Bulletin of Experimental Biology and Medicine最新文献

We compared the expression of heat shock proteins (HSP-27, HSP-60, HSP-70, HSP90) in skin keratinocytes of patients with atopic dermatitis and healthy donors. Keratinocytes were obtained by scraping from apparently intact skin of the forearm. Keratinocytes were stained with monoclonal antibodies and analyzed by flow cytometry. The expression of HSPs in patients was significantly increased in comparison with healthy donors and depended on the disease severity according to the SCORAD index. During remission, HSP expression decreased, but did not reach the control values in most patients. A significant increase in the levels of phosphorylated HSP forms was observed during exacerbation of atopic dermatitis, reflecting the stress activity associated with this condition.

Intranasal administration of the neurotoxic fragment of β-amyloid protein Aβ25-35 for 14 days to aged C57Bl/6 mice induces impairment of passive avoidance conditioning and reduces the content of IL-10 in the prefrontal cortex and hippocampus without changing the content of IL-4 in these brain structures. Co-administration of Aβ25-35 with anti-glutamate antibodies reversed spatial memory impairment, restores the levels of IL-10, and reduces the content of IL-4 in the prefrontal cortex and hippocampus of aged C57Bl/6 mice.

We compared the therapeutic effects of dietary adjustment and fish oil in rats with experimental non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet. The NAFLD rats were either maintained on high-fat diet, or transferred from high-fat diet to normal diet, or received a diet with lard replaced with fish oil. Control rats received normal diet throughout the experiment. The liver coefficient, blood lipids, activities of transaminases, and the severity of hepatic steatosis in NAFLD rats were improved by both dietary adjustment and fish oil (p < 0.05). Dietary adjustment led to a significant decrease in the levels of inflammatory factors in the liver of NAFLD rats (p < 0.05); in rats receiving fish oil, these parameters also tended to decrease. A large number of inflammatory cells were found in the colonic mucosa of rats fed with high-fat diet and the serum level of LPS in these rats was higher than in the control. Neither dietary adjustment, nor fish oil consumption reduced the serum level of LPS in NAFLD rats. Thus, dietary adjustment and fish oil administration improved the levels of blood lipids and liver inflammation in NAFLD rats. The beneficial effect of dietary adjustment on the level of liver inflammation in NAFLD was more pronounced.

We performed a comprehensive in vitro study of a potential antiglioma compound from the class of NO donors, a nitrosyl iron complex with N-ethylthiourea (ETM), as an activator of redox-regulated mechanisms of cellular response. The effect of ETM on glioblastoma cells is accompanied by enhanced ROS generation, accumulation of intracellular NO, a decrease in mitochondrial membrane potential, and induction of caspase-3-dependent apoptosis. The studied complex acts as an activator of Nrf2 transcription factor, and the Nrf2/HO-1-dependent pathway plays a major role in regulating redox processes triggered by this complex. Induction of this pathway does not necessarily suppress the expression of NF-κB and its target genes, but prevents activation of NF-κB-mediated mechanisms of tumor cell protection. Nrf2 activation by ETM inhibits ferroptosis in glioblastoma cells, yet does not prevent apoptotic cell death. It can be assumed that the scenario of glioblastoma cell death under the effect of Nrf2 activators is largely determined by the ability of cells to quickly reconfigure the antioxidant system under conditions of oxidative stress.

Existing approaches to the treatment of Alzheimer's disease are ineffective because they do not stop neurodegenerative processes in the brain and do not promote the regeneration of the nervous tissue. Cell therapy is a promising strategy for the treatment of this disease. This review discusses clinical studies of cell-based therapies for Alzheimer's disease, evaluates their therapeutic potential, and proposes strategies for developing safe, accessible, and effective cell products.

The dynamics of protein oxidative modification, superoxide dismutase (SOD) activity, and reduced glutathione levels were studied in the control and prenatally-stressed male rats following immobilization stress. The control group consisted of intact males not exposed to prenatal stress. Prenatal stress was modeled by immobilizing pregnant rats for 1 h per day on gestational days 15-19. Male offspring (3-months-old) were subjected to a 20 min immobilization stress. In both groups, the specified parameters were assessed at baseline (no stress), immediately after stress, and after 1, 3, and 24 h of post-stress. Prenatal stress attenuated the reactivity of these redox indicators, whereas control animals exhibited pronounced pro- and antioxidant responses following immobilization. These findings suggest that prenatal stress impairs the adaptive capacity of the redox system in adult offspring.

The myocardial response was evaluated in adult male Wistar rats subjected to early postnatal stress (maternal separation) and subsequently administered a single intraperitoneal injection of LPS from E. coli O26:B6 (Sigma-Aldrich) at a dose of 2.5 mg/kg (MS + LPS group). Control animals were neither exposed to early postnatal stress nor treated with LPS, while the comparison group consisted of non-stressed animals that received LPS (LPS group). Both the LPS and MS + LPS groups exhibited an increased proportion of p53⁺ cardiomyocytes and elevated plasma troponin I levels in comparison with the control. In the MS + LPS group, a significant increase in the number of nucleoli per cardiomyocyte nucleus and a higher proportion of eNOS⁺ cardiomyocytes were observed relative to both the control and LPS groups. These findings indicate that animals exposed to early postnatal stress display an exaggerated myocardial response to LPS in comparison with the non-stressed counterparts.

The global spread of multidrug-resistant pathogens underscores the urgent need for novel therapeutic strategies against bacterial infections. One promising approach is phage therapy, which utilizes lytic bacteriophages that exhibit high specificity for their bacterial hosts. In this study, we isolated a novel bacteriophage, vB_EcoA_PHZVL, belonging to the family Autographiviridae, which demonstrates potent lytic activity against a clinical strain of adherent-invasive Escherichia coli (AIEC) isolated from a patient with Crohn's disease (CD). We further demonstrated that both plaque morphology and phage adsorption efficiency are influenced by the composition of the culture medium and the carbon source, likely due to alterations in LPS structure on the bacterial surface. These findings enhance our understanding of phage-host interactions and highlight the potential of vB_EcoA_PHZVL as a candidate for phage-based therapy in CD.

A histological and immunohistochemical analysis (IHC) of the motor cortex and subventricular zone (a neurogenic region) in the right cerebral hemisphere of ICR mice was performed following traumatic brain injury (TBI) induced at the bregma level. Hematoxylin-eosin and cresyl violet staining revealed that TBI causes significant damage to the motor cortex, including tissue edema, neuroinflammation, vascular congestion, cellular and tissue degeneration, disruption of the vascular network, astrolysis, and glial scar formation. Concurrently, the number of neurons in the motor cortex was reduced, while the number of glial cells increased. IHC analysis showed a decreased population of DCX⁺ proliferating neuroblasts in the subventricular zone, migration of NeuN⁺ neurons from this neurogenic niche toward the injured motor cortex, and impaired migration of GFAP⁺ astrocytes. To mitigate neuroinflammation, it is proposed to suppress bone marrow hematopoietic activity and prevent the mobilization of inflammatory cells from the bone marrow into the systemic circulation.

Hypergravity (HG) and microgravity (MG) modulate Ca²⁺ entry into the cytosol of cardiomyocytes via both voltage-gated and mechanically gated Ca²⁺ channels. The last include members of the TRP channel family with TRPM7 being the predominant subtype. We investigated the relationship between changes in TRPM7 channel protein synthesis and the abundance of its corresponding mRNA in cardiomyocytes from rats exposed to HG or MG for 14 days. Using transcriptome sequencing with normalization of "raw reads" by the TPM (Transcripts Per Kilobase Million) method, we found that TRPM7 TPM values significantly increased after HG exposure and significantly decreased after MG. Western blotting of TRPM7 protein levels confirmed a pronounced upregulation under HG and a substantial downregulation under MG. These changes may lead to altered ion conductance through mechanically gated channels in cardiomyocytes.