Targeting proprotein convertase subtilisin/kexin type 7 in macrophages as a therapeutic strategy to mitigate myocardial infarction-induced inflammation.

Myocardial infarction (MI), a major form of coronary artery disease (CAD), triggers a severe inflammatory response in the heart, resulting in increased cell death and adverse ventricular remodeling. Despite treatment advancements, MI remains a significant risk factor for heart failure, underscoring the necessity for a more in-depth exploration of immune cell mechanisms. Proprotein convertase subtilisin/kexin type 7 (PCSK7), expressed in various tissues and immune cells, has been implicated in cardiovascular disease, yet its specific role in cardiac immune cells remains poorly understood.

Extracellular peroxiredoxin 5 exacerbates atherosclerosis via the TLR4/MyD88 pathway.

Backgroungd And Aims: Peroxiredoxin 5 (PRDX5), an atypical 2-Cys peroxiredoxin (PRDX), is known to regulate global oxidative stresses and inflammatory responses. Inflammation and oxidative stress are pivotal factors in the development of atherosclerosis, especially in the context of vascular endothelial dysfunction. However, effects of PRDX5 on atherosclerosis remain unclear.

Ninjurin1 deficiency differentially mitigates colorectal cancer induced by azoxymethane and dextran sulfate sodium in male and female mice.

This study investigated the role of Ninjurin1 (Ninj1), encoding a small transmembrane protein, in colitis-associated colon tumorigenesis in relation to sex hormones. Male and female wild-type (WT) and Ninj1 knockout (KO) mice were treated with azoxymethane (AOM) and dextran sulfate sodium (DSS), with or without testosterone propionate (TP). At week 2 (acute colitis stage), Ninj1 KO exhibited an alleviation in the colitis symptoms in both male and female mice.

N-terminal acetylation of Set1-COMPASS fine-tunes H3K4 methylation patterns.

H3K4 methylation by Set1-COMPASS (complex of proteins associated with Set1) is a conserved histone modification. Although it is critical for gene regulation, the posttranslational modifications of this complex that affect its function are largely unexplored. This study showed that N-terminal acetylation of Set1-COMPASS proteins by N-terminal acetyltransferases (NATs) can modulate H3K4 methylation patterns.

Peroxiredoxin 3 Deficiency Exacerbates DSS-Induced Acute Colitis via Exosomal miR-1260b-Mediated Barrier Disruption and Proinflammatory Signaling.

Peroxiredoxin3 (Prdx3) is an intracellular antioxidant enzyme that is specifically localized in mitochondria and protects against oxidative stress by removing mitochondrial reactive oxygen species (ROS). The intestinal epithelium provides a physical and biochemical barrier that segregates host tissues from commensal bacteria to maintain intestinal homeostasis. An imbalance between the cellular antioxidant defense system and oxidative stress has been implicated in the pathogenesis of inflammatory bowel disease (IBD).

Primary Cilium in Neural Crest Cells Crucial for Anterior Segment Development and Corneal Avascularity.

Purpose: Intraflagellar transport 46 (IFT46) is an integral subunit of the IFT-B complex, playing a key role in the assembly and maintenance of primary cilia responsible for transducing signaling pathways. Despite its predominant expression in the basal body of cilia, the precise role of Ift46 in ocular development remains undetermined. This study aimed to elucidate the impact of neural crest (NC)-specific deletion of Ift46 on ocular development.

Pancreatic β-cell mitophagy as an adaptive response to metabolic stress and the underlying mechanism that involves lysosomal Ca release.

Mitophagy is an excellent example of selective autophagy that eliminates damaged or dysfunctional mitochondria, and it is crucial for the maintenance of mitochondrial integrity and function. The critical roles of autophagy in pancreatic β-cell structure and function have been clearly shown. Furthermore, morphological abnormalities and decreased function of mitochondria have been observed in autophagy-deficient β-cells, suggesting the importance of β-cell mitophagy.

Unbalanced Redox With Autophagy in Cardiovascular Disease.

Precise redox balance is essential for the optimum health and physiological function of the human body. Furthermore, an unbalanced redox state is widely believed to be part of numerous diseases, ultimately resulting in death. In this review, we discuss the relationship between redox balance and cardiovascular disease (CVD).

Progerinin, an Inhibitor of Progerin, Alleviates Cardiac Abnormalities in a Model Mouse of Hutchinson-Gilford Progeria Syndrome.

Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare human premature aging disorder that precipitates death because of cardiac disease. Almost all cases of HGPS are caused by aberrant splicing of the gene that results in the production of a mutant Lamin A protein termed progerin. In our previous study, treatment with Progerinin has been shown to reduce progerin expression and improve aging phenotypes in vitro and in vivo HGPS models.

Complexation of drug and hapten-conjugated aptamer with universal hapten antibody for pancreatic cancer treatment.

Owing to a lack of reliable markers and therapeutic targets, pancreatic ductal adenocarcinoma (PDAC) remains the most lethal malignant tumor despite numerous therapeutic advances. In this study, we utilized cell-SELEX to isolate a DNA aptamer recognizing the natural conformation of the target on the cell surface. PAp7T8, an aptamer optimized by size and chemical modification, exhibited specific targeting to pancreatic cancer cells and orthotopic xenograft pancreatic tumors.

Endothelial PTP4A1 mitigates vascular inflammation via USF1/A20 axis-mediated NF-κB inactivation.

Aims: The nuclear factor-κB (NF-κB) signalling pathway plays a critical role in the pathogenesis of multiple vascular diseases. However, in endothelial cells (ECs), the molecular mechanisms responsible for the negative regulation of the NF-κB pathway are poorly understood. In this study, we investigated a novel role for protein tyrosine phosphatase type IVA1 (PTP4A1) in NF-κB signalling in ECs.

2'-5' oligoadenylate synthetase‑like 1 (OASL1) protects against atherosclerosis by maintaining endothelial nitric oxide synthase mRNA stability.

Endothelial nitric oxide synthase (eNOS) decreases following inflammatory stimulation. As a master regulator of endothelial homeostasis, maintaining optimal eNOS levels is important during cardiovascular events. However, little is known regarding the mechanism of eNOS protection.

Impaired TFEB activation and mitophagy as a cause of PPP3/calcineurin inhibitor-induced pancreatic β-cell dysfunction.

Macroautophagy/autophagy or mitophagy plays crucial roles in the maintenance of pancreatic β-cell function. PPP3/calcineurin can modulate the activity of TFEB, a master regulator of lysosomal biogenesis and autophagy gene expression, through dephosphorylation. We studied whether PPP3/calcineurin inhibitors can affect the mitophagy of pancreatic β-cells and pancreatic β-cell function employing FK506, an immunosuppressive drug against graft rejection.

The antioxidant enzyme Peroxiredoxin-1 controls stroke-associated microglia against acute ischemic stroke.

Ischemic stroke is the leading cause of immortal disability and death worldwide. For treatment in the acute phase, it is necessary to control excessive reactive oxygen species (ROS) damage during ischemia/reperfusion (I/R). Microglia are well known to be closely associated with excessive ROS response in the early stage of I/R.

Plasma Membrane Localization of CD36 Requires Vimentin Phosphorylation; A Mechanism by Which Macrophage Vimentin Promotes Atherosclerosis.

Vimentin is a type III intermediate filament protein expressed in cells of mesenchymal origin. Vimentin has been thought to function mainly as a structural protein and roles of vimentin in other cellular processes have not been extensively studied. Our current study aims to reveal functions of vimentin in macrophage foam cell formation, the critical stage of atherosclerosis.

Peroxiredoxin 2 deletion impairs hippocampal-dependent memory via exacerbating transient ischemia-induced oxidative damage.

Peroxiredoxin 2 (Prx2) regulates oxidative stress response in neuronal injury. The present study examined the effects of Prx2 deletion on transient global ischemia-induced hippocampal-dependent memory impairment. First, 20-min bilateral common carotid artery occlusion (BCCAO)-reperfusion and sham-operated control procedures were conducted in 6- or 7-month-old Prx2 knockout and wild-type mice.

Peroxiredoxin 3 deficiency induces cardiac hypertrophy and dysfunction by impaired mitochondrial quality control.

Mitochondrial quality control (MQC) consists of multiple processes: the prevention of mitochondrial oxidative damage, the elimination of damaged mitochondria via mitophagy and mitochondrial fusion and fission. Several studies proved that MQC impairment causes a plethora of pathological conditions including cardiovascular diseases. However, the precise molecular mechanism by which MQC reverses mitochondrial dysfunction, especially in the heart, is unclear.

miR-125a-5p attenuates macrophage-mediated vascular dysfunction by targeting Ninjurin1.

Ninjurin1 (Ninj1), an adhesion molecule, regulates macrophage function in hyaloid regression, multiple sclerosis, and atherosclerosis. However, its biological relevance and the mechanism underlying its function in vascular network integrity have not been studied. In this study, we investigated the role of Ninj1 in physiological (postnatal vessel formation) and pathological (endotoxin-mediated inflammation and diabetes) conditions and developed a strategy to regulate Ninj1 using specific micro (mi)RNAs under pathological conditions.

ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1.

C1q/TNF-related protein 1 (CTRP1) is a CTRP family member that has collagenous and globular C1q-like domains. The secreted form of CTRP1 is known to be associated with cardiovascular and metabolic diseases, but its cellular roles have not yet been elucidated. Here, we showed that cytosolic CTRP1 localizes to the endoplasmic reticulum (ER) membrane and that knockout or depletion of CTRP1 leads to mitochondrial fission defects, as demonstrated by mitochondrial elongation.

Peroxiredoxins as Potential Targets for Cardiovascular Disease.

Increased oxidative stress (OS) is considered a common etiology in the pathogenesis of cardiovascular disease (CVD). Therefore, the precise regulation of reactive oxygen species (ROS) in cardiovascular cells is essential to maintain normal physiological functions. Numerous regulators of cellular homeostasis are reportedly influenced by ROS.

compensates for in mice in the amino-terminal acetylation pathway.

Amino-terminal acetylation is catalyzed by a set of N-terminal acetyltransferases (NATs). The NatA complex (including X-linked Naa10 and Naa15) is the major acetyltransferase, with 40-50% of all mammalian proteins being potential substrates. However, the overall role of amino-terminal acetylation on a whole-organism level is poorly understood, particularly in mammals.