Evaluation of the Immunosafety of Cucurbit[n]uril In Vivo.

Cucurbiturils are a family of macrocyclic oligomers capable of forming host-guest complexes with various molecules. Due to noncovalent binding to drug molecules and low toxicity, cucurbiturils has been extensively investigated as potential carriers for drug delivery. However, the immune system's interactions with different drug carriers, including cucurbiturils, are still under investigation. In this study, we focused on cucurbiturils' immunosafety and immunomodulation properties in vivo. We measured blood counts and lymphocyte subpopulations in blood, spleen, and bone marrow, and assessed the in vivo toxicity to spleen and bone marrow cells after intraperitoneal administration to BALB/c mice. When assessing the effect of cucurbit[6]uril on blood parameters after three intraperitoneal injections within a week in laboratory animals, a decrease in white blood cells was found in mice after injections of cucurbit[6]util, but the observed decrease in the number of white blood cells was within the normal range. At the same time, cucurbit[7]uril and cucurbit[8]uril did not affect the leukocyte counts of mice after three injections. Changes in the number of platelets, erythrocytes, and monocytes, as well as in several other indicators, such as hematocrit or erythrocyte volumetric dispersion, were not detected. We show that cucurbiturils do not have immunotoxicity in vivo, with the exception of a cytotoxic effect on spleen cells after сucurbit[7]uril administration at a high dosage. We also evaluated the effect of cucurbiturils on cellular and humoral immune responses. We founded that cucurbiturils in high concentrations affect the immune system in vivo, and the action of various cucurbiturils differs in different homologues, which is apparently associated with different interactions in the internal environment of the body.

Transduction of Brain Neurons in Juvenile Chum Salmon (Oncorhynchus keta) with Recombinant Adeno-Associated Hippocampal Virus Injected into the Cerebellum during Long-Term Monitoring.

Corpus cerebelli in juvenile chum salmon is a multiprojective region of the brain connected via afferent and efferent projections with the higher regions of the brainstem and synencephalon, as well as with multiprojection regions of the medulla oblongata and spinal cord. During the postembryonic development of the cerebellum in chum salmon, Oncorhynchus keta, the lateral part of the juvenile cerebellum gives rise to the caudomedial part of the definitive cerebellum, which is consistent with the data reported for zebrafish and mouse cerebellum. Thus, the topographic organization of the cerebellum and its efferents are similar between fish (chum salmon and zebrafish) and mammals, including mice and humans. The distributions of recombinant adeno-associated viral vectors (rAAVs) after an injection of the base vector into the cerebellum have shown highly specific patterns of transgene expression in bipolar neurons in the latero-caudal lobe of the juvenile chum tectum opticum. The distribution of rAAVs in the dorsal thalamus, epithalamus, nucleus rotundus, and pretectal complex indicates the targeted distribution of the transgene via the thalamo-cerebellar projections. The detection of GFP expression in the cells of the epiphysis and posterior tubercle of juvenile chum salmon is associated with the transgene's distribution and with the cerebrospinal fluid flow, the brain ventricles and its outer surface. The direct delivery of the rAAV into the central nervous system by intracerebroventricular administration allows it to spread widely in the brain. Thus, the presence of special projection areas in the juvenile chum salmon cerebellum, as well as outside it, and the identification of the transgene's expression in them confirm the potential ability of rAAVs to distribute in both intracerebellar and afferent and efferent extracerebellar projections of the cerebellum.

Promoting effect of Zn in high-loading Zn/Ni-SiO2 catalysts for selective hydrogen evolution from methylcyclohexane.

The dehydrogenation of methylcyclohexane to toluene was investigated over high-loading monometallic Ni-SiO2 and bimetallic Zn/Ni-SiO2 catalysts. The catalysts were prepared by the impregnation coupled with the advantageous heterophase sol-gel technique. Their performance was tested in a fixed-bed flow reactor at 250-350 °C, 0.1 MPa pressure, equimolar ratio H2/Ar (24 nL h-1 in total), and a methylcyclohexane feed rate of 12 mL h-1. Information regarding the structure of Ni-Zn catalysts was obtained by N2 and CO adsorption, temperature-programmed reduction, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, in situ X-ray diffraction, and in situ X-ray absorption spectroscopy. The results have shown that the addition of zinc leads to the hindrance of Ni reducibility along with weakening the Ni interaction with the silica matrix. This behavior particularly indicated the formation of solid oxide nickel-zinc solutions. The catalytic properties of Zn-modified catalysts in the dehydrogenation of methylcyclohexane appeared significantly superior to their Ni-Cu counterparts. For example, the selectivity of Zn/Ni-SiO2 catalysts toward toluene formation increased markedly with a decrease in the Ni : Zn mass ratio, achieving 97% at 350 °C over the sample with Ni : Zn = 80 : 20. This is attributed to the promoting geometric and electronic effects arising from the formation of bimetallic Ni-Zn solid solutions. Moreover, a deeper reduction of zinc and a more efficient formation of solid bimetallic solutions are observed after the catalytic tests.

Ni-Cu High-Loaded Sol-Gel Catalysts for Dehydrogenation of Liquid Organic Hydrides: Insights into Structural Features and Relationship with Catalytic Activity.

The heightened interest in liquid organic hydrogen carriers encourages the development of catalysts suitable for multicycle use. To ensure high catalytic activity and selectivity, the structure-reactivity relationship must be extensively investigated. In this study, high-loaded Ni-Cu catalysts were considered for the dehydrogenation of methylcyclohexane. The highest conversion of 85% and toluene selectivity of 70% were achieved at 325 °C in a fixed-bed reactor using a catalyst with a Cu/Ni atomic ratio of 0.23. To shed light on the relationship between the structural features and catalytic performance, the catalysts were thoroughly studied using a wide range of advanced physicochemical tools. The activity and selectivity of the proposed catalysts are related to the uniformity of Cu distribution and its interaction with Ni via the formation of metallic solid solutions. The method of introduction of copper in the catalyst plays a crucial role in the effectiveness of the interaction between the two metals.

Preparation and Characterization of a Glycyrrhizic Acid-Based Drug Delivery System for Allergen-Specific Immunotherapy.

The most effective method of treating allergic diseases, aimed not at relieving symptoms, but at eliminating the cause of the disease, is allergen-specific immunotherapy (AIT). To reduce the risk of side effects and improve the delivery of allergens to the mucosa, various delivery systems, such as liposomes, dendrimers, nanoparticles, etc., can be used. To date, there are data on the creation of delivery systems based on glycyrrhizic acid (GA) and its derivatives, but such a delivery system has not been used for allergen-specific therapy until now. It is also known that GA has an anti-inflammatory effect, shifts the balance towards Th1, and increases the number of Treg cells, meaning that it could potentially enhance the anti-allergic effect of AIT and reduce the risk of unwanted side effects. Thus, the study of the immunomodulatory effect of the supramolecular complexes (micelles) of GA with extracts of allergens holds promise for the development of new drugs for AIT.