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[Phenotypic characteristics and functional alterations of lipopolysaccharide-induced low-density neutrophil].

OBJECTIVE: To observe the generation of low-density neutrophil (LDN) induced by lipopolysaccharide (LPS) stimulation in vitro to simulate a septic environment, and to analyze their generation mechanism, phenotype, and functional characteristics. METHODS: 1) Analysis of LDN proportion in septic patients: A case-control study was conducted. Peripheral blood samples were collected from 45 septic patients admitted to the intensive care unit (ICU) of Suzhou Municipal Hospital from June 2022 to January 2024, and from 32 age- and sex-matched healthy volunteers as the control group. The proportion of

Neutrophil diversity and function in health and disease.

Neutrophils, the most abundant type of granulocyte, are widely recognized as one of the pivotal contributors to the acute inflammatory response. Initially, neutrophils were considered the mobile infantry of the innate immune system, tasked with the immediate response to invading pathogens. However, recent studies have demonstrated that neutrophils are versatile cells, capable of regulating various biological processes and impacting both human health and disease. Cytokines and other active mediators regulate the functional activity of neutrophils by activating multiple receptors on these cells,

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… trap (NET) that accompanies neutrophil death. 61 Volker Brinkmann popularized the term “NETosis” in 2004 to describe the phenomenon of neutrophils fighting pathogens by “committing suicide“. 62 Death may not be the only outcome for neutrophils in sterile inflammation. … These extracellular traps possess the capacity to inflict damage on virulent pathogens. 182 Not all instances of NET development result in neutrophil death following the extracellular release of DNA. …

Изображение миэломы экзосома0002724 поощрение остеокластогенеза через miR-4753-3p/IFIT1 и ось RANK в болезни костей миэломы.

КОЛИЧЕСТВО: Болезнь кости миеломы (МБД) вызвана чрезмерной активацией остеокласта и постепенным разрушением костей, однако роль экзосомных круговых РНК (КРН) из клеток миэломы остается неясной. МЕТОДЫ: Экзосомы из клеток U266 и MM1S были изолированы и использовались для лечения THP-1 клетки. Остеокластная дифференциация была оценена с помощью анализа пятен и ресорбции костей. Для выявления совпадающих пятен вокруг РНК была проведена последовательность последовательности экзосомы U266 и крови пациента MBD. Сеть ceRNA была построена с помощью циркбанка и миРТарбазы в сочетании с одноклеточной RN

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… M2 macrophages-derived exosomes for osteonecrosis of femoral head treatment: modulating neutrophil extracellular traps formation and endothelial phenotype transition . Bone Res . ( 2025 ) 13 : 42 . doi: 10.1038/s41413-025-00412-5 40169566 PMC11961764 31 Yin C Fu L Guo S Liang Y Shu T Shao W . …

Cinobufagin Suppresses Lipid Peroxidation and Inflammation in Osteoporotic Mice by Promoting the Delivery of miR-3102-5p by Macrophage-Derived Exosomes.

BackgroundCinobufagin, the primary active compound in toad venom, is commonly used for anti-tumor, anti-inflammatory, and analgesic purposes. However, its specific bone-protective effects remain uncertain. This research aims to ascertain the bone-protective properties of cinobufagin and investigate underlying mechanisms.MethodsMice were ovariectomized to establish an osteoporosis model, followed by intraperitoneal injections of cinobufagin and cinobufagin-treated RAW.264.7-derived exosomes for therapy. MicroCT, HE staining, and TRAP staining were employed to evaluate bone mass and therapeutic

Osteoclast Activation and Inflammatory Bone Diseases: Focusing on Receptors in Osteoclasts.

Bone homeostasis depends on the balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. An increasing number of studies have revealed that under inflammatory conditions, osteoclast overactivation is responsible for bone loss in relevant bone diseases. Multiple signaling pathways such as receptor activator of nuclear factor-kappa B ligand (RANKL) signaling are involved in osteoclast activation. These signaling pathways rely on various receptors expressed on the surface of osteoclast progenitor cells (OPCs) or osteoclasts, which are activated by their correspo

Hemostasis at the edge between physiology and cancer.

Hemostasis lies at the edge between physiology and cancer, where the coagulation cascade-initiated by tissue factor, thrombin generation, and fibrin deposition-shifts from vascular repair to tumor promotion. The interplay between coagulation and cancer is now recognized as a two-way street, with tumor cells activating the clotting system and coagulation components feeding back to promote malignancy. Tumor cells not only foster proliferation and invasion by overexpressing tissue factor and activating Protease-Activated Receptors (PAR1/PAR2) signalling, but they also induce endothelial cells and

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… Wang H Neutrophil extracellular traps in homeostasis and disease Signal Transduct Target Ther 2024 9 1 235 10.1038/s41392-024-01933-x 39300084 PMC11415080 Wang H et al (2024) Neutrophil extracellular traps in homeostasis and disease. … associated with neutrophil extracellular traps. …

Immune mechanism of low bone mineral density caused by ankylosing spondylitis based on bioinformatics and machine learning.

Background and Objective: This study aims to find the key immune genes and mechanisms of low bone mineral density (LBMD) in ankylosing spondylitis (AS) patients. Methods: AS and LBMD datasets were downloaded from the GEO database, and differential expression gene analysis was performed to obtain DEGs. Immune-related genes (IRGs) were obtained from ImmPort. Overlapping DEGs and IRGs got I-DEGs. Pearson coefficients were used to calculate DEGs and IRGs correlations in the AS and LBMD datasets. Louvain community discovery was used to cluster the co-expression network to get gene modules. The modu

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… As the most significant pathway of the AS key module, neutrophil extracellular traps (NETs) formation attracted our attention. … In addition to the above genes, neutrophil extracellular traps (NETs) formation has attracted our attention as an essential mechanism of AS. …

The Conundrum of Cancer-Associated Thrombosis: Lesson Learned from Two Intriguing Cases and Literature Review.

The correlation between cancer and venous thromboembolism (VTE) is solid, whereas the knowledge about cancer-related arterial thromboembolism (ATE) still needs a deeper investigation to clarify its pathogenesis. We describe two cases that represent useful hints for a comprehensive review of the thrombotic issue. A 75-year-old man with advanced rectal cancer treated with fluoropyrimidines suffered two catheter-related VTE events managed according to current guidelines. There was no indication for "extended" anticoagulant therapy for him, but during antithrombotic wash-out and fluoropyrimidines

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… Neutrophil extracellular traps (NETs)—Formation and implications. Acta Biochim. Pol. 2013;60:277–284. doi: 10.18388/abp.2013_1983. 40. Warnatsch A., Ioannou M., Wang Q., Papayannopoulos V. Inflammation. Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis. … Neutrophil Extracellular Traps: Villains and Targets in Arterial, Venous, and Cancer-Associated Thrombosis. Arterioscler. Thromb. Vasc. Biol. 2019;39:1724–1738. doi: 10.1161/ATVBAHA.119.312463. 43. …

Multiple Myeloma-Derived Extracellular Vesicles Induce Osteoclastogenesis through the Activation of the XBP1/IRE1α Axis.

Bone disease severely affects the quality of life of over 70% of multiple myeloma (MM) patients, which daily experience pain, pathological fractures, mobility issues and an increased mortality. Recent data have highlighted the crucial role of the endoplasmic reticulum-associated unfolded protein response (UPR) in malignant transformation and tumor progression; therefore, targeting of UPR-related molecules may open novel therapeutic avenues. Endoplasmic reticulum (ER) stress and UPR pathways are constitutively activated in MM cells, which are characterized by an increased protein turnover as a

Exploring the FGF/FGFR System in Ocular Tumors: New Insights and Perspectives.

Ocular tumors are a family of rare neoplasms that develop in the eye. Depending on the type of cancer, they mainly originate from cells localized within the retina, the uvea, or the vitreous. Even though current treatments (e.g., radiotherapy, transpupillary thermotherapy, cryotherapy, chemotherapy, local resection, or enucleation) achieve the control of the local tumor in the majority of treated cases, a significant percentage of patients develop metastatic disease. In recent years, new targeting therapies and immuno-therapeutic approaches have been evaluated. Nevertheless, the search for nov

Multimodality Imaging Reveals Rare Hereditary Transthyretin Amyloidosis Mimicking Hypertrophic Cardiomyopathy.

BACKGROUND: Distinguishing hypertrophic cardiomyopathy from phenocopies remains a diagnostic challenge in younger patients presenting with unexplained ventricular hypertrophy. CASE SUMMARY: A 52-year-old Moroccan woman previously diagnosed with nonobstructive hypertrophic cardiomyopathy presented with recurrent pericardial chest pain, poorly tolerating angiotensin-converting enzyme inhibitors and beta-blockers. Cardiac magnetic resonance showed asymmetric hypertrophy and papillary muscle hypertrophy suggestive of hypertrophic cardiomyopathy, with markedly elevated native T1 mapping and extrac

Aberrant NSUN2-mediated m5C modification of exosomal LncRNA MALAT1 induced RANKL-mediated bone destruction in multiple myeloma.

The impact of exosome-mediated crosstalk between multiple myeloma (MM) cells and osteoclasts (OCs) on bone lesions remains to be investigated. Here, we identified NSUN2 and YBX1-mediated m5C modifications upregulated LncRNA MALAT1 expression in MM cells, which could be transported to OCs via exosomes and promote bone lesions. Methodologically, RNA-seq was carried out to detect the cargoes of exosomes. TRAP staining and WB were used to evaluate osteoclastogenesis in vitro. Micro-CT and bone histomorphometric analyses were performed to identify bone destruction in vivo. RNA pull-down, RIP, MeRIP

Correlation Between Systemic Inflammation Response Index and Systemic Immune-Inflammation Index and Disease Activity of Lupus Nephritis in Children.

Objectives: Lupus nephritis (LN) is a severe manifestation of pediatric systemic lupus erythematosus (SLE) requiring accurate disease activity assessment. This study evaluated the association of the Systemic Inflammation Response Index (SIRI) and the Systemic Immune-Inflammation Index (SII) with disease activity in children with LN. Methods: In this cross-sectional study, 52 children with LN aged 1 month to 18 years treated at Dr. Hasan Sadikin General Hospital, Indonesia, were included. SIRI and SII were calculated from complete blood counts, and disease activity was assessed using the Mexica

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… Neutrophil extracellular traps and systemic lupus erythematosus. J. Clin. Cell. Immunol. 2013;4:139. doi: 10.4172/2155-9899.1000139. 25. … Neutrophil extracellular traps stimulate IgG2 production from B lymphocytes in systemic lupus erythematosus. Front. Med. 2021;8:635436. doi: 10.3389/fmed.2021.635436. 40. Liu L., De Leeuw K., Van Goor H., Van Der Meer B.D., Arends S., Westra J. …

Septic Hyperinflammation-Is There a Role for Extracorporeal Blood Purification Techniques?

This manuscript investigates the role of extracorporeal blood purification techniques in managing septic hyperinflammation, a critical aspect of sepsis characterized by an uncontrolled immune response leading to multiorgan dysfunction. We provide an overview of sepsis, focusing on the dynamics of immune response, the involvement of neutrophils, and the role of the endothelium in the disease's progression. It evaluates the effectiveness of various blood purification methods, including high-cut-off membranes, high-volume hemofiltration, adsorption techniques, and albumin dialysis, in removing cy

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… Neutrophil extracellular trap formation and nuclease activity in septic patients. BMC Anesthesiol. 2020;20:15. doi: 10.1186/s12871-019-0911-7. 19. Ortmann W., Kolaczkowska E. Age is the work of art? Impact of neutrophil and organism age on neutrophil extracellular trap formation. … Neutrophil extracellular traps in sepsis. Shock. 2014;42:286–294. doi: 10.1097/SHK.0000000000000221. 21. Kaplan M.J., Radic M. Neutrophil extracellular traps: Double-edged swords of innate immunity. J. Immunol. 2012;189:2689–2695. doi: 10.4049/jimmunol.1201719. 22. …

Mastocytosis-derived extracellular vesicles deliver miR-23a and miR-30a into pre-osteoblasts and prevent osteoblastogenesis and bone formation.

Osteoporosis and other manifestations of bone disease are frequent in patients with systemic mastocytosis (SM) in association with the presence of mast cell infiltrates in bone marrow, although the mechanisms behind bone disease remain poorly understood. We find that extracellular vesicles (EVs) released by neoplastic mast cells and present in the serum of patients with SM (SM-EVs) block osteoblast differentiation and mineralization in culture, and when injected into mice diminish the expression of osteoblast markers, and trabecular bone volume and microarchitecture. We demonstrate that miRNA-

Promotion of Bone Lesions Through the Myeloma Integrin α6-Mediated Osteolytic Signaling.

Osteolytic destruction is a hallmark of multiple myeloma and impairs myeloma patients' quality of life. However, the molecular mechanism underlying the pathogenesis of myeloma-associated bone disease remains unclear. In this study, we demonstrate the role of myeloma cell-expressed integrin α6 in bone. Integrin α6 binds to laminin 8 and epidermal growth factor receptor on mesenchymal stem cells (MSCs) to form a trimer complex and upregulates the secretion of osteolytic cytokines from both myeloma cells and MSCs, leading to enhanced bone resorption and reduced bone formation. Thus, this study el

AIMP1 promotes multiple myeloma malignancy through interacting with ANP32A to mediate histone H3 acetylation.

BackgroundMultiple myeloma (MM) is the second most common hematological malignancy. An overwhelming majority of patients with MM progress to serious osteolytic bone disease. Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) participates in several steps during cancer development and osteoclast differentiation. This study aimed to explore its role in MM.MethodsThe gene expression profiling cohorts of MM were applied to determine the expression of AIMP1 and its association with MM patient prognosis. Enzyme-linked immunosorbent assay, immunohistochemistry, and Western blotti

MSC-EV therapy for bone/cartilage diseases.

Mesenchymal stromal cells (MSCs) have been utilized in cell therapy for various diseases. Recent studies have demonstrated that extracellular vesicles (EVs) released by MSCs play an important role in their therapeutic activities. EVs contain a variety of bioactive molecules such as proteins, messenger RNAs (mRNAs), and micro RNAs (miRNAs) and modify the function of the recipient cells by transferring these molecules. Despite the promising potential of EV therapy as a substitute for MSC therapy, there are challenges that need to be addressed for the clinical success of EV therapy. EV quality ha

TSP-1 interaction with RANK and OPG: implications for bone remodeling and osteolytic bone metastasis.

Excessive bone disruption, driven by upregulation of bone-degrading osteoclasts, occurs in several pathologies, including breast cancer osteolytic bone metastasis, a condition associated with poor prognosis and diminished quality of life for patients. The matricellular protein thrombospondin-1 (TSP-1) plays pleiotropic roles in physiological and pathological remodeling of several tissues, including bone, and in shaping the microenvironment of primary tumors and metastasis. This study aimed to explore the role of TSP-1 in bone remodeling associated with osteolytic bone metastasis. We have ident

The inhibition of RANKL-induced osteoclastogenesis through the suppression of p38 signaling pathway by naringenin and attenuation of titanium-particle-induced osteolysis.

The aim of this study was to assess the effect of naringenin on osteoclastogenesis and titanium particle-induced osteolysis. Osteolysis from wear-induced particles and aseptic loosening are the most frequent late complications of total joint arthroplasty leading to revision of the prosthesis. Osteolysis during aseptic loosening is most likely due to increased bone resorption by osteoclasts. Through in vitro studies, we demonstrated that naringenin, a naturally occurring flavanone in grapefruit and tomatoes, exerts potent inhibitory effects on the ligand of the receptor activator of nuclear fac