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Immunomodulatory Nanosystems.

Immunotherapy has emerged as an effective strategy for the prevention and treatment of a variety of diseases, including cancer, infectious diseases, inflammatory diseases, and autoimmune diseases. Immunomodulatory nanosystems can readily improve the therapeutic effects and simultaneously overcome many obstacles facing the treatment method, such as inadequate immune stimulation, off-target side effects, and bioactivity loss of immune agents during circulation. In recent years, researchers have continuously developed nanomaterials with new structures, properties, and functions. This Review provi

Emerging Modes of Treatment of IgA Nephropathy.

IgA nephropathy is the most common primary glomerulonephritis with potentially serious outcome leading to end stage renal disease in 30 to 50% of patients within 20 to 30 years. Renal biopsy, which might be associated with risks of complications (bleeding and others), still remains the only reliable diagnostic tool for IgA nephropathy. Therefore, the search for non-invasive diagnostic and prognostic markers for detection of subclinical types of IgA nephropathy, evaluation of disease activity, and assessment of treatment effectiveness, is of utmost importance. In this review, we summarize treat

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… The key component of the lectin pathway demonstrates Mannose-binding lectin associated serine protease 2 (MASP-2), which elevates the production of C3 convertase and leads to further inflammatory consequences. …

Immunosuppression in Glomerular Diseases: Implications for SARS-CoV-2 Vaccines and COVID-19.

BackgroundGlomerular diseases (GD) are chronic conditions that often involve immune dysfunction and require immunosuppressive therapy (IST) to control underlying pathogenesis. Unfortunately, such diseases appear to heighten risks of severe outcomes in COVID-19 and predispose to other infections that may be life-threatening. Thus, averting preventable infections is imperative in GD patients.SummaryThe advent of vaccines demonstrated to be safe and efficacious against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has favorably impacted the COVID-19 pandemic epidemiology. However,

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… These include narsoplimab − a monoclonal Ab inhibitor of the mannose-binding lectin serine protease (MASP2) involved in alternative C′ pathway activation − in clinical trials for treatment of IgA nephropathy [ 82 ]. …

Subject index

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… hemodialysis long-term, safety/efficacy of citrate anticoagulation for, 557–564 stroke incidence in, 1058–1066 Malnutrition hemodialysis complications, nephrology core curriculum, 1123–1124 management guidelines for dialysis patients, S3:102–106 rHuEPO response in long-term hemodialysis and, 1073–1083 Mannose-binding … lectin in host defense mechanisms, renal sarcoidosis and, 580–587 mesangial deposits in Henoch-Schönlein purpura nephritis, 295–302 Mannose-binding lectin-associated serine protease-1, in Henoch-Schönlein purpura nephritis, 295–302 Mast cell chymase, in ischemic kidney of severe unilateral renovascular …

Host impairments in patients with neoplastic diseases.

Healthy individuals possess an immune system comprising physical barriers, innate and acquired immunity as well as the indigenous microflora that populate the body surfaces. The immune system maintains constant vigilance over the body at the cellular level as well as at the interface between the host integument and the resident microflora. However, neoplastic diseases and their treatment often lead to impaired immunity resulting in an increased risk of infections due to viruses, bacteria, fungi, and protozoa. This chapter explores the various aspects of host impairment focusing on the componen

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… Several studies have shown SNPs in complement components (mannose-binding lectin), NK receptors, and PRRs resulting in increased risk of bacterial and fungal infections [ 108 – 110 ]. …

Targeting B cells in IgA nephropathy: from pathogenic insight to therapeutic horizon.

Immunoglobulin A nephropathy (IgAN) remains the most common primary glomerulonephritis globally. Advances in mucosal immunology have illuminated the role of dysregulated B cell activity, galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1-specific antibody formation in driving disease pathogenesis. Therapeutic targeting of the mucosal immune system and, more specifically, B cell survival and differentiation pathways have entered late-stage development, offering a mechanistically guided approach to disease modification. Targeting of the gut-associated lymphoid tissue of the terminal ileum, B cell ac

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… Histologic deposition of C3, C4d and mannose-binding lectin predicts faster progression and worse outcomes. …

Dendritic cell biology and its role in tumor immunotherapy.

As crucial antigen presenting cells, dendritic cells (DCs) play a vital role in tumor immunotherapy. Taking into account the many recent advances in DC biology, we discuss how DCs (1) recognize pathogenic antigens with pattern recognition receptors through specific phagocytosis and through non-specific micropinocytosis, (2) process antigens into small peptides with proper sizes and sequences, and (3) present MHC-peptides to CD4+ and CD8+ T cells to initiate immune responses against invading microbes and aberrant host cells. During anti-tumor immune responses, DC-derived exosomes were discovere

Nanobodies for Medical Imaging: About Ready for Prime Time?

Recent advances in medical treatments have been revolutionary in shaping the management and treatment landscape of patients, notably cancer patients. Over the last decade, patients with diverse forms of locally advanced or metastatic cancer, such as melanoma, lung cancers, and many blood-borne malignancies, have seen their life expectancies increasing significantly. Notwithstanding these encouraging results, the present-day struggle with these treatments concerns patients who remain largely unresponsive, as well as those who experience severely toxic side effects. Gaining deeper insight into t

Blood hypercoagulability and thrombosis mechanisms in cancer patients -A brief review.

Patients with malignant tumors are prone to present hypercoagulability of blood and form thrombosis, and its pathogenesis is complex involving various factors from clinical and histopathological to genetic influences. Current studies on the potential mechanism of blood hypercoagulability in patients with malignant tumors focus on the following aspects but are not limited: (1) tumor cells release coagulant-promoting substances, (2) tumor cells interact with the fibrinolytic system, (3) tumor cell-mediated platelet activation, (4) tumor-associated complement activation, and (5) genetic factors a

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… Fig. 5 Cancer-associated complement activation Cancer-associated complement is a kind of innate immune molecule, which participates in immune response and inflammation, inhibits microbial infection and the clearance of apoptotic cells through classical pathway, bypass pathway, and mannose-binding lectin …

Engaging natural killer cells for cancer therapy via NKG2D, CD16A and other receptors.

The field of immuno-oncology has revolutionized cancer patient care and improved survival and quality of life for patients. Much of the focus in the field has been on exploiting the power of the adaptive immune response through therapeutic targeting of T cells. While these approaches have markedly advanced the field, some challenges remain, and the clinical benefit of T cell therapies does not extend to all patients or tumor indications. Alternative strategies, such as engaging the innate immune system, have become an intense area of focus in the field. In particular, the engagement of natural

Nanobodies Enhancing Cancer Visualization, Diagnosis and Therapeutics.

Worldwide, cancer is a serious health concern due to the increasing rates of incidence and mortality. Conventional cancer imaging, diagnosis and treatment practices continue to substantially contribute to the fight against cancer. However, these practices do have some risks, adverse effects and limitations, which can affect patient outcomes. Although antibodies have been developed, successfully used and proven beneficial in various oncology practices, the use of antibodies also comes with certain challenges and limitations (large in size, poor tumor penetration, high immunogenicity and a long

Targeting Selectins and Their Ligands in Cancer.

Aberrant glycosylation is a hallmark of cancer cells with increased evidence pointing to a role in tumor progression. In particular, aberrant sialylation of glycoproteins and glycolipids has been linked to increased immune cell evasion, drug evasion, drug resistance, tumor invasiveness, and vascular dissemination, leading to metastases. Hypersialylation of cancer cells is largely the result of overexpression of sialyltransferases (STs). Differentially, humans express twenty different STs in a tissue-specific manner, each of which catalyzes the attachment of sialic acids via different glycosidi

Biologics and Non-Biologics Immunosuppressive Treatments for IgA Nephropathy in Both Adults and Children.

Immunoglobulin A nephropathy represents the most prevalent cause of glomerulonephritis worldwide and may lead to renal failure in a relevant number of cases in both paediatric and adult subjects. Although their pathogenesis is still largely unclear, evidence of immune abnormalities provides the background for the use of immunosuppressive drugs, such as corticosteroids, calcineurin inhibitors, and antiproliferative and alkylating agents. Unfortunately, these treatments fail to achieve a sustained remission in a significant percentage of affected patients and are burdened by significant toxiciti

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… Previous studies have suggested that both the alternative (AP) and the mannose-binding lectin (MBL) pathways may be involved [ 64 , 65 , 66 ]. Therefore, targeting the complement pathway may represent an attractive therapeutic strategy. …

New insights into CAR T-cell hematological toxicities: manifestations, mechanisms, and effective management strategies.

Chimeric antigen receptor (CAR) T-cell therapy represents a highly efficacious treatment modality demonstrated to enhance outcomes in patients afflicted with malignancies, particularly those enduring relapsed or refractory hematological malignancies. However, the escalating adoption of CAR T-cell therapy has unveiled several life-threatening toxicities, notably cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infections, and hematological toxicities (HTs), thereby hindering the broad implementation of CAR T-cell therapy. HTs encompass a spectrum

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… These proteins include complement3 (C3), C4a, C4b, mannose-binding lectin 2 (MBL2), C8A, C8b, CRP, alpha-2-macroglobulin (A2M), clusterin (CLU), and fibrinogen alpha chain (FGA) [ 131 ]. … T-cell therapy-associated hemophagocytic lymphohistiocytosis Immune effector cell-associated HLH-like syndrome Nuclear factor kappa B IL-18 binding protein Macrophage activation syndrome National Comprehensive Cancer Network CAR-T-associated coagulopathy Disseminated intravascular coagulation Mannose-binding …

Metagenomic Next-Generation Sequencing Reveals Individual Composition and Dynamics of Anelloviruses during Autologous Stem Cell Transplant Recipient Management.

Over recent years, there has been increasing interest in the use of the anelloviruses, the major component of the human virome, for the prediction of post-transplant complications such as severe infections. Due to an important diversity, the comprehensive characterization of this viral family over time has been poorly studied. To overcome this challenge, we used a metagenomic next-generation sequencing (mNGS) approach with the aim of determining the individual anellovirus profile of autologous stem cell transplant (ASCT) patients. We conducted a prospective pilot study on a homogeneous patient

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… Mannose-binding lectin gene variants and infections in patients receiving autologous stem cell transplantation BMC Immunol. 2014 15 17 10.1186/1471-2172-15-17 24886325 PMC4013431 2. De Vlaminck I. Khush K.K. Strehl C. Kohli B. Luikart H. Neff N.F. Okamoto J. Snyder T.M. Cornfield D.N. Nicolls M.R. …

Keyword Index for Volume 88

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Biocompatibility in hemodialysis: artificial membrane and human blood interactions.

Hemodialysis, a cornerstone therapy for chronic kidney disease, represented a crucial advance in the evolution of artificial organs. While its success is largely due to its efficiency in removing uremic toxins, an equally important challenge is to uphold the primum non nocere principle by minimizing the harmful effects of membrane-blood interactions. This review examines the complex mechanisms and key interactions underlying membrane biocompatibility, including complement activation, inflammation, and coagulation disturbances, paving the way for their clinical implications. We also summarize r

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… Lectin pathway The primary event in complement activation through the lectin pathway is the binding of ficolin-2 and mannose-binding lectin (MBL) to the membrane. …

Chronic granulomatous disease secondary to a rare compound heterozygote mutation in an adolescent cured by hematopoietic stem cell transplantation: a case report.

BackgroundChronic granulomatous disease (CGD) is a rare inherited primary immunodeficiency characterized by recurrent infections and aberrant inflammation due to defects in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex.Case presentationWe report a case of recurrent pneumonia and significantly elevated IgE levels in an adolescent. Metagenomic next-generation (mNGS) sequencing contributed to the identification of Burkholderia multivorans in bronchoalveolar lavage fluid and the initiation of appropriate treatment. Whole exome sequencing (WES) revealed two point mutations

Shaping the Innate Immune Response by Dietary Glucans: Any Role in the Control of Cancer?

β-glucans represent a heterogeneous group of naturally occurring and biologically active polysaccharides found in many kinds of edible mushrooms, baker's yeast, cereals and seaweeds, whose health-promoting effects have been known since ancient times. These compounds can be taken orally as food supplements or as part of daily diets, and are safe to use, nonimmunogenic and well tolerated. A main feature of β-glucans is their capacity to function as biological response modifiers, exerting regulatory effects on inflammation and shaping the effector functions of different innate and adaptive immuni

Clusterin and pentraxin 3 are markers of severity during febrile neutropenia in adults with haematological malignancies receiving intensive chemotherapy.

The identification of predictive biomarkers of severity can improve patient management because febrile neutropenia can be associated with significant morbidity and mortality. We prospectively studied pentraxin 3 (PTX3), a soluble innate immunity receptor, and clusterin (CLU), a chaperone protein that binds extracellular histones during sepsis, in patients experiencing febrile neutropenia after intensive treatment for haematological malignancies. One hundred and forty-three adult patients were included, with 158 episodes of neutropenia analysed. Febrile neutropenia was observed in 119 patients