Oxidative Stress and Low-Grade Inflammation in Polycystic Ovary Syndrome: Controversies and New Insights

The pathophysiology of Polycystic Ovary Syndrome (PCOS) is quite complex and different mechanisms could contribute to hyperandrogenism and anovulation, which are the main features of the syndrome. Obesity and insulin-resistance are claimed as the principal factors contributing to the clinical presentation; in normal weight PCOS either, increased visceral adipose tissue has been described. However, their role is still debated, as debated are the biochemical markers linked to obesity per se. Oxidative stress (OS) and low-grade inflammation (LGI) have recently been a matter of researcher attention; they can influence each other in a reciprocal vicious cycle. In this review, we summarize the main mechanism of radical generation and the link with LGI. Furthermore, we discuss papers in favor or against the role of obesity as the first pathogenetic factor, and show how OS itself, on the contrary, can induce obesity and insulin resistance; in particular, the role of GH-IGF-1 axis is highlighted. Finally, the possible consequences on vitamin D synthesis and activation on the immune system are briefly discussed. This review intends to underline the key role of oxidative stress and low-grade inflammation in the physiopathology of PCOS, they can cause or worsen obesity, insulin-resistance, vitamin D deficiency, and immune dyscrasia, suggesting an inverse interaction to what is usually considered.     

Microwave hybrid fast sintering of red clay ceramics

This work aimed to examine the performance of the hybrid sintering of clay ceramic in a microwave furnace, compared to the sintering process in a conventional furnace. The raw materials were subjected to X-ray fluorescence, loss on ignition (LOI), X-ray diffraction, particle size distribution, real specific mass, and thermogravimetric analyses. The red clay ceramic mass was prepared, extruded, pre-sintered in a conventional furnace at 600°C/60 min, and sintered at temperatures between 700 °C and 1100 °C. The sintering conventional (resistive oven) was carried out for 60 min with a heating rate of 10°C/min. In the microwave furnace, the sintering times were 5, 10, and 15 min, with a heating rate of 50°C/min, with a sintering chamber coated with silicon carbide (susceptor). The sintered specimens were characterized according to linear shrinkage, water absorption, apparent porosity, apparent specific mass, X-ray diffraction, Raman spectroscopy analysis, spectroscopy analysis in the ultraviolet and visible regions, microhardness, and scanning electron microscopy. The results showed that microwave sintering promoted an increase in the microhardness and apparent specific mass, and reduction in water absorption and apparent porosity values, due to greater densification in the microstructure. The best results occurred for specimens sintered at 1100°C.     

Characterisation of the Dynamic Interactions between Complex N-Glycans and Human CD22

CD22 (Siglec-2) is a B-cell surface inhibitory protein capable of selectively recognising sialylated glycans, thus dampening autoimmune responses against self-antigens. Here we have characterised the dynamic recognition of complex-type N-glycans by human CD22 by means of orthogonal approaches including NMR spectroscopy, computational methods and biophysical assays. We provide new molecular insights into the binding mode of sialoglycans in complex with h-CD22, highlighting the role of the sialic acid galactose moieties in the recognition process, elucidating the conformational behaviour of complex-type N-glycans bound to Siglec-2 and dissecting the formation of CD22 homo-oligomers on the B-cell surface. Our results could enable the development of additional therapeutics capable of modulating the activity of h-CD22 in autoimmune diseases and malignancies derived from B-cells.     

Discovery of New Antiproliferative Imidazopyrazole Acylhydrazones Able To Interact with Microtubule Systems

Even though immunotherapy has radically changed the search for anticancer therapies, there are still many different pathways that are open to intervention with traditional small molecules. To expand our investigation in the anticancer field, we report here a new series of compounds in which our previous pyrazole and imidazopyrazole scaffolds are linked to a differently decorated phenyl ring through an acylhydrazone linker. Preliminary tests on the library were performed at the National Cancer Institute (USA) against the full NCI 60 cell panel. The best compounds among the imidazopyrazole series were then tested by immunofluorescence staining for their inhibition of cell proliferation, apoptosis induction, and their effect on the cell cycle and on microtubules. Two compounds, in particular 4-benzyloxy-3-methoxybenzyliden imidazopyrazole-7-carbohydrazide showed good growth inhibition, with IC₅₀ values in the low-micromolar range, and induced apoptosis. Both compounds altered the cell-cycle phases with the appearance of polyploid cells. Immunofluorescence analysis evidenced microtubules alterations; tubulin polymerization assays and docking studies suggested the tubulin system to be the possible, although not exclusive, target of the new acylhydrazone series reported here.     

Antifungal and antimycotoxigenic effects of Zingiber officinale,Cinnamomum zeylanicum and Cymbopogon martinii essential oils against Fusarium verticillioides

ABSTRACT

There is an increasing demand for fungi control in grains, especially toxigenic. Also, there is growing concern on the use of synthetic fungicides; thus alternatives are needed. The aim of this study was to evaluate the antifungal and antimycotoxigenic action of essential oils (EOs) from Zingiber officinale, Cinnamomum zeylanicum and Cymbopogon martinii against Fusarium verticillioides, a spoilage and toxigenic fungus. Essential oils were first chemically characterised by gas chromatography coupled to mass spectrometry, and their antioxidant potential was measured by the DPPH, ABTS and FRAP methods. Minimum inhibitory concentration (MIC) and disc diffusion were used to assess antifungal activity. Scanning electron microscopy was used to evaluate morphological changes in the fungus. Antimycotoxigenic activity of the EOs against the production of fumonisin B₁ and B₂ by F. verticillioides was evaluated using ultra-high-performance liquid chromatography system. Z. officinale, C. zeylanicum and C. martinii EOs were predominantly composed by zingiberene and geranial; eugenol; and geraniol, respectively. All the EOs had high antioxidant power, especially that from C. zeylanicum. The MICs were 250, 500 and 2,000 µg mL^?1 for C. zeylanicum, C. martinii and Z. officinale EOs, respectively. Mycelial reduction of F. verticillioides was observed when EOs were used, and the lowest activity was detected in the Z. officinale EO. Overall, the tested EOs promoted structural damage to the fungal cell wall, decreased conidia size and mycelial reduction. Antimycotoxigenic evaluation of the EOs evidenced a significant reduction (p < .05) in the production of fumonisins B₁ and B₂ with all the EOs evaluated in the study. These results suggest that especially C. zeylanicum and C. martinii EOs are highly useful for controlling F. verticillioides and fumonisins production.     

Gastric Adenocarcinomas and Signet-Ring Cell Carcinoma: Unraveling Gastric Cancer Complexity through Microbiome Analysis—Deepening Heterogeneity for a Personalized Therapy

Gastric cancer (GC) is the fifth most prevalent cancer worldwide and the third leading cause of global cancer mortality. With the advances of the omic studies, a heterogeneous GC landscape has been revealed, with significant molecular diversity. Given the multifaceted nature of GC, identification of different patient subsets with prognostic and/or predictive outcomes is a key aspect to allow tailoring of specific treatments. Recently, the involvement of the microbiota in gastric carcinogenesis has been described. To deepen this aspect, we compared microbiota composition in signet-ring cell carcinoma (SRCC) and adenocarcinoma (ADC), two distinct GC subtypes. To this purpose, 10 ADC and 10 SRCC and their paired non-tumor (PNT) counterparts were evaluated for microbiota composition through 16S rRNA analysis. Weighted and unweighted UniFrac and Bray–Curtis dissimilarity showed significant community-level separation between ADC and SRCC. Through the LEfSe (linear discriminant analysis coupled with effect size) tool, we identified potential microbial biomarkers associated with GC subtypes. In particular, SRCCs were significantly enriched in the phyla Fusobacteria, Bacteroidetes, Patescibacteria, whereas in the ADC type, Proteobacteria and Acidobacteria phyla were found. Overall, our data add new insights into GC heterogeneity and may contribute to deepening the GC classification.     

Simulation of vacuum distillation to produce alcohol-free beer

Several processes have been developed for producing alcohol-free beer while maintaining desirable sensory characteristics. One of the most popular thermal processes used is distillation, where not only ethanol but volatile aromatic components are partly or completely removed from the beer. Based on data from the literature and using the Aspen Plus simulator, this study evaluates and compares the aroma profiles of alcohol-free beers obtained by continuous vacuum distillation with different pressures and processes. Three processes were simulated at pressures of 60, 102, and 200 mbar. The first (Process A) was a standard continuous vacuum distillation, where the bottom product was an alcohol-free beer. In the second (Process B), the bottom product was blended with a standard beer that had not undergone any thermal process. In the third (Process C), part of the top stream was mixed with the bottom product. This study considered eight major compounds in beer: ethanol, propanol, isobutanol, 2-methyl-1-butanol, 3-methyl-1-butanol, ethyl acetate, diacetyl and isoamyl acetate. The three simulated pressure ranges showed similar results, indicating that reducing the pressure below 200 mbar did not improve separation. Further, vacuum distillation did not remove diacetyl from the beer. Processes B and C resulted in beer that was richer in flavour compounds. Furthermore, when these processes were compared to Process A, the concentration of esters was markedly higher. © 2019 The Institute of Brewing & Distilling     

Structural and Functional Characterization of 4-Hydroxyphenylacetate 3-Hydroxylase from Escherichia coli

The hydroxylation of phenols into polyphenols, which are valuable chemicals and pharmaceutical products, is a challenging reaction. The search for green synthetic processes has led to considering microorganisms and pure hydroxylases as catalysts for phenol hydroxylation. Herein, we report the structural and functional characterization of the flavin adenine dinucleotide (FAD)-dependent 4-hydroxyphenylacetate 3-monooxygenase from Escherichia coli, named HpaB. It is shown that this enzyme enjoys a relatively broad substrate specificity, which allows the conversion of a number of non-natural phenolic compounds, such as tyrosol, hydroxymandelic acid, coumaric acid, hydroxybenzoic acid and its methyl ester, and phenol, into the corresponding catechols. The reaction can be performed by using a simple chemical assay based on formate as the electron donor and the organometallic complex [Rh(bpy)Cp*(H₂O)]²⁺ (Cp*: 1,2,3,4,5-pentamethylcyclopentadiene, bpy: 2,2′-bipyridyl) as the catalyst for FAD reduction. The availability of a crystal structure of HpaB in complex with FAD at 1.8 Å resolution opens up the possibility of the rational tuning of the substrate specificity and activity of this interesting class of phenol hydroxylases.