The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection involves dysregulations of iron metabolism, and although the mechanism of this pathology is not yet fully ...understood, correction of iron metabolism pathways seems a promising pharmacological target. The previously observed effect of inhibiting SARS-CoV-2 infection by ferristatin II, an inducer of transferrin receptor 1 (TfR1) degradation, prompted the study of competition between Spike protein and TfR1 ligands, especially lactoferrin (Lf) and transferrin (Tf). We hypothesized molecular mimicry of Spike protein as cross-reactivity of Spike-specific antibodies with Tf and Lf. Thus, strong positive correlations (R
2
> 0.95) were found between the level of Spike-specific IgG antibodies present in serum samples of COVID-19-recovered and Sputnik V-vaccinated individuals and their Tf-binding activity assayed with peroxidase-labeled anti-Tf. In addition, we observed cross-reactivity of Lf-specific murine monoclonal antibody (mAb) towards the SARS-CoV-2 Spike protein. On the other hand, the interaction of mAbs produced to the receptor-binding domain (RBD) of the Spike protein with recombinant RBD protein was disrupted by Tf, Lf, soluble TfR1, anti-TfR1 aptamer, as well as by peptides RGD and GHAIYPRH. Furthermore, direct interaction of RBD protein with Lf, but not Tf, was observed, with affinity of binding estimated by K
D
to be 23 nM and 16 nM for apo-Lf and holo-Lf, respectively. Treatment of Vero E6 cells with apo-Lf and holo-Lf (1–4 mg/mL) significantly inhibited SARS-CoV-2 replication of both Wuhan and Delta lineages. Protective effects of Lf on different arms of SARS-CoV-2-induced pathogenesis and possible consequences of cross-reactivity of Spike-specific antibodies are discussed.
Among the properties of lactoferrin (LF) are bactericidal, antianemic, immunomodulatory, antitumour, antiphlogistic effects. Previously we demonstrated its capacity to stabilize in vivo HIF-1-alpha ...and HIF-2-alpha, which are redox-sensitive multiaimed transcription factors. Various tissues of animals receiving recombinant human LF (rhLF) responded by expressing the HIF-1-alpha target genes, hence such proteins as erythropoietin (EPO), ceruloplasmin, etc. were synthesized in noticeable amounts. Among organs in which EPO synthesis occurred were brain, heart, spleen, liver, kidneys and lungs. Other researchers showed that EPO can act as a protectant against severe brain injury and status epilepticus in rats. Therefore, we tried rhLF as a protector against the severe neurologic disorders developed in rats, such as the rotenone-induced model of Parkinson’s disease and experimental autoimmune encephalomyelitis as a model of multiple sclerosis, and observed its capacity to mitigate the grave symptoms. Moreover, an intraperitoneal injection of rhLF into mice 1 h after occlusion of the medial cerebral artery significantly diminished the necrosis area measured on the third day in the ischaemic brain. During this period EPO was synthesized in various murine tissues. It was known that EPO induces nuclear translocation of Nrf2, which, like HIF-1-alpha, is a transcription factor. In view that under conditions of hypoxia both factors demonstrate a synergistic protective effect, we suggested that LF activates the Keap1/Nrf2 signaling pathway, an important link in proliferation and differentiation of normal and malignant cells. J774 macrophages were cultured for 3 days without or in the presence of ferric and ferrous ions (RPMI-1640 and DMEM/F12, respectively). Then cells were incubated with rhLF or Deferiprone. Confocal microscopy revealed nuclear translocation of Nrf2 (the key event in Keap1/Nrf2 signaling) induced by apo-rhLF (iron-free, RPMI-1640). The reference compound Deferiprone (iron chelator) had the similar effect. Upon iron binding (in DMEM/F12) rhLF did not activate the Keap1/Nrf2 pathway. Added to J774, apo-rhLF enhanced transcription of Nrf2-dependent genes coding for glutathione S-transferase P and heme oxygenase-1. Western blotting revealed presence of Nrf2 in mice brain after 6 days of oral administration of apo-rhLF, but not Fe-rhLF or equivalent amount of PBS. Hence, apo-LF, but not holo-LF, induces the translocation of Nrf2 from cytoplasm to the nucleus, probably due to its capacity to induce EPO synthesis.
Data on the production of antiprotons at an angle of 40° in the laboratory system in collisions of 50-GeV protons with C, Al, Cu, and W nuclear targets have been obtained in the SPIN experiment ...(IHEP, Protvino, Russia). Invariant cross sections have been measured at transverse momenta up to
p
T
≈ 2.6 GeV/
c
. The an-alysis of the momentum spectra has shown that multinucleon (multiquark) configurations inside a nucleus are involved in the production of antiprotons.
The photophysical properties of indotricarbocyanine dyes upon complexation with serum albumin were studied. The technique using electrophoresis to detect their formation was optimized. The area in ...which the studied dye was localized on the surface of the gel plate was searched for by recording the fluorescence spectra of the dye before protein fixation and visualization followed by completion of the protocol for obtaining the electrophoregrams because the dye was degraded by acids. Excitation used radiation of a semiconductor laser with a wavelength of 684 nm, which excited fluorescence of the studied dyes, to minimize the possible influence of luminescence of the gel components. It was established that the position of the maxima and the half-width of the fluorescence spectra of dyes with an o-phenylene bridge in the conjugation chain in the regions of the electrophoregram corresponding to the location of albumin coincided with the characteristic emission of the dyes in the initial solutions with albumin, which revealed that covalently bonded complexes of the dyes with albumin formed.
The SPIN experiment is carried out with the aim of studying inclusive production of charged particles with high transverse momenta in hard proton−nucleus and nucleus−nucleus interactions. A ...single-arm narrow-aperture spectrometer is used in the study. The uniqueness of the experiment is in the high intensity of the proton (10
12
−10
13
protons/s) and ion (of the order of 5 × 10
9
ions/s) beams ejected from the U-70 accelerator, which makes it possible to measure inclusive cross sections varying by seven orders of magnitude. The SPIN setup is able to detect particles with momenta in a kinematic domain of nucleon−nucleon interactions as well as beyond its limits. The spectrometer equipment and the features of the measurement procedure are described.
Data on the production of positively charged particles emitted at an angle of 40
(in the laboratory frame) with transverse momenta of up to 2.7 GeV
in the interaction of 50-GeV
protons with carbon, ...aluminum, copper, and tungsten nuclear targets are presented. Particular attention is given to studying the production of light nuclear fragments, such as deuterons (
) and tritons (
). An analysis of data on
and
particles gives grounds to state that these fragments arise via a local mechanism of their direct knockout from nuclei. The results were obtained in the SPIN experiment at the Institute for High Energy Physics (IHEP, Protvino).
The structure, phase composition, hardness, and elasticity modulus of sintered Fe–Cu–Ni–Sn–CrB
2
composites and their tribological properties under dry and wet friction have been studied by X-ray ...diffraction, scanning electron microscopy, microindentation, and tribological testing. The obtained results have demonstrated that the microstructure and mechanical and tribological properties of these composites depend on the CrB
2
additive content. The Fe–Cu–Ni–Sn–CrB
2
composites incorporate the α-Fe, γ-Fe, and Cu phases and a certain fraction of the crystalline Cu
9
NiSn
3
, NiSn
3
, and CrB
2
phases. The hardness and elasticity modulus of these composites are almost independent of the friction medium (dry or wet), and the friction force and the wear rate are variable. The Fe–Cu–Ni–Sn–CrB
2
composites are superior to the Fe–Cu–Ni–Sn composites in their mechanical and tribological properties. The addition of 2 wt % of CrB
2
to the 51Fe–32Cu–9Ni–8Sn composite has decreased the friction force from 220 to 170 mN and the wear rate from 7.41 × 10
–2
to 3.41 × 10
–2
mm
3
/(N m) under dry friction and, respectively, from 200 to 140 mN and from 8.19 × 10
–2
to 4.10 × 10
–2
mm
3
/(N m) under wet friction. A further growth in the CrB
2
content in the composites leads to an increase in the wear rate. The mechanism of increase in the wear resistance of the composite containing 2 wt % of CrB
2
as compared to the initial composite implies the formation of a more fine-grained structure with an optimal combination of the hardness and elasticity modulus. The Fe–Cu–Ni–Sn–CrB
2
composites can be used as a material for the matrix of composite diamond-containing materials subjected to strong wear.
The first data on the yield of the lightest nuclear fragments (protons
p
, deuterons
d
, and tritons
t
) with high transverse momenta
p
T
at an angle of 40° in the laboratory reference frame from ...nuclear targets bombarded by 50-GeV/
c
protons and 20A-GeV/
c
carbon nuclei obtained in the SPIN experiment (IHEP, Protvino, Russia) have been reported. It has been shown that the
pA
and C
A
data can be described within a common scaling approach, which possibly indicates that the mechanism of formation of high-
p
T
nuclear fragments is common for these reactions.
To assess the role of endogenous lactoferrin (LF) in the formation of the molecular phenotype of human breast cancer (BC) cell lines with varying degrees of malignancy, including ...cisplatin/doxorubicin resistant cell lines, and identify possible impact of exogenous LF.
5 breast cell lines of different origin - MCF-10 A, MCF-7, including doxorubicin/cisplatin resistant ones, T47D, MDA-MB-231, and MDA-MB-468. Immunocytochemistry: expression of LF, Ki-67, adhesion molecules E- and N-cadherin, CD44, CD24 rating the invasive potential of cells.
Expression of LF in human BC cell lines varies. It is associated with the heterogeneity of molecular profiles of cell lines in terms of adhesion. A link has been established between the level of LF expression in the resistant cell line MCF-7/CP and MCF-7/Dox, features of their molecular profile and invasive properties. Exogenous LF was shown to be capable of modifying the molecular profile and invasive properties of all the studied cell lines including resistant ones (MCF-7/CP and MCF-7/Dox).
The sensitivity of cytostatic-resistant cell lines (MCF-7/CP and MCF-7/Dox) tends to increase under the influence of exogenous LF. It is likely that this effect is due to LF-mediated inhibition of the expression of proteins associated with drug resistance.
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