Inhibitory action of viruses of the tick-borne encephalitis complex differing in neurovirulence on mouse tumors in vivo

1967 ◽  
Vol 64 (2) ◽  
pp. 885-887
Author(s):  
E. N. Levkovich ◽  
G. I. Sergeeva
Author(s):  
Young-Min Han ◽  
Min Sun Kim ◽  
Juyeong Jo ◽  
Daiha Shin ◽  
Seung-Hae Kwon ◽  
...  

AbstractThe fine-tuning of neuroinflammation is crucial for brain homeostasis as well as its immune response. The transcription factor, nuclear factor-κ-B (NFκB) is a key inflammatory player that is antagonized via anti-inflammatory actions exerted by the glucocorticoid receptor (GR). However, technical limitations have restricted our understanding of how GR is involved in the dynamics of NFκB in vivo. In this study, we used an improved lentiviral-based reporter to elucidate the time course of NFκB and GR activities during behavioral changes from sickness to depression induced by a systemic lipopolysaccharide challenge. The trajectory of NFκB activity established a behavioral basis for the NFκB signal transition involved in three phases, sickness-early-phase, normal-middle-phase, and depressive-like-late-phase. The temporal shift in brain GR activity was differentially involved in the transition of NFκB signals during the normal and depressive-like phases. The middle-phase GR effectively inhibited NFκB in a glucocorticoid-dependent manner, but the late-phase GR had no inhibitory action. Furthermore, we revealed the cryptic role of basal GR activity in the early NFκB signal transition, as evidenced by the fact that blocking GR activity with RU486 led to early depressive-like episodes through the emergence of the brain NFκB activity. These results highlight the inhibitory action of GR on NFκB by the basal and activated hypothalamic-pituitary-adrenal (HPA)-axis during body-to-brain inflammatory spread, providing clues about molecular mechanisms underlying systemic inflammation caused by such as COVID-19 infection, leading to depression.


Sensors ◽  
2021 ◽  
Vol 21 (10) ◽  
pp. 3366
Author(s):  
Aneline Dolet ◽  
Rita Ammanouil ◽  
Virginie Petrilli ◽  
Cédric Richard ◽  
Piero Tortoli ◽  
...  

Multispectral photoacoustic imaging is a powerful noninvasive medical imaging technique that provides access to functional information. In this study, a set of methods is proposed and validated, with experimental multispectral photoacoustic images used to estimate the concentration of chromophores. The unmixing techniques used in this paper consist of two steps: (1) automatic extraction of the reference spectrum of each pure chromophore; and (2) abundance calculation of each pure chromophore from the estimated reference spectra. The compared strategies bring positivity and sum-to-one constraints, from the hyperspectral remote sensing field to multispectral photoacoustic, to evaluate chromophore concentration. Particularly, the study extracts the endmembers and compares the algorithms from the hyperspectral remote sensing domain and a dedicated algorithm for segmentation of multispectral photoacoustic data to this end. First, these strategies are tested with dilution and mixing of chromophores on colored 4% agar phantom data. Then, some preliminary in vivo experiments are performed. These consist of estimations of the oxygen saturation rate (sO2) in mouse tumors. This article proposes then a proof-of-concept of the interest to bring hyperspectral remote sensing algorithms to multispectral photoacoustic imaging for the estimation of chromophore concentration.


1937 ◽  
Vol 37 (3) ◽  
pp. 471-473 ◽  
Author(s):  
J. Gordon ◽  
N. Wood

In earlier papers (Gordon, 1930) it was shown that congo red has an inactivating effect on serum complement, both haemolytic and bactericidal, and that this effect can be reversed by treating the serum and congo red mixture with charcoal, the charcoal removing the congo red and leaving the complement active again. A similar reversal of inactivation is obtained by using instead of the charcoal, heated serum (55° C. for 30 min.) or protein solutions. Later (Gordon, 1931), it was shown that congo red had an inactivating effect on the haemolysins of Streptococcus haemolyticus and B. welchii. The reversibility of this effect was not so easy to demonstrate as with complement. Charcoal had a destructive effect on the haemolysins and so could not be used. It was found, however, that when the concentration of congo red was just sufficient to neutralize the streptococcal haemolysin, the addition of cuprammonium artificial silk adsorbed the congo red and liberated the haemolysin. In the case of B. welchii this method of reversal was not suitable, as the artificial silk had a destructive effect on the haemolysin. Instead, reversibility was demonstrated by adding ox serum to the mixture of congo red and haemolysin. This brought about a redistribution of the congo red between the ox serum and the haemolysin and if the amount of congo red used had been only just sufficient to neutralize the haemolysin of B. welchii, then the haemolytic activity could again be demonstrated. Gordon and Robson (1933) showed that congo red interfered with the anaphylactic reaction tested both in vivo and in vitro, the guinea-pig uterus being used in the in vitro experiments, in which the inhibitory action of the dye was shown to be reversible. It was suggested that the congo red interfered with the entrance of antigen into the cell.


2021 ◽  
Author(s):  
Robin Loesch ◽  
Stefano Caruso ◽  
Valerie Paradis ◽  
Cecile Godard ◽  
Angelique Gougelet ◽  
...  

Background and aims: One-third of hepatocellular carcinomas (HCCs) have mutations that activate the β-catenin pathway with mostly CTNNB1 mutations. Mouse models using Adenomatous polyposis coli (Apc) loss-of-functions (LOF) are widely used to mimic β-catenin-dependent tumorigenesis. Considering the low prevalence of APC mutations in human HCCs we aimed to generate hepatic tumors through CTNNB1 exon 3 deletion (βcatΔex3) and to compare them to hepatic tumors with Apc LOF engineered through a frameshift in exon 15 (Apcfs-ex15). Methods: We used hepatic-specific and inducible Cre-lox mouse models as well as a hepatic-specific in vivo CRISPR/Cas9 approach using AAV vectors, to generate Apcfs-ex15 and βcatΔex3 hepatic tumors harboring activation of the β-catenin pathway. Tumors generated by the Cre-lox models were analyzed phenotypically using immunohistochemistry and were selected for transcriptomic analysis using RNA-sequencing. Mouse RNAseq data were compared to human RNAseq data (normal tissues (8), HCCs (48) and hepatoblastomas (9)) in an integrative analysis. Tumors generated via CRISPR were analyzed using DNA sequencing and immunohistochemistry. Results: Mice with βcatΔex3 alteration in hepatocytes developed liver tumors. Generated tumors were indistinguishable from those arising in Apcfs-ex15 mice. Both Apcfs-ex15 and βcatΔex3 mouse models induced two phenotypically distinct tumors (differentiated or undifferentiated). Integrative analysis of human and mouse tumors showed that mouse differentiated tumors are close to human well differentiated CTNNB1-mutated tumors, while undifferentiated ones are closer to human mesenchymal hepatoblastomas, and are activated for YAP signaling. Conclusion: Apcfs-ex15 and βcatΔex3 mouse models similarly induce tumors transcriptionally close to either well differentiated β-Catenin activated human HCCs or mesenchymal hepatoblastomas.


2009 ◽  
Vol 101 (4) ◽  
pp. 1774-1780 ◽  
Author(s):  
Ziyi Sun ◽  
Dao-Qi Zhang ◽  
Douglas G. McMahon

Hemi-gap-junction (HGJ) channels of retinal horizontal cells (HCs) function as transmembrane ion channels that are modulated by voltage and calcium. As an endogenous retinal neuromodulator, zinc, which is coreleased with glutamate at photoreceptor synapses, plays an important role in shaping visual signals by acting on postsynaptic HCs in vivo. To understand more fully the regulation and function of HC HGJ channels, we examined the effect of Zn2+ on HGJ channel currents in bass retinal HCs. Hemichannel currents elicited by depolarization in Ca2+-free medium and in 1 mM Ca2+ medium were significantly inhibited by extracellular Zn2+. The inhibition by Zn2+ of hemichannel currents was dose dependent with a half-maximum inhibitory concentration of 37 μM. Compared with other divalent cations, Zn2+ exhibited higher inhibitory potency, with the order being Zn2+ > Cd2+ ≈ Co2+ > Ca2+ > Ba2+ > Mg2+. Zn2+ and Ca2+ were found to modulate HGJ channels independently in additivity experiments. Modification of histidine residues with N-bromosuccinimide suppressed the inhibitory action of Zn2+, whereas modification of cysteine residues had no significant effect on Zn2+ inhibition. Taken together, these results suggest that zinc acts on HGJ channels in a calcium-independent way and that histidine residues on the extracellular domain of HGJ channels mediate the inhibitory action of zinc.


1996 ◽  
Vol 118 (8) ◽  
pp. 1875-1877 ◽  
Author(s):  
L.C. Stanfa ◽  
V. Chapman ◽  
N. Kerr ◽  
A.H. Dickenson

2001 ◽  
Vol 85 (02) ◽  
pp. 303-308 ◽  
Author(s):  
Michael Rolf ◽  
Charles Brearley ◽  
Martyn Mahaut-Smith

SummarySimultaneous measurements of [Ca2+]i and light transmission were used to examine the relationship between P2X1 receptor activation and functional platelet responses. The P2X1 agonist α,β-MeATP evoked a transient [Ca2+]i increase and a reversible decrease in light transmission; both responses required external Ca2+ and the nucleotidase apyrase. The transmission response was due to shape change only, verified by scanning electron microscopy and insensitivity to Reopro, a GPIIbIIIa antagonist. α,β-MeATP stimulated smaller shape changes than ADP, however P2X1 responses had a lifespan of <2 h following resuspension in saline and may be considerably larger in vivo. A peak [Ca2+]i increase of >50 nM was required for detectable shape change. Overlap of concentration-response relationships for α,β-MeATP-evoked [Ca2+]i and shape change suggests that other second messengers are not involved. Therefore, the physiological P2X1 agonist ATP can contribute to platelet activation, in contrast to its previously described inhibitory action at metabotropic platelet purinoceptors.


2015 ◽  
Vol 6 (8) ◽  
pp. 2693-2700 ◽  
Author(s):  
Aditya Arvindekar ◽  
Tanaji More ◽  
Pavan V. Payghan ◽  
Kirti Laddha ◽  
Nanda Ghoshal ◽  
...  

The 1,8-dihydroxyanthraquinones from the culinary and medicinally important plant Rheum emodi exert anti-hyperglycemic potential but notably different α-glucosidase actions as established by in vitro, in vivo, kinetics and molecular docking studies.


Sign in / Sign up

Export Citation Format

Share Document