Immune-mediated mechanisms of (mal)adaptive renal tissue repair

The aim of this thesis is to increase our knowledge into the immunopathogenesis of renal sterile inflammatory diseases, with a focus on the innate immune response activation by the danger protein S100A8/A9 and the receptor TREM-1. We found that S100A8/A9 is a pivotal player in renal repair following hypoxic damage, through an immune-regulatory role resulting in the alternative activation of macrophages. By controlling excessive M2 polarization, S100A8/A9 fine-tunes the adaptive response of the kidney to IR-induced AKI ( Chapter 2 ). Conversely, in chronically inflamed kidneys, S100A8/A9 contributes to the development of fibrosis possibly through a direct effect on dedifferentiation and apoptosis in tubular epithelial cells. This effect was independent of S100A8/A9-induced inflammation and recruitment of leukocytes into the kidney ( Chapter 3 ). Instead, TREM-1 is not involved in the amplification of acute renal damage and inflammation in preclinical model of acute kidney injury. Additionally, renal transplanted patients carrying the TREM1 gene variant p.Thr25Ser do not show any association with pathological consequences after transplantation ( Chapter 5 ). TREM-1, however, limits the maladaptive repair post IR-induced AKI, through a direct effect on tubular epithelial mitochondrial homeostasis and energy production, empowering cell cycle progression. The metabolic advantage provided by TREM-1 is indispensable for tubular proliferation, which sustains renal repair and accelerates the recovery from IR ( Chapter 6 ). In the preclinical model of chronic kidney disease TREM-1 and its adapter molecule DAP12 are not involved in the development of renal fibrosis. DAP12, partly through TREM-1, modulates the renal inflammatory response following unilateral ureteral obstruction ( Chapter 7 )

Effect of layered double hydroxide intercalated with fluoride ions on the physical, biological and release properties of a dental composite resin

OBJECTIVES: The aim of this work was the preparation of a new fluoride-releasing dental material characterized by a release of fluoride relatively constant over time without any initial toxic burst effect. This type of delivery is obtained by a matrix controlled elution and elicits the beneficial effect of a low amount of fluoride on human dental pulp stem cells (hDPSCs) towards mature phenotype. METHODS: The modified hydrotalcite intercalated with fluoride ions (LDH-F), used as filler, was prepared via ion exchange procedure and characterized by X-ray diffraction and FT-IR spectroscopy. The LDH-F inorganic particles (0.7, 5, 10, 20wt.%) were mixed with a photo-activated Bis-GMA/TEGDMA (45/55wt/wt) matrix and novel visible-light cured composites were prepared. The dynamic thermo-mechanical properties were determined by dynamic mechanical analyzer. The release of fluoride ions in physiological solution was determined using a ionometer. Total DNA content was measured by a PicoGreen dsDNA quantification kit to assess the proliferation rate of hDPSCs. Alkaline phosphatase activity (ALP) was measured in presence of fluoride resins. RESULTS: Incorporation of even small mass fractions (e.g. 0.7 and 5wt.%) of the fluoride LDH in Bis-GMA/TEGDMA dental resin significantly improved the mechanical properties of the pristine resin, in particular at 37°C. The observed reinforcement increases on increasing the filler concentration. The release of fluoride ions resulted very slow, lasting months. ALP activity gradually increased for 28 days in hDPSCs cell grown, demonstrating that low concentrations of fluoride contributed to the cell differentiation. CONCLUSIONS: The prepared composites containing different amount of hydrotalcite filler showed improved mechanical properties, slow fluoride release and promoted hDPSCs cell proliferation and cell differentiation

OER nelle Università italiane: primi risultati di un'indagine conoscitiva del Gruppo CRUI OA-OER

Le OER si inseriscono nell'ambito del movimento Open Access e dell'accesso aperto alla conoscenza, ritenuta come bene comune e prevedono licenze aperte costruite nel rispetto dei diritti di proprietà intellettuale dell’autore come stabilito dalle convenzioni internazionali e dalle normative europee e nazionali. All’inizio del 2006, nell’ambito della Commissione biblioteche della CRUI, è stato costituito il Gruppo di lavoro per l’Open Access, coordinato dal prof. Roberto Delle Donne, con il compito di dare attuazione ai principi della Dichiarazione di Berlino. Il Gruppo CRUI Open Access ha creato un sottogruppo OER. Durante l'avvio della discussione del Sottogruppo OA-OER, ci si è accordati sull'idea di realizzare un'indagine e di creare una mappa dello stato dell'arte di OER in Italia. Il contributo presenta i primi risultati dell'indagine sulle OER nelle Università italiane

Ofd1 Controls Dorso-Ventral Patterning and Axoneme Elongation during Embryonic Brain Development.

Oral-facial-digital type I syndrome (OFDI) is a human X-linked dominant-male-lethal developmental disorder caused by mutations in the OFD1 gene. Similar to other inherited disorders associated to ciliary dysfunction OFD type I patients display neurological abnormalities. We characterized the neuronal phenotype that results from Ofd1 inactivation in early phases of mouse embryonic development and at post-natal stages. We determined that Ofd1 plays a crucial role in forebrain development, and in particular, in the control of dorso-ventral patterning and early corticogenesis. We observed abnormal activation of Sonic hedgehog (Shh), a major pathway modulating brain development. Ultrastructural studies demonstrated that early Ofd1 inactivation results in the absence of ciliary axonemes despite the presence of mature basal bodies that are correctly orientated and docked. Ofd1 inducible-mediated inactivation at birth does not affect ciliogenesis in the cortex, suggesting a developmental stage-dependent role for a basal body protein in ciliogenesis. Moreover, we showed defects in cytoskeletal organization and apical-basal polarity in Ofd1 mutant embryos, most likely due to lack of ciliary axonemes. Thus, the present study identifies Ofd1 as a developmental disease gene that is critical for forebrain development and ciliogenesis in embryonic life, and indicates that Ofd1 functions after docking and before elaboration of the axoneme in vivo

Local reactions to the second dose of the BNT162 COVID-19 vaccine

Multiple strategies have been implemented worldwide to fight the burden of the pandemic caused by COVID-19, with vaccination being one of the most promising.1 Notably, the first vaccine to be authorized in Italy was the BNT162 mRNA-based vaccine, which has also been approved in the USA, United Kingdom, and Canada.1,2 As a matter of fact, RNA vaccines are immunogenic and cost-effective.

A Case of Ketron-Goodman Disease

Pagetoid reticulosis (PR) is a rare form of cutaneous T-cell lymphoma [Mod Pathol 2000;13:502–510]. Two variants of the disease are described: the localized type Woringer-Kolopp disease (WKD) and the disseminated type Ketron-Goodman disease (KGD). KGD may have disseminated lesions, high rate of recurrence and a guarded prognosis [Mod Pathol 2000;13:502–510]. In patients with KGD, therefore, long-term observation is necessary. Disappearance of cutaneous lesions does not mean resolution of the disease [J Am Acad Dermatol 2002;47:183–186]. Herein we report the case of an 84-year-old man with erythematous patches of the trunk and the upper and lower extremities in whom the diagnosis of KGD was made. We describe this case for the rarity of this pathology and for the good response to therapy (IFN)

Transverse orange nail lesions following SARS-CoV-2 infection

We report the case of an 89-year-old woman in a nursing home who amid an outbreak of coronavirus disease 2019 (COVID-19) presented cough and asthenia