Takotsubo Syndrome and Cerebral Cardioembolism: Case Report to Redefine the Short-term Prognosis

Takotsubo cardiomyopathy is characterized by transient hypo-kinesis of the left ventricular apex or midventricular segments, without significant stenosis affecting coronary arteries. This cardiomyopathy is well known to be related to cerebral infarction, although scarce data describe the real timing of this adverse event.We report the case of a 69-year-old woman who experienced Takotsubo cardiomyopathy, and developed cardiogenic cerebral embolism on the fourth day from the onset of symptoms.Takotsubo patients could be effectively at high risk for stroke; thus, we should pay attention to rule out ventricular thrombosis, consider immediately anticoagulant therapy, and revise Takotsubo prognosis because its complications

An X-ray burst from a magnetar enlightening the mechanism of fast radio bursts

Fast radio bursts (FRBs) are millisecond radio pulses originating from powerful enigmatic sources at extragalactic distances. Neutron stars with large magnetic fields (magnetars) have been considered as the sources powering the FRBs, but the connection requires further substantiation. Here we report the detection by the AGILE satellite on 28 April 2020 of an X-ray burst in temporal coincidence with a bright FRB-like radio burst from the Galactic magnetar SGR 1935+2154. The burst observed in the hard X-ray band (18-60 keV) lasted about 0.5 s, it is spectrally cut off above 80 keV and implies an isotropically emitted energy of about 1040 erg. This event demonstrates that a magnetar can produce X-ray bursts in coincidence with FRB-like radio bursts. It also suggests that FRBs associated with magnetars can emit X-ray bursts. We discuss SGR 1935+2154 in the context of FRBs with low-intermediate radio energies in the range 1038-1040 erg. Magnetars with magnetic fields B ≈ 1015 G may power these FRBs, and new data on the search for X-ray emission from FRBs are presented. We constrain the bursting X-ray energy of the nearby FRB 180916 to be less than 1046 erg, smaller than that observed in giant flares from Galactic magnetars

Potential role of IL-10-treated dendritic cells in the control of the immune response to allergens

Several lines of evidence indicate that a defect in immunoregulatory mechanisms is involved in the pathogenesis of allergic asthma. The aim of this study is to determine whether IL-10-treated dendritic cells (DC) are able to modulate allergen-specific T cell responses in children affected by allergic asthma. 41 children (4-14 years) allergic to House Dust Mite (HDM), and 10 healthy age-matched children were recruited. DC were differentiated from peripheral blood CD14+ precursors and cultured with GM-CSF and IL-4 for 5 days. Der p2 (a major HDM allergen) was added alone or in combination with IL-10 for 48 hours to obtain Dp2-DC and IL10 Dp2-DC, respectively. Alternatively, DC were differentiated in the presence of IL-10 and pulsed with Der p2 during the 2 last days of culture (Dp2-DC10). The ability of the resulting DC to stimulate allergen-specific autologous T cells and to promote allergen-specific T cell anergy was analyzed. Dp2-DC induced allergen-specific T cell proliferation in 32 out of 41 patients but not in healthy controls. In 25 out of 26 allergic patients IL10 Dp2-DC and Dp2 DC10 induced a significantly lower allergen-specific T cell proliferation. The analysis of DC phenotype showed that IL-10 treatment significantly downregulated CD86 expression on Dp2-DC. However, no correlation between the reduction of CD86 expression and of T cell proliferation was observed. Dp2-DC stimulation induced a Th2 cytokine profile characterized by an increase of IL-5, IL-13 and IL-4 production and IL-5/IFN-gamma ratio. In the same patients, the co-culture with both IL-10 Dp2-DC and Dp2-DC10 caused a marked reduction of IL-5 production and of IL-13, with a parallel decrease of IL-5/IFN-gamma ratio. Moreover, in 8 children we observed an increase in IL-10 production. T cell lines generated with Dp2-DC10, compared to those generate with Dp2-DC, were hyporesponsive to reactivation with Der p2 in 4 out of 5 patients tested, both in terms of proliferation and cytokine production: IL-5, IL-13, and IL-5/IFN-gamma ratio. Our data show that IL-10 reduced the stimulatory capacity of DC through a mechanism independent from the downregulation of costimulatory signals. IL-10 treatment of DC promoted a suppression of allergen-specific Th2 cell responses. Moreover, Dp2-DC10 are able to promote T cell anergy associated with a reduction in the Th2 cytokine production. These results represent an important step forward to the prospective clinical application of Dp2-DC10 to modulate allergen-specific T cells responses in vivo

Potential role of IL-10-treated dendritic cells in the control of the immune response to allergens

Several lines of evidence indicate that a defect in immunoregulatory mechanisms is involved in the pathogenesis of allergic asthma. The aim of this study is to determine whether IL-10-treated dendritic cells (DC) are able to modulate allergen-specific T cell responses in children affected by allergic asthma. 41 children (4-14 years) allergic to House Dust Mite (HDM), and 10 healthy age-matched children were recruited. DC were differentiated from peripheral blood CD14+ precursors and cultured with GM-CSF and IL-4 for 5 days. Der p2 (a major HDM allergen) was added alone or in combination with IL-10 for 48 hours to obtain Dp2-DC and IL10 Dp2-DC, respectively. Alternatively, DC were differentiated in the presence of IL-10 and pulsed with Der p2 during the 2 last days of culture (Dp2-DC10). The ability of the resulting DC to stimulate allergen-specific autologous T cells and to promote allergen-specific T cell anergy was analyzed. Dp2-DC induced allergen-specific T cell proliferation in 32 out of 41 patients but not in healthy controls. In 25 out of 26 allergic patients IL10 Dp2-DC and Dp2 DC10 induced a significantly lower allergen-specific T cell proliferation. The analysis of DC phenotype showed that IL-10 treatment significantly downregulated CD86 expression on Dp2-DC. However, no correlation between the reduction of CD86 expression and of T cell proliferation was observed. Dp2-DC stimulation induced a Th2 cytokine profile characterized by an increase of IL-5, IL-13 and IL-4 production and IL-5/IFN-gamma ratio. In the same patients, the co-culture with both IL-10 Dp2-DC and Dp2-DC10 caused a marked reduction of IL-5 production and of IL-13, with a parallel decrease of IL-5/IFN-gamma ratio. Moreover, in 8 children we observed an increase in IL-10 production. T cell lines generated with Dp2-DC10, compared to those generate with Dp2-DC, were hyporesponsive to reactivation with Der p2 in 4 out of 5 patients tested, both in terms of proliferation and cytokine production: IL-5, IL-13, and IL-5/IFN-gamma ratio. Our data show that IL-10 reduced the stimulatory capacity of DC through a mechanism independent from the downregulation of costimulatory signals. IL-10 treatment of DC promoted a suppression of allergen-specific Th2 cell responses. Moreover, Dp2-DC10 are able to promote T cell anergy associated with a reduction in the Th2 cytokine production. These results represent an important step forward to the prospective clinical application of Dp2-DC10 to modulate allergen-specific T cells responses in vivo

Spontaneous formation of magnetic-plasmonic liposomes with tunable optical and magnetic properties

Magnetoplasmonic NPs have shown remarkable potential in hyperthermia, Magnetic Resonance Imaging (MRI), and Surface Enhanced Raman Scattering (SERS) imaging and diagnostics. However, despite their potential, effective clinical translation remains extremely limited due to a lack of fundamental knowledge about the biological response to these materials, and ongoing efforts seek to bridge the gap between nanomaterial production and effective application. To overcome these hurdles, the combination of inorganic NPs with lipid membranes has emerged as a promising strategy for the biocompatibilization of nanomaterials, preserving the inherent properties of each component and exhibiting novel synergistic functionalities. In this study, we synthesize magnetic-plasmonic-liposome adducts via spontaneous self-assembly. The interaction between magnetic-plasmonic NPs and liposomes was addressed from a physicochemical point of view as a function of liposome composition and concentration. By combining Cryogenic Microscopy, UV-visible spectroscopy and Dynamic Light Scattering we demonstrated that the rigidity of the lipid membrane affects the aggregation of the NPs and the colloidal stability of the NPs-vesicle hybrids. The magnetic responsivity of the hybrids is enhanced as a consequence of the colocalization and crowding of NPs on the lipid membranes and can be finely modulated by varying the number of particles per vesicle. Overall, these results pave the way for the development of multifunctional materials with controlled magnetic-plasmonic properties for a variety of technological applications

Differentiation of type 1 T regulatory (Tr1) cells by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway

Type 1 T regulatory (Tr1) cells suppress immune responses in vivo and in vitro and play a key role in maintaining tolerance to self- and non–self-antigens. Interleukin-10 (IL-10) is the crucial driving factor for Tr1 cell differentiation, but the molecular mechanisms underlying this induction remain unknown. We identified and characterized a subset of IL-10–producing human dendritic cells (DCs), termed DC-10, which are present in vivo and can be induced in vitro in the presence of IL-10. DC-10 are CD14+, CD16+, CD11c+, CD11b+, HLA-DR+, CD83+, CD1a−, CD1c−, express the Ig-like transcripts (ILTs) ILT2, ILT3, ILT4, and HLA-G antigen, display high levels of CD40 and CD86, and up-regulate CD80 after differentiation in vitro. DC-10 isolated from peripheral blood or generated in vitro are potent inducers of antigen-specific IL-10–producing Tr1 cells. Induction of Tr1 cells by DC-10 is IL-10–dependent and requires the ILT4/HLA-G signaling pathway. Our data indicate that DC-10 represents a novel subset of tolerogenic DCs, which secrete high levels of IL-10, express ILT4 and HLA-G, and have the specific function to induce Tr1 cells.Silvia Gregori, Daniela Tomasoni, Valentina Pacciani, Miriam Scirpoli, Manuela Battaglia, Chiara Francesca Magnani, Ehud Hauben, and Maria-Grazia Roncarol

Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis

T cells are crucial mediators of the skin damage in psoriasis. We here show that interleukin-21 (IL-21), a T cell-derived cytokine, is highly expressed in the skin of individuals with psoriasis, stimulates human keratinocytes to proliferate and causes epidermal hyperplasia when injected intradermally into mice. In the human psoriasis xenograft mouse model, blockade of IL-21 activity resolves inflammation and reduces keratinocyte proliferation. Blocking IL-21 may represent a new therapeutic strategy in psoriasis

The origin and legacy of the Etruscans through a 2000-year archeogenomic time transect

The origin, development, and legacy of the enigmatic Etruscan civilization from the central region of the Italian peninsula known as Etruria have been debated for centuries. Here we report a genomic time transect of 82 individuals spanning almost two millennia (800 BCE to 1000 CE) across Etruria and southern Italy. During the Iron Age, we detect a component of Indo-European–associated steppe ancestry and the lack of recent Anatolian-related admixture among the putative non–Indo-European–speaking Etruscans. Despite comprising diverse individuals of central European, northern African, and Near Eastern ancestry, the local gene pool is largely maintained across the first millennium BCE. This drastically changes during the Roman Imperial period where we report an abrupt population-wide shift to ~50% admixture with eastern Mediterranean ancestry. Last, we identify northern European components appearing in central Italy during the Early Middle Ages, which thus formed the genetic landscape of present-day Italian populations