Therapeutic Potential and Main Methods of Obtaining Selenium Nanoparticles.

This review presents the latest data on the importance of selenium nanoparticles in human health, their use in medicine, and the main known methods of their production by various methods. In recent years, a multifaceted study of nanoscale complexes in medicine, including selenium nanoparticles, has become very important in view of a number of positive features that make it possible to create new drugs based on them or significantly improve the properties of existing drugs. It is known that selenium is an essential trace element that is part of key antioxidant enzymes. In mammals, there are 25 selenoproteins, in which selenium is a key component of the active site. The important role of selenium in human health has been repeatedly proven by several hundred works in the past few decades; in recent years, the study of selenium nanocomplexes has become the focus of researchers. A large amount of accumulated data requires generalization and systematization in order to improve understanding of the key mechanisms and prospects for the use of selenium nanoparticles in medicine, which is the purpose of this review.

Novel Dimethylacetamide-Containing Formulation Improves Infraorbital Anaesthesia Efficacy in Rats with Periodontitis.

BACKGROUND: To evaluate acute toxicity and local anaesthetic activity of a formulation containing a novel dimethylacetamide derivative, antioxidant, and vasoconstrictor in rats with chronic periodontitis. METHODS: Novel anaesthetic dimethylacetamide-containing formulation LHT-15-32 was studied as 2% water solution. Its acute intravenous and subcutaneous toxicity was determined in mice. Pain sensitivity threshold of the upper second molar was determined in rats with experimental periodontitis. Oxidative stress activity and total antioxidant capacity were determined in rats' gingival mucosa by induced chemiluminescence. Local changes were evaluated in periodontal tissue by morphological examination. Tissue IL-1ß, IL-10, and TNF-α concentration was quantitatively assessed by an enzyme-linked immunosorbent assay. LHT-15-31 Na-blocking activity was studied on isolated neurons of Limnaea stagnalis' parapharyngeal ganglion. Isolated sciatic nerve of Rana radibunda was perfused with different concentrations of LHT-15-32 to assess its conductivity. Statistical analysis was used, and continuous variables were presented as mean ± square deviation. The normality of distribution was determined using ANOVA. Newman-Keuls parametric criterion was used for intergroup comparison. LD50 indexes were calculated by probit analysis. RESULTS: LHT-15-32 acute intravenous and subcutaneous toxicity was lower than that of its active substance. The formulation by infraorbital administration induced deep dental anaesthesia which lasted over 70 min and activated the local antioxidant defense system and decreased IL-1ß level in gingival tissue. LHT-15-32 triggered tissue reparation around the impacted upper molar in rats assessed five days after administration. At 10-6 to 10-3 M concentration, LHT-15-32 inhibited sciatic nerve conductivity and blocked Na+ channels of isolated neurons in a dose-dependent manner. CONCLUSIONS: The formulation may be considered as an effective and safe approach to anaesthetize upper molars with periodontitis.

Programmed death-ligand 1 signaling pathway involves in bladder cancer growth and progression.

CONTEXT: Exploration of the biological property of programmed death-ligand 1 (PD-L1) signaling that may impact bladder tumor growth in humanized animals and cell culture. AIMS: The aim of this study is to evaluate how PD-L1 signaling involves bladder cancer growth and progression. SETTINGS AND DESIGN: This study design involves experimental in vivo and in vivo study. SUBJECTS AND METHODS: A role of PD-L1 signaling pathway inhibition for bladder cancer growth was assessed in humanized immunodeficient animals carried main molecular subtypes of bladder carcinoma patient-derived xenografts and provided with selective anti-PD-L1 treatment; bladder cancer cells invasiveness was evaluated in mixed RT112/84 cells + CD4+ cells culture incubated with PD-L1 blocker durvalumab. We used two-tailed Student's t-test to explore differences between main and control subgroups. Significance of intergroup comparison was measured with one-way ANOVA followed by the Tukey's or Newman-Keul's criterion. Survival curves were analyzed with Gehan's criterion with the Yate's correction. Differences were considered statistically significant at P < 0.05. RESULTS: Anti-PD-L1 intervention increased survival of the animals carried both primary and relapsed luminal noninvasive, muscular invasive, and relapsed luminal bladder cancer xenografts. There was significant retardation of tumor volume duplication time in aforementioned subgroups correlated with PD-L1 expression. Durvalumab treatment in concentration-dependent manner inhibited tumor cells invasiveness of mixed RT112 + CD4+ culture cells with its maximum at the highest studied concentration (10 µM). CONCLUSIONS: Obtained data constituted the pivotal role of programmed cell death-1/PD-L1 signaling pathway in bladder cancer development and progression. The results will have major implications for further clinical investigations.

Novel aminochromone derivative inhibits tumor growth on xenograft model of lung cancer in mice.

2-Amino-4H-chromene derivatives possess anticancer property proved on different in vivo and in vitro models of malignancies such breast, nasopharyngeal, bladder, ovary carcinomas, astrocytoma, and osteosarcoma. We assumed it might be effective to apply one of the derivatives as promising approach to lung carcinoma treatment. to evaluate how novel 4-aryl substituted 2-amino-4H-chromene derivative AX-554 impacts tumor growth and progression, as well as possible mechanisms for anticancer effect development on in vivo patient-derived heterotopic xenograft model of lung carcinoma in mice. This was an experimental in vivo study. 40 nu/nu BALB/c female mice were randomly allocated into four equal groups: Intact, control, reference, and main group. Animals of three latter groups were ingrafted with human-derived lung adenocarcinoma. Antitumor and antimetastatic action of AX-554 novel aminochromone derivative as a substance were studied. Mice survival was registered. Kinase of anaplastic lymphoma (ALK), tubulin Beta-3 (TUBB3), and c-mesenchymal-epithelial transition (MET) concentrations in the prime tumor nodes homogenates were determined by quantitative enzyme-linked immunosorbent assay. Dannet's parametric criterion and the nonparametric exact Fisher test were used. The normality of the distribution was determined using ANOVA. The survival curve was analyzed using Gehan's criterion with the Yates's correction. Aminochromone derivative possesses an inhibitory effect on human lung adenocarcinoma transplanted into nu/nu BALB/c female mice, as well as significant antimetastatic activity. About 50 mg/kg/day AX-554 intragastric course increases animals' life expectancy of more than 3.3 times when compared with the control and induces remission in 60% of cases. The anticancer effect of the derivative is due to anti-ALK-mediated activation of tumor cells apoptosis and suppression TUBB3-dependent cell proliferation.