Lipopolysaccharide and D-galactosamine induced lethality and apoptotic liver injury is dependent on endogenously produced tumor necrosis factor (TNF)-alpha. The present study was undertaken to determine whether membrane-associated or secreted TNF-alpha signaling through the p55 or p75 receptor was responsible for survival and hepatic injury after lipopolysaccharide administration in D-galactosamine-sensitized mice. Transgenic mice expressing null forms of TNF-alpha, the p55 and p75 receptor, and mice expressing only a cell-associated form of TNF-alpha were challenged with 8 mg D-galactosamine and 100 ng lipopolysaccharide. Mortality and apoptotic liver injury were only seen in wild-type and p75 knockout mice. p75 Knockout mice had significantly higher concentrations of plasma TNF-alpha than any other experimental group (P

The COVID-19 pandemic has undoubtedly affected education at all levels, including medical and dental education. Our study aimed to assess the effectiveness of the blended learning in conservative dentistry with endodontics. The students had theoretical classes in a remote form (using the e-learning portal and Teams communicator) and practical classes with the participation of patients in the appropriate sanitary regime. The author’s survey was conducted among fourth-year dental students. The online questionnaire consisted of 5 parts: self-evaluation, evaluation of theoretical e-learning classes, evaluation of practical clinical classes, evaluation of safety, and evaluation of performed blended learning. The majority of respondents declared that their learning effectiveness increased during the pandemic. Most surveyed students preferred remote learning in asynchronous form (e-learning portals) to synchronous form (virtual meetings in real-time). All respondents described the provided personal protective equipment as sufficient or even as excessive. Our students were very satisfied with the proposed blended-learning model and would like to continue it even after the pandemic has ended. Among the advantages, they particularly mentioned the increase in efficiency and the individualised pace of learning, while the disadvantage was the limitation of social contacts. The appropriate use of modern technology can effectively revolutionise dental education.

Glioblastoma multiforme (GBM) is the most common type of malignant gliomas, characterized by genetic instability, intratumoral histopathological variability and unpredictable clinical behavior. Disappointing results in the treatment of gliomas with surgery, radiation and chemotherapy have fuelled a search for new treatment modalities. Malignant gliomas express preferentially a number of surface markers that may be exploited as therapeutic targets, such as tenascin-C (TN-C), an extracellular matrix glycoprotein that contributes to tumor cell adhesion, invasion, migration and proliferation. In this paper we describe a novel strategy for human brain tumors therapy based on RNA interference (RNAi) and its application after surgery (intervention with RNAi) to inhibit TN-C synthesis. We present data of 46 patients suffering from brain tumors resected and treated with dsRNA with the sequence homology of tenascin-C mRNA (ATN-RNA). The specific effect of ATN-RNA on TN-C downregulation was proved with antibodies against TN-C in glioblastoma multiforme cultured cells. A significant improvement in overall survival (OS) without loosing the quality of life (QOL) of patients was observed. MRI and CT studies showed tumor growth delay or lack of tumor recurrence. This novel therapy based on RNA interference shows a hopeful therapeutical potential. To our knowledge the intervention with RNAi (iRNAi) method is the first protocol of RNAi application in human brain tumor treatment.

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Nodularin is a hepatotoxin from a cyanobacterium, Nodularia spumigena, that inhibits protein phosphatases 1 and 2 and posseses tumor-promoting activity. The aim of this paper was to examine whether nodularin is able to induce oxidative stress in mouse liver tissue and whether melatonin (protective compound against oxidative damage) could supress the activity of nodularin. We studied the effect of nodularin (1, 5, and 10 microg/kg body weight) and melatonin (5, 10, and 15 mg/kg body weight) administration on the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in mouse liver. Intraperitoneal treatment of mice with nodularin per 7 days decreased the activities of all estimated enzymes in a dose-dependent manner. Intraperitoneal treatment of animals with melatonin per 7 days increased the activities of SOD, CAT, and GSH-Px and this effect was concentration-dependent. Co-treatment (nodularin 5 microg/kg body weight + melatonin 5, 10, and 15 mg/kg body weight per 7 days) and post-treatment with melatonin (nodularin 5 microg/kg body weight per 7 days + melatonin 5, 10, and 15 mg/kg body weight per next 7 days) increased the activities of SOD, CAT, and GSH-Px in comparison to the nodularin group. No significant differences from the nodularin group were noted in the group after pre-treatment with melatonin. In conclusion, these findings suggest that oxidative damage may be involved in the toxicity of nodularin. Moreover, co-treatment and post-treatment with 10 and 15 mg/kg body weight of melatonin may protect against nodularin-induced oxidative stress. There was no protective effect of pre-treatment with melatonin.

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We report here a new method for inhibition of RNA viruses induced by dsDNA. We demonstrated that both long dsDNA molecules and short interfering DNA with a sequence complementary to that of viral RNA inhibited tobacco mosaic virus expression and prevented virus spread. Also, the expression of the HIV‐1 gp41 gene in HeLa cells was inhibited by complementary short interfering DNA. We showed that Dicer processed dsDNA, which suggests activation of the cellular machinery involved in silencing of RNA. For the silencing of viral RNA effected with dsDNA, we coined the term DNA interference technology.