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The sex differences of infection and inflammatory diseases particularly appear at reproductive age and depend on the sex hormone level, varied between male and female. There are a few sets of data about the sex differences of infection and inflammatory diseases course, including systemic inflammatory response syndrome (SIRS) and sepsis, of newborns. The aim of our research was the estimation of morphological and immunological manifestation of SIRS of the newborn Wistar rats. Investigations were carried out on male and female two-day-old Wistar rats (10-12 g). SIRS was modeled by intraperitoneal injection of LPS (E. coli, O26: B6 strain, Sigma) in high dose--15mg/kg. We did not find out any sex differences of the liver lesions severity between newborn males and females after LPS injection. The levels of endotoxin and estradiol in the serum, as the number of neutrophils in the intra-alveolar septa of the lungs, were higher in males than females with SIRS. Production of IL-2 and TNF-α by the spleen cells of males was higher than that in control group that reflects polarization predominantly on the Th1-type immune response. The secretion of IL-2, TNF-α, and I F N-γ by ConA activated spleen cells of females decreased that reflects the suppression of Th1-type immune response. We suppose that the LPS administration in the high dose causes the multidirectional reaction of the immune system of neonatal males and females Wistar rats. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the leading cause of dementia among the elderly. Neuropathologically, AD is characterized by the deposition of a 39- to 42-amino acid long β-amyloid (Aβ) peptide in the form of senile plaques. Several post-translational modifications (PTMs) in the N-terminal domain have been shown to increase the aggregation and cytotoxicity of Aβ, and specific Aβ proteoforms (e.g., Aβ with isomerized D7 (isoD7-Aβ)) are abundant in the senile plaques of AD patients. Animal models are indispensable tools for the study of disease pathogenesis, as well as preclinical testing. In the presented work, the accumulation dynamics of Aβ proteoforms in the brain of one of the most widely used amyloid-based mouse models (the 5xFAD line) was monitored. Mass spectrometry (MS) approaches, based on ion mobility separation and the characteristic fragment ion formation, were applied. The results indicated a gradual increase in the Aβ fraction of isoD7-Aβ, starting from approximately 8% at 7 months to approximately 30% by 23 months of age. Other specific PTMs, in particular, pyroglutamylation, deamidation, and oxidation, as well as phosphorylation, were also monitored. The results for mice of different ages demonstrated that the accumulation of Aβ proteoforms correlate with the formation of Aβ deposits. Although the mouse model cannot be a complete analogue of the processes occurring in the human brain in AD, and several of the observed parameters differ significantly from human values supposedly due to the limited lifespan of the model animals, this dynamic study provides evidence on at least one of the possible mechanisms that can trigger amyloidosis in AD, i.e., the hypothesis on the relationship between the accumulation of isoD7-Aβ and the progression of AD-like pathology. [ABSTRACT FROM AUTHOR]

Innate immunity reactions are core to any immunological process, including systemic inflammation and such extremes as acute respiratory distress syndrome (ARDS) and cytokine storm. Macrophages, the key cells of innate immunity, show high phenotypic plasticity: depending on microenvironmental cues, they can polarize into M1 (classically activated, pro-inflammatory) or M2 (alternatively activated, anti-inflammatory). The anti-inflammatory M2 macrophage polarization-based cell therapies constitute a novel prospective modality. Systemic administration of 'educated' macrophages is intended at their homing in lungs in order to mitigate the pro-inflammatory cytokine production and reduce the risks of 'cytokine storm' and related severe complications. Acute respiratory distress syndrome (ARDS) is the main mortality factor in pneumonia including SARS-CoV-associated cases. This study aimed to evaluate the influence of infusions of RAW 264.7 murine macrophage cell line polarized towards M2 phenotype on the development of LPS-induced ARDS in mouse model. The results indicate that the M2-polarized RAW 264.7 macrophage infusions in the studied model of ARDS promote relocation of lymphocytes from their depots in immune organs to the lungs. In addition, the treatment facilitates expression of M2-polarization markers Arg1 , Vegfa and Tgfb and decreases of M1-polarization marker Cd38 in lung tissues, which can indicate the anti-inflammatory response activation. However, treatment of ARDS with M2-polarized macrophages didn't change the neutrophil numbers in the lungs. Moreover, the level of the Arg1 protein in lungs decreased throughtout the treatment with M2 macrophages, which is probably because of the pro-inflammatory microenvironment influence on the polarization of macrophages towards M1. Thus, the chemical polarization of macrophages is unstable and depends on the microenvironment. This adverse effect can be reduced through the use of primary autologous macrophages or some alternative methods of M2 polarization, notably siRNA-mediated., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Timur Fatkhudinov reports financial support was provided by 10.13039/501100006769Russian Science Foundation., (© 2023 Published by Elsevier Ltd.)