Phenoloxidases of different sizes are modulated by LPS inoculation into Ciona intestinalis tunic and pharynx

In the present study, to further characterize the pro-phenoloxidase (proPO) and active phenoloxidase (PO) involved in the Ciona intestinalis inflammatory response, tunic and pharynx homogenate supernatants were separated on high pressure liquid chromatography and fractions were assayed for the PO activity before and after LPS inoculation, as well as before and after trypsin treatment which activates proPO. The LPS inoculation per se did not significantly change the basal PO activity of the tunic homogenate supernatant (THS) and pharynx homogenate supernatant (PHS) restricted in two confluent peaks, whereas a significant enhancement was observable after the trypsin treatment. This trypsin effect suggests that proPO is the main component of the HPLC separated fractions, and indicates that LPS inoculation mainly challenges the pro-enzyme production by tunic cells and hemocytes, as well as the activation of the serine-protease pathway. The protein size analysis and DOPA-MBTH assay, disclose two active proteins of 90.0 and 170.0 kDa differently contained in the two main chromatographic peaks. Due to the SDS activating effect on the proenzyme analyzed by SDS-PAGE, the size of proPO could not be shown, whereas modulation of an oligomerization process of the 90 kDa component is suggested

Bortezomib modulates CHIT1 and YKL40 in monocyte-derived osteoclast and in myeloma cells

Osteolytic bone disease is a common manifestation of multiple myeloma (MM) that leads to progressive skeleton destruction and is the most severe cause of morbidity in MM patients.It results from increased osteolytic activity and decrease osteoblastic function. Activation of mammalian chitinases CHIT1 and YKL40 is associated with osteoclast (OCs) differentiation and bone digestion. In the current study, we investigated the effect of two Bortezomib’s concentration (BO) (2.5 nM and 5nM) on osteoclastogenesis by analyzing regulation of chitinase expression. OCs exposition to BO was able to inhibit the expression of different OCs markers such as RANK, CTSK, TRAP and MMP9. In addition BO-treatment reduced CHIT1 enzymatic activity and both CHIT1 and YKL40 mRNA expression levels and cytoplasmatic and secreted protein. Moreover, immunofluorescence evaluation of mature OCs showed that BO was able to translocate YKL40 into the nucleus, while CHIT1 remained into the cytoplasm. Since MM cell lines such as U266, SKM-M1 and MM1 showed high levels of CHIT1 activity, we analyzed bone resorption ability of U266 using dentin disc assay resorption pits. Silencing chitinase proteins in U266 cell line with specific siRNAs, resulted in pits number reduction on dentine discs. In conclusion, we showed that BO decreases osteoclastogenesis and reduces bone resorption in OCs and U266 cell line by modulating the chitinases CHIT1 and YKL40. These results indicate that chitinases may be a therapeutic target for bone disease in MM patients

PNPLA3 GG Genotype and Carotid Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease

BACKGROUND AND AIM: To evaluate if the presence of carotid atherosclerosis in patients with NAFLD, could be related to gene variants influencing hepatic fat accumulation and the severity of liver damage. METHODS: We recorded anthropometric, metabolic and histological data(Kleiner score) of 162 consecutive, biopsy-proven Sicilian NAFLD patients. Intima-media thickness(IMT), IMT thickening(IMT≥1 mm) and carotid plaques(focal thickening of >1.3 mm at the level of common carotid artery) were evaluated using ultrasonography. IL28B rs12979860 C>T, PNPLA3 rs738409 C>G, GCKR rs780094 C>T, LYPLAL1 rs12137855 C>T, and NCAN rs2228603 C>T single nucleotide polymorphisms were also assessed. The results were validated in a cohort of 267 subjects with clinical or histological diagnosis of NAFLD from Northern Italy, 63 of whom had follow-up examinations. RESULTS: Carotid plaques, IMT thickening and mean maximum IMT were similar in the two cohorts, whereas the prevalence of diabetes, obesity, NASH, and PNPLA3 GG polymorphism(21%vs.13%, p = 0.02) were significantly higher in the Sicilian cohort. In this cohort, the prevalence of carotid plaques and IMT thickening was higher in PNPLA3 GG compared to CC/CG genotype(53%vs.32%, p = 0.02; 62%vs.28%, p<0.001, respectively). These associations were confirmed at multivariate analyses (OR2.94;95%C.I. 1.12–7.71, p = 0.02, and OR4.11;95%C.I. 1.69–9.96, p = 0.002, respectively), although have been observed only in patients <50years. Also in the validation cohort, PNPLA3 GG genotype was independently associated with IMT thickening in younger patients only (OR: 6.00,95%C.I. 1.36–29, p = 0.01), and to IMT progression (p = 0.05) in patients with follow-up examinations. CONCLUSION: PNPLA3 GG genotype is associated with higher severity of carotid atherosclerosis in younger patients with NAFLD. Mechanisms underlying this association, and its clinical relevance need further investigations

Due testi a confronto

The two parallel biographies, the Syriac Life of Peter the Iberian, the Georgian prince who converted to Christianity, and the Life of Melania the Younger, the Roman patrician, have come down to us through a manuscript tradition and attest to the spread of monastic practices in Palestine around the 5th century. The texts allow us to investigate this phenomenon through the interpretation of selected passages which show how the common narrative of some certain significant events attests to the existence (and the fervent activity) of monastic circuits in Gaza, marked by particular lifestyles and guided by doctrinal choices. This inquiry, as well as providing important information on a certain kind of monasticism, offers the chance to make useful comparisons with the other forms of monasticism that enlivened the East in Late Antiquity

Alfabeti dal Sinai e dintorni. Tradizione monastica e parenesi attraverso gli alfabeti (4o-12o secolo)

=L’articolo, dopo aver brevemente esplorato la tradizione degli alfabeti spirituali nel mondo greco, esamina tre esempi di alfabeti monastici più propriamente parenetici e che provengono – o sono ritenuti essere provenienti – dal Sinai : i Capita paraenetica di Nilo Sinaita (in realtà evagriani), i due alfabeti inseriti nel ventiseiesimo gradino della Scala Paradisi di Giovanni Climaco e le Centurie sulla vigilanza e la virtù di Esichio di Batos. Il primo è un alfabeto gnomico che si risolve in una raccolta di sentenze pitagoriche e neopitagoriche inserite in una cornice monastica e che sembra andare in direzione della cristianizzazione di opere filosofiche (si veda ad esempio l’Enchiridion di Epitteto). I due alfabeti climachei sono funzionali al primo e al terzo stadio della vita monastica, cioè ai principianti e ai perfetti. Infine, i capitoli alfabetici di Esichio sono un testo di meditazione, probabilmente destinato alle cerchie più interne della comunità monastica di riferimento.L’article, après avoir brièvement exploré la tradition des alphabets spirituels dans le monde grec, examine trois exemples d’alphabets monastiques plus proprement parénétiques et qui proviennent – ou sont censés provenir – du Sinaï : les Capita paraenetica de Nil le Sinaïte (en réalité évagriens), les deux alphabets insérés dans le degré 26 de la Scala Paradisi de Jean Climaque et les Centuries sur la tempérance et la vertu d’Hésychius de Batos. Le premier est un alphabet gnomique qui se résume à une collection de sentences pythagoriciennes et néopythagoriciennes insérées dans un cadre monastique et qui semble aller dans le sens de la christianisation d’oeuvres philosophiques (par exemple l’Enchiridion d’Épictète). Les deux alphabets du Climaque correspondent au premier et au troisième stade de la vie monastique, c’est-à-dire les débutants et les parfaits. Enfin, les chapitres alphabétiques d’Hésychius sont un texte de méditation, probablement destiné aux cercles plus internes de la communauté monastique concernée.Parrinello Rosa maria. Alfabeti dal Sinai e dintorni. Tradizione monastica e parenesi attraverso gli alfabeti (4o-12o secolo). In: Revue des études byzantines, tome 69, 2011. pp. 135-158

Predicazione e teologia politica: sulle omelie di Leone VI il Saggio (866-912)

ITALIANO: Nel panorama della storia della predicazione bizantina, spicca la figura di Leone VI il Saggio, l’imperatore-predicatore. Fu un personaggio poliedrico e versatile, abilissimo politico, legislatore, stratega, spregiudicato quanto basta per contrapporsi alla gerarchia ecclesiastica allo scopo di piegarla ai propri fini. L’articolo esamina la peculiare teologia politica di Leone, ricercandone le tracce nelle omelie, in particolar modo nella lunga e articolata Laudatio funebris di Giovanni Crisostomo, in cui egli riprende una fonte rielaborandola in modo apparentemente minimo, ma in realtà decisivo, con piccole inserzioni significative con cui ribadisce la stretta unione, ma non la sudditanza, tra ius e potere imperiale. / ENGLISH: In the framework of the history of Byzantine preaching, Leo VI the Wise, the emperor-preacher, stands out. He was a multifaceted and versatile character, a skilled politician, legislator, strategist, and unscrupulous enough to oppose the church hierarchy in order to bend it to his own ends. The article examines Leo’s unique political theology, by searching for its traces in homilies, especially in the long and articulated Laudatio funebris Iohannis Chrisostomi, in which he reclaims a source by re-elaborating it in a way that seems minor but is in fact quite decisive. He achieves this with small yet meaningful insertions which reaffirm the close union, but not the subjection, between ius and imperial power

Direzione spirituale tra ortodossia ed eresia. Dalle scuole filosofiche antiche al Novecento

I saggi qui raccolti affrontano il tema direzione spirituale dal mondo antico a quello contemporaneo senza però gli schemi di ciò che Marc Bloch definì «l’idolo» o «l’ossessione delle origini».Lo stesso termine “direzione spirituale” non sempre compare, ma si autodefinisce in un contesto di rapporto maestro e discepolo per un miglioramento spirituale, morale od etico. Esso, visto nel lungo periodo, pone anche il problema di sapere se è “sempre la stessa cosa”, poiché nella sua identicità e immutabilità interviene inoltre senza dubbio un fattore di soggettività: la diversità dei protagonisti, della loro provenienza sociale, culturale o spirituale