Orexin-A Attenuates the Inflammatory Response in Sepsis-Associated Encephalopathy by Modulating Oxidative Stress and Inhibiting the ERK/NF-κB Signaling Pathway in Microglia and Astrocytes.

Background: Oxidative stress-induced inflammation is a major pathogenic mechanism in sepsis-associated encephalopathy (SAE). We hypothesized that regulation of reactive oxygen species (ROS) by the neuropeptide orexin-A could prevent SAE-induced oxidative stress and inflammation. Therefore, the aim of this study was to investigate the effects of orexin-A on oxidative stress and inflammation in SAE in mice.

Spatiotemporal ATF3 Expression Determines VSMC Fate in Abdominal Aortic Aneurysm.

Background: Abdominal aortic aneurysm (AAA) is a catastrophic disease with little effective therapy, likely due to the limited understanding of the mechanisms underlying AAA development and progression. ATF3 (activating transcription factor 3) has been increasingly recognized as a key regulator of cardiovascular diseases. However, the role of ATF3 in AAA development and progression remains elusive.

Pyroptosis in cardiovascular diseases: Pumping gasdermin on the fire.

Pyroptosis is a form of programmed cell death associated with activation of inflammasomes and inflammatory caspases, proteolytic cleavage of gasdermin proteins (forming pores in the plasma membrane), and selective release of proinflammatory mediators. Induction of pyroptosis results in amplification of inflammation, contributing to the pathogenesis of chronic cardiovascular diseases such as atherosclerosis and diabetic cardiomyopathy, and acute cardiovascular events, such as thrombosis and myocardial infarction. While engagement of pyroptosis during sepsis-induced cardiomyopathy and septic shock is expected and well documented, we are just beginning to understand pyroptosis involvement in the pathogenesis of cardiovascular diseases with less defined inflammatory components, such as atrial fibrillation.

Gasdermin D-dependent platelet pyroptosis exacerbates NET formation and inflammation in severe sepsis.

Platelets have emerged as key inflammatory cells implicated in the pathology of sepsis, but their contributions to rapid clinical deterioration and dysregulated inflammation have not been defined. Here, we show that the incidence of thrombocytopathy and inflammatory cytokine release was significantly increased in patients with severe sepsis. Platelet proteomic analysis revealed significant upregulation of gasdermin D (GSDMD).

A Unique SUMO-Interacting Motif of Trx2 Is Critical for Its Mitochondrial Presequence Processing and Anti-oxidant Activity.

Objective: Mitochondrial thioredoxin 2 (Trx2) is a vital mitochondrial redox protein that mediates normal protein thiol reduction and provides electrons to peroxiredoxin 3 (Prx3) to scavenge HO in mitochondria. It has been widely reported that Trx2 deletion in cells or mice generates massive reactive oxygen species (ROS) which have been implicated in many pathological processes. On the contrary, how ROS regulate Trx2 processing and activity remains to be elucidated.

Endothelial AIP1 Regulates Vascular Remodeling by Suppressing NADPH Oxidase-2.

AIP1 expression is downregulated in human atherosclerotic plaques and global deletion of AIP1 in mice exacerbates atherosclerosis in ApoE-KO mouse models. However, the direct role of AIP1 in endothelium, vascular remodeling and associated vascular diseases has not been determined. We used endothelial cell (EC)-specific AIP1-deficient (AIP1-ECKO) mice to define the role of AIP1 in vascular remodeling and intima-media thickening in a mouse carotid artery ligation model characterized by both neointimal hyperplasia and inward vessel remodeling.

The Role of NOX4 and TRX2 in Angiogenesis and Their Potential Cross-Talk.

The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) family is the major source of reactive oxygen species (ROS) in the vascular system. In this family, NOX4, a constitutive active form of NOXs, plays an important role in angiogenesis. Thioredoxin 2 (TRX2) is a key mitochondrial redox protein that maintains normal protein function and also provides electrons to peroxiredoxin 3 (PRX3) to scavenge H₂O₂ in mitochondria.

Mechanistic Role of Thioredoxin 2 in Heart Failure.

Thioredoxin 2 (Trx2) is a pivotal mitochondrial protein that regulates redox signaling. The mitochondrial Trx2 is expressed ubiquitously, but it is found at the highest levels in metabolically active tissues like the heart. Global gene knockout of Trx2 results in embryonic lethality, likely due to the increased cellular oxidative stress.

Selective Detection of 8-Oxo-2'-deoxyguanosine in Single-Stranded DNA via Nanopore Sensing Approach.

We have developed a nanopore sensing approach for the selective detection of 8-oxo-2'-deoxyguanosine (8-oxoG) in single-stranded DNA. First, 1,12-dodecanediamine is coupled with 8-oxoG-containing DNA molecules in high yield which leaves a free amine group for subsequent attaching of an adamantane moiety. After incubation with cucurbit[7]uril, the host-guest complex-modified DNA hybrid is translocated through an α-hemolysin nanopore.