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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]

It was previously found that the severity of LPS-induced systemic inflammatory response (SIRS) in rats is determined by resistance to hypoxia and the level of Hif1a expression. Individual differences in the level of Hif1a and NFkb expression in the liver were studied in relation to the severity of inflammatory and immune reactions in LPS-induced SIRS in rats without previous placement in a ventilated decompression chamber. During the early periods after SIRS modeling, rats with high expression of the Hif1a and NFkb genes associated with increased expression of pro- and anti-inflammatory cytokines are identified. These animals have a high blood level of corticosterone, low number of neutrophils in the interalveolar septa, and a predominance of T cells over B cells in the peripheral blood. The obtained data can be used to develop new approaches to the individual prediction of the severity of sepsis and SIRS in intensive care units, which will increase the effectiveness of therapy and reduce mortality rate., (© 2025. Springer Science+Business Media, LLC, part of Springer Nature.)

The international consensus Sepsis-3 in 2016 defined sepsis as life-threatening organ dysfunction caused by a disruption of the host response to infection. One of the main mechanisms leading to the death of patients with sepsis is an imbalance of the immune response to pathogens. Activation of immune cells, in particular neutrophils, plays a key role in the mechanisms of sepsis. During sepsis, the number of immature neutrophils in the blood increases, PD-L1 neutrophils appear, which have an immunosuppressive function, and the number of Neu1 subtype of neutrophils, characterized by high expression of the NF-kB inhibitor, the chemokine CXCL8, olfactomedine, which regulates the production of cytokines, and myeloperoxidase, increases. When the inflammatory response generalizes, the phagocytic and bactericidal functions of neutrophils are disrupted. An important role in the mechanisms of sepsis is played by the formation of neutrophil extracellular traps, extracellular DNA, and the nuclear non-histone protein HMGB1, which are DAMPs and have proinflammatory activity. The development of approaches to predicting the development and course of sepsis in injuries and infectious and inflammatory diseases based on assessing the functional activity of neutrophils and their phenotype is a promising area of research, in particular approaches to regulating the functioning of neutrophils using miRNA.

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.)

Background: Doxorubicin is a well-known antitumor drug that is not employed for chemotherapy of brain tumors. Indeed, doxorubicin does not penetrate across the blood-brain barrier in therapeutic concentrations., Objective: To study the antitumor effect of doxorubicin combined with nitrosorbide on intracranial experimental glioblastoma 101/8 in rats., Material and Methods: Male Wistar rats ( n =86) with intracranial implanted glioblastoma 101/8 received doxorubicin (i.v. 1.5 mg/kg thrice) alone or in combination with nitrosorbide (i.v or orally, 0.5 mg/kg thrice) in 2, 5 and 8 days after implantation. Efficacy was assessed considering survival and brain tumor volume in 14 days after tumor implantation., Results: Combination of doxorubicin and nitrosorbide significantly increased survival (57% and 155%, respectively) and slowed down tumor growth (16±12 and 8±6 mm 3 , respectively) compared to doxorubicin alone. Effectiveness of nitrosorbide alone was trivial., Conclusion: Nitric oxide donor nitrosorbide considerably potentiated the antitumor effect of doxorubicin against intracranial 101/8 glioblastoma in rats.

Comparative analysis of the hormonal profile was performed in 12 and 16 patients with mild and moderately severe chronic obstructive pulmonary disease (COPD) respectively, in 25 patients with chronic bronchitis, 13 smokers without respiratory symptoms and dysfunction of external respiration, and in healthy non-smokers. Patients with moderately severe COPD had lower concentrations of total and free testosterone and DHEA than smokers with chronic bronchitis and mild COPD. Blood androsterone level positively correlated with the forced expiratory volume during the first second and inversely related to the duration of smoking and severity of coughing.