The synthesis and functionalization of iron oxide nanoparticles (IONPs) is versatile, which has enhanced the interest in studying them as theranostic agents over recent years. As IONPs begin to be ...used for different biomedical applications, it is important to know how they affect the immune system and its different cell types, especially their interaction with the macrophages that are involved in their clearance. How immune cells respond to therapeutic interventions can condition the systemic and local tissue response, and hence, the final therapeutic outcome. Thus, it is fundamental to understand the effects that IONPs have on the immune response, especially in cancer immunotherapy. The biological effects of IONPs may be the result of intrinsic features of their iron oxide core, inducing reactive oxygen species (ROS) and modulating intracellular redox and iron metabolism. Alternatively, their effects are driven by the nanoparticle coating, for example, through cell membrane receptor engagement. Indeed, exploiting these properties of IONPs could lead to the development of innovative therapies. In this review, after a presentation of the elements that make up the tumor immunological microenvironment, we will review and discuss what is currently known about the immunomodulatory mechanisms triggered by IONPs, mainly focusing on macrophage polarization and reprogramming. Consequently, we will discuss the implications of these findings in the context of plausible therapeutic scenarios for cancer immunotherapy.
Higgs-mass predictions in the MSSM and beyond Slavich, P.; Heinemeyer, S.; Bagnaschi, E. ...
European physical journal. C, Particles and fields,
05/2021, Letnik:
81, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Predictions for the Higgs masses are a distinctive feature of supersymmetric extensions of the Standard Model, where they play a crucial role in constraining the parameter space. The discovery of a ...Higgs boson and the remarkably precise measurement of its mass at the LHC have spurred new efforts aimed at improving the accuracy of the theoretical predictions for the Higgs masses in supersymmetric models. The “
Precision SUSY Higgs Mass Calculation Initiative
” (KUTS) was launched in 2014 to provide a forum for discussions between the different groups involved in these efforts. This report aims to present a comprehensive overview of the current status of Higgs-mass calculations in supersymmetric models, to document the many advances that were achieved in recent years and were discussed during the KUTS meetings, and to outline the prospects for future improvements in these calculations.
The general relationship between weather and climate with recreation and tourism has been widely acknowledged, but research on more activity-specific assessments is still required. The links between ...atmospheric conditions and visitation to the Nature Park of Cabárceno, an outdoor zoo located in Cantabria (Northern Spain), have been analyzed by conducting in situ surveys and comparing the daily number of attendants and meteorological parameters from a nearby weather station. The sensitivity of zoo visitation to weather variability was seasonally dependent, so winter attendance is directly related to the frequency of dry, warm, calm, and cloudless days; in summer, attendance was less sensitive to weather, with visitors attending in largest numbers during mild, cloudy, and breezy days. Moreover, a dissociation exists between perception and behavior during the period of the largest influx of visitors: visitors remark the importance of weather when planning the activity, but they show little flexibility when visiting. Socio-economic factors (origin of visitors, family structure) fade the weather influence.
Systemic lupus erythematosus is a chronic, multifactorial autoimmune disease of complex etiology, characterized by loss of tolerance to nuclear autoantigens, expansion of autoreactive T and B cell ...clones, polyclonal B cell activation that gives rise to hypergammaglobulinemia, and increased autoantibody production, as well as immune complex deposition and multiorgan tissue inflammation. As disease progresses, immune cells, mainly T cells and macrophages, infiltrate affected organs and amplify the local inflammatory response. Natural killer cells are large, granular lymphocytes that are an important link between the innate and adaptive immune systems; variations in their activity correlate with several autoimmune diseases. To date, the literature has disregarded natural killer cells as relevant modulators in systemic lupus erythematosus pathogenesis, as these cells are few in number and show a dysfunctional phenotype in patients with active systemic lupus erythematosus. This review focuses on research that could help define the role of natural killer cells in systemic lupus erythematosus and their function in regulating this autoimmune disorder in nonlymphoid organs.
Abstract Polyethylenimine (PEI) is widely used as transfection agent in preclinical studies, both in vitro and in vivo. Due to their unique chemical and physical properties, SPIONs (superparamagnetic ...iron oxide nanoparticles) have been thoroughly studied as nanocarriers. PEI appears to activate different immune cells to an inflammatory response (M1/TH 1), whereas the SPION-induced response seems to be context-dependent; the immunogenicity of the combination of these components has not been studied. Here we show that PEI-coated SPIONs (PMag) activate macrophages, as determined by measuring IL-12 secretion into culture medium and upregulation of several genes linked to the M1 phenotype. PMag-induced phosphorylation of p38 MAPK, p44/p42 MAPK and JNK, and upregulation of CD40, CD80, CD86 and I-A/I-E activation markers. PMag-induced macrophage activation depended partially on TLR4 (Toll-like receptor 4) and ROS (reactive oxygen species) signaling. Comparison of these responses with the LPS (lipopolysaccharide)-induced phenotype showed differences in gene expression profiling. PMag positively modulated podosome formation in murine macrophages, but hampered gelatin degradation by these cells. In conclusion, PMag induced an M1-like phenotype that was partially dependent on both TLR4 and ROS. These results show the adjuvant potential of PMag and suggest their use in vaccination schedules.
The spatial and temporal variability of the summer (July–August) climate beach-based tourism aptitude along the Atlantic coast of SW Europe from 1973 to 2017 and its links with the atmospheric ...circulation has been analyzed, combining an empirical index and a circulation pattern approach. Three different coastal sectors were defined from a PCA analysis: Galicia-N of Portugal, the Gulf of Biscay, and the western coast of France and the English Channel. Each region experienced a contrasted evolution due to geographical factors such as latitude, orography and exposure to the prevailing circulation patterns. No significant increase in aptitude was found because the background warming has not been balanced by trends in cloudiness or precipitation. Several possible causes are discussed, from local to large-scale, such as the recent evolution of the summer NAO pattern impacting the northernmost region.
Cold air pools (CAPs) are one of the most severe weather conditions experienced across many basins worldwide, related to episodes of extreme cold temperatures, poor air quality, and disruption of ...transportation networks. This study offers a basic climatology of CAPs in the southern Spanish Plateau and investigates its evolution since 1961 and their links with local, synoptic, and large‐scale climate variability. It is based on the comparison of meteorological records from two stations, one in the Sistema Central Range (Navacerrada, 1,894 m asl) and another at the plain (Madrid‐Barajas, 609 m asl). Accuracy and representativeness of both locations to depict the spatial and temporal variability of CAPs was also tested. CAPs days (defined as the simultaneous occurrence of a daily minimum temperature difference above 0.1°C between both stations) were found to occur year‐round, but the most frequent and intense occur in winter (NDJ). Some typical features of CAPs, such as local mesoscale processes (katabatic and anabatic flows) in connection with synoptic (advection of mid‐troposphere warm air masses during high‐pressure regimes) and hemispheric (a positive phase of the North Atlantic Oscillation) variability were also observed, leading to a sheltered boundary layer at the bottom of southern Spanish Plateau, decoupled from the free troposphere. By night, CAPs have maintained both their frequency and intensity, which means that the frequency of extremely cold nights on the plain has remained relatively stable (despite global warming). By day, an enhanced warming of the high‐elevation site has increased the temperature difference between the mountains and the plain during CAP days.
Cold air pools (CAPs) are identified. CAPs are a common wintertime (NDJ) phenomenon which combines local, synoptic, and large‐scale processes. No long‐term trend was found either in the CAP ocurrence or their strength.
Hyperthermia has emerged as a promising alternative to conventional cancer therapies and in fact, traditional hyperthermia is now commonly used in combination with chemotherapy or surgery during ...cancer treatment. Nevertheless, non-specific application of hyperthermia generates various undesirable side-effects, such that nano-magnetic hyperthermia has arisen a possible solution to this problem. This technique to induce hyperthermia is based on the intrinsic capacity of magnetic nanoparticles to accumulate in a given target area and to respond to alternating magnetic fields (AMFs) by releasing heat, based on different principles of physics. Unfortunately, the clinical implementation of nano-magnetic hyperthermia has not been fluid and few clinical trials have been carried out. In this review, we want to demonstrate the need for more systematic and basic research in this area, as many of the sub-cellular and molecular mechanisms associated with this approach remain unclear. As such, we shall consider here the biological effects that occur and why this theoretically well-designed nano-system fails in physiological conditions. Moreover, we will offer some guidelines that may help establish successful strategies through the rational design of magnetic nanoparticles for magnetic hyperthermia.
The Helios protein (encoded by the
gene) is a member of the Ikaros transcription family and it has recently been proposed as a promising biomarker for systemic lupus erythematosus (SLE) disease ...progression in both mouse models and patients. Helios is beginning to be studied extensively for its influence on the T regulatory (Treg) compartment, both CD4
Tregs and KIR
/Ly49
CD8
Tregs, with alterations to the number and function of these cells correlated to the autoimmune phenomenon. This review analyzes the most recent research on Helios expression in relation to the main immune cell populations and its role in SLE immune homeostasis, specifically focusing on the interaction between T cells and tolerogenic dendritic cells (tolDCs). This information could be potentially useful in the design of new therapies, with a particular focus on transfer therapies using immunosuppressive cells. Finally, we will discuss the possibility of using nanotechnology for magnetic targeting to overcome some of the obstacles related to these therapeutic approaches.
There is increasing interest in modulating the redox homeostasis of tumors since high levels of reactive oxygen species (ROS) make them more vulnerable to changes in these species. Nanomedicine ...offers promise in this context as such applications may provoke biological responses that induce ROS production. Indeed, iron oxide nanoparticles (IONPs) can induce ROS accumulation through the so-called Fenton reaction of iron, further augmenting the ROS in tumors and overloading the antioxidant system beyond its capacity, thereby driving oxidative stress to a level that is incompatible with cell survival. Here, three different coatings for IONPs were compared to assess their intrinsic capacity to induce ROS production in cells. Of these coatings, dimercaptosuccinic acid-coated IONPs (DMSA-NPs) provoked the strongest ROS production, which was associated with the ability to reprogram the metabolism of cancer cells. This latter phenomenon involved shutting-down oxidative phosphorylation (OXPHOS), shifting mitochondrial morphology towards a more elongated phenotype, reducing the total mitochondrial mass and ultimately, blocking cell proliferation by inducing G0/G1 cell cycle arrest. Consequently, the data obtained highlights the importance of studying the chemical properties of IONPs, presenting DMSA-NPs as a novel tool to induce oxidative stress in cancer cells and alter their cell fate.
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