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1.
J Clin Invest ; 131(22)2021 11 15.
Article in English | MEDLINE | ID: mdl-34779418

ABSTRACT

Metabolic pathways regulate immune responses and disrupted metabolism leads to immune dysfunction and disease. Coronavirus disease 2019 (COVID-19) is driven by imbalanced immune responses, yet the role of immunometabolism in COVID-19 pathogenesis remains unclear. By investigating 87 patients with confirmed SARS-CoV-2 infection, 6 critically ill non-COVID-19 patients, and 47 uninfected controls, we found an immunometabolic dysregulation in patients with progressed COVID-19. Specifically, T cells, monocytes, and granulocytes exhibited increased mitochondrial mass, yet only T cells accumulated intracellular reactive oxygen species (ROS), were metabolically quiescent, and showed a disrupted mitochondrial architecture. During recovery, T cell ROS decreased to match the uninfected controls. Transcriptionally, T cells from severe/critical COVID-19 patients showed an induction of ROS-responsive genes as well as genes related to mitochondrial function and the basigin network. Basigin (CD147) ligands cyclophilin A and the SARS-CoV-2 spike protein triggered ROS production in T cells in vitro. In line with this, only PCR-positive patients showed increased ROS levels. Dexamethasone treatment resulted in a downregulation of ROS in vitro and T cells from dexamethasone-treated patients exhibited low ROS and basigin levels. This was reflected by changes in the transcriptional landscape. Our findings provide evidence of an immunometabolic dysregulation in COVID-19 that can be mitigated by dexamethasone treatment.


Subject(s)
Basigin/physiology , COVID-19/immunology , Dexamethasone/pharmacology , SARS-CoV-2 , T-Lymphocytes/metabolism , Adult , COVID-19/metabolism , Cyclophilin A/physiology , Fatty Acids/metabolism , Female , Humans , Male , Middle Aged , Mitochondria/pathology , Reactive Oxygen Species/metabolism
2.
Inorg Chem ; 56(4): 2100-2107, 2017 Feb 20.
Article in English | MEDLINE | ID: mdl-28150938

ABSTRACT

Poly(ethylene oxide) (PEO)-based polymer fibers, containing different amounts of the conductive salt LiBF4 and the plasticizer succinonitrile, were prepared by an electrospinning process. This process resulted in fiber membranes of several square centimeters area and an overall thickness of ∼100 µm. All membranes are characterized by scanning electron microscopy, differential scanning calorimetry, X-ray diffraction, impedance spectroscopy, cyclic voltammetry (CV), and solid-state NMR spectroscopy, to evaluate the influence of the preparation process and the composition on the conductivity of the materials. Impedance spectroscopy was used to measure the conductivities and activation barriers for the different membranes. The highest conductivity of 2 × 10-4 S/cm at room temperature and 9 × 10-4 S/cm at 328 K is reached for a PEO/SN/LiBF4 (36:8:1) membrane, featuring an activation energy of 31 kJ/mol. Li mobilities, as deduced from the evaluation of the temperature dependence of the 7Li NMR line width and the overall electrochemical performance, are found to be distinctively superior to nonspun samples, synthesized via conventional solution casting. The same trend was found for the conductivities. NMR spectroscopy clearly substantiated that the mobility of the PEO segments drastically increases with the addition of succinonitrile pushing the conductivity to reasonable high values. In CV experiments the reversible Li transport through the dry membrane was evaluated and proved. This study shows that electrospinning provides a direct synthesis of solvent-free solid-state electrolyte membranes, ready to use in electrochemical applications.

3.
Inorg Chem ; 55(15): 7764-76, 2016 Aug 01.
Article in English | MEDLINE | ID: mdl-27410400

ABSTRACT

NaCd4P3 and NaCd4As3 were synthesized via short-way transport using the corresponding elements and CdI2 as mineralizer. At room temperature, the two ß-polymorphs adopt the RbCd4As3 structure type which has been recently reported for alkali metal (A)-d(10) transition metal (T)-pnictides (Pn). The title compounds crystallize rhombohedrally in space group R3̅m at room temperature and show reversible phase transitions to incommensurately modulated α-polymorphs at lower temperatures. The low-temperature phases are monoclinic and can be described in space group Cm(α0γ)s with q vectors of q = (-0.04,0,0.34) for α-NaCd4P3 and q1 = (-0.02,0,0.34) for α-NaCd4As3. Thermal properties, Raman spectroscopy, and electronic structures have been determined. Both compounds are Zintl phases with band gaps of 1.05 eV for ß-NaCd4P3 and ∼0.4 eV for ß-NaCd4As3.

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