Mariella Errede

• MD, PhD
• University of Bari Aldo Moro

The rapidly developing field of renal spheroids and organoids has emerged as a valuable tool for modeling nephrotoxicity, kidney disorders, and kidney development. However, existing studies have relied on intricate and sophisticated differentiation protocols to generate organoids and tubuloids, necessitating the external administration of multiple...

Background: Pathological grade is a morphological parameter of clear cell−renal cell carcinoma (ccRCC) and an independent predictor of cancer-specific survival. The aim of this study was to identify grade-dependent metabolic signatures and corresponding gene and protein expression changes that connect variations in cancer metabolism with nuclear gr...

Background/Objectives: Telomerase reverse transcriptase (TERT) is the catalytic subunit of the telomerase enzyme responsible for telomere length maintenance and is an important cancer hallmark. Our study aimed to clarify the mRNA expression of TERT in peritoneal mesothelioma (PeM), and to explore the relationship between its expression and the clin...

Correction for ‘ Lactiplantibacillus plantarum HEAL9 attenuates cognitive impairment and progression of Alzheimer's disease and related bowel symptoms in SAMP8 mice by modulating microbiota-gut-inflammasome-brain axis’ by C. Di Salvo et al. , Food Funct. , 2024, 15 , 10323–10338, https://doi.org/10.1039/D4FO02075H.

Glioblastoma is one of the most deadly human cancers characterized by high degrees of vascularization, but targeting its vasculature has resulted in very limited success so far. Angiogenesis, the growth of new blood vessels, is highly dynamic during brain development, enters a mostly quiescent state in the adult homeostatic brain, and is reactivate...

HEAL9 alleviates cognitive decline and normalizes colonic motility in the prodromal AD via microbiota-gut-inflammasome-brain axis. HEAL9 can represent a suitable therapeutical option for the treatment of early AD and related intestinal symptoms.

The rapidly developing field of renal spheroids and organoids has emerged as a valuable tool for modeling nephrotoxicity, kidney disorders, and kidney development. However, existing studies have relied on intricate and sophisticated differentiation protocols to generate organoids and tubuloids, necessitating the external administration of multiple...

The rapidly developing field of renal spheroids and organoids has emerged as a valuable tool for modeling nephrotoxicity, kidney disorders, and kidney development. However, existing studies have relied on intricate and sophisticated differentiation protocols to generate organoids and tubuloids, necessitating the external administration of multiple...

Pericyte and their tunnelling nanotubes (P-TNTs) have been described as involved in the early phases of angiogenesis in the human normal developing brain and glioblastoma, being a common feature of combined endothelium/pericyte vessel sprouts. Based on the few data available so far about this ‘alternative’ pericyte-TNT-driven mode of angiogenesis,...

The autophagy process recycles dysfunctional cellular components and protein aggregates by sequestering them in autophagosomes directed to lysosomes for enzymatic degradation. A basal level of autophagy is essential for skeletal muscle maintenance. Increased autophagy occurs in several forms of muscular dystrophy and in the merosin-deficient congen...

Several studies have provided interesting evidence about the role of the bidirectional communication between the gut and brain in the onset and development of several pathologic conditions, including inflammatory bowel diseases (IBDs), neurodegenerative diseases, and related comorbidities. Indeed, patients with IBD can experience neurologic disorde...

Glioblastoma is amongst the deadliest human cancers and is highly vascularized. Angiogenesis is very dynamic during brain development, almost quiescent in the adult brain but reactivated in vascular-dependent CNS pathologies including brain tumors. The onco-fetal axis describes the reactivation of fetal programs in tumors, but its relevance in endo...

Dermatomyositis (DM) and immune-mediated necrotizing myopathy (IMNM) are two rare diseases belonging to the group of idiopathic inflammatory myopathies (IIM). Muscle involvement in DM is characterized by perifascicular atrophy and poor myofiber necrosis, while IMNM is characterized by myofiber necrosis with scarce inflammatory infiltrates. Muscle b...

Background: Vascular co-option is one of the main features of brain tumor progression. It is identified using histopathological analysis, but no antibody-specific markers were found, and no universally accepted histological features were defined. Methods: We employed double immunohistochemical stainings for CD31, P-gp, S100A10, and mitochondria on...

Vascular co-option is a non-angiogenic mechanism whereby tumor growth and progression move on by hijacking the pre-existing and nonmalignant blood vessels and is employed by various tumors to grow and metastasize.The histopathological identification of co-opted blood vessels is complex, and no specific markers were defined, but it is critical to de...

Background In myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), several areas of demyelination are detectable in mouse cerebral cortex, where neuroinflammation events are associated with scarce inflammatory infiltrates and blood–brain barrier (BBB) impairment. In this condition, the administration of...

Successful neuroprotection is only possible with contemporary microvascular protection. The prevention of disease-induced vascular modifications that accelerate brain damage remains largely elusive. An improved understanding of pericyte (PC) signalling could provide important insight into the function of the neurovascular unit (NVU), and into the i...

Mounting evidence has linked the metabolic disease to neurovascular disorders and cognitive decline. Using a murine model of a high‐fat high‐sugar diet mimicking obesity‐induced type 2 diabetes mellitus (T2DM) in humans, we show that pro‐inflammatory mediators and altered immune responses damage the blood‐brain barrier (BBB) structure, triggering a...

Objectives: To study the phenotype of macrophage infiltrates and their role in angiogenesis in different idiopathic inflammatory myopathies (IIMs). Methods: The density and distribution of the subpopulations of macrophages subsets (M1, inducible nitric oxide+, CD11c+; M2, arginase-1+), endomysial capillaries (CD31+, FLK1+), degenerating (C5b-9+)...

To date, pharmacological strategies designed to accelerate bone fracture healing are lacking. We subjected 8-week-old C57BL/6 male mice to closed, transverse, mid-diaphyseal tibial fractures and treated them with intraperitoneal injection of a vehicle or r-irisin (100 µg/kg/weekly) immediately following fracture for 10 days or 28 days. Histological...

Central nervous system diseases involving the parenchymal microvessels are frequently associated with a ‘microvasculopathy’, which includes different levels of neurovascular unit (NVU) dysfunction, including blood–brain barrier alterations. To contribute to the understanding of NVU responses to pathological noxae, we have focused on one of its cell...

The myokine Irisin, produced during physical exercise, has an anabolic effect on bone, both in vitro and in vivo. Very recently, using a controlled in vitro 3D cell model to mimic the bone microenvironment aboard the International Space Station, it has been shown that Irisin treatment in microgravity prevents the down-regulation of the transcriptio...

Irisin is a myokine produced by skeletal muscle during exercise in both mice and humans. We previously showed that irisin treatment ameliorates immobility-induced osteoporosis and muscular atrophy in mice. Data in humans showed a positive association between irisin and bone mineral density (BMD) in athletes and a population of healthy children. How...

Glioblastoma (GBM) is amongst the deadliest human cancers and is characterized by high levels of vascularisation. Angiogenesis is highly dynamic during brain development and almost quiescent in the adult brain, but is reactivated in vascular-dependent CNS pathologies such as brain tumors. Nucleolin (NCL) is a known regulator of cell proliferation a...

Pericytes are integral part of neurovascular unit and play a role in the maintenance of blood-brain barrier integrity, angiogenesis, and cerebral blood flow regulation. Despite their important functional roles, a univocal phenotypic identification is still emerging also for the lack of a “pan-pericyte” marker. In the present study, we describe in d...

Vanadium, a transition series metal released during some industrial activities, induces oxidative stress and lipid peroxidation. Ameliorative effect of a pure compound from the methanolic extract of Moringa oleifera leaves, code-named MIMO2, in 14-day old mice administered with vanadium (as sodium metavanadate 3 mg/kg) for 2 weeks was assessed. Res...

P-Glycoprotein (P-gp) is a 170-kDa transmembrane glycoprotein that works as an efflux pump and confers multidrug resistance (MDR) in normal tissues and tumors, including nervous tissue and brain tumors. In the developing telencephalon, the endothelial expression of P-gp, and the subcellular localization of the transporter at the luminal endothelial...

Background and aim: Patients with Parkinson's disease (PD) are often characterized by functional gastrointestinal disorders. Such disturbances can occur at all stages of PD and precede the typical motor symptoms of the disease by many years. However, the morphological alterations associated with intestinal disturbances in PD are undetermined. This...

Aims: Systemic Lupus Erythematosus (SLE) is a connective tissue disease characterized by a wide range of pleomorphic pictures, including mucocutaneous, renal, musculoskeletal and neurological symptoms. It involves oral tissues, with hyposalivation, tooth decay, gingivitis, angular cheilitis, ulcers and glossitis. Temporomandibular disorders represe...

Previous results showed that intermittently administered irisin improves bone mass in normal mice and prevents the development of disuse-induced osteoporosis and muscular atrophy in hindlimb-suspended mice, a murine model able to mimic the absence of mechanical loading. A recent study showed that irisin increases survival of osteocytes acting throu...

During experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis associated with blood-brain barrier (BBB) disruption, oligodendrocyte precursor cells (OPCs) overexpress proteoglycan nerve/glial antigen 2 (NG2), proliferate, and make contacts with the microvessel wall. To explore whether OPCs may actually be recruited within t...

Cognitive deficit has been identified in one third of patients affected by Duchenne Muscular Dystrophy, primarily attributed to loss of the short Dp71 dystrophin, the major brain dystrophin isoform. In this study, we investigated for the first time the Dp71 and Dp71-associated proteins cellular localization and expression in human neurons obtained...

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription with many important functions, including regulation of cell proliferation, differentiation, survival, angiogenesis, and immune response. MATERIALS AND METHODS:...

Background: Nanotubular structures, denoted tunneling nanotubes (TNTs) have been described in recent times as involved in cell-to-cell communication between distant cells. Nevertheless, TNT-like, long filopodial processes had already been described in the last century as connecting facing, growing microvessels during the process of cerebral cortex...

With the aim of elucidating the relationship between Stat3 expression and tumor vessels abnormalities in the PCNLs, in this study we evaluated Stat3 and pStat3 expression by Real-time PCR and by immunohistochemistry in biopsy sections from PCNSL patients. Correlations of the expression levels with the presence of aberrant vessels were analyzed by c...

Annexin A1 is a potent anti-inflammatory molecule that has been extensively studied in the peripheral immune system, but has not as yet been exploited as a therapeutic target/agent. In the last decade, we have undertaken the study of this molecule in the central nervous system (CNS), focusing particularly on the primary interface between the periph...

In adult CNS, nerve/glial-antigen 2 (NG2) is expressed by oligodendrocyte progenitor cells (OPCs) and is an early marker of pericyte activation in pathological conditions. NG2 could, therefore, play a role in experimental autoimmune encephalomyelitis (EAE), a disease associated with increased blood–brain barrier (BBB) permeability, inflammatory inf...

Background and aims: Intestinal fibrosis is a complication of inflammatory bowel disease (IBD). Although fibrostenosis is a rare event in ulcerative colitis (UC), there is evidence that a fibrotic rearrangement of colon occurs in the later stages. This is a retrospective study aimed at examining the histopathological features of colonic wall in bo...

The blood-brain barrier (BBB) is altered in mdx mouse, an animal model to study Duchenne muscular dystrophy (DMD). Our previous work demonstrated that perivascular glial endfeet control the selective exchanges between blood and neuropil as well as the BBB development and integrity; the alterations of dystrophin and dystrophin-associated protein com...

Nerve/glial-antigen 2 (NG2), expressed by oligodendrocyte progenitor cells (OPC), essential for remyelination, and by pericytes, crucial for blood-brain-barrier (BBB) integrity, could be implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). To understand its possible role, we induced EAE with MOG in NG2KO and wild-type...

Background. Intestinal fibrosis is a common complication of inflammatory bowel diseases, affecting patients with both Crohn’s disease and ulcerative colitis (UC). Of note, the progression of intestinal fibrosis has been recently considered to depend on distinct processes from those involved in inflammation [1]. In this context, angiogen- esis is cu...

The chemokine CCL2 has been considered as a mediator of inflammation in different diseases of the central nervous system, including experimental autoimmune encephalomyelitis (EAE), where the chemokine mediates extravasation of mononuclear leukocytes and loss of microvessel barrier function [1]. Previous studies have demonstrated that cellular sourc...

Experimental autoimmune encephalomyelitis (EAE), an induced autoimmune disease of the central nervous system, simulates the main histopathological and clinical aspects of multiple sclerosis including the impairment of the blood-brain barrier (BBB). In several experimental models of human neurodegenerative diseases, the intravenous (iv) injection of...

Bowel inflammatory fibrosis has been largely investigated, but an integrated assessment of remodelling in inflamed colon is lacking. This study evaluated tissue and cellular changes occurring in colonic wall upon induction of colitis, with a focus on neuromuscular compartment. Colitis was elicited in rats by 2,4-dinitrobenzenesulfonic acid (DNBS)....

This study was conducted on human developing brain by laser confocal and transmission electron microscopy (TEM) to make a detailed analysis of important features of blood-brain barrier (BBB) microvessels and possible control mechanisms of vessel growth and differentiation during cerebral cortex vascularization. The BBB status of cortex microvessels...

Bcl-6 translocation is a genetic alteration that is commonly detected in Primary Central Nervous System Lymphoma. The role of this protein in cerebral tumors is unclear. In this study we investigated Bcl-6 translocation and its transcriptional and translational levels in formalin-fixed, paraffin-embedded cerebral tissue sections from Glioblastoma (...

Intestinal fibrosis in inflammatory bowel disease is a dynamic, multifactorial process, which involve multiple cell types and interconnected events [1]. Angiogenesis is a hallmark of active gut disease and closely related to fibrogenetic processes. Endothelial cells and pericytes of neovessels have been found to be able to differentiate into fibrob...

The CXC chemokine axis formed by CXCL12 and its receptors CXCR4/CXCR7 is involved in CNS development enhancing migration and differentiation of neuronal precursors [1, 2]. According to these data, our recent studies have demonstrated that during human cerebral cortex development, radial glia (RG) cells express high levels of CXCL12, which finds its...

The blood brain barrier (BBB) phenotype of brain endothelial cells (ECs) is the result of the influence and interaction from all the cell components of neurovascular unit (pericytes, astrocytes, oligodendrocytes, microglia, neurons) and basal lamina molecules. Pericyte-associated NG2, a transmembrane chondroitin sulphate proteoglycan, modulates EC...

NG2/CSPG4 is a complex surface-associated proteoglycan (PG) recognized to be a widely expressed membrane component of glioblastoma (WHO grade IV) cells and angiogenic pericytes. To determine the precise expression pattern of NG2/CSPG4 on glioblastoma cells and pericytes, we generated a panel of >60 mouse monoclonal antibodies (mAbs) directed agains...

This study investigates glio-vascular interactions in human fetal brain at midgestation, specifically examining the expression and immunolocalization of the CXCL12/CXCR4/CXCR7 ligand-receptor axis and its possible role in the vascular patterning of the developing brain. At midgestation, the telencephalic vesicles are characterized by well developed...

Chemokine CXCL12 (also called stromal-derived factor-1, SDF-1) together with its cognate receptors CXCR4 and CXCR7 represents a well characterized chemokine system in developing and adult CNS, being involved in axonal pathfinding and neuronal regeneration [1]. Moreover it has been recently demonstrated that a distinct subpopulation of glioma cells...

The pathophysiology of cerebral cortical lesions in multiple sclerosis (MS) is not understood. We investigated cerebral cortex microvessels during immune-mediated demyelination in the MS model chronic murine experimental autoimmune encephalomyelitis (EAE) by immunolocalization of the endothelial cell tight junction (TJ) integral proteins claudin-5...

During human foetal brain vascularization, activated CD31+/CD105+ endothelial cells are characterized by the emission of filopodial processes which also decorate the advancing tip of the vascular sprout. Together with filopodia, both the markers also reveal a number of plasma membrane-derived microvesicles (MVs) which are concentrated around the ti...

Supplementary material 3 . Online Resource 3. A typical, initial vascular sprout shown by horseradish peroxidase injection during chick embryo optic tectum development (Roncali et al., Acta Neuropathol. 70:193–201, 1986 and unpublished observations)

Experimentally induced autoimmune encephalomyelitis (EAE) in mice provides an animal model that shares many features with human demyelinating diseases such as multiple sclerosis (MS). To what extent the cerebral cortex is affected by the process of demyelination and how the corollary response of the oligodendrocyte lineage is explicated are still n...

Cerebral cavernous malformations (CCMs) often cause hemorrhages that can result in severe clinical manifestations, including hemiparesis and seizures. The underlying mechanisms of the aggressive behavior of CCMs are undetermined to date, but alterations of vascular matrix components may be involved. We compared the localization of the tight junctio...

One of the main putative causes of therapy refractory epilepsy in mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis is the overexpression of multidrug transporters (MDTs) at the blood-brain barrier (BBB). It steps up the removal of antiepileptic drugs (AEDs) out of the brain cells across the BBB resulting in a low concentration of AED...

In this work we addressed the putative role of NG2 in the control of endothelial tight junction (TJ) dismantling, blood-brain barrier (BBB) breakdown, and leukocyte transendothelial migration in inflammatory/degenerative neurological disorders. During CNS development two cell types are known to express the transmembrane proteoglycan NG2, namely oli...

Experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), is characterized by vascular changes, particularly endothelial tight junction (TJ) protein (claudin-5 and occludin) alterations. During blood-brain barrier function, the vascular wall components, endothelial cells, pericytes and perivascular astrocyte...

The identification of stem cells resident in the adult central nervous system has redirected the focus of research into demyelinating diseases, such as multiple sclerosis, mainly affecting the brain white matter. This immunocytochemical and morphometrical study was carried out by confocal microscopy in the adult mouse cerebral cortex, with the aim...

Aggrecan is a component of the CNS extracellular matrix (ECM) and we show here that the three primary alternative spliced transcripts of the aggrecan gene found in cartilage are also present in the adult CNS. Using a unique panel of core protein-directed antibodies against human aggrecan we further show that different aggrecan isoforms are deposite...