Tumor metastasis and recurrence: The role of perioperative NETosis.

Although surgical resection of tumor mass remains the mainstay of curative therapeutic management for solid tumors, accumulating studies suggest that these procedures promote tumor recurrence and metastasis. Regarded as the first immune cells to fight against infectious or inflammatory insults from surgery, neutrophils along with their ability of neutrophil extracellular traps (NETs) production has attracted much attention. A growing body of evidence suggests that NETs promote cancer metastasis by stimulating various stages, including local invasion, colonization, and growth.

Preventing postsurgical colorectal cancer relapse: A hemostatic hydrogel loaded with METTL3 inhibitor for CAR-NK cell therapy.

Colorectal cancer (CRC) recurrence post-surgery remains a major challenge. While Chimeric Antigen Receptor (CAR)-engineered natural killer (NK) cells hold immense therapeutic potential, their intratumoral infiltration ability remains limited, hampering efficacy. Building upon prior research suggesting that chemokines like C-X-C motif chemokine ligand 9 (CXCL9) and C-X-C motif chemokine ligand 10 (CXCL10) recruit CAR-NK cells, we hypothesized that tumor cell m6A methylation, regulated by Methyltransferase-like 3 (METTL3), influences chemokine secretion.

Novel injectable adhesive hydrogel loaded with exosomes for holistic repair of hemophilic articular cartilage defect.

Hemophilic articular cartilage damage presents a significant challenge for surgeons, characterized by recurrent intraarticular bleeding, a severe inflammatory microenvironment, and limited self-repair capability of cartilage tissue. Currently, there is a lack of tissue engineering-based integrated therapies that address both early hemostasis, anti-inflammation, and long-lasting chondrogenesis for hemophilic articular cartilage defects. Herein, we developed an adhesive hydrogel using oxidized chondroitin sulfate and gelatin, loaded with exosomes derived from bone marrow stem cells (BMSCs) (Hydrogel-Exos).

Mesenchymal stem cell-derived extracellular vesicles accelerate diabetic wound healing by inhibiting NET-induced ferroptosis of endothelial cells.

Impaired angiogenesis is a major factor contributing to delayed wound healing in diabetes. Dysfunctional mitochondria promote the formation of neutrophil extracellular traps (NETs), obstructing angiogenesis during wound healing. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown promise in promoting tissue repair and regeneration in diabetes; however, the precise pathways involved in this process remain unclear.

Neutrophil extracellular trap-induced ferroptosis promotes abdominal aortic aneurysm formation via SLC25A11-mediated depletion of mitochondrial glutathione.

Background: Neutrophil extracellular traps (NETs) induce oxidative stress, which may initiate ferroptosis, an iron-dependent programmed cell death, during abdominal aortic aneurysm (AAA) formation. Mitochondria regulate the progression of ferroptosis, which is characterized by the depletion of mitochondrial glutathione (mitoGSH) levels. However, the mechanisms are poorly understood.

Protein disulfide isomerase cleaves allosteric disulfides in histidine-rich glycoprotein to regulate thrombosis.

The essence of difference between hemostasis and thrombosis is that the clotting reaction is a highly fine-tuned process. Vascular protein disulfide isomerase (PDI) represents a critical mechanism regulating the functions of hemostatic proteins. Herein we show that histidine-rich glycoprotein (HRG) is a substrate of PDI.

PDIA2 has a dual function in promoting androgen deprivation therapy induced venous thrombosis events and castrate resistant prostate cancer progression.

Androgen deprivation therapy (ADT) is the first line of treatment for metastatic prostate cancer (PCa) that effectively delays the tumor progression. However, it also increases the risk of venous thrombosis event (VTE) in patients, a leading cause of mortality. How a pro-thrombotic cascade is induced by ADT remains poorly understood.

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) drives angiotensin II-induced vascular remodeling through regulating mitochondrial fragmentation.

Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a novel instigator for mitochondrial dysfunction, and plays an important role in the pathogenesis of cardiovascular diseases. However, the role and mechanism of DNA-PKcs in angiotensin II (Ang II)-induced vascular remodeling remains obscure.

Methods: Rat aortic smooth muscle cells (SMC) and VSMC-specific DNA-PKcs knockout (DNA-PKcs) mice were employed to examine the role of DNA-PKcs in vascular remodeling and the underlying mechanisms.

Bone Homeostasis Modulating Orthopedic Adhesive for the Closed-Loop Management of Osteoporotic Fractures.

Patients with osteoporotic fractures often require effective fixation and subsequent bone repair. However, currently available materials are often limited functionally, failing to improve this cohort's outcomes. Herein, kaempferol-loaded mesoporous bioactive glass nanoparticles (MBGNs)-doped orthopedic adhesives are prepared to assist osteoporotic fracture fixation and restore dysregulated bone homeostasis, including promoting osteoblast formation while inhibiting osteoclastic bone-resorbing activity to synergistically promote osteoporotic fracture healing.

Mulberry extract upregulates cholesterol efflux and inhibits p38 MAPK-NLRP3-mediated inflammation in foam cells.

The accumulation of foam cells in arterial intima and the accompanied chronic inflammation are considered major causes of neoatherosclerosis and restenosis. However, both the underlying mechanism and effective treatment for the disease are yet to be uncovered. In this study, we combined transcriptome profiling of restenosis artery tissue and bioinformatic analysis to reveal that NLRP3 inflammasome is markedly upregulated in restenosis and that several restenosis-related DEGs are also targets of mulberry extract, a natural dietary supplement used in traditional Chinese medicine.

Mesenchymal stem cell-derived extracellular vesicles protect against abdominal aortic aneurysm formation by inhibiting NET-induced ferroptosis.

Neutrophil extracellular traps (NETs) play an important role in abdominal aortic aneurysm (AAA) formation; however, the underlying molecular mechanisms remain unclear. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) may exert therapeutic effects on AAA through their immunomodulatory and regenerative abilities. This study aimed to examine the role and mechanism of MSC-EVs in regulating the development of NET-mediated AAA.

The role of long non-coding RNA in abdominal aortic aneurysm.

The abdominal aortic aneurysm (AAA) is characterized by segmental expansion of the abdominal aorta and a high mortality rate. The characteristics of AAA suggest that apoptosis of smooth muscle cells, the production of reactive oxygen species, and inflammation are potential pathways for the formation and development of AAA. Long non-coding RNA (lncRNA) is becoming a new and essential regulator of gene expression.

Novel Self-Expanding Interwoven Nitinol Stent for Treating Femoropopliteal Artery Disease: 12-Month Results of Single-Center First-in-Man Study.

Purpose: To evaluate the safety and efficacy of Innospring stent, a novel self-expanding interwoven nitinol stent, in treating femoropopliteal atherosclerotic lesions.

Methods: A prospective, single-center, single-arm, first-in-human study enrolled 15 patients (mean age 73.1 years; 13 men) to evaluate the safety and efficacy of the Innospring stent monitored by core laboratories.

Neutrophil Extracellular Traps Delay Diabetic Wound Healing by Inducing Endothelial-to-Mesenchymal Transition via the Hippo pathway.

Diabetic foot ulcers (DFUs) are among the most frequent complications of diabetes with significant morbidity and mortality. Diabetes can trigger neutrophils to undergo histone citrullination by protein arginine deiminase 4 (encoded by in mice) and release neutrophil extracellular traps (NETs). The specific mechanism of NETs-mediated wound healing impairment in diabetes remains unknown.

CircRNA circCOL1A1 Acts as a Sponge of miR-30a-5p to Promote Vascular Smooth Cell Phenotype Switch through Regulation of Smad1 Expression.

Phenotypic switch of vascular smooth muscle cells (VSMCs) plays an important role in the pathogenesis of atherosclerosis. The mRNA expression of the synthetic biomarker Collagen Type I Alpha 1 Chain () gene is upregulated during the switch of VSMCs from the contractile to the synthetic phenotype. The association of noncoding circular RNAs transcribed by the gene with VSMC phenotype alteration and atherogenesis remains unclear.

Neutrophil extracellular traps induce abdominal aortic aneurysm formation by promoting the synthetic and proinflammatory smooth muscle cell phenotype via Hippo-YAP pathway.

The neutrophil plays an important role during abdominal aortic aneurysm (AAA) formation by undergoing histone citrullination with peptidyl arginine deiminase 4 (encoded by Padi4) and releasing neutrophil extracellular traps (NETs). However, the specific role of NETs during AAA formation is elusive. We found the levels of NET components in serum and tissues were found to be significantly associated with the clinical outcome of AAA patients.

Disulfiram accelerates diabetic foot ulcer healing by blocking NET formation via suppressing the NLRP3/Caspase-1/GSDMD pathway.

Diabetic foot ulcer (DFU) is among the most frequent complications of diabetes and is associated with significant morbidity and mortality. Excessive neutrophil extracellular traps (NETs) delay wound healing in diabetic patients. Therefore, interventions targeting NET release need to be developed to effectively prevent NET-based wound healing impairment.

Construction and analysis of competing endogenous RNA network and patterns of immune infiltration in abdominal aortic aneurysm.

Background: Various studies have highlighted the role of circular RNAs (circRNAs) as critical molecular regulators in cardiovascular diseases, but its role in abdominal aortic aneurysm (AAA) is unclear. This study explores the potential molecular mechanisms of AAA based on the circRNA-microRNA (miRNA)-mRNA competing endogenous RNA (ceRNA) network and immune cell infiltration patterns.

Methods: The expression profiles of circRNAs (GSE144431) and mRNAs (GSE57691 and GSE47472) were obtained from the Gene Expression Omnibus (GEO).

Electrochemiluminescence biosensor for DNA adenine methylation methyltransferase based on CRISPR/Cas12a trans-cleavage-induced dual signal enhancement.

In this work, an electrochemiluminescence (ECL) biosensor with dual signal enhancement was constructed and used for DNA adenine methylation methyltransferase (Dam MTase) detection. At present of Dam MTase, restriction endonuclease (DPnI) cleaves hairpin DNA (HP) and releases the HP stem end as a single strand that can activate CRISPR/Cas12a trans-cleavage activity. Assisted by trans-cleavage, the distance between the signal quenching factor ferrocene (Fc) and the ECL signal unit increased, and the repulsion between the signal unit and the Indium Tin Oxides (ITO) electrode decreased.

Neutrophil extracellular traps mediate mA modification and regulates sepsis-associated acute lung injury by activating ferroptosis in alveolar epithelial cells.

Neutrophil extracellular traps (NETs) production is a major strategy employed by polymorphonuclear neutrophils (PMNs) to fight against microbes. NETs have been implicated in the pathogenesis of various lung injuries, although few studies have explored NETs in sepsis-associated acute lung injury (SI-ALI). Here, we demonstrate a major contribution of NETs to the pathology of sepsis-associated ALI by inducing ferroptosis of alveolar epithelial cells.

The requirement of phosphoenolpyruvate carboxykinase 1 for angiogenesis in vitro and in vivo.

We here examined the potential biological function of phosphoenolpyruvate carboxykinase 1 (PCK1) in angiogenesis. shRNA- or CRISPR-Cas9-induced PCK1 depletion potently inhibited endothelial cell proliferation, migration, sprouting, and tube formation, whereas ectopic PCK1 overexpression exerted opposite activity. In HUVECs, Gα expression and Akt activation were decreased following PCK1 depletion, but were augmented by ectopic PCK1 overexpression.

Diagnostic and Prognostic Value of Neutrophil Extracellular Trap Levels in Patients With Acute Aortic Dissection.

Background: Acute aortic dissection (AAD) is a fatal disease demanding prompt diagnosis and proper treatment. There is a lack of serum markers that can effectively assist diagnosis and predict prognosis of AAD patients.

Methods: Ninety-six AAD patients were enrolled in this study, and 249 patients with chest pain due to acute myocardial infarction, pulmonary embolism, intramural hematoma, angina or other causes and 80 healthy controls were included as control group and healthy control group.

Neutrophil extracellular traps promote metastasis in gastric cancer patients with postoperative abdominal infectious complications.

Postoperative abdominal infectious complication (AIC) is associated with metastasis in locally advanced gastric cancer (GC) patients after radical gastrectomy. However, the underlying mechanism remains unclear. Herein, we report that neutrophil extracellular traps (NETs), the DNA meshes released by neutrophils in response to infection, could promote GC cells proliferation, invasion, migration and epithelial-mesenchymal transition dependent on TGF-β signaling.

SOX2-OT induced by PAI-1 promotes triple-negative breast cancer cells metastasis by sponging miR-942-5p and activating PI3K/Akt signaling.

Triple-negative breast cancer (TNBC) has an aggressive biological behavior and poor outcome. Our published study showed that PAI-1 could induce the migration and metastasis of TNBC cells. However, the underlying mechanism by which PAI-1 regulates TNBC metastasis has not been addressed.