Diagnostic and Therapeutic Aspects of Monoclonal Gammopathies of Renal Significance (MGRS): An Update.

Monoclonal gammopathy of renal significance (MGRS) refers to a group of renal disorders caused by a monoclonal immunoglobulin (MIg), secreted by a non-malignant B-cell clone. Unlike overt multiple myeloma or B-cell proliferation, MGRS does not meet those diagnostic criteria. However, it is associated with significant morbidity, due to severe renal, and sometimes systemic, lesions induced by the MIg.

Circulating RKIP and pRKIP in Early-Stage Lung Cancer: Results from a Pilot Study.

Lung cancer (LC) is the leading cause of cancer-related deaths. Although low-dose computed tomography (LD-CT) reduces mortality, its clinical use is limited by cost, radiation, and false positives. Therefore, there is an urgent need for non-invasive and cost-effective biomarkers.

mTOR and SGLT-2 Inhibitors: Their Synergistic Effect on Age-Related Processes.

The aging process contributes significantly to the onset of chronic diseases, which are the primary causes of global mortality, morbidity, and healthcare costs. Numerous studies have shown that the removal of senescent cells from tissues extends lifespan and reduces the occurrence of age-related diseases. Consequently, there is growing momentum in the development of drugs targeting these cells.

The Onset of Antinuclear Antibodies (ANAs) as a Potential Risk Factor for Mortality and Morbidity in COVID-19 Patients: A Single-Center Retrospective Study.

The immune system's amplified response to SARS-CoV-2 may lead to the production of autoantibodies, but their specific impact on disease severity and outcome remains unclear. This study aims to assess if hospitalized COVID-19 patients face a worse prognosis based on ANA presence, even without autoimmune diseases. We performed a retrospective, single-center, observational cohort study, enrolling 638 COVID-19 patients hospitalized from April 2020 to March 2021 at Hospital "Policlinico Riuniti" of Foggia (Italy).

Dendritic Cells: A Bridge between Tolerance Induction and Cancer Development in Transplantation Setting.

Dendritic cells (DCs) are a heterogeneous group of antigen-presenting cells crucial for fostering allograft tolerance while simultaneously supporting host defense against infections and cancer. Within the tumor microenvironment, DCs can either mount an immune response against cancer cells or foster immunotolerance, presenting a dual role. In immunocompromised individuals, posttransplant malignancies pose a significant health concern, with DCs serving as vital players in immune responses against cancer cells.

PMMA dialyzers modulate both humoral and cell-mediate immune response to anti-COVID-19 vaccine (BNT162b2) in a cohort of chronic hemodialyzed patients.

Patients on hemodialysis (HD) have a high risk of death from COVID-19. We evaluated the humoral and cell-mediated immune response to BNT162b2 (Pfizer-BioNTech) vaccine in HD patients, comparing HD with Poly-methyl-methacrylate (PMMA) and HD with Polysulphone (PS). Samples were collected before vaccination (T0) and 14-days after the 2ndvaccine (T2) in a TG (TG, n = 16-Foggia) and in a VG (CG, n = 36-Novara).

Kinetics of Different Blood Biomarkers during Polymyxin-B Extracorporeal Hemoperfusion in Abdominal Sepsis.

Introduction: Comparison of the marker kinetics procalcitonin, presepsin, and endotoxin during extracorporeal hemoperfusion with polymyxin-B adsorbing cartridge (PMX-HA) has never been described in abdominal sepsis. We aimed to compare the trend of three biomarkers in septic post-surgical abdominal patients in intensive care unit (ICU) treated with PMX-HA and their prognostic value.

Methods: Ninety abdominal post-surgical patients were enrolled into different groups according to the evidence of postoperative sepsis or not.

Hypoxic State of Cells and Immunosenescence: A Focus on the Role of the HIF Signaling Pathway.

Hypoxia activates hypoxia-related signaling pathways controlled by hypoxia-inducible factors (HIFs). HIFs represent a quick and effective detection system involved in the cellular response to insufficient oxygen concentration. Activation of HIF signaling pathways is involved in improving the oxygen supply, promoting cell survival through anaerobic ATP generation, and adapting energy metabolism to meet cell demands.

MUC1 Expression Affects the Immunoflogosis in Renal Cell Carcinoma Microenvironment through Complement System Activation and Immune Infiltrate Modulation.

Mucin1 (MUC1), a glycoprotein associated with an aggressive cancer phenotype and chemoresistance, is aberrantly overexpressed in a subset of clear cell renal cell carcinoma (ccRCC). Recent studies suggest that MUC1 plays a role in modulating cancer cell metabolism, but its role in regulating immunoflogosis in the tumor microenvironment remains poorly understood. In a previous study, we showed that pentraxin-3 (PTX3) can affect the immunoflogosis in the ccRCC microenvironment by activating the classical pathway of the complement system (C1q) and releasing proangiogenic factors (C3a, C5a).

Unraveling the Link between Interferon-α and Systemic Lupus Erythematosus: From the Molecular Mechanisms to Target Therapies.

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease with a wide range of clinical expressions. The kidney is often affected, usually within 5 years of the onset of SLE, and lupus nephropathy (LN) carries a high risk for increased morbidity. The clinical heterogeneity of the disease is accompanied by complex disturbances affecting the immune system with inflammation and tissue damage due to loss of tolerance to nuclear antigens and the deposition of immune complexes in tissues.

Urinary epidermal growth factor/monocyte chemotactic peptide 1 ratio as non-invasive predictor of Mayo clinic imaging classes in autosomal dominant polycystic kidney disease.

Background: Age- and height-adjusted total kidney volume is currently considered the best prognosticator in patients with autosomal dominant polycystic kidney disease. We tested the ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 for the prediction of the Mayo Clinic Imaging Classes.

Methods: Urinary epidermal growth factor and monocyte chemotactic peptide 1 levels were measured in two independent cohorts (discovery, n = 74 and validation set, n = 177) and healthy controls (n = 59) by immunological assay.

Understanding Mechanisms of RKIP Regulation to Improve the Development of New Diagnostic Tools.

One of the most dangerous aspects of cancer cell biology is their ability to grow, spread and form metastases in the main vital organs. The identification of dysregulated markers that drive intracellular signalling involved in the malignant transformation of neoplastic cells and the understanding of the mechanisms that regulate these processes is undoubtedly a key objective for the development of new and more targeted therapies. RAF-kinase inhibitor protein (RKIP) is an endogenous tumour suppressor protein that affects tumour cell survival, proliferation, and metastasis.

Metabolic Fingerprinting of Fabry Disease: Diagnostic and Prognostic Aspects.

Fabry disease (FD) is an X-linked lysosomal disease due to a deficiency in the activity of the lysosomal-galactosidase A (GalA), a key enzyme in the glycosphingolipid degradation pathway. FD is a complex disease with a poor genotype-phenotype correlation. In the early stages, FD could involve the peripheral nervous system (acroparesthesias and dysautonomia) and the ski (angiokeratoma), but later kidney, heart or central nervous system impairment may significantly decrease life expectancy.

Oxidative Stress and Ischemia/Reperfusion Injury in Kidney Transplantation: Focus on Ferroptosis, Mitophagy and New Antioxidants.

Although there has been technical and pharmacological progress in kidney transplant medicine, some patients may experience acute post-transplant complications. Among the mechanisms involved in these conditions, ischemia/reperfusion (I/R) injury may have a primary pathophysiological role since it is one of the leading causes of delayed graft function (DGF), a slow recovery of the renal function with the need for dialysis (generally during the first week after transplantation). DGF has a significant social and economic impact as it is associated with prolonged hospitalization and the development of severe complications (including acute rejection).

Therapeutic Approach for Recurrent Focal Segmental Glomerulosclerosis in Pediatric Renal Transplant Recipients: A Single-Center Experience.

Introduction: Recurrence of focal segmental glomerulosclerosis (FSGS) after kidney transplantation (KTx) develops in 40% of patients, leading to graft loss in half of cases. Extracorporeal apheretic treatments, combined with immunosuppressive drugs, seem to be the most promising therapies, but at now limited reports are available, mainly in pediatric patients.

Objective: We aimed to assess the efficacy of immunoadsorption (IA) to treat recurrent FSGS in pediatric patients.

mTOR inhibitors improve both humoral and cellular response to SARS-CoV-2 messenger RNA BNT16b2 vaccine in kidney transplant recipients.

Kidney transplant recipients (KTRs) have been considered as patients at higher risk of SARS-CoV-2-related disease severity, thus COVID-19 vaccination was highly recommended. However, possible interferences of different immunosuppression with development of both humoral and T cell-mediated immune response to COVID-19 vaccination have not been determined. Here we evaluated the association between mTOR-inhibitors (mTOR-I) and immune response to mRNA BNT162b2 (Pfizer-BioNTech) vaccine in KTR.

Chronic rhinosinusitis with nasal polyposis (CRSwNP): the correlation between expression of Galectin-10 and Clinical-Cytological Grading (CCG).

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is typically characterized by Type 2 inflammation. Several biomarkers of eosinophilic inflammation, including Galectin-10, also known as Charcot-Leyden crystal protein (CLCP), have been identified to establish eosinophilic infiltration of polyps, a reliable predictor of recurrence. We aimed to evaluate the Galectin-10 expression in nasal polyps of patients with CRSwNP and to assess the correlation of Charcot-Leyden crystals expression to the severity of CRSwNP according to Clinical-Cytological Grading (CCG).

Role of Complement in Regulating Inflammation Processes in Renal and Prostate Cancers.

For decades, the complement system, the central pillar of innate immune response, was recognized as a protective mechanism against cancer cells and the manipulation of complement effector functions in cancer setting offered a great opportunity to improve monoclonal antibody-based cancer immunotherapies. Similarly, cellular senescence, the process of cell cycle arrest that allow DNA and tissue repair has been traditionally thought to be able to suppress tumor progression. However, in recent years, extensive research has identified the complement system and cellular senescence as two main inducers of tumour growth in the context of chronic, persistent inflammation named inflammaging.

Peripheral nervous system manifestations of Shiga toxin-producing E. coli-induced haemolytic uremic syndrome in children.

Background: The Neurological involvement is the most common extra-renal complication of Shiga toxin-producing E. coli-hemolytic uremic syndrome (HUS) or typical HUS. On brain magnetic resonance examination, main neurological signs encompass acute lesions of the basal ganglia and the white matter, which could usually regress after Eculizumab infusion.

CD40 Cross-Linking Induces Migration of Renal Tumor Cell through Nuclear Factor of Activated T Cells (NFAT) Activation.

CD40 crosslinking plays an important role in regulating cell migration, adhesion and proliferation in renal cell carcinoma (RCC). CD40/CD40L interaction on RCC cells activates different intracellular pathways but the molecular mechanisms leading to cell scattering are not yet clearly defined. Aim of our study was to investigate the main intracellular pathways activated by CD40 ligation and their specific involvement in RCC cell migration.

The Pathogenic Role of PI3K/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review.

The PI3K/AKT pathway is one of the most frequently over-activated intracellular pathways in several human cancers. This pathway, acting on different downstream target proteins, contributes to the carcinogenesis, proliferation, invasion, and metastasis of tumour cells. A multi-level impairment, involving mutation and genetic alteration, aberrant regulation of miRNAs sequences, and abnormal phosphorylation of cascade factors, has been found in multiple cancer types.

Pathological diagnosis of Coronavirus-related nephropathy: insight from postmortem studies.

A novel coronavirus pneumonia first occurred in Wuhan, China in early December 2019; the causative agent was identified and named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the World Health Organization (WHO), and the resulting disease termed coronavirus disease 2019 (COVID-19), according to the WHO coronavirus disease situation reports. This condition has spread rapidly all over the world and caused more than 125 million cases globally, with more than 2 million related deaths. Two previous outbreaks due to zoonotic coronaviruses have occurred in the last 20 years, namely the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), causing high morbidity and mortality in human populations upon crossing the species barriers.

Protein-Bound Uremic Toxins and Immunity.

Protein-bound uremic toxins (PBUTs) are bioactive microbiota metabolites originated exclusively from protein fermentation of the bacterial community resident within the gut microbiota, whose composition and function is profoundly different in the chronic kidney disease (CKD) population. PBUTs accumulate in the later stages of CKD because they cannot be efficiently removed by conventional hemodialysis due to their high binding affinity for albumin, worsening their toxic effects, especially at the cardiovascular level. The accumulation of uremic toxins, along with oxidative stress products and pro-inflammatory cytokines, characterizes the uremic status of CKD patients which is increasingly associated to a state of immune dysfunction including both immune activation and immunodepression.

CTL ELISPOT Assay and T Cell Detection.

Enzyme-linked immune absorbent spot (Elispot) is a quantitative method for measuring relevant parameters of T-cell activation. The sensitivity of Elispot allows the detection of low-frequency antigen-specific T-cells that secrete cytokines and effector molecules, such as granzyme B and perforin. Cytotoxic T-cell (CTL) studies have taken advantage with this high-throughput technology by providing insights of quantity and immune kinetics.