NGF modulates trkANGFR/p75NTR in αsMA-expressing conjunctival fibroblasts from human ocular cicatricial pemphigoid (OCP)

OBJECTIVE: In a previous study, we reported the upregulation of Nerve Growth Factor (NGF) and trkANGFR expression in Ocular Cicatricial Pemphigoid (OCP), an inflammatory and remodeling eye disease. Herein, we hypothesize a potential NGF-driven mechanism on fibroblasts (FBs) during OCP remodeling events. To verify, human derived OCP-FBs were isolated and characterized either at baseline or after NGF exposure. MATERIALS AND METHODS: Conjunctival biopsies were obtained from 7 patients having OCP and 6 control subjects (cataract surgery). Both conjunctivas and primary FB cultures were characterised for αSMA, NGF and trkANGFR/p75NTR expression. Subcultures were exposed to NGF and evaluated for αSMA, NGF, trkANGFR/p75NTR expression as well as TGFβ1/IL4 release. For analysis, early and advanced subgroups were defined according to clinical parameters. RESULTS: OCP-conjunctivas showed αSMA-expressing FBs and high NGF levels. Advanced OCP-FBs showed higher αSMA expression associated with higher p75NTR and lower trkANGFR expression, as compared to early counterparts. αSMA expression was in keeping with disease severity and correlated to p75NTR. NGF exposure did not affect trkANGFR levels in early OCP-FBs while decreased both αSMA/p75NTR expression and TGFβ1/IL4 release. These effects were not observed in advanced OCP-FBs. CONCLUSIONS: Taken together, these data are suggestive for a NGF/p75NTR task in the potential modulation of OCP fibrosis and encourages further studies to fully understand the underlying mechanism occurring in fibrosis. NGF/p75NTR might be viewed as a potential therapeutic target

Nerve growth factor has a modulatory role on human primary fibroblast cultures derived from vernal keratoconjunctivitis-affected conjunctiva

Purpose: To evaluate the role of nerve growth factor (NGF) in remodeling processes of vernal keratoconjunctivitis (VKC). VKC is a chronic inflammatory disorder of the conjunctiva and is characterized by marked tissue remodeling. NGF, a pleiotrophic factor with documented profibrogenic activities, is produced by inflammatory and structural cells populating the VKC conjunctiva and is increased in the serum and tears of VKC patients.Methods: Primary cultures of VKC-derived fibroblasts (VKC-FBs) were exposed to increasing NGF concentrations (1500 ng/ml) to evaluate and compare the expression of alpha-smooth muscle actin (alpha SMA, a defining myofibroblast marker), collagens (types I and IV), and metalloproteinases and tissue inhibitors (MMP9/TIMP1, MMP2/TIMP2) at the biochemical as well as molecular levels.Results: Endogenous NGF was increased in the VKC-FB supernatant, as compared to healthy-FB supernatant. VKC-FBs expressed aSMA and increased types I and IV collagens. VKC-FBs, and in particular all aSMA positive cells, expressed both trkA(NGFR) and p75(NTR), while healthy-FBs only expressed trkA(NGFR). Exogenous NGF did not change aSMA expression, while aSMA expression was enhanced by specific neutralization of p75(NTR). NGF (10 ng/ml) exposure significantly decreased type I collagen expression, without affecting type IV collagen, and increased MMP9mRNA and protein.Conclusions: The autocrine modulation of differentiation and response of VKC-FBs to NGF exposure with downregulation of type I collagen and upregulation of MMP9 expression supports a relevant role for NGF in tissue remodeling of VKC

Nature-Inspired Processes and Structures: New Paradigms to Develop Highly Bioactive Devices for Hard Tissue Regeneration

Material scientists are increasingly looking to natural structures as inspiration for new-generation functional devices. Particularly in the medical field, the need to regenerate tissue defects claims, since decades, biomaterials with the ability to instruct cells toward formation and organization of new tissue. It is today increasingly accepted that biomimetics is a leading concept for biomaterials development. In fact, there is increasing evidence that the use of biomedical devices showing substantial mimicry of the composition and multi-scale structure of target native tissues have enhanced regenerative ability. As a relevant example, biomimetic materials have high potential to solve degenerative diseases affecting the musculoskeletal system, namely, bone, cartilage and articular tissues, which is of pivotal importance for most of human abilities, such as walking, running, manipulating, and chewing. In this respect, the adoption of nature-inspired processes and structures is an emerging fabrication concept, uniquely able to provide biomaterials with superior biological performance. The chapter will give an overview of the most recent results obtained in the field of hard tissue regeneration by using 3D biomaterials obtained by nature-inspired approaches. The main focus is given to porous hydroxyapatite-based ceramic or hybrid scaffolds for regeneration of bone and osteochondral tissues in neurosurgery and orthopedics

A study of the oxidehydration of 1,2-propanediol to propanoic acid with bifunctional catalysts

[EN] The gas-phase oxidehydration (ODH) of 1,2-propanediol to propionic acid has been studied as an intermediate step in the multi-step transformation of bio-sourced glycerol into methylmethacrylate. The reaction involves the dehydration of 1,2-propanediol into propionaldehyde, which occurs in the presence of acid active sites, and a second step of oxidation of the aldehyde to the carboxylic acid. The two reactions were carried out using a cascade strategy and multifunctional catalysts, made of W-Nb-O, W-V-O and W-Mo-V-O hexagonal tungsten bronzes, the same systems which are also active and selective in the ODH of glycerol into acrylic acid. Despite the similarities of reactions involved, the ODH of 1,2-propanediol turned out to be less selective than glycerol ODH, with best yield to propanoic acid no higher than 13%, mainly because of the parallel reaction of oxidative cleavage, occurring on the reactant itself, which led to the formation of C-1-C-2 compounds.Bandinelli, C.; Lambiase, B.; Tabanelli, T.; De Maron, J.; Dimitratos, N.; Basile, F.; Concepción Heydorn, P.... (2019). A study of the oxidehydration of 1,2-propanediol to propanoic acid with bifunctional catalysts. Applied Catalysis A General. 582:1-9. https://doi.org/10.1016/j.apcata.2019.05.036S1958

Studio della trasformazione di 1,2-propandiolo ad acido propionico

Il presente lavoro ha riguardato lo studio della trasformazione one-pot in fase gas di 1,2-propandiolo ad acido propionico, impiegando il pirofosfato di vanadile (VPP), (VO)2P2O7, e due differenti sistemi a base di bronzi di tungsteno con struttura esagonale (HTB), gli ossidi misti W1V0,3 e W1Mo0,5V0,1. Il processo richiede un catalizzatore con due differenti funzionalità: una acida, principalmente di tipo Brønsted, fornita nel VPP dai gruppi P-OH presenti sulla sua superficie, e negli HTB dai gruppi W-OH sulla loro superficie e dagli ioni H+ nei canali esagonali dell’ossido; e una ossidante, fornita nel VPP dal V, e negli HTB da V e Mo incorporati nella struttura esagonale. I risultati delle prove di reattività hanno consentito di dedurre gli aspetti principali dello schema della reazione one-pot di disidratazione-ossidazione dell’1,2-propandiolo ad acido propionico. I catalizzatori provati non possiedono la combinazione ottimale di proprietà acide e redox necessarie per ottenere elevate rese in acido propionico. Le scarse proprietà ossidanti portano a un accumulo di propionaldeide, che reagisce con l’1,2-propandiolo a dare diossolani, e inoltre dà luogo alla formazione di altri sottoprodotti. È perciò necessario incrementare le proprietà ossidanti del catalizzatore, in modo da accelerare la trasformazione della propionaldeide ad acido propionico, ed evitare quindi che le proprietà acide del catalizzatore, necessarie per compiere il primo stadio di disidratazione di 1,2-propandiolo, siano causa di reazioni parassite di trasformazione dell’aldeide stessa

Preliminary evidence of the efficacy of probiotic eye-drop treatment in patients with vernal keratoconjunctivitis

Probiotics have been shown to improve allergic inflammation. The aim of this study was to evaluate the efficacy of Lactobacillus Acidophilus eye-drops in controlling signs and symptoms of vernal keratoconjunctivitis (VKC)

In vivo characterization of doxycycline effects on tear metalloproteinases in patients with chronic blepharitis

Matrix metalloproteinases (MMPs) have a role in the pathogenesis of rosacea-associated chronic blepharitis. Doxycycline is largely used as a treatment for recalcitrant chronic blepharitis. It has been shown in vitro that doxycycline inhibits MMPs activation. The aim of this study was to investigate in vivo the effect of doxycycline in modulating MMPs in patients with chronic idiopathic blepharitis

Nerve growth factor and tissue repair remodeling: trkA(NGFR) and p75(NTR), two receptors one fate

This review deals with the role of nerve growth factor (NGF) in healing process as a result of injury. The role of both trkA(NGFR) and p75(NTR) specific NGF receptors and their contribution in the complex network of tissue repair process, is discussed and highlighted in view of recent findings. In fact, NGF represents a significant advance in the treatment of etiologically different ulcers (corneal ulcers, pressure ulcers, post-viral infections, chemical burns) and might shorten the recovery process. For these diseases, no specific treatment is actually available. It is reasonable that apart from NGF and/or neurotrophins a different time-course of trkA(NGRF)/p75(NTR) expression, might regulate the final process. In summary, these novel findings on the potential pro-healing capacity of NGF might open new possibilities for this growth factor in modulating the healing processes in several pathological conditions

Nerve growth factor modulates toll-like receptor (TLR) 4 and 9 expression in cultured primary VKC conjunctival epithelial cells

To investigate if nerve growth factor (NGF) might modulate toll-like receptor (TLR) 4 and 9 expression in primary cultures of vernal keratoconjunctivitis (VKC)-derived conjunctival epithelial cells (VKC-ECs)

Human idiopathic epiretinal membranes express NGF and NGF receptors

Glial cells and fibroblasts (FBs) play a key role in epiretinal membrane (ERM) development and progression. Myofibroblasts (myoFBs), arising from these cells, can lead to the hypertrophic scars and tissue contraction observed in ERMs. Nerve growth factor (NGF) and transforming growth factor-beta1 (TGF-beta1) play a crucial role in FB activities. Therefore, the authors evaluated myoFBs in ERMs and NGF, trkA(NGFR and p75(NTR) expression, as well as TGF-beta1/TGF-betaRII levels in both ERMs and vitreous