Blastic plasmacytoid dendritic cell neoplasm: Genomics mark epigenetic dysregulation as a primary therapeutic target

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy for which there is still no effective B therapy. In order to identify genetic alterations useful for a new treatment design, we used whole-exome sequencing to analyze 14 BPDCN patients and the patient-derived CAL-1 cell line. The functional enrichment analysis of mutational data reported the epigenetic regulatory program to be the most significantly undermined (P<0.0001). In particular, twenty-five epigenetic modifiers were found mutated (e.g. ASXL1, TET2, SUZ12, ARID1A, PHF2, CHD8); ASXL1 was the most frequently affected (28.6% of cases). To evaluate the impact of the identified epigenetic mutations at the gene-expression and Histone H3 lysine 27 trimethylation/acetylation levels, we performed additional RNA and pathology tissue-chromatin immunoprecipitation sequencing experiments. The patients displayed enrichment in gene signatures regulated by methylation and modifiable by decitabine administration, shared common H3K27-acetylated regions, and had a set of cell-cycle genes aberrantly up-regulated and marked by promoter acetylation. Collectively, the integration of sequencing data showed the potential of a therapy based on epigenetic agents. Through the adoption of a preclinical BPDCN mouse model, established by CAL-1 cell line xenografting, we demonstrated the efficacy of the combination of the epigenetic drugs 5’-azacytidine and decitabine in controlling disease progression in vivo

Pathogenetic and diagnostic significance of microRNA deregulation in peripheral T-cell lymphoma not otherwise specified

Peripheral T-cell lymphomas not otherwise specified (PTCLs/NOS) are rare and aggressive tumours whose molecular pathogenesis and diagnosis are still challenging. The microRNA (miRNA) profile of 23 PTCLs/NOS was generated and compared with that of normal T-lymphocytes (CD4+, CD8+, naive, activated). The differentially expressed miRNA signature was compared with the gene expression profile (GEP) of the same neoplasms. The obtained gene patterns were tested in an independent cohort of PTCLs/NOS. The miRNA profile of PTCLs/NOS then was compared with that of 10 angioimmunoblastic T-cell lymphomas (AITLs), 6 anaplastic large-cell lymphomas (ALCLs)/ALK+ and 6 ALCLs/ALK - . Differentially expressed miRNAs were validated in an independent set of 20 PTCLs/NOS, 20 AITLs, 19 ALCLs/ALK - and 15 ALCLs/ALK+. Two hundred and thirty-six miRNAs were found to differentiate PTCLs/NOS from activated T-lymphocytes. To assess which miRNAs impacted on GEP, a multistep analysis was performed, which identified all miRNAs inversely correlated to different potential target genes. One of the most discriminant miRNAs was selected and its expression was found to affect the global GEP of the tumours. Moreover, two sets of miRNAs were identified distinguishing PTCL/NOS from AITL and ALCL/ALK - , respectively. The diagnostic accuracy of this tool was very high (83.54%) and its prognostic value validated

Competition between starter cultures and wild microbial population in sausage fermentation: A case study regarding a typical italian salami (ventricina)

The work reports a case study describing how the competition wild microflora vs. starter cultures affects the final product characteristics. This study regards an industrial lot of Ventricina, an Italian long-ripened traditional fermented sausages, produced using starter cultures. After ripening, some relevant organoleptic defects (off-odour, crust formation) were observed. Therefore, analyses were carried out in the inner and outer sausage section to explain this phenomenon. Microbiological analyses indicated a high meat batter contamination and metagenomic analyses evidenced the inability of LAB starter cultures to lead the fermentation process. The results of this not controlled fermentation were the accumulation of high levels of biogenic amines (including histamine) and the formation of a volatile profile different if compared with similar products. Indeed, the volatilome analysis revealed unusually high amounts of molecules such as isovaleric acid, propanoic acid, 1-propanol, which can be responsible for off-odours. This study demonstrated that starter culture use needs to be modulated in relation to production parameters to avoid safety and organoleptic concerns

Maximizing the antioxidant capacity of Padina pavonica by choosing the right drying and extraction methods

Marine algae are becoming an interesting source of biologically active compounds with a promising application as nutraceuticals, functional food ingredients, and therapeutic agents. The effect of drying (freeze-drying, oven-drying, and shade-drying) and extraction methods (shaking at room temperature, shaking in an incubator at 60 \ub0C, ultrasound-assisted extraction (UAE), and microwave-assisted extraction (MAE)) on the total phenolics content (TPC), total flavonoids content (TFC), and total tannins content (TTC), as well as antioxidant capacity of the water/ethanol extracts from Padina pavonica were investigated. The TPC, TFC, and TTC values of P. pavonica were in the range from 0.44 \ub1 0.03 to 4.32 \ub1 0.15 gallic acid equivalents in mg/g (mg GAE/g) dry algae, from 0.31 \ub1 0.01 to 2.87 \ub1 0.01 mg QE/g dry algae, and from 0.32 \ub1 0.02 to 10.41 \ub1 0.62 mg CE/g dry algae, respectively. The highest TPC was found in the freeze-dried sample in 50% ethanol, extracted by MAE (200 W, 60 \ub0C, and 5 min). In all cases, freeze-dried samples extracted with ethanol (both 50% and 70%) had the higher antioxidant activity, while MAE as a green option reduces the extraction time without the loss of antioxidant activity in P. pavonica

Ethanol to gasoline and sustainable aviation fuel precursors: an innovative cascade strategy over Zr-based multifunctional catalysts in the gas phase

In the biorefinery context, bioethanol upgrading has been identified as a valuable approach to develop a circular economy for fuels and chemicals production. In this work, the gas-phase, continuous flow catalytic upgrading of ethanol to blends with features close to those suitable for jet fuel is tackled through an innovative strategy based on the promotion of several reactions in cascade. Catalytic transfer hydrogenation, aldol condensation, dehydrogenative coupling, and ketonization reactions were combined in a one-pot approach over a relatively simple and cheap catalytic system consisting of copper nanoparticles supported on zirconium (and lanthanum) oxides. The resulting cascade reaction scheme led to the production of a blend of oxygenated adducts in the C6-C14 range with promising properties for use as jet fuel. By tailoring the features of the non-innocent support and/ or co-feeding hydrogen to the reactor, up to 40% selectivity for the jet fuel range fraction, with ethanol conversion above 85%, was achieved during the first 6 h of time on stream, simultaneously enhancing catalyst stability and lifetime

Sustainable isosorbide production by a neat one-pot MW-assisted catalytic glucose conversion

In the context of exploitation of new biomass-derived platform chemicals, isosorbide (1,4:3,6-dianhydro-D-sorbitol), obtained by the two-fold dehydration of sorbitol, is gaining increasing interest in several potential industrial applications. Seeking for more sustainable, efficient, and economically competitive green processes, the use of heterogeneous catalysts under microwave (MW) irradiation has been adopted for the development of a neat one-pot process from glucose. MW-assisted catalytic processes have shown the potential to reduce the reaction time and improve the selectivity, due to the interaction of MW with the reaction medium through the production of hot spots on the catalyst surface. Ru/C, Ru/Al2O3 and Ru/TiO2 were tested for glucose hydrogenation to sorbitol, while the dehydration step was favored by the addition of beta Zeolites (360:1 SiO2:Al2O3) allowing high isosorbide selectivity (>85 %). An extended structural and morphological characterization before and after the catalytic tests allowed to establish structure-activity relationships. Yields up to 47.1 % have been obtained directly from glucose in 1.5 h, achieving a considerable reduction of reaction time without the use of a solvent. thus paving the way for further investigations on biomass conversion into value-added products. With this aim, direct isosorbide production from milled cellulose was investigated. While the isosorbide yields still need to be improved, the dual role of formic acid both as acid catalyst for cellulose hydrolysis and H-donor for the reduction step was promisingly clarified

1-Butanol dehydration and oxidation over vanadium phosphate catalysts

The transformation of 1-butanol into either butenes or maleic anhydride was carried out both with and without oxygen, using V/P/O catalysts. With vanadyl pyrophosphate prepared by coprecipitation, at temperature lower than 240 ◦C and without oxygen, selectivity to butenes was higher than 90%, but a slow deactivation took place. At temperature higher than 300 ◦C and in the presence of air, maleic and phthalic anhydrides were the prevailing products, with selectivity of 60% and 14%, respectively. Catalytic performance was affected by crystallinity and acidity. αI-VOPO4 showed a poor performance in the absence of air, with a quick deactivation due to coke accumulation; but it displayed an excellent selectivity to butenes (close to 98%) at temperatures lower than 320 ◦C in the presence of air, with stable performance. At temperature higher than 360 ◦C, α I-VOPO4 was reduced to vanadyl pyrophosphate and catalyzed the direct oxidation of 1-butanol into maleic anhydride, but with 35% selectivit

Tandem reductive catalytic upgrading of orange peel waste derived methyl levulinate and limonene into γ-valerolactone and p-cymene promoted by Pd/ZrO2 and ZrO2 catalysts

Orange peel waste (OPW), a significant biomass byproduct derived from the juice processing industry, can be used as valuable resource to produce various chemicals, including methyl levulinate (ML) and limonene (LIM). This study introduces a tandem catalytic process involving the dehydrogenation of LIM into p-cymene and the (transfer) hydrogenation of ML into γ-valerolactone (GVL), unlocking the full potential of OPW chemo-catalytic valorisation in the spirit of circular economy. This process is promoted by the heterogeneous Pd/ZrO2 and t-ZrO2 catalysts in the presence of ethanol as hydrogen-donor solvent. Under batch conditions, Pd/ZrO2 not only shows superior performance in the transfer hydrogenation of ML compared to t-ZrO2, but also promotes the conversion of LIM into p-cymene primarily through the hydrogenation/dehydrogenation route. Most important, Pd/ZrO2 exhibits good activity in the simultaneous upgrading of both ML and LIM across various ML:LIM ratios. Continuous gas-flow conditions result in improved outcomes in terms of ML and LIM conversion, as well as GVL and CYM selectivity. Notably, a strong correlation between CYM and H2 yields has been established providing compelling evidence for the LIM isomerization-dehydrogenation pathway. However, the simultaneous upgrading of LIM and ML was found to be not efficient in the gas-phase due to side oligomerization reactions

Glycerol Carbonate as a Versatile Alkylating Agent for the Synthesis of β-Aryloxy Alcohols

The possibility to use glycerol carbonate (GlyC) as an innovative alkylating agent for phenolic compounds in solventless conditions and in the presence of a catalytic amount of both homogeneous and heterogeneous bases is herein described. In particular, the peculiar, polyfunctional structure of GlyC allows one to obtain the formation not only of the mono-phenoxy-1,2-propanediol (MPP) analogue but also of 1,3-diphenoxy-2-propanol (DPP), the latter being elusive using the more traditional, toxic, and carcinogenic reagents such as glycidol and/or 3-chloro-1,2-propandiol. The production of DPP is indeed possible due to the in situ formation of a reactive intermediate, 4-(phenoxy)methyl-1,3-dioxolane-2-one (PhOGlyC), which may undergo a consecutive nucleophilic attack of a phenolate, leading to the selective formation of the disubstituted product. This reaction is nonetheless in competition with PhOGlyC decarboxylation that finally limits DPP yield up to 20%, with an MPP yield up to roughly 60% in the optimized conditions (atmospheric pressure, 140 degrees C, 5 h using Cs2CO3 as the basic catalyst) starting directly from a GlyC/phenolic mixture. For this reason, a multistep synthetic strategy has also been developed, first by obtaining the quantitative formation and isolation of the PhOGlyC intermediate and then by promoting the consecutive reaction with phenol, in this way obtaining a DPP yield of 66% after only 1 h of reaction at 170 degrees C. The obtained phenyl glyceryl ethers are interesting drugs scaffolds (i.e., guaifenesin, mephenesin), intermediates in the preparation of active pharmaceutical ingredients (e.g., chlorphenesin carbamate, methocarbamol), and hydrotropic solvents; preliminary evaluations of MPP and DPP biodegradability and use as alternative surfactants have also been described in this paper

Peripheral t‐cell lymphoma, not otherwise specified : Clinical manifestations, diagnosis, and future treatment

Peripheral T‐cell lymphoma, not otherwise specified (PTCL_NOS) corresponds to about one fourth of mature T‐cell tumors, which overall represent 10–12% of all lymphoid malignancies. This category comprises all T‐cell neoplasms, which do not correspond to any of the distinct entities listed in the WHO (World Health Organization) Classification of Tumours of Haematopoietic and Lymphoid Tissues. In spite of the extreme variability of morphologic features and phenotypic profiles, gene expression profiling (GEP) studies have shown a signature that is distinct from that of all remaining PTCLs. GEP has also allowed the identification of subtypes provided with prognostic relevance. Conversely to GEP, next‐generation sequencing (NGS) has so far been applied to a limited number of cases, providing some hints to better understand the pathobiology of PTCL_NOS. Although several pieces of information have emerged from pathological studies, PTCL_NOS still remains a tumor with a dismal prognosis. The usage of CHOEP (cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide) followed by autologous stem cell transplantation may represent the best option, by curing about 50% of the patients whom such an approach can be applied to. Many new drugs have been proposed without achieving the expected results. Thus, the optimal treatment of PTCL_NOS remains unidentified