect of nitro-oleic

The oxidant hydrogen peroxide (H2O2) serves as a signaling molecule that alters many aspects of cardiovascular functions and contributes to cardiovascular diseases. Recent studies suggest that cytoglobin – a member of the globin family - may promote electron transfer reactions with proposed functions in H2O2 decomposition. In the present study, we directly examined the ability of cytoglobin to decompose

Ferroptosis is a regulated form of cell death driven by lipid peroxidation, with 15-lipoxygenase (15LOX) enzyme playing a critical role in catalyzing the oxygenation of polyunsaturated fatty acid-containing phospholipids, such as 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphoethanolamine (SAPE), to initiate this process. The molecular oxygen required for this catalytic reaction is subject to continuous

The results of protein thiols reacting with oxidants may be different in the presence or absence of glutathione (GSH). Upon exposure to oxidants, such as Cu2+ and polysulfide, the multiple drug resistant regulator MarR dimer in Escherichia coli is believed to form tetramers linked by disulfide bonds between its Cys80 thiols. We confirmed this observation in the absence of GSH; however, the MarR-Cys80