Conjugation with Methylsulfonylmethane Improves Hyaluronic Acid Anti-Inflammatory Activity in a Hydrogen Peroxide-Exposed Tenocyte Culture In Vitro Model

Rotator cuff tears (RCTs) and rotator cuff disease (RCD) are important causes of disability in middle-aged individuals affected by nontraumatic shoulder dysfunctions. Our previous studies have demonstrated that four different hyaluronic acid preparations (HAPs), including Artrosulfur\uae hyaluronic acid (HA) (Alfakjn S.r.l., Garlasco, Italy), may exert a protective effect in human RCT-derived tendon cells undergoing oxidative stress damage. Recently, methylsulfonylmethane (MSM) (Barentz, Paderno Dugnano, Italy) has proven to have anti-inflammatory properties and to cause pain relief in patients affected by tendinopathies. This study aims at evaluating three preparations (Artrosulfur\uae HA, MSM, and Artrosulfur\uae MSM + HA) in the recovery from hydrogen peroxide-induced oxidative stress damage in human tenocyte. Cell proliferation, Lactate Dehydrogenase (LDH) release, and inducible nitric oxide synthases (iNOS) and prostaglandin E2 (PGE2) modulation were investigated. In parallel, expression of metalloproteinases 2 (MMP2) and 14 (MMP14) and collagen types I and III were also examined. Results demonstrate that Artrosulfur\uae MSM + HA improves cell escape from oxidative stress by decreasing cytotoxicity and by reducing iNOS and PGE2 secretion. Furthermore, it differentially modulates MMP2 and MMP14 levels and enhances collagen III expression after 24 h, proteins globally related to rapid acceleration of the extracellular matrix (ECM) remodelling and thus tendon healing. By improving the anti-cytotoxic effect of HA, the supplementation of MSM may represent a feasible strategy to ameliorate cuff tendinopathies

Conjugation with Methylsulfonylmethane improves Hyaluronic Acid anti-inflammatory activity in a hydrogen peroxide-exposed tenocyte culture in vitro model

Abstract: Rotator cuff tears (RCTs) and rotator cuff disease (RCD) are important causes of disability in middle-aged individuals affected by nontraumatic shoulder dysfunctions. Our previous studies have demonstrated that four different hyaluronic acid preparations (HAPs), including Artrosulfur® hyaluronic acid (HA), may exert a protective effect in human RCT-derived tendon cells undergoing oxidative stress damage. Recently, methylsulfonylmethane (MSM) has proven to have anti-inflammatory properties and to cause pain relief in patients affected by tendinopathies. This study aims at evaluating three preparations (Artrosulfur® HA, MSM, and Artrosulfur® MSM + HA) in the recovery from hydrogen peroxide-induced oxidative stress damage in human tenocyte. Cell proliferation, Lactate Dehydrogenase (LDH) release, and inducible nitric oxide synthases (iNOS) and prostaglandin E2 (PGE2) modulation were investigated. In parallel, expression of metalloproteinases 2 (MMP2) and 14 (MMP14) and collagen types I and III were also examined. Results demonstrate that Artrosulfur® MSM + HA improves cell escape from oxidative stress by decreasing cytotoxicity and by reducing iNOS and PGE2 secretion. Furthermore, it differentially modulates MMP2 and MMP14 levels and enhances collagen III expression after 24 h, proteins globally related to rapid acceleration of the extracellular matrix (ECM) remodelling and thus tendon healing. By improving the anti-cytotoxic effect of HA, the supplementation of MSM may represent a feasible strategy to ameliorate cuff tendinopathies

Dual Acting Carbon Monoxide Releasing Molecules and Carbonic Anhydrase Inhibitors Differentially Modulate Inflammation in Human Tenocytes

Sustained oxidative stress and inflammation have been reported as the major factors responsible for the failure of tendon healing during rotator cuff tears (RCTs) and rotator cuff disease (RCD). Although, their therapeutic management remains still challenging. Carbonic anhydrases (CAs) are involved in many pathological conditions, and the overexpression of both CA9 and 12 in inflamed joints has been recently reported. Consequently, a selective CA9/12 inhibition could be a feasible strategy for improving tendon recovery after injury. In addition, since carbon monoxide (CO) has been proven to have an important role in modulating inflammation, CO releasing molecules (CORMs) can be also potentially suitable compounds. The present study aims at evaluating five newly synthesized dual-mode acting CA inhibitors (CAIs)-CORMs compounds, belonging to two chemical scaffolds, on tendon-derived human primary cells under H2O2 stimulation in comparison with Meloxicam. Our results show that compounds 2 and 7 are the most promising of the series in counteracting oxidative stress-induced cytotoxicity and display a better profile in terms of enhanced viability, decreased LDH release, and augmented tenocyte proliferation compared to Meloxicam. Moreover, compound 7, as a potent superoxide scavenger, exerts its action inhibiting NF-kB translocation and downregulating iNOS, whereas compound 2 is more effective in increasing collagen I deposition. Taken together, our data highlight a potential role of CA in RCTs and RCD and the prospective effectiveness of compounds acting as CAI-CORM during inflammation

RAS/BRAF mutational status in familial non‑medullary thyroid carcinomas: A retrospective study

There are contrasting views on whether familial non‑medullary thyroid carcinomas (FNMTCs) are characterized by aggressive behavior, and limited evidence exists on the prognostic value of BRAF and RAS mutations in these tumors. Thus, in the present study, clinicopathological features were analyzed in 386 non‑medullary thyroid carcinomas (NMTCs), subdivided in 82 familial and 304 sporadic cases. Furthermore, the RAS and BRAF mutational statuses were investigated in a subgroup of 34 FNMTCs to address their clinical and biological significance. The results demonstrated that, compared with sporadic NMTCs, FNMTCs are characterized by significantly higher rates of multicentricity and bilaterality and are more frequently associated with chronic autoimmune thyroiditis. Notably, a statistically significant difference in the rates of multicentricity was observed by subgrouping familial tumors according to the number of relatives involved; those with ≥3 affected relatives were more likely to be multicentric. Furthermore, the FNMTC cohort exhibited higher rates of tumors >4 cm in size with extrathyroidal or lymph node involvement. However, no significant difference was observed. Similarly, no differences were observed with respect to the age of onset or the patient outcome. The mutational profiling exhibited a rate of 58.8% for BRAF V600E mutations in familial tumors, which is at the upper limit of the mutational frequency observed in historical series of sporadic thyroid cancer. A high rate of NRAS mutations (17.6%) was also observed, mostly in the follicular variant histotype. Notably, compared with BRAF/RAS‑wild type FNMTCs, the familial carcinomas bearing BRAF or NRAS mutations exhibited slightly higher rates of bilaterality and multicentricity, in addition to increased frequency of locally advanced stage or lymph node involvement. The present data support the theory that FNMTCs are characterized by clinicopathological features that resemble a more aggressive phenotype and suggest that RAS/BRAF mutational analysis deserves to be further evaluated as a tool for the identification of FNMTCs with a potentially unfavorable prognosis

A green approach for the valorisation of Arundo donax L. and paper mill waste to produce the advanced biofuel n-Butyl Levulinate

The continue depletion of fossil sources and their environmental impact represent one of the main problems of this century. Therefore, a lot of studies have been recently performed in order to produce sustainable advanced biofuels. These components are directly obtained from not edible lignocellulosic biomasses and can totally or partially replace fossil fuel. In this work, the feasible production of the advanced biofuel n-Butyl Levulinate (BL) from an herbaceous lignocellulosic biomass and an industrial paper mill waste has been investigated and optimized. Alkyl levulinates can be produced from cellulosic fraction of biomasses. Up to now, several studies have been focused on the possible production of these compounds through a two-step process: a preliminary acid hydrolysis of the biomass to levulinic acid, followed by the purification of levulinic acid and its esterification to the target molecule. This strategy is obviously limited by the high cost connected with the overall process. By contrast, the one-pot alcoholysis of raw biomasses directly to the target product represents an innovative easier and cheaper approach. Starting form two different kinds of raw biomasses (Arundo donax L. and industrial paper mill waste), the direct acid-catalysed alcoholysis to n-butyl levulinate has been studied, employing n-butanol as solvent and H2SO4 as homogeneous catalyst (0.6-1.2 wt%). With both the considered biomasses, BL yields around 35 mol% have been achieved with high loading of feedstock between 14 and 20 wt%. Furthermore, the feasibility of our process has been tested, employing both microwave and traditional heating system, reaching the BL molar yield of 38 mol% with the high biomass loading of 20 wt% starting from A. donax L. Finally, the BL yield of 33 mol% was achieved with the extremely low catalyst loading of 0.6 wt% working with biomass loading up to 20 wt% of A. donax L., at 200°C for 180 minutes employing traditional heating. This obtained result is very promising because the employed reaction parameters, in particular the very low acid concentration, make our process promising and feasible especially from an industrial point of view

CD200 as a Potential New Player in Inflammation during Rotator Cuff Tendon Injury/Repair: An In Vitro Model

Rotator cuff tendon (RCT) disease results from multifactorial mechanisms, in which inflammation plays a key role. Pro-inflammatory cytokines and tendon stem cell/progenitor cells (TSPCs) have been shown to participate in the inflammatory response. However, the underlying molecular mechanism is still not clear. In this study, flow cytometry analyses of different subpopulations of RCT-derived TSPCs demonstrate that after three days of administration, TNFα alone or in combination with IFNγ significantly decreases the percentage of CD146+CD49d+ and CD146+CD49f+ but not CD146+CD109+ TSPCs populations. In parallel, the same pro-inflammatory cytokines upregulate the expression of CD200 in the CD146+ TSPCs population. Additionally, the TNFα/IFNγ combination modulates the protein expression of STAT1, STAT3, and MMP9, but not fibromodulin. At the gene level, IRF1, CAAT (CAAT/EBPbeta), and DOK2 but not NF-κb, TGRF2 (TGFBR2), and RAS-GAP are modulated. In conclusion, although our study has several important limitations, the results highlight a new potential role of CD200 in regulating inflammation during tendon injuries. In addition, the genes analyzed here might be new potential players in the inflammatory response of TSPCs

Per una storia dell’arte in Basilicata tra XII e XIII secolo: due casi a confronto,

Nel contributo si traccia un profilo dello stato degli studi sulla Basilicata medievale considerando le fonti visivo–oggettuali . In un contesto estremamente articolato, è analizzata la produzione artistica dei centri di Venosa, Lagopesole Melfi e Acerenza, luoghi per eccellenza della ‘trasmigrazione’ di idee e modelli estranei alle tradizioni locali, in funzione del nuovo corso impresso alla situazione meridionale dalla nuovissima alleanza tra la chiesa della Riforma e i dominatori normanni. Legato alla cultura di questi luoghi è Sarolo, un artista residente a Muro Lucano a capo di una bottega in cui lavora con il fratello Ruggero, con il quale rma nel 1197 il portale di Pierno vicino a San Fele – una chiesa di pellegrinaggio sorta nelle vicinanze della via Herculea – e nel 1209 uno dei due bassorilievi della cattedrale di Rapolla, raf guranti rispettivamente Adamo ed Eva e una Annunciazione Sarolo a partire dal Bertaux è stato considerato da parte della critica del Novecento – nel tentativo di definire per il periodo medievale una realtà artistica autoctona della regione – l’autore di molte opere tra cui lo stesso portale della cattedrale di Acerenza. Su questo artista e sulla sua produzione si propone una diversa lettura che analizza nel dettaglio le opere da lui firmate, i modelli culturali ed artistici, i rapporti con la committenza, il ruolo nei diversi cantieri, identificando nell’ecclettismo della sua produzione la motivazione delle numerose attribuzioni. Nella stessa rea geografica, sul versante della produzione pittorica sono presi in considerazione gli affreschi della cappella del castello di Lagopesole, sui quali, diveramente dai casi analizzati in precedenza, pochi sono gli interventi critici su queste pitture, di una qualità non particolarmente eccelsa anche a causa del pessimo stato di conservazione in cui ci sono giunti. L’interesse nei confronti di queste testimonianze nasce dall’incertezza della cronologia e dalla enigmatica presenza di un pannello votivo raffigurante un cavaliere ed una dinanzi a un grande stemma d’azzurro alla croce d’argento caricata di cinque conchiglie di San Giacomo di rosso. La cosa che colpisce di questi affreschi è la loro presenza nell’ambito di una cappella destinata a un imperatore prima, Federico II, e a un sovrano poi, ovvero Carlo I d’Angiò. Attraverso l’analisi delle fasi costruttive di questa zona del castello, del valore dello stesso pannello votivo e dello stilem delle pitture gli affreschi sono attribuiti ad una bottega certamente non degna di una committenza imperiale, ma la cui presenza ricopre un ruolo molto più importante delle capacità artistiche dei suoi pittori, dal momento che potrebbe rappresentare l’unica testimonianza certa di una fase della vita del castello fino ad ora solo ipotizzata, perché celata dalle tante trasformazioni e rimaneggiamenti avvenuti proprio a partire dagli anni Quaranta del XIII secolo

Tra Oriente e Occidente. Istituzioni religiose a Barletta nel Medioevo (sec. XI-XV)

Nel volume si affrontano, per la prima volta in modo organico, le vicende relative alla Chiesa di Barletta nel contesto della storia del Mezzogiorno d'Italia. L'apporto delle grandi esperienze canonicati e militari di Terrasanta, la sistemazione e il radicamento dei grandi ordini monastici femminili e maschili, i rapporti consolidati nel tempo con i canonici di San Giovanni in Laterano a Roma, la riottosità di un clero espressione di una solida élite militare e burocratica fortemente radicata nel territorio e largamente beneficiata dalla Corona siciliana, la particolarità della presenza di più sedi episcopali (tranese, cannelle e nazarena), fanno di Barletta un caso di studio particolare e di notevole interesse. Il volume ospita contributi di storia e di storia dell'arte