Tryptophan Metabolites at the Crossroad of Immune-Cell Interaction via the Aryl Hydrocarbon Receptor: Implications for Tumor Immunotherapy

The Aryl hydrocarbon receptor (AhR) is a critical regulator of both innate and adaptive immune responses, with potent immunomodulatory effects that makes this receptor an attractive molecular target for novel therapeutics. Accumulating evidence indicates that diverse—both host’s and microbial—tryptophan metabolites profoundly regulate the immune system in the host via AhR, promoting either tolerance or immunity, largely as a function of the qualitative and quantitative nature of the metabolites being contributed by either source. Additional findings indicate that host and microbiota-derived tryptophan metabolic pathways can influence the outcome of immune responses to tumors. Here, we review recent studies on the role and modalities of AhR activation by various ligands, derived from either host-cell or microbial-cell tryptophan metabolic pathways, in the regulation of immune responses. Moreover, we highlight potential implications of those ligands and pathways in tumor immunotherapy, with particular relevance to checkpoint-blockade immune intervention strategies.     

Supporting NGNs Core Software Services: A Hybrid Architecture and its Performance Analysis

In the last few years telco providers are striving to migrate their services from the traditional Public Switch Telephone Network to so called Next Generation Networks (NGNs) based on standard IP connectivity. This switch is expected to produce a cost degression of 50% for CAPital EXpenditure, while OPerating EXpences remains fairly stable due to network management and energy costs. At the same time, the instantiation of new telco services (Voice over IP, video conferencing, etc.) and the support of third party applications (such as support to smartphone applications, etc.) are expected to produce a big increase of the load of a telco provider at the core level. The goal of this work is to show how management and energy costs can be effectively reduced by leveraging autonomic approaches to move some NGN services toward the telco network edge while still providing Quality of Service (QoS) levels comparable with those provided by a traditional fully-managed infrastructure. This is done by taking into consideration the increase of the load of such services that is expected to raise by one order of magnitude in the near future. Specifically, we propose a hybrid architecture letting telco administrators reduce the number of servers in the provider managed network by exploiting home devices in the computation and by organizing them in a self-configuring Peer to Peer system; in this way it is possible to reduce the overall system and operational costs. Our claims are supported by an experimental study based on both simulations and theoretical models that analyze the trade-off between the number of servers and home devices in order to guarantee a service within QoS constraints. Experiments are carried out on a realistic model that abstracts the lookup procedures within the NGN of a big telco provider (i.e., finding the IP address of a given unique user profile).     

High‐Temperature Structural Evolution of the Disordered LiMn1.5Ni0.5O4

In this work, we present our recent results about the changes induced on a crystalline bulk LiMn_1.5Ni_0.5O₄ disordered cubic spinel phase by thermal treatments carried out under different back atmospheres (vacuum and air). Our aim is to describe the structural changes induced by temperature in various conditions both on the long range (by means of XRD) and on the short range around Mn/Ni metal sites (by means of EXAFS) and to investigate the reversible oxygen loss and adsorption upon heating and cooling, respectively. In summary, the LiMn_1.5Ni_0.5O₄ phase suffers large structural modifications above 650°C both under vacuum and air. These alterations are closely related to the occurrence of large oxygen vacancies in the anionic sublattice due to spontaneous oxygen loss via the gas phase. Apparently, local and long‐range distortions from the pristine disordered cubic spinel structure are completely reversible in air upon cooling from high temperature, whereas under vacuum, the structural alterations are permanent.     

Human Cell Encapsulation in Gel Microbeads with Cosynthesized Concentric Nanoporous Solid Shells

Encapsulation of therapeutic cells in core–shell microparticles has great promise for the treatment of a range of health conditions. Unresolved challenges related to control of the particle morphology, mechanical stability, and immunogenicity hinder dissemination of this promising approach. Here, a novel polymer material for cell encapsulation and a combined novel, easy to control, synthesis method are introduced. Core–shell cell encapsulation is demonstrated with a concentric core–shell morphology formed during a single UV exposure, resulting in particles that consist of a synthetic hydrogel core of polyethylene glycol diacrylate and a solid, but porous, shell of off‐stoichiometric thiol‐ene. The encapsulated human cells in 100 µm diameter particles have >90% viability. The average shell thickness is controlled between 7 and 13 µm by varying the UV exposure, and the shell is measured to be permeable to low molecular weight species (<180 Da) but impermeable to higher molecular weight species (>480 Da). The unique material properties and the orthogonal control of the microparticle core size, shell thickness, shell permeability, and shell surface properties address the key unresolved challenges in the field, and are expected to enable faster translation of novel cell therapy concepts from research to clinical practice.     

Sigma-1 Receptor Agonists Acting on Aquaporin-Mediated H2O2 Permeability: New Tools for Counteracting Oxidative Stress

Sigma1 Receptor (S1R) is involved in oxidative stress, since its activation is triggered by oxidative or endoplasmic reticulum stress. Since specific aquaporins (AQP), called peroxiporins, play a relevant role in controlling H₂O₂ permeability and ensure reactive oxygen species wasted during oxidative stress, we studied the effect of S1R modulators on AQP-dependent water and hydrogen peroxide permeability in the presence and in the absence of oxidative stress. Applying stopped-flow light scattering and fluorescent probe methods, water and hydrogen peroxide permeability in HeLa cells have been studied. Results evidenced that S1R agonists can restore water permeability in heat-stressed cells and the co-administration with a S1R antagonist totally counteracted the ability to restore the water permeability. Moreover, compounds were able to counteract the oxidative stress of HeLa cells specifically knocked down for S1R. Taken together these results support the hypothesis that the antioxidant mechanism is mediated by both S1R and AQP-mediated H₂O₂ permeability. The finding that small molecules can act on both S1R and AQP-mediated H₂O₂ permeability opens a new direction toward the identification of innovative drugs able to regulate cell survival during oxidative stress in pathologic conditions, such as cancer and degenerative diseases.     

The Effect of Natural Ingredients (Amaranth and Pumpkin Seeds) on the Quality Properties of Chicken Burgers

The objective of the current study was to include natural ingredients in the formulation of chicken burgers to improve their quality properties (physicochemical, cooking, oxidation and sensorial properties) during 4 days of refrigerated storage at 4 °C. Chicken burgers were processed added with amaranth (1 and 2%) or pumpkin seeds (1 and 2%) in addition to control. Lipid oxidation was assessed by monitoring malonaldehyde formation with 2-thiobarbituric acid reactive substances (TBARS) assay and antioxidant capacity by ABTS, DPPH and FRAPS methods. Natural ingredients (amaranth and pumpkin seeds) used in manufacturing of chicken burgers may improve their cooking characteristics, as well as lipid stability during storage (this effect was stronger when amaranth was added). Moreover, the impact of these ingredients on sensory quality attributes of chicken burgers was not significant; even in some cases (burgers with 2% amaranth), the overall acceptability was scored as higher than control burgers.     

Evaluation of Controlled Ovarian Stimulation Protocols in Patients with Normal and Low Ovarian Reserve: Analyses of miRNAs and Selected Target Genes Involved in the Proliferation of Human Cumulus Cells and Oocyte Quality

The oocyte and the surrounding cumulus cells (CCs) are deeply linked by a complex bidirectional cross-talk. In this light, the molecular analysis of the CCs is nowadays considered to be precious in providing information on oocyte quality. It is now clear that miRNAs play a key role in several ovarian functions, such as folliculogenesis, steroidogenesis, and ovulation. Thus, in this study, specific miRNAs, together with their target genes, were selected and investigated in CCs to assess the response of patients with normal (NR) and low (LR) ovarian reserve to two different controlled ovarian stimulation (COS) protocols, based on rFSH and hMG. Moreover, a Fourier transform infrared microspectroscopy (FTIRM) analysis was performed to evaluate DNA conformational changes in CCs and to relate them with the two COS protocols. The results evidenced a modulation of the expression of miRNAs and related target genes involved in CCs’ proliferation, in vasculogenesis, angiogenesis, genomic integrity, and oocyte quality, with different effects according to the ovarian reserve of patients. Moreover, the COS protocols determined differences in DNA conformation and the methylation state. In particular, the results clearly showed that treatment with rFSH is the most appropriate in NR patients with normal ovarian reserve, while treatment with hMG appears to be the most suitable in LR patients with low ovarian reserve.     

Accuracy and biases in predicting the chemical and physical traits of many types of cheeses using different visible and near-infrared spectroscopic techniques and spectrum intervals

Near-infrared spectroscopy (NIRS) has been widely used to determine various composition traits of many dairy products in the industry. In the last few years, near-infrared (NIR) instruments have become more and more accessible, and now, portable devices can be easily used in the field, allowing the direct measurement of important quality traits. However, the comparison of the predictive performances of different NIR instruments is not simple, and the literature is lacking. These instruments may use different wavelength intervals and calibration procedures, making it difficult to establish whether differences are due to the spectral interval, the chemometric approach, or the instrument's technology. Hence, the aims of this study were (1) to evaluate the prediction accuracy of chemical contents (5 traits), pH, texture (2 traits), and color (5 traits) of 37 categories of cheese; (2) to compare 3 instruments [2 benchtop, working in reflectance (R) and transmittance (T) mode (NIRS-R and NIRS-T, respectively) and 1 portable device (VisNIRS-R)], using their entire spectral ranges (1100–2498, 850–1048, and 350–1830 nm, respectively, for NIRS-R, NIRS-T and VisNIRS-R); (3) to examine different wavelength intervals of the spectrum within instrument, comparing also the common intervals among the 3 instruments; and (4) to determine the presence of bias in predicted traits for specific cheese categories. A Bayesian approach was used to develop 8 calibration models for each of 13 traits. This study confirmed that NIR spectroscopy can be used to predict the chemical composition of a large number of different cheeses, whereas pH and texture traits were poorly predicted. Color showed variable predictability, according to the trait considered, the instrument used, and, within instrument, according to the wavelength intervals. The predictive performance of the VisNIRS-R portable device was generally better than the 2 laboratory NIRS instruments, whether with the entire spectrum or selected intervals. The VisNIRS-R was found suitable for analyzing chemical composition in real time, without the need for sample uptake and processing. Our results also indicated that instrument technology is much more important than the NIR spectral range for accurate prediction equations, but the visible range is useful when predicting color traits, other than lightness. Specifically for certain categories (i.e., caprine, moldy, and fresh cheeses), dedicated calibrations seem to be needed to obtain unbiased and more accurate results.