Microglia are macrophage cells residing in the brain, where they exert a key role in neuronal protection. Through the gut-brain axis, metabolites produced by gut commensal microbes can influence brain functions, including microglial activity. The nuclear factor erythroid 2-related factor 2 (NRF2) is a key regulator of the oxidative stress response in microglia, controlling the expression of cytoprotective genes.
View Article and Find Full Text PDFNeurodegenerative disorders are the main cause of cognitive and physical disabilities, affect millions of people worldwide, and their incidence is on the rise. Emerging evidence pinpoints a disturbance of the communication of the gut-brain axis, and in particular to gut microbial dysbiosis, as one of the contributors to the pathogenesis of these diseases. In fact, dysbiosis has been associated with neuro-inflammatory processes, hyperactivation of the neuronal immune system, impaired cognitive functions, aging, depression, sleeping disorders, and anxiety.
View Article and Find Full Text PDFBetween 15-20% of patients with end stage renal disease (ESRD) do not know the cause of the primary kidney disease and can develop complications after kidney transplantation. We performed a genetic screening in 300 patients with kidney transplantation, or undiagnosed primary renal disease, in order to identify the primary disease cause and discriminate between overlapping phenotypes. We used a custom-made panel for next-generation sequencing (Agilent technology, Santa Clara, CA, USA), including genes associated with Fabry disease, podocytopaties, complement-mediated nephropathies and Alport syndrome-related diseases.
View Article and Find Full Text PDFThe long non-coding RNAs (lncRNA) play an important role in several biological processes, including some renal diseases. Nevertheless, little is known about lncRNA that are expressed in the healthy kidneys and involved in renal cell homeostasis and development, and even less is known about lncRNA involved in the maintenance of human adult renal stem/progenitor cells (ARPCs) that have been shown to be very important for renal homeostasis and repair processes. Through a whole-genome transcriptome screening, we found that the HOTAIR lncRNA is highly expressed in renal progenitors and potentially involved in cell cycle and senescence biological processes.
View Article and Find Full Text PDFBackground: Delayed graft function (DGF) leads to a reduced graft survival. Donors' features have been always considered as key pathogenic factors in this setting. The aim of our study was to evaluate the recipients' characteristics in the development of DGF.
View Article and Find Full Text PDFUrethral stenosis is a pathological condition that consists in the narrowing of the urethral lumen because of the formation of scar tissue. Unfortunately, none of the current surgical approaches represent an optimal solution because of the high stricture recurrence rate. In this context, we preliminarily explored the potential of an insoluble type-I collagen from horse tendon as scaffolding material for the development of innovative devices for the regeneration of injured urethral tracts.
View Article and Find Full Text PDFMonoclonal gammopathy of undetermined significance (MGUS) represents the pre-clinical stage of Multiple Myeloma (MM) with the 5% of MGUS progresses to MM. Although the progression from MGUS to MM has not been completely characterized, it is possible to monitor the DNA modifications of patients diagnosed with MGUS to detect early specific genomic abnormalities, including copy number variations (CNV). The CNVs of chromosome 1q and chromosome 13q are associated with a worse prognosis in MM.
View Article and Find Full Text PDFDiabetic nephropathy (DN) is the most frequent cause of end-stage renal disease. Tubulointerstitial accumulation of lysine 63 (K63)-ubiquitinated (Ub) proteins is involved in the progression of DN fibrosis and correlates with urinary miR-27b-3p downregulation. We explored the renoprotective effect of an inhibitor of K63-Ub (NSC697923), alone or in combination with the ACE-inhibitor ramipril, in vitro and in vivo.
View Article and Find Full Text PDFAdult Renal Stem/Progenitor Cells (ARPCs) have been recently identified in the human kidney and several studies show their active role in kidney repair processes during acute or chronic injury. However, little is known about their immunomodulatory properties and their capacity to regulate specific T cell subpopulations. We co-cultured ARPCs activated by triggering Toll-Like Receptor 2 (TLR2) with human peripheral blood mononuclear cells for 5 days and 15 days and studied their immunomodulatory capacity on T cell subpopulations.
View Article and Find Full Text PDFBackground: Immunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulonephritis. The role of the microbiota and mucosal immunity in the pathogenesis of IgAN remains a key element. To date, the hypothetical relationship between commensal bacteria, elevated tumour necrosis factor (TNF) superfamily member 13 [also known as B-cell activating factor (BAFF)] levels, perturbed homoeostasis of intestinal-activated B cells and intestinal IgA class switch has not been clearly shown in IgAN patients.
View Article and Find Full Text PDFInt J Mol Sci
September 2020
Chronic antibody-mediated rejection (CAMR) is the major cause of kidney transplant failure. The molecular mechanisms underlying this event are still poorly defined and this lack of knowledge deeply influences the potential therapeutic strategies. The aim of our study was to analyze the phosphoproteome of peripheral blood mononuclear cells (PBMCs), to identify cellular signaling networks differentially activated in CAMR.
View Article and Find Full Text PDFIgA Nephropathy (IgAN) is a primary glomerulonephritis problem worldwide that develops mainly in the 2nd and 3rd decade of life and reaches end-stage kidney disease after 20 years from the biopsy-proven diagnosis, implying a great socio-economic burden. IgAN may occur in a sporadic or familial form. Studies on familial IgAN have shown that 66% of asymptomatic relatives carry immunological defects such as high IgA serum levels, abnormal spontaneous in vitro production of IgA from peripheral blood mononuclear cells (PBMCs), high serum levels of aberrantly glycosylated IgA1, and an altered PBMC cytokine production profile.
View Article and Find Full Text PDFDiabetic Nephropathy (DN) is a chronic complication of diabetes and the primary cause of end stage renal disease. Differential diagnosis for DN requires invasive histological investigation, thus there is need for non-invasive biomarkers to discriminate among different histological lesions in diabetic patients. With the aim to identify a pattern of differentially expressed miRNAs in kidney biopsies of DN patients, we assayed miRNA expression in kidney biopsies from DN patients, diabetic patients with membranous nephropathy and patients with normal histology.
View Article and Find Full Text PDFEndothelial dysfunction is a hallmark of LPS-induced acute kidney injury (AKI). Endothelial cells (ECs) acquired a fibroblast-like phenotype and contributed to myofibroblast generation through the endothelial-to-mesenchymal transition (EndMT) process. Of note, human adult renal stem/progenitor cells (ARPCs) enhance the tubular regenerative mechanism during AKI but little is known about their effects on ECs.
View Article and Find Full Text PDFToll-like receptors (TLRs) represent one of the bridges that regulate the cross-talk between the innate and adaptive immune systems. TLRs interact with molecules shared and preserved by the pathogens of origin but also with endogenous molecules (damage/danger-associated molecular patterns (DAMPs)) that derive from injured tissues. This is probably why TLRs have been found to be expressed on several kinds of stem/progenitor cells (SCs).
View Article and Find Full Text PDFAfter light absorption, melanin converts very rapidly the energy gained into heat. The time scale of this process ranges from tens of femtoseconds to a few nanoseconds. Femtosecond transient absorption allows for exploration of such photo-induced carrier dynamics to observe the de-excitation pathways of the biological complex.
View Article and Find Full Text PDFIn 1975, Holliday and Pugh as well as Riggs independently hypothesized that DNA methylation in eukaryotes could act as a hereditary regulation mechanism that influences gene expression and cell differentiation. Interest in the study of epigenetic processes has been inspired by their reversibility as well as their potentially preventable or treatable consequences. Recently, we have begun to understand that the features of DNA methylation are not the same for all cells.
View Article and Find Full Text PDFAberrant microRNA (miR) expression has an important role in tumour progression, but its involvement in bone marrow fibroblasts of multiple myeloma patients remains undefined. We demonstrate that a specific miR profile in bone marrow fibroblasts parallels the transition from monoclonal gammopathy of undetermined significance (MGUS) to myeloma. Overexpression of miR-27b-3p and miR-214-3p triggers proliferation and apoptosis resistance in myeloma fibroblasts via the FBXW7 and PTEN/AKT/GSK3 pathways, respectively.
View Article and Find Full Text PDFJ Mol Med (Berl)
July 2018
Unlabelled: Diabetic nephropathy patients (DN) are characterized by increased lysine63 ubiquitination (Lys63-Ub) at the tubular level. Autophagy is deregulated under diabetic conditions, even though the molecular mechanisms and the consequences of this alteration need to be elucidated. The aim of this study was to investigate the link between Lys63-Ub and autophagy in DN and the involvement of these two processes in tubular cell fate.
View Article and Find Full Text PDFCollagen and matrix metalloproteinases (MMP) play a pivotal role in the pathophysiology of Pelvic Organ Prolapse (POP) as a switch between type I and III collagen together with a simultaneous activation of MMPs have been observed in the vaginal wall. The aim of this study was to evaluate the Advanced Glycation End (AGE) products, ERK1/2 and transforming growth factor (TGF)-β/Smad pathway expression in muscularis propria in women with POP compared with control patients. We examined 20 patients with POP and 10 control patients treated for uterine fibromatosis.
View Article and Find Full Text PDFThe reinforcement of the defense mechanism of fish, through the administration of immunostimulants, is considered as a promising alternative to vaccines. Natural immunostimulants such as polyphenols, flavanoids, pigments and essential oils can modulate the innate immune response. In lower vertebrates, melano-macrophage centres, i.
View Article and Find Full Text PDFFish Shellfish Immunol
January 2015
Infectious diseases and breeding conditions can influence fish health status. Furthermore it is well known that human and animal health are strongly correlated. In lower vertebrates melano-macrophage centres, clusters of pigment-containing cells forming the extracutaneous pigment system, are widespread in the stroma of the haemopoietic tissue, mainly in kidney and spleen.
View Article and Find Full Text PDFMelanogenesis is mostly studied in melanocytes and melanoma cells, but much less is known about other pigment cell systems. Liver, spleen, kidney, and other organs of lower vertebrates harbour a visceral pigment cell system with an embryonic origin that differs from that of melanocytes. In teleosts, melanin-containing cells occur in the reticulo-endothelial system and are mainly in the kidney and spleen.
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