The MAPK/ERK/p38 are signal transduction pathways that couple intracellular responses to the external stimuli. Contrary to ERK protein which is part of the survival route, presence of p38 could have an impact on cell injury. Tolerance induced by ischemic preconditioning (IPC) is a phenomenon of tissue adaptation, which results in increased tolerance to lethal ischemia-reperfusion injury (IRI). Paper describes changes in MAPK protein pathways after brain IPC. Ischemia was induced by 4-vessels occlusion and rats were preconditioned by sub-lethal ischemia. Western blot and immunohistochemistry identified ERK/p38 proteins in injured areas. The highest level of the pERK was detected at 24 h in IPC groups. A contrary pattern of MAPK/p38 activation was observed in this group, where the lowest level of p38 was displayed at 24 h after ischemia. This suggests that the MAPK signal transduction might have a potential role in tissues response subjected to IRI and in the phenomenon of tolerance.

Simvastatin is a cholesterol-lowering agent whose functional significance and neuroprotective mechanism in ischemic brain injury is not yet solved. The purpose of this study is to evaluate the effect of simvastatin on ischemic brain injury. We examined the endoplasmic reticulum stress response (UPR/unfolded protein response), by measuring the mRNA and protein levels of specific genes such as ATF6, GRP78, and XBP1 after 15 min 4-VO ischemia and different times of reperfusion (1, 3, and 24 h). The results from the group of naïve ischemic rats were compared with results from the group of pre-treated animals with simvastatin. The results of the experiments showed significant increase in all genes at the mRNA level in ischemic phase (about 43% for XBP1, 58% for GRP78, and 39% for ATF6 more than control). The protein level of XBP1 was decreased in pre-treated animals at ischemic phase and first hour of reperfusion (about 15% less), and did not reach control levels. The protein levels of GRP78 were maximal at third hour of reperfusion in statin group with a small decrease at 24 h of reperfusion in both groups. The levels of ATF6 mRNA in statin-treated animals was higher in comparison to non-statin animals at the ischemic phase and the third hour of reperfusion (about 35% higher), which was also translated into the higher protein level. This could indicate that one of the main proteins targeted to enhance neuroprotective effect to ER during the first two hours of reperfusion was ATF6 protein, the levels of which were 60% higher than in non-treated animals. These data suggest that simvastatin, in addition to the proposed neuroprotective effect, exerts a neuroprotective role in the attenuation of ER stress response after acute ischemic/reperfusion insult.

Ischemic tolerance can be developed by prior ischemic non-injurious stimulus preconditioning. The molecular mechanisms underlying ischemic tolerance are not yet fully understood. The purpose of this study is to evaluate the effect of preconditioning/preischemia on ischemic brain injury. We examined the endoplasmic reticulum stress response (unfolded protein response (UPR)) by measuring the mRNA and protein levels of specific genes such as ATF6, GRP78, and XBP1 after 15 min 4-VO ischemia and different times of reperfusion (1, 3, and 24 h). The data from the group of naïve ischemic rats were compared with data from the group of preconditioned animals. The results of the experiments showed significant changes in the gene expression at the mRNA level in the all ischemic/reperfusion phases. The influence of preischemia on protein level of XBP was significant in later ischemic times and at 3 h, the reperfusion reached 230% of the controls. The protein levels of GRP78 in preischemic animals showed a significant increase in ischemic and reperfusion times. They exceeded to 50% levels of corresponding naïve ischemic/reperfusion groups. Preconditioning also induced remarkable changes in the levels of ATF6 protein in the ischemic phase (about 170%). The levels of ATF6 remained elevated in earlier reperfusion times (37 and 62%, respectively) and persisted significantly elevated after 24 h of reperfusion. This data suggest that preconditioning paradigm (preischemia) underlies its neuroprotective effect by the attenuation of ER stress response after acute ischemic/reperfusion insult.

Ischemic preconditioning (IPC) represents the phenomenon of CNC adaptation, which results in increased tolerance of CNS to lethal ischemia. Brain ischemia/reperfusion (IRI) initiates a catastrophic cascade in which many subcellular organelles play an important role. The Golgi apparatus, which is a part of secretory pathways (SP), represents the Ca(2+) store and regulates secretion of proteins for growth/reorganization of neuronal circuit by secretory Ca(2+)ATPases (SPCA1). The purpose of this study is to evaluate the effect of IRI and preconditioning on SPCA1 gene expression and oxidative damage after 4-vessel occlusion for 15 min and after being exposed to different reperfusion periods. Rats were preconditioned by 5 min of sub-lethal ischemia and 2 days later, 15 min of lethal ischemia was induced. Our experiments conclusively showed IRI-induced depression of SPCA activity and lipo- and protein oxidation in rat hippocampal membranes. IRI also activates the induction of SPCA1 gene expression in later reperfusion periods. IPC partially suppresses lipo- and protein oxidation in hippocampal membranes and leads to partiall rovery of the ischemic-induced depression of SPCA activity. In addition, IPC initiates earlier cellular response to the injury by the significant elevation of mRNA expression to 142% comparing to 1 h of corresponding reperfusion and to 11% comparing to 24 h of corresponding reperfusion, respectively. Similar patterns were observed on the translational level by Western blot analysis. Our results indicate the specific SPCA1 expression pattern in ischemic hippocampus. It also shows that the SPCA expression and the post-translational changes induced by ischemia are modulated by the IPC. This might serve to understand the molecular mechanisms involved in the structural integrity and function of the SP after ischemic challenge. It also suggests that there is a correlation of SPCA function with the role of SP in the response to pre-ischemic challenge.

Various forms of social media (SM) appear to be very popular among young people because they provide information and entertainment, including a wide range of web technologies such as blogs, wikis, online social networks, and virtual networks. SM plays a huge role in the lives of children and teenagers, especially during the COVID-19 pandemic, when the computer becomes not only a means of entertainment or leisure, but also a necessary and everyday means of education and communication with other people. Thus, COVID-19 has brought a radical change, not only in the daily schedule and leisure time of pupils and students, but also in the perception of the procedures used by this specific group in the online space. Through our own research, using structured interviews and a questionnaire, we examine the use of SM as a tool to promote sustainable well-being in a group of high school students from various schools in central Slovak Republic (formerly Czechoslovakia). The research confirms that during the pandemic, the use of SM by the young respondents contributes significantly to well-being. This is the case when SM is used by high school students as a tool in promoting: (1) personal interests; (2) motivation; (3) communication and interpersonal connectivity; (4) preferred forms of online education; and (5) online games. The article presents a set of recommendations regarding the use of SM as a tool for sustaining the well-being of young people during the pandemic.

The study determines whether hyperhomocysteinemia (risk factor of brain ischemia) alone or in combination with ischemic preconditioning (IPC) affects the ischemia-induced changes in gene expression of secretory pathways Ca(2+)-ATPase (SPCA1). Hyperhomocysteinemia was induced by subcutaneous administration of homocysteine (Hcy; 0.45 µmol/g body weight) twice a day at 8 h intervals for 14 days. Rats were preconditioned by 5 min ischemia and 2 days later, 15 min of global forebrain ischemia was induced by four vessel occlusion. We observed that hyperhomocysteinemia significantly decreased the level of SPCA1 mRNA in the cortex. Pre-ischemic challenge was noticeable in both brain areas. In the cortex, pre-ischemia in Hcy group led to the abrupt stimulation of the mRNA expression by 249% within the Hcy ischemic group and by 321% in the Hcy control. Values further exceeded those observed in the naive control. In the hippocampus, the differences between naive and Hcy groups were not observed. IPC initiated elevation of mRNA expression to 159% (p < 0.05) of control with Hcy and to 131% (p < 0.01) of ischemia with Hcy, respectively. Documented response of SPCA gene to IPC in hyperhomocysteinemic group might suggest a correlation of SPCA expression consistent with the role of cross-talks between intracellular Ca(2+) stores including secretory pathways in the tolerance phenomenon.

4-hydroxynonenal (HNE) is a highly toxic product of lipid peroxidation (LPO). Its role in the inhibition of cytochrome c oxidase activity and oxidative modifications of mitochondrial lipids and proteins were investigated. The exposure of mitochondria isolated from rat heart to HNE resulted in a time- and concentration-dependent inhibition of cytochrome c oxidase activity with an IC50 value of 8.3 +/- 1.0 microM. Immunoprecipitation-Western blot analysis showed the formation of HNE adducts with cytochrome c oxidase subunit I. The loss of cytochrome c oxidase activity was also accompanied by reduced thiol group content and increased HNE-lysine fluorescence. Furthermore, there was a marked increase in conjugated diene formation indicating LPO induction by HNE. Fluorescence measurements revealed the formation of bityrosines and increased surface hydrophobicity of HNE-treated mitochondrial membranes. Superoxide dismutase + catalase and the HO* radical scavenger mannitol partially prevented inhibition of cytochrome c oxidase activity and formation of bityrosines. These findings suggest that HNE induces formation of reactive oxygen species and its damaging effect on mitochondria involves both formation of HNE-protein adducts and oxidation of membrane lipids and proteins by free radicals.

Man is born into a tangle of standard processes and behaviour patterns created and modified over time. Through gradual socialization, he acquires the attributes of his own culture and gets acquainted with the admissible modus operandi for the social group he is a member of; he also deepens these principles and confronts them with the experiences of others. Stereotyping is a process that represents the initial classification of phenomena and people, which it categorizes into groups and assigns them positive or negative characteristics. Stereotypes form the ideas that people have about themselves and ,their' group with which they identify and are aimed at members of other groups with which they do not identify. Negative stereotypes about other people arise from pursuing one's own positive social identity and positive self-presentation. Stereotyping of believers occurs precisely because of perceived differences between ,we' and ,them' (for example, in attitudes and values, possibly in ,religious' practice). Stereotypes are often the unconscious ,beginning' of a range of known intolerant attitudes; they can lead to racism, anti-Semitism, ethnic discrimination, and other forms of intolerance. According to the experts, no nation has innate attitudes to hate, as they cannot be inherited in a biological--psychological sense. Intolerance is acquired, often to justify negative attitudes and behaviours. Using the qualitative method of guided group interviews (the so-called focus group), we examine the existence of stereotypes in university students towards their religious classmates. We consider the potential of social exclusion of young believers due to stereotypes and present current measures in prevention.