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Human antigen R-regulated CCL20 contributes to osteolytic breast cancer bone metastasis.

Breast cancer mainly spreads to bone, causing decreased survival of patient. Human antigen R (HuR) and chemokines are important molecules associated with mRNA stability and cell-cell interaction in cancer biology. Here, HuR knockdown inhibited bone metastasis and osteolysis of metastatic breast cancer cells in mice and HuR expression promoted the metastatic ability of cancer cells via CCL20 and GM-CSF. In contrast with the findings for GM-CSF, ELAVL1 and CCL20 expressions were markedly increased in breast tumor tissues and ELAVL1 expression showed a strong positive correlation with CCL20 expre

The role and mechanisms of mesenchymal stem cells in postoperative cognitive dysfunction via immune network regulation.

Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients after surgery. Its pathophysiology is complex. Neuroinflammation, oxidative stress, and immune imbalance are all involved in this process. These changes can affect postoperative recovery and reduce patients' quality of life. As population aging continues to increase, the prevention and treatment of POCD have become important clinical issues. In recent years, mesenchymal stem cells (MSCs) have attracted attention in neurological diseases because of their immunomodulatory and tissue healing abili

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… Regulatory effects of MSCs on neutrophils Surgical stress or injury activates neutrophils, leading to the release of neutrophil extracellular traps (NETs), which are primarily composed of DNA and granular protein complexes [ 83 ]. … Human Amniotic Membrane Mesenchymal Stem Cells inhibit Neutrophil Extracellular Traps through TSG-6 [J]. Sci Rep. 2017;7(1):12426. 10.1038/s41598-017-10962-2 PMC5622031 28963485 84. …

Comprehensive Review of Methodology to Detect Reactive Oxygen Species (ROS) in Mammalian Species and Establish Its Relationship with Antioxidants and Cancer.

Evidence suggests that reactive oxygen species (ROS) mediate tissue homeostasis, cellular signaling, differentiation, and survival. ROS and antioxidants exert both beneficial and harmful effects on cancer. ROS at different concentrations exhibit different functions. This creates necessity to understand the relation between ROS, antioxidants, and cancer, and methods for detection of ROS. This review highlights various sources and types of ROS, their tumorigenic and tumor prevention effects; types of antioxidants, their tumorigenic and tumor prevention effects; and abnormal ROS detoxification in

Emerging advances in drug delivery systems (DDSs) for optimizing cancer complications.

The management and treatment of tumor complications pose continuous challenges due to the inherent complexity. However, the advent of drug delivery systems (DDSs) brings promising opportunities to address the tumor complications using innovative technological approaches. This review focuses on common oncological complications, including cancer thrombosis, malignant serous effusion, tumor-associated infections, cancer pain, and treatment-related complications. Emphasis was placed on the application and potential of DDSs in mitigating and treating these tumor complications, and we delved into th

Exosomes play a role in multiple myeloma bone disease and tumor development by targeting osteoclasts and osteoblasts.

Progression of multiple myeloma (MM) is largely dependent on the bone marrow (BM) microenvironment wherein communication through different factors including extracellular vesicles takes place. This cross-talk not only leads to drug resistance but also to the development of osteolysis. Targeting vesicle secretion could therefore simultaneously ameliorate drug response and bone disease. In this paper, we examined the effects of MM exosomes on different aspects of osteolysis using the 5TGM1 murine model. We found that 5TGM1 sEVs, or 'exosomes', not only enhanced osteoclast activity, they also blo

Mesenchymal stem cells in the treatment of osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) has recently associated to the increase in antiresorptive and anti-angiogenic drugs prescriptions in the treatment of oncologic and osteoporotic patients. The physiopathogenesis of MRONJ remains unclear and available treatments are unsatisfactory. Newer pharmacological treatments have shown good results, but are not curative and could have major side effects. At the same time as pharmacological treatments, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality for tissue regeneration and repair. MSCs are multi-potentia

16th International Congress on Antiphospholipid Antibodies Task Force Report on Antiphospholipid Syndrome Treatment Trends.

Antiphospholipid syndrome (APS), an acquired autoimmune thrombophilia, is characterised by thrombosis and/or pregnancy morbidity in association with persistent antiphospholipid antibodies. The 16th International Congress on Antiphospholipid Antibodies Task Force on APS Treatment Trends reviewed the current status with regard to existing and novel treatment trends for APS, which is the focus of this Task Force report. The report addresses current treatments and developments since the last report, on the use of direct oral anticoagulants in patients with APS, antiplatelet agents, adjunctive ther

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… Increasing evidence suggests that aPL-related thrombosis is mediated by neutrophil activation, leading to release of extracellular chromatin-based structures, termed neutrophil extracellular traps (NETs) through a process known as NETosis. 13 The key cellular and humoral molecular interactions of aPL … In vivo role of neutrophil extracellular traps in antiphospholipid antibody-mediated venous thrombosis: in vivo role of NETs in APS . Arthritis Rheumatol 2017 ; 69 : 655 – 667 . 27696751 10.1002/art.39938 PMC5329054 14 Bordin G Boldorini R Meroni PL. …

The Role of Platelet Dysfunctions in the Pathogenesis of the Hemostatic-Coagulant System Imbalances.

Platelet dysfunction plays a critical role in the pathogenesis of various disorders affecting the hemostatic-coagulant system. This review aims to explore the mechanisms by which platelet dysfunctions contribute to the disruption of hemostasis, leading to an increased risk of both thrombosis and bleeding. Platelets, traditionally known for their role in clot formation, can exhibit altered functionality under pathological conditions such as cardiovascular diseases, metabolic disorders, and autoimmune diseases, impacting their interaction with coagulation factors and vascular endothelium. The re

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… This results in the formation of neutrophil extracellular traps (NETs), which ensnare circulating microbes and limit their spread. Studies show that activated platelets, when adhering to neutrophils, can initiate NET formation, or NETosis. … Intravascular neutrophil extracellular traps capture bacteria from the bloodstream during sepsis Cell Host Microbe 2012 12 324 333 10.1016/j.chom.2012.06.011 22980329 50. Ma A.C. Kubes P. Platelets, neutrophils, and neutrophil extracellular traps (NETs) in sepsis J. Thromb. …

Cancer-Associated Thrombosis: A New Light on an Old Story.

Cancer-associated thrombosis (CAT) is a rising and significant phenomenon, becoming the second leading cause of death in cancer patients. Pathophysiology of CAT differs from thrombosis in the non-cancer population. There are additional risk factors for thrombosis specific to cancer including cancer type, histology, and treatment, such as chemotherapy. Recently developed scoring systems use these risk factors to stratify the degree of risk and encourage thromboprophylaxis in intermediate- to high-risk patients. Anticoagulation is safely used for prophylaxis and treatment of CAT. Both of these h

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… Neutrophil Extracellular Traps Neutrophil extracellular traps (NETs) are web-like structures released by neutrophils and composed of DNA fibres coated with histones and proteases [ 31 ]. Though they are a physiological response to infection, recent studies have identified their role in CAT. … Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice. Blood. 2017;129:1357–1367. doi: 10.1182/blood-2016-09-741298. 35. Demers M., Wagner D.D. Neutrophil extracellular traps. Oncoimmunology. 2013;2:e22946. doi: 10.4161/onci.22946. 36. …

The PI3K inhibitor buparlisib suppresses osteoclast formation and tumour cell growth in bone metastasis of lung cancer, as evidenced by multimodality molecular imaging.

Non‑small cell lung cancer (NSCLC) metastasis commonly occurs in bone, which often results in pathological fractures. Sustained phosphoinositide‑3‑kinase (PI3K) signalling promotes the growth of PI3K‑dependent NSCLC and elevates osteoclastogenic potential. The present study investigated the effects of a PI3K inhibitor on NSCLC growth in bone and osteoclast formation, and aimed to determine whether it could control symptoms associated with bone metastasis. A bone metastasis xenograft model was established by implanting NCI‑H460‑luc2 lung cancer cells, which contain a phosphatidylinositol‑​4,5‑b

Exosomes: A new option for osteoporosis treatment.

Osteoporosis is a systemic bone disease characterized by reduced bone mass and destruction of bone microarchitecture, leading to increased bone fragility and susceptibility to fracture. However, the pathogenesis and molecular mechanisms of this disease remain unclear. Extracellular vesicles, structures originating from the plasma membrane and ranging from 30 nm to 5 µm in diameter, play an important role in intercellular communication in the bone microenvironment. Exosomes are extracellular vesicles that deliver cargo molecules, including endogenous proteins, lipids and nucleic acids. These ca

The Complosome: An Emerging Intracellular Complement Network in Cancer Development and Therapy.

The complement system is traditionally recognized as a major effector of innate immunity, essential for pathogen clearance, inflammation and the maintenance of tissue homeostasis. In recent years, however, its role in cancer has been substantially redefined. Beyond its canonical extracellular activity, complement has emerged as a multifaceted regulator of tumor biology, acting not only within the tumor microenvironment but also intracellularly through the recently described intracellular complement system (complosome). While extracellular complement primarily shapes immune responses and the tu

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… This facilitated neutrophil recruitment, promotes the formation of neutrophil extracellular traps (NETs), and thereby traps circulating tumor cells, enabling metastatic colonization [ 88 ]. However, C3 can also exhibit tumor-suppressive effects. … Complement C5a Induces the Formation of Neutrophil Extracellular Traps by Myeloid-Derived Suppressor Cells to Promote Metastasis. Cancer Lett. 2022;529:70–84. doi: 10.1016/j.canlet.2021.12.027. 101. Valdivia A., Isac A.M., Cardenas H., Zhao G., Zhang Y., Huang H., Wei J. …

Prognostic utility of macrophage polarization (CD68/CD163 ratio) in Egyptian JAK2 positive myeloproliferative neoplasm patients: a single center study.

BackgroundMyeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders with variable clinical outcomes influenced by the bone marrow microenvironment. Tumor-associated macrophages (TAMs), particularly the M1 (CD68⁺) and M2 (CD163⁺) subtypes, play critical roles in inflammation, fibrosis, and immune modulation. This study evaluates CD68- and CD163-positive macrophage frequencies across MPN subtypes and their clinical/prognostic significance.MethodsIn this retrospective cohort study, 121 patients with histopathologically confirmed BCR::ABL1-negative, JAK2V617F-positive MPNs were assess

Endothelial dysfunction and hemostatic imbalance in CAR T-cell-associated toxicities: pathophysiological insights and the role of circulating biomarkers.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed or refractory hematologic malignancies. While its clinical efficacy is well established, CAR T-cell therapy is frequently associated with severe immune-mediated toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), coagulopathy, and hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS). Increasing evidence suggests that endothelial dysfunction, hemostatic imbalance, and complement activation are key contributors to the pathogenesis of

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… Neutrophil extracellular traps NETs are web-like structures composed of DNA, histones, and granule proteins released by neutrophils in response to inflammatory stimuli. … Abstract B048: Neutrophil extracellular traps-targeting DNase I enhances the therapeutic efficacy of CAR-T cell adoptive immunotherapy in a syngeneic murine metastasis model . …

Immune Dysfunction in Uremia 2020.

Cardiovascular disease and infections are major causes for the high incidence of morbidity and mortality of patients with chronic kidney disease. Both complications are directly or indirectly associated with disturbed functions or altered apoptotic rates of polymorphonuclear leukocytes, monocytes, lymphocytes, and dendritic cells. Normal responses of immune cells can be reduced, leading to infectious diseases or pre-activated/primed, giving rise to inflammation and subsequently to cardiovascular disease. This review summarizes the impact of kidney dysfunction on the immune system. Renal failur

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… Neutrophil Extracellular Traps Beside microbial uptake and the secretion of antimicrobials, neutrophils release NETs to eliminate invading microbes including bacteria, fungi, and parasites. … How Neutrophil Extracellular Traps Become Visible J. Immunol. Res. 2016 2016 4604713 10.1155/2016/4604713 27294157 PMC4884809 42. Kim J.K. Lee H.W. Joo N. Lee H.S. Song Y.R. Kim H.J. Kim S.G. …

Advances in the Pathogenesis and Treatment of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a genetically predisposed, female-predominant disease, characterized by multiple organ damage, that in its most severe forms can be life-threatening. The pathogenesis of SLE is complex and involves cells of both innate and adaptive immunity. The distinguishing feature of SLE is the production of autoantibodies, with the formation of immune complexes that precipitate at the vascular level, causing organ damage. Although progress in understanding the pathogenesis of SLE has been slower than in other rheumatic diseases, new knowledge has recently led to the d

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… In SLE, LDGs are characterized by an increased ability to form neutrophil extracellular traps (NETs), released during their apoptosis (NETosis) [ 72 ]. … To NET or not to NET:current opinions and state of the science regarding the formation of neutrophil extracellular traps Cell Death Differ. 2019 26 395 408 10.1038/s41418-018-0261-x 30622307 PMC6370810 73. Apel F. Zychlinsky A. Kenny E.F. …

Humanized Bone Model Identifies BMP6 as a Multifunctional Regulator in Myeloma Bone Disease.

Multiple myeloma (MM) is a plasma cell malignancy that disrupts bone homeostasis by suppressing osteogenesis and promoting osteoclast activity. While most therapeutic interventions to date have focused on targeting tumor cells and reducing osteolysis, we investigate whether osteoinductive strategies can restore bone formation and counteract disease progression. Using a human bone marrow-like scaffold model that enables direct in vivo evaluation of tumor-stroma interactions and human bone formation, we demonstrate that MM-derived mesenchymal stromal cells (MSCs) retain osteogenic potential but

Alterations in Salivary Proteome following Single Twenty-Minute Session of Yogic Breathing.

Yogic breathing (YB) has been suggested to reduce stress and blood pressure and increase cognitive processes. However, alterations after YB at the molecular level are not well established. Twenty healthy volunteers were randomized into two groups (N = 10 per group): YB or attention controls (AC). The YB group performed two YB exercises, each for ten minutes, for a total of twenty minutes in a single session. AC group read a text of their choice for 20 minutes. Saliva was collected at baseline and at 5, 10, 15, and 20 minutes. Using Mass Spectrometry (MS), we initially found that 22 proteins we

Suppression Effect of Astaxanthin on Osteoclast Formation In Vitro and Bone Loss In Vivo.

Osteoporosis is characterized by a reduction of the bone mineral density (BMD) and microarchitectural deterioration of the bone, which lead to bone fragility and susceptibility to fracture. Astaxanthin (AST) has a variety of biological activities, such as a protective effect against asthma or neuroinflammation, antioxidant effect, and decrease of the osteoclast number in the right mandibles in the periodontitis model. Although treatment with AST is known to have an effect on inflammation, no studies on the effect of AST exposure on bone loss have been performed. Thus, in the present study, we

Complement C3a promotes the formation of osteoclasts by inhibiting Sirt1 to activate the PI3K/PDK1/SGK3 pathway in patients with multiple myeloma.

BACKGROUND: Myeloma bone disease (MBD) is the most common complication of multiple myeloma (MM). Our previous study showed that the complement C3a activates osteoclasts to participate in the pathogenesis of MBD; however, its mechanism of action is diverse and complex. Studies have shown that the Sirtuin (Sirt) family of proteins (i.e., Sirt1-7) are expressed in human bone and cartilage, and participate in bone metabolic balance. METHODS AND RESULTS: We measured the levels of complement C3a, Sirt1, osteoclast-related genes, and bone disease-related biological indicators using enzyme-linked imm