22 research outputs found
Human iPSC-derived neural crest stem cells can produce EPO and induce erythropoiesis in anemic mice.
Inadequate production of erythropoietin (EPO) leads to anemia. Although erythropoiesis-stimulating agents can be used to treat anemia, these approaches are limited by high costs, adverse effects, and the need for frequent injections. Developing methods for the generation and transplantation of EPO-producing cells would allow for the design of personalized and complication-free therapeutic solutions. In mice, the first EPO source are neural crest cells (NCCs), which ultimately migrate to the fetal kidney to differentiate into EPO-producing fibroblasts. In humans however, it remains unknown whether NCCs can produce EPO in response to hypoxia. Here, we developed a new protocol to differentiate human induced pluripotent stem cells (hiPSCs) into NCCs and showed that cthese cells can produce functional EPO that can induce human CD34+ hematopoietic progenitor differentiation into erythroblasts in vitro. Moreover, we showed that hiPSC-derived NCCs can be embedded in clinical-grade atelocollagen scaffolds and subcutaneously transplanted into anemic mice to produce human EPO, accelerate hematocrit recovery, and induce erythropoiesis in the spleen. Our findings provide unprecedented evidence of the ability of human NCCs to produce functional EPO in response to hypoxia, and proof-of-concept for the potential clinical use of NCC-containing scaffolds as cell therapy for renal and non-renal anemia
Photo-Induced Bandgap Renormalization Governs the Ultrafast Response of Single-Layer MoS2.
Transition metal dichalcogenides (TMDs) are emerging as promising two-dimensional (2D) semiconductors for optoelectronic and flexible devices. However, a microscopic explanation of their photophysics, of pivotal importance for the understanding and optimization of device operation, is still lacking. Here, we use femtosecond transient absorption spectroscopy, with pump pulse tunability and broadband probing, to monitor the relaxation dynamics of single-layer MoS2 over the entire visible range, upon photoexcitation of different excitonic transitions. We find that, irrespective of excitation photon energy, the transient absorption spectrum shows the simultaneous bleaching of all excitonic transitions and corresponding red-shifted photoinduced absorption bands. First-principle modeling of the ultrafast optical response reveals that a transient bandgap renormalization, caused by the presence of photoexcited carriers, is primarily responsible for the observed features. Our results demonstrate the strong impact of many-body effects in the transient optical response of TMDs even in the low-excitation-density regime
Tunable broadband light emission from graphene
Graphene is an ideal material for integrated nonlinear optics thanks to its
strong light-matter interaction and large nonlinear optical susceptibility.
Graphene has been used in optical modulators, saturable absorbers, nonlinear
frequency converters, and broadband light emitters. For the latter application,
a key requirement is the ability to control and engineer the emission
wavelength and bandwidth, as well as the electronic temperature of graphene.
Here, we demonstrate that the emission wavelength of graphene s broadband
hot carrier photoluminescence can be tuned by integration on photonic cavities,
while thermal management can be achieved by out-of-plane heat transfer to
hexagonal boron nitride. Our results pave the way to graphene-based ultrafast
broadband light emitters with tunable emission.Comment: 22 pages, 5 Figure
PET and MRI Bases Treatment Planning Systems: a Methodology for a Realistic Evaluation of the Dose and Fluence Distributions in BNCT and GdNCT
The article focuses on the methodology for a realistic evaluation of the dose and fluence distributions in Neutron Capture Therapy (NCT), based on the Treatment Planning System (TPS) that takes into account the real macroscopic distribution of the neutron capturer. The neutron capturers considered in the present study are 10B and 157Gd, used in BNCT and GdNCT respectively.JRC.F.3-High Flux and Future Reactor
Dispositivo sensore a base di silicio cristallino, in particolare per la rilevazione di ossigeno a temperatura ambiente in atmosfera inerte.
Si tratta di un dispositivo sensore a base di silicio nanostrutturato particolarmente adatto alla rilevazione dell'ossigeno. Il principio di funzionamento utilizza le variazione dell'intensità di fotoluminescenza in presenza di ossigeno adsorbito. La particolarità del sensore è quella di riuscire a funzionare a temperatura ambiente
Add-On Cyclic Angiotensin-(1-7) with Cyclophosphamide Arrests Progressive Kidney Disease in Rats with ANCA Associated Glomerulonephritis
Rapidly progressive crescentic glomerulonephritis associated with anti-neutrophil cytoplasmic antibodies (ANCA-GN) is a major cause of renal failure. Current immunosuppressive therapies are associated with severe side effects, intensifying the need for new therapeutic strategies. The activation of Mas receptor/Angiotensin-(1-7) axis exerted renoprotection in chronic kidney disease. Here, we investigated the effect of adding the lanthionine-stabilized cyclic form of angiotensin-1-7 [cAng-(1-7)] to cyclophosphamide in a rat model of ANCA-GN. At the onset of proteinuria, Wistar Kyoto rats with ANCA-GN received vehicle or a single bolus of cyclophosphamide, with or without daily cAng-(1-7). Treatment with cAng-(1-7) plus cyclophosphamide reduced proteinuria by 85% vs. vehicle, and by 60% vs. cyclophosphamide, and dramatically limited glomerular crescents to less than 10%. The addition of cAng-(1-7) to cyclophosphamide protected against glomerular inflammation and endothelial rarefaction and restored the normal distribution of parietal epithelial cells. Ultrastructural analysis revealed a preserved GBM, glomerular endothelium and podocyte structure, demonstrating that combination therapy provided an additional layer of renoprotection. This study demonstrates that adding cAng-(1-7) to a partially effective dose of cyclophosphamide arrests the progression of renal disease in rats with ANCA-GN, suggesting that cAng-(1-7) could be a novel clinical approach for sparing immunosuppressants
Recommended from our members
Raman spectroscopy of graphene under ultrafast laser excitation.
The equilibrium optical phonons of graphene are well character-ized in terms of anharmonicity and electron-phonon interactions, however their non-equilibrium properties in the presence of hot charge carriers are still not fully explored. Here we study the Ra-man spectrum of graphene under ultrafast laser excitation with 3ps pulses, which trade off between impulsive stimulation and spectral resolution. We localize energy into hot carriers, generating non-equilibrium temperatures in the ∼ 1700-3100K range, far exceeding that of the phonon bath, while simultaneously detecting the Raman response. The linewidth of both G and 2D peaks show an increase as function of the electronic temperature. We explain this as a re-sult of the Dirac cones’ broadening and electron-phonon scattering in the highly excited transient regime, important for the emerging field of graphene-based photonics and optoelectronics
Sirtuin 3 Deficiency Aggravates Kidney Disease in Response to High-Fat Diet through Lipotoxicity-Induced Mitochondrial Damage
Sirtuin 3 (SIRT3) is the primary mitochondrial deacetylase that controls the antioxidant pathway and energy metabolism. We previously found that renal Sirt3 expression and activity were reduced in mice with type 2 diabetic nephropathy associated with oxidative stress and mitochondrial abnormalities and that a specific SIRT3 activator improved renal damage. SIRT3 is modulated by diet, and to assess whether Sirt3 deficiency aggravates mitochondrial damage and accelerates kidney disease in response to nutrient overloads, wild-type (WT) and Sirt3−/− mice were fed a high-fat-diet (HFD) or standard diet for 8 months. Sirt3−/− mice on HFD exhibited earlier and more severe albuminuria compared to WT mice, accompanied by podocyte dysfunction and glomerular capillary rarefaction. Mesangial matrix expansion, tubular vacuolization and inflammation, associated with enhanced lipid accumulation, were more evident in Sirt3−/− mice. After HFD, kidneys from Sirt3−/− mice showed more oxidative stress than WT mice, mitochondria ultrastructural damage in tubular cells, and a reduction in mitochondrial mass and energy production. Our data demonstrate that Sirt3 deficiency renders mice more prone to developing oxidative stress and mitochondrial abnormalities in response to HFD, resulting in more severe kidney diseases, and this suggests that mitochondria protection may be a method to prevent HFD-induced renal injury
Endothelial Glycocalyx of Peritubular Capillaries in Experimental Diabetic Nephropathy: A Target of ACE Inhibitor-Induced Kidney Microvascular Protection
Peritubular capillary rarefaction is a recurrent aspect of progressive nephropathies. We previously found that peritubular capillary density was reduced in BTBR ob/ob mice with type 2 diabetic nephropathy. In this model, we searched for abnormalities in the ultrastructure of peritubular capillaries, with a specific focus on the endothelial glycocalyx, and evaluated the impact of treatment with an angiotensin-converting enzyme inhibitor (ACEi). Mice were intracardially perfused with lanthanum to visualise the glycocalyx. Transmission electron microscopy analysis revealed endothelial cell abnormalities and basement membrane thickening in the peritubular capillaries of BTBR ob/ob mice compared to wild-type mice. Remodelling and focal loss of glycocalyx was observed in lanthanum-stained diabetic kidneys, associated with a reduction in glycocalyx components, including sialic acids, as detected through specific lectins. ACEi treatment preserved the endothelial glycocalyx and attenuated the ultrastructural abnormalities of peritubular capillaries. In diabetic mice, peritubular capillary damage was associated with an enhanced tubular expression of heparanase, which degrades heparan sulfate residues of the glycocalyx. Heparanase was also detected in renal interstitial macrophages that expressed tumor necrosis factor-α. All these abnormalities were mitigated by ACEi. Our findings suggest that, in experimental diabetic nephropathy, preserving the endothelial glycocalyx is important in order to protect peritubular capillaries from damage and loss