Magnetic Molecularly Imprinted Nano-Conjugates for Effective Extraction of Food Components—A Model Study of Tyramine Determination in Craft Beers

In this paper, magnetic molecularly imprinted nano-conjugates were synthesized to serve as selective sorbents in a model study of tyramine determination in craft beer samples. The molecularly imprinted sorbent was characterized in terms of morphology, structure, and composition. The magnetic dispersive solid phase extraction protocol was developed and combined with liquid chromatography coupled with mass spectrometry to determine tyramine. Ten samples of craft beers were analyzed using a validated method, revealing tyramine concentrations in the range between 0.303 and 126.5 mg L⁻¹. Tyramine limits of detection and quantification were 0.033 mg L⁻¹ and 0.075 mg L⁻¹, respectively. Therefore, the fabricated molecularly imprinted magnetic nano-conjugates with a fast magnetic responsivity and desirable adsorption performance could be an effective tool for monitoring tyramine levels in beverages.     

Astroglial and Microglial Purinergic P2X7 Receptor as a Major Contributor to Neuroinflammation during the Course of Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system that leads to the progressive disability of patients. A characteristic feature of the disease is the presence of focal demyelinating lesions accompanied by an inflammatory reaction. Interactions between autoreactive immune cells and glia cells are considered as a central mechanism underlying the pathology of MS. A glia-mediated inflammatory reaction followed by overproduction of free radicals and generation of glutamate-induced excitotoxicity promotes oligodendrocyte injury, contributing to demyelination and subsequent neurodegeneration. Activation of purinergic signaling, in particular P2X7 receptor-mediated signaling, in astrocytes and microglia is an important causative factor in these pathological processes. This review discusses the role of astroglial and microglial cells, and in particular glial P2X7 receptors, in inducing MS-related neuroinflammatory events, highlighting the importance of P2X7R-mediated molecular pathways in MS pathology and identifying these receptors as a potential therapeutic target.     

Tolerogenic Dendritic Cell-Based Approaches in Autoimmunity

Dendritic cells (DCs) dictate the outcomes of tissue-specific immune responses. In the context of autoimmune diseases, DCs instruct T cells to respond to antigens (Ags), including self-Ags, leading to organ damage, or to becoming regulatory T cells (Tregs) promoting and perpetuating immune tolerance. DCs can acquire tolerogenic properties in vitro and in vivo in response to several stimuli, a feature that opens the possibility to generate or to target DCs to restore tolerance in autoimmune settings. We present an overview of the different subsets of human DCs and of the regulatory mechanisms associated with tolerogenic (tol)DC functions. We review the role of DCs in the induction of tissue-specific autoimmunity and the current approaches exploiting tolDC-based therapies or targeting DCs in vivo for the treatment of autoimmune diseases. Finally, we discuss limitations and propose future investigations for improving the knowledge on tolDCs for future clinical assessment to revert and prevent autoimmunity. The continuous expansion of tolDC research areas will lead to improving the understanding of the role that DCs play in the development and treatment of autoimmunity.     

Total antioxidant activity and trace elements in human milk: the first 4 months of breast-feeding

The content of many nutrients in breast milk are dependent on the nutritional status of the lactating woman. This is particularly true for fat and water-soluble vitamins, some of which have antioxidant properties. The aim of the study entertained herein was to evaluate the changes in total antioxidant status of human milk during the first 4 months of lactation, and to correlate such changes with the contents in specific antioxidant oligoelements (Cu, Zn, Mn and Se). Milk samples were collected from (31) lactating women recruited at the Service of Obstetrics of the Hospital de São João in Porto, after 1, 4, 8, 12 and 16 weeks after birth. The total antioxidant status (TAS) of human milk was measured by the Randox^® commercial kit and trace metals by ICP-MS (inductively coupled plasma-mass spectrometry). The results found for TAS and oligoelements under study show a decrease in the concentration of these parameters from 7 days to 4 months of breast-feeding and significant correlations (p < 0.05) were found between TAS and Cu, Zn and Se (not Mn). The decreases of Cu, Zn and Se were also correlated, but not proportional between them, suggesting diverse excretion mechanisms for all. Between primipara and multipara women, a significant difference was found only for Cu and Zn concentrations at 7 days of lactation, but not for the other metals or TAS. With respect to the mother’s age, no correlation was found, either for trace metal concentrations or TAS.     

Efficient In Vitro and In Vivo Anti-Inflammatory Activity of a Diamine-PEGylated Oleanolic Acid Derivative

Recent evidence has shown that inflammation can contribute to all tumorigenic states. We have investigated the anti-inflammatory effects of a diamine-PEGylated derivative of oleanolic acid (OADP), in vitro and in vivo with inflammation models. In addition, we have determined the sub-cytotoxic concentrations for anti-inflammatory assays of OADP in RAW 264.7 cells. The inflammatory process began with incubation with lipopolysaccharide (LPS). Nitric oxide production levels were also determined, exceeding 75% inhibition of NO for a concentration of 1 µg/mL of OADP. Cell-cycle analysis showed a reversal of the arrest in the G0/G1 phase in LPS-stimulated RAW 264.7 cells. Furthermore, through Western blot analysis, we have determined the probable molecular mechanism activated by OADP; the inhibition of the expression of cytokines such as TNF-α, IL-1β, iNOS, and COX-2; and the blocking of p-IκBα production in LPS-stimulated RAW 264.7 cells. Finally, we have analyzed the anti-inflammatory action of OADP in a mouse acute ear edema, in male BL/6J mice treated with OADP and tetradecanoyl phorbol acetate (TPA). Treatment with OADP induced greater suppression of edema and decreased the ear thickness 14% more than diclofenac. The development of new derivatives such as OADP with powerful anti-inflammatory effects could represent an effective therapeutic strategy against inflammation and tumorigenic processes.     

Polyphenolic Composition and Antioxidant Activity of Galician Monovarietal Wines from Native and Experimental Non-Native White Grape Varieties

Galicia region (Northwestern Spain) wine production is mainly focused to high-quality white wines. The polyphenolic composition and the antioxidant activity have been determined to characterize the wines obtained from white grape varieties (Albariño, Branco Lexitimo, Caiño blanco, Godello, Loureiro, Torrontes, and Treixadura) grown in Galician protected production areas, and the wines elaborated with non-native varieties experimentally grown in Galicia (Chardonnay, Gewürztraminer, Pinot blanc, Pinot gris, Riesling, and Sauvignon blanc). Since Albariños are the varietal wines with the highest production and commercialization extension, we have studied their polyphenolic composition as a function of the production subarea. Three vintage years (2010, 2011, and 2012) have been considered to account for climate variability. Liquid chromatography with diode array and mass spectrometry detection was used to obtain the phenolic profiles. Wines from native grapes could be fully discriminated by their phenolic composition, with only Albariño being partially confused with other varietal wines. Albariño wines produced in O Rosal and Ribera do Ulla could be clearly differentiated, whereas Condado do Tea and Val do Salnés wines were partially confused. The polyphenolic profile was enough to differentiate the wines obtained from non-native grapes. The total polyphenols content and the antioxidant activity of white wines elaborated in Galicia were comparable, although significant differences were found among varieties.     

Mitochondria-Induced Immune Response as a Trigger for Neurodegeneration: A Pathogen from Within

Symbiosis between the mitochondrion and the ancestor of the eukaryotic cell allowed cellular complexity and supported life. Mitochondria have specialized in many key functions ensuring cell homeostasis and survival. Thus, proper communication between mitochondria and cell nucleus is paramount for cellular health. However, due to their archaebacterial origin, mitochondria possess a high immunogenic potential. Indeed, mitochondria have been identified as an intracellular source of molecules that can elicit cellular responses to pathogens. Compromised mitochondrial integrity leads to release of mitochondrial content into the cytosol, which triggers an unwanted cellular immune response. Mitochondrial nucleic acids (mtDNA and mtRNA) can interact with the same cytoplasmic sensors that are specialized in recognizing genetic material from pathogens. High-energy demanding cells, such as neurons, are highly affected by deficits in mitochondrial function. Notably, mitochondrial dysfunction, neurodegeneration, and chronic inflammation are concurrent events in many severe debilitating disorders. Interestingly in this context of pathology, increasing number of studies have detected immune-activating mtDNA and mtRNA that induce an aberrant production of pro-inflammatory cytokines and interferon effectors. Thus, this review provides new insights on mitochondria-driven inflammation as a potential therapeutic target for neurodegenerative and primary mitochondrial diseases.     

Using wind velocity estimated from a reanalysis to minimize the variability of aggregated wind farm production over Europe

In this work we use the mean‐variance portfolio optimization, using as input the power derived from the wind and density results of meteorological model simulations (ERA‐Interim reanalysis), to minimize the variability of the wind power produced in a large region. The methodology involves selecting the placement of the wind farms on a high spatial resolution grid. We used the EU‐28 region to check the method and perform sensitivity tests. We studied the influence of the ratio between the total installed power of the whole domain (P_t) and the maximum power that can be installed per cell (P_mi) on the variability of wind power yield. The results show that the reliability of the electrical system improves when P_mi grows and worsens when P_t grows. A quadratic fit relates the variability of the system and the aforementioned ratio. The optimization procedure tends to select groups of terrain cells where wind farms should be installed. These groups grow when more energy production is demanded of the system, but they roughly maintain their location. There is some evidence that in a larger region greater system reliability could be achieved. Most of the selected cells have either a high or a low capacity factor and those with the latter are crucial in enhancing system reliability.     

Palladium‐Catalyzed Synthesis of Selectively Substituted Phenanthridine Derivatives

Selectively substituted phenanthridine derivatives are obtained by a facile reaction of o‐alkylated aryl iodides, o‐bromoarenesulfonylanilines and activated olefins in the presence of palladium and norbornene as catalysts. The reaction takes place under mild conditions to give the products in satisfactory yields using readily available starting materials.