Evaluation of the Catalytic Activity of Metal Phosphates and Related Oxides in the Ketonization of Propionic Acid

In recent years, the upgrading of lignocellulose bio-oils from fast-pyrolysis by means of ketonization has emerged as a frontier research domain to produce a new generation of biofuels. Propionic acid (PA) ketonization is extensively investigated as a model reaction over metal oxides, but the activity of other materials, such as metal phosphates, is mostly unknown. Therefore, PA ketonization was preliminarily investigated in the gas phase over both phosphates and oxides of Al, Zr, and La. Their catalytic activity was correlated to the physicochemical properties of the materials characterized by means of XRD, XRF, BET N2 porosimetry, and CO2- and NH3-TPD. Noteworthy, monoclinic ZrO2 proved to be the most promising candidate for the target reaction, leading to a 3-pentanone productivity as high as 5.6 h 121 in the optimized conditions. This value is higher than most of those reported for the same reaction in both the academic and patent literature

Niobium and Zirconium Phosphates as Green and Water-Tolerant Catalysts for the Acid-Catalyzed Valorization of Bio-Based Chemicals and Real Lignocellulosic Biomasses

Commercial niobium and synthesized zirconium phosphates were tested as water-tolerant heterogeneous acid catalysts in the hydrothermal conversion of different bio-based substrates. Different acid-catalyzed reactions were performed using biomass-derived model compounds and more complex real lignocellulosic biomasses as the substrate. The conversion of glucose and cellulose was preliminarily investigated. Then, a wide plethora of raw lignocellulosic biomasses, such as conifer wood sawdust, Jerusalem artichoke, sorghum, miscanthus, foxtail millet, hemp and Arundo donax, were valorized towards the production of water-soluble saccharides, 5-hydroxymethylfurfural (HMF), levulinic acid (LA) and furfural. The different catalytic performances of the two phosphates were explained on the basis of their acid features, total acidity, Brønsted/Lewis acid sites ratio and strength. Moreover, a better insight into their structure–acidity relationship was proposed. The different acid properties of niobium and zirconium phosphates enabled us to tune the reaction towards target products, achieving from glucose maximum HMF and LA yields of 24.4 and 24.0 mol%, respectively. Remarkably, when real Jerusalem artichoke biomass was adopted in the presence of niobium and zirconium phosphate, maximum yields of furanic compounds and cellulose-derived sugars of 12.7 and 50.0 mol%, respectively, were obtained, after only 1 h of reaction. The synthesized hydrolysates, which were found to be rich in C5 and C6 carbohydrates, can be better exploited for the cascade production of more added-value bio-products

Keratinocytes regulate the threshold of inflammation by inhibiting T cell effector functions

Whilst the importance of keratinocytes as a first-line defense has been widely investigated, little is known about their interactions with non-resident immune cells. In this study, the impact of human keratinocytes on T cell effector functions was analyzed in an antigen-specific in vitro model of allergic contact dermatitis (ACD) to nickel sulfate. Keratinocytes partially inhibited T cell proliferation and cytokine production. This effect was dependent on the keratinocyte/T cell ratio and was partially reversible by increasing the number of autologous dendritic cells. The inhibition of T cell proliferation by keratinocytes was independent of the T cell subtype and antigen presentation by different professional antigen-presenting cells. Autologous and heterologous keratinocytes showed comparable effects, while the fixation of keratinocytes with paraformaldehyde abrogated the immunosuppressive effect. The separation of keratinocytes and T cells by a transwell chamber, as well as a cell-free keratinocyte supernatant, inhibited T cell effector functions to the same amount as directly co-cultured keratinocytes, thus proving that soluble factor/s account for the observed suppressive effects. In conclusion, keratinocytes critically control the threshold of inflammatory processes in the skin by inhibiting T cell proliferation and cytokine production

MHC Class I+/II− Dendritic Cells Induce Hapten-Specific Immune Responses In Vitro and In Vivo

Activation requirements and biologic properties of hapten-specific, major histocompatibility complex class I-restricted CD8+ T lymphocytes are not fully understood. To address this issue, a novel CD45+/major histocompatibility complex class I+(H-2k)/II−/CD80+ dendritic cell line, termed 80/1, which is capable of stimulating naïve, allogeneic CD8+ but not CD4+ T cells in vitro, was derivatized with trinitrobenzenesulfonic acid and co-cultured for 4 d with syngeneic, naïve CD8+ T cells. Results obtained showed that trinitrophenyl-derivatized, but not underivatized 80/1 dendritic cells, can induce vigorous proliferation of CD8+ T cells. T-cell blasts generated in this fashion were able to lyse syngeneic, trinitrophenyl-derivatized targets but failed to lyse underivatized or trinitrophenyl-derivatized syngeneic, major histocompatibility complex class I− mutant cells or allogeneic targets. The ability of 80/1 dendritic cells to prime naïve, syngeneic T cells in vivo was tested in a contact hypersensitivity model. C3H/HeN mice were injected subcutaneously with identical numbers of (i) trinitro-phenyl-derivatized 80/1 dendritic cells; (ii) trinitro-phenyl-derivatized 80/1 dendritic cells fragmented by freeze-thawing cycles; (iii) trinitrophenyl-derivatized fibrosarcoma L929; and (iv) trinitrophenyl-derivatized lymphoma R1.1 cells. Whereas live trinitrophenyl-derivatized 80/1 dendritic cells were able to sensitize for contact hypersensitivity, killed hapten-derivatized 80/1 dendritic cells or control cells failed to do so. Thus, we conclude that 80/1 dedritic cells, when compared with major histocompatibility complex class I+ non-dendritic cells, can effectively prime naive, syngeneic CD8+ T cells for hapten-specific responses, probably due to their better costimulatory and migratory properties

Children and adults affected by Cri du Chat syndrome: Care's recommendations

Our objective is to collect data and information for a better care and follow up in Cri du Chat patients. We conducted a literature review in August 2017 and then discuss the outcomes within the ABC (Associazione Bambini Cri du Chat, Italian CdC families support group). A proposal for clinical, laboratory and imaging work up should be performed at various ages in CdC patients. Follow up and rehabilitation should continue lifelong as some improvements can be obtained also in older ages and not to lose acquired skills

The biocompatibility of porous vs non-porous bone cements: a new methodological approach.

Composite cements have been shown to be biocompatible, bioactive, with good mechanical properties and capability to bind to the bone. Despite these interesting characteristic, in vivo studies on animal models are still incomplete and ultrastructural data are lacking. The acquisition of new ultrastructural data is hampered by uncertainties in the methods of preparation of histological samples due to the use of resins that melt methacrylate present in bone cement composition. A new porous acrylic cement composed of polymethyl-metacrylate (PMMA) and β-tricalcium-phosphate (p-TCP) was developed and tested on an animal model. The cement was implanted in femurs of 8 New Zealand White rabbits, which were observed for 8 weeks before their sacrifice. Histological samples were prepared with an infiltration process of LR white resin and then the specimens were studied by X-rays, histology and scanning electron microscopy (SEM). As a control, an acrylic standard cement, commonly used in clinical procedures, was chosen. Radiographic ultrastructural and histological exams have allowed finding an excellent biocompatibility of the new porous cement. The high degree of osteointegration was demonstrated by growth of neo-created bone tissue inside the cement sample. Local or systemic toxicity signs were not detected. The present work shows that the proposed procedure for the evaluation of biocompatibility, based on the use of LR white resin allows to make a thorough and objective assessment of the biocompatibility of porous and non-porous bone cements

TSLP-activated dendritic cells induce human T follicular helper cell differentiation through OX40-ligand.

T follicular helper cells (Tfh) are important regulators of humoral responses. Human Tfh polarization pathways have been thus far associated with Th1 and Th17 polarization pathways. How human Tfh cells differentiate in Th2-skewed environments is unknown. We show that thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) promote human Tfh differentiation from naive CD4 T cells. We identified a novel population, distinct from Th2 cells, expressing IL-21 and TNF, suggestive of inflammatory cells. TSLP-induced T cells expressed CXCR5, CXCL13, ICOS, PD1, BCL6, BTLA, and SAP, among other Tfh markers. Functionally, TSLP-DC-polarized T cells induced IgE secretion by memory B cells, and this depended on IL-4Rα. TSLP-activated DCs stimulated circulating memory Tfh cells to produce IL-21 and CXCL13. Mechanistically, TSLP-induced Tfh differentiation depended on OX40-ligand, but not on ICOS-ligand. Our results delineate a pathway of human Tfh differentiation in Th2 environments

Laser ablation is superior to TACE in large-sized hepatocellular carcinoma: A pilot case-control study

Background:Limited therapies are available for large ( 6540 mm) unresectable hepatocellular carcinoma (HCC). Currently, the standard treatment with transarterial chemoembolisation (TACE) is unsatisfactory with high recurrence rate and limited effect on survival. Laser Ablation (LA) has emerged as a relatively new technique characterized by high efficacy and good safety. This study is aimed to evaluate the efficacy of LA in comparison to TACE in patients with large HCC. Methods: Eighty-two patients with a single HCC nodule 6540 mm (BCLC stage A or B) were enrolled in this case-control study. Forty-one patients were treated with LA and 41 patients were treated with TACE. Response to therapy was evaluated according to the mRECIST criteria. Survival was calculated with Kaplan-Meier from the time of cancer diagnosis to death with values censored at the date of the last follow-up. Results: Twenty-six (63.4%) and 8 (19.5%) patients had a complete response after LA and TACE, respectively (p < 0.001). Subsequently we stratified the HCCs in 3 categories according to the nodule size: 40-50 mm, 51-60 mm, and > 60 mm. LA resulted superior to TACE especially in nodules ranging between 51 and 60 mm in diameter, with a complete response rate post-LA and post-TACE of 75% and 14.3%, respectively (p = 0.0133). The 36 months cumulative survival rate in patients treated with LA and TACE was 55.4% and 48.8%, respectively. The disease recurrence rates after LA and TACE were 19.5% and 75.0%, respectively. Conclusions: LA is a more effective therapeutic option than TACE in patients with solitary large HCC

Inhibition of inflammatory and proliferative responses of human keratinocytes exposed to the sesquiterpene lactones dehydrocostuslactone and costunolide

The imbalance of the intracellular redox state and, in particular, of the glutathione (GSH)/GSH disulfide couple homeostasis, is involved in the pathogenesis of a number of diseases. In many skin diseases, including psoriasis, oxidative stress plays an important role, as demonstrated by the observation that treatments leading to increase of the local levels of oxidant species ameliorates the disease. Recently, dehydrocostuslactone (DCE) and custonolide (CS), two terpenes naturally occurring in many plants, have been found to exert various anti-inflammatory and pro-apoptotic effects on different human cell types. These compounds decrease the level of the intracellular GSH by direct interaction with it, and, therefore, can alter cellular redox state. DCE and CS can trigger S-glutathionylation of various substrates, including the transcription factor STAT3 and JAK1/2 proteins. In the present study, we investigated on the potential role of DCE and CS in regulating inflammatory and proliferative responses of human keratinocytes to cytokines. We demonstrated that DCE and CS decreased intracellular GSH levels in human keratinocytes, as well as inhibited STAT3 and STAT1 phosphorylation and activation triggered by IL-22 or IFN-\u3b3, respectively. Consequently, DCE and CS decreased the IL-22- and IFN-\u3b3-induced expression of inflammatory and regulatory genes in keratinocytes, including CCL2, CXCL10, ICAM-1 and SOCS3. DCE and CS also inhibited proliferation and cell-cycle progression-related gene expression, as well as they promoted cell cycle arrest and apoptosis. In parallel, DCE and CS activated the anti-inflammatory EGFR and ERK1/2 molecules in keratinocytes, and, thus, wound healing in an in vitro injury model. Taken together, our findings encourage the employment of DCE and CS in psoriasis, as they could efficiently counteract the pro-inflammatory effects of IFN-\u3b3 and IL-22 on keratinocytes, revert the apoptosis-resistant phenotype, as well as inhibit hyperproliferation in the psoriatic epidermis

T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays

Chemicals can elicit T-cell-mediated diseases such as allergic contact dermatitis and adverse drug reactions. Therefore, testing of chemicals, drugs and protein allergens for hazard identification and risk assessment is essential in regulatory toxicology. The seventh amendment of the EU Cosmetics Directive now prohibits the testing of cosmetic ingredients in mice, guinea pigs and other animal species to assess their sensitizing potential. In addition, the EU Chemicals Directive REACh requires the retesting of more than 30,000 chemicals for different toxicological endpoints, including sensitization, requiring vast numbers of animals. Therefore, alternative methods are urgently needed to eventually replace animal testing. Here, we summarize the outcome of an expert meeting in Rome on 7 November 2009 on the development of T-cell-based in vitro assays as tools in immunotoxicology to identify hazardous chemicals and drugs. In addition, we provide an overview of the development of the field over the last two decades