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- Medina, LMP, et al.
(författare)
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Targeted plasma proteomics reveals signatures discriminating COVID-19 from sepsis with pneumonia
- 2023
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Ingår i: Respiratory research. - : Springer Science and Business Media LLC. - 1465-993X. ; 24:1, s. 62-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCOVID-19 remains a major public health challenge, requiring the development of tools to improve diagnosis and inform therapeutic decisions. As dysregulated inflammation and coagulation responses have been implicated in the pathophysiology of COVID-19 and sepsis, we studied their plasma proteome profiles to delineate similarities from specific features.MethodsWe measured 276 plasma proteins involved in Inflammation, organ damage, immune response and coagulation in healthy controls, COVID-19 patients during acute and convalescence phase, and sepsis patients; the latter included (i) community-acquired pneumonia (CAP) caused by Influenza, (ii) bacterial CAP, (iii) non-pneumonia sepsis, and (iv) septic shock patients.ResultsWe identified a core response to infection consisting of 42 proteins altered in both COVID-19 and sepsis, although higher levels of cytokine storm-associated proteins were evident in sepsis. Furthermore, microbiologic etiology and clinical endotypes were linked to unique signatures. Finally, through machine learning, we identified biomarkers, such as TRIM21, PTN and CASP8, that accurately differentiated COVID-19 from CAP-sepsis with higher accuracy than standard clinical markers.ConclusionsThis study extends the understanding of host responses underlying sepsis and COVID-19, indicating varying disease mechanisms with unique signatures. These diagnostic and severity signatures are candidates for the development of personalized management of COVID-19 and sepsis.
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- Khan, D, et al.
(författare)
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Short-term CFTR inhibition reduces islet area in C57BL/6 mice
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 11244-
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Tidskriftsartikel (refereegranskat)abstract
- Cystic fibrosis-related diabetes (CFRD) worsens CF lung disease leading to early mortality. Loss of beta cell area, even without overt diabetes or pancreatitis is consistently observed. We investigated whether short-term CFTR inhibition was sufficient to impact islet morphology and function in otherwise healthy mice. CFTR was inhibited in C57BL/6 mice via 8-day intraperitoneal injection of CFTRinh172. Animals had a 7-day washout period before measures of hormone concentration or islet function were performed. Short-term CFTR inhibition increased blood glucose concentrations over the course of the study. However, glucose tolerance remained normal without insulin resistance. CFTR inhibition caused marked reductions in islet size and in beta cell and non-beta cell area within the islet, which resulted from loss of islet cell size rather than islet cell number. Significant reductions in plasma insulin concentrations and pancreatic insulin content were also observed in CFTR-inhibited animals. Temporary CFTR inhibition had little long-term impact on glucose-stimulated, or GLP-1 potentiated insulin secretion. CFTR inhibition has a rapid impact on islet area and insulin concentrations. However, islet cell number is maintained and insulin secretion is unaffected suggesting that early administration of therapies aimed at sustaining beta cell mass may be useful in slowing the onset of CFRD.
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- Soderholm, S, et al.
(författare)
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A photoelectron spectroscopy and x-ray absorption study of Bi2Sr2CaCu2O8 single crystal with adsorbed Cs : On the origin of the states affected by electron doping and evidence for spatially resolved electron doping
- 1996
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Ingår i: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 8:9, s. 1307-1320
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Tidskriftsartikel (refereegranskat)abstract
- The influence of electron doping, via deposition of small amounts of Cs, on the electronic structure of Bi2Sr2CaCu2O8 has been studied by high-resolution photoelectron spectroscopy (PES) and x-ray absorption spectroscopy (XAS), utilizing synchrotron radiation. The changes in the electronic structure were monitored by PES of the valence band and of the O Is, Bi 4f, Bi 5d, Ca 2p and Sr 3d core levels, and by XAS at the O Is, Cu 2p and Ca 2p edges. The experimental data suggest that the loss of the Fermi edge and the loss of spectral intensity down to about 2 eV below the Fermi level, and the substantial loss of spectral intensity of the pre-edge structure in the O 1s XAS spectrum are mainly due to annihilation of states with O 2p character in the Cu-O layer. It is evident from bulk- and surface-sensitive XAS spectra that the electron doping by Cs affects the electronic structure more strongly close to the surface. This implies that the doping occurs locally and that the charge transfer between the different layers in the unit cell is not uniform. Thus it seems possible to alter the electronic properties of Bi2Sr2CaCu2O8 locally through spatially resolved electron doping. When larger amounts of Cs are deposited, a chemical reaction occurs which causes a disruption of the Bi-O layer. This deposition regime is characterized by the presence of caesium oxide and reduced (metallic) Bi.
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