Synthesis and biological activity of hydrazones of 5α-steroids.

Condensation reactions catalyzed by acetic acid of severalarylhydrazine (2,4-dinitrophenyl hydrazine) and hydrazides (hydrazides of bromobenzoic and salicylic acid, benzofuran-2- and indol-2-carboxylicacid) with 3β-acetoxy- and 3β-hydroxy-5α-pregn-16-en-20-one (1 and 2), epiandrosterone (6) and 5α-androst-2-en-17- one (9) were studied for the purpose of synthesizing potentially bioactive 5-steroidal hydrazones. The starting ketones (1,2,6,9) were synthesized on the bases of aglicon of steroidal saponine - tigogenin isolated from plant “Yucca gloriosa” introduced in Georgia. The structures of synthesized new hydrazones (3-5,7,8,10,11) were established by NMR 1H, 13C and mass-spectral data. The antiviral activity some of them (7,8,10,11) were studied

SARS-Cov-2 Spike Protein Antibody Titers In Cord Blood After Vaccination Against Covid-19 During Pregnancy

In the early months of the COVID-19 pandemic, pregnant patients faced uncertain risks associated with severe acute respiratory syndrome SARS-CoV-2 viral infection. Aim of the study was to determine the titer of specific maternal and umbilical cord antibodies against SARS-CoV-2 viral protein S receptor domain after maternal antenatal vaccination. The paper presents preliminary results of the study proceeded in the department. 13 patients vaccinated during different gestational age have been included in the study. All patients participating in this study were vaccinated with two doses of BNT162b2 mRNA COVID-19 vaccine between the 4 to 31 week of gestation. The in vitro qualitative and quantitative determination of antibodies against SARS-CoV-2 viral protein S receptor domain in serum samples was performed by using an electrochemiluminescence immunoassay.  Study results demonstrated that, vaccination against SARS-Cov-2 viral infection during pregnancy is accompanied with adequate production of antibodies that probably may defense neonates from severe infection at least within 6 month of life. Study has revealed positive correlation between time interval of vaccination and delivery for the presence of high titers of SARS-Cov-2 viral protein S receptor domain antibodies in neonatal cord blood, which may allow future determination of the optimal timing of COVID-19 vaccination in pregnant women although this problem need more future studies

Elastic modulus of tree frog adhesive toe pads

Previous work using an atomic force microscope in nanoindenter mode indicated that the outer, 10- to 15-μm thick, keratinised layer of tree frog toe pads has a modulus of elasticity equivalent to silicone rubber (5–15 MPa) (Scholz et al. 2009), but gave no information on the physical properties of deeper structures. In this study, micro-indentation is used to measure the stiffness of whole toe pads of the tree frog, Litoria caerulea. We show here that tree frog toe pads are amongst the softest of biological structures (effective elastic modulus 4–25 kPa), and that they exhibit a gradient of stiffness, being stiffest on the outside. This stiffness gradient results from the presence of a dense network of capillaries lying beneath the pad epidermis, which probably has a shock absorbing function. Additionally, we compare the physical properties (elastic modulus, work of adhesion, pull-off force) of the toe pads of immature and adult frogs

Knockdown of interleukin-10 induces the redistribution of sigma1-receptor and increases the glutamate-dependent NADPH-oxidase activity in mouse brain neurons

BACKGROUND: In the central nervous system, interleukin-10 (IL-10) provides trophic and survival effects directly on neurons, modulates neurite plasticity, and has a pivotal importance in the neuronal regeneration in neurodegenerative and neuroinflammatory conditions. This cytokine is primarily produced by glial cells and has beneficial effects on the neuronal viability. However, the mechanisms of IL-10-elicited neuroprotection are not clear RESULTS: Membrane preparations, isolated from wild-type (Wt) and IL-10 knockout (KO) mice brain were used in this study. It has been shown that compared to wild-type mice, in IL-10 KO mice brain, the amount of immunoglobulin binding protein (BiP) is greatly increased, whereas the content of sigma receptor-1 (SigR1) is not changed significantly. Co-immunoprecipitation experiments have shown that the association of SigR1 with small GTPase Rac1 (Ras-related C3 botulinum toxin substrate 1), NR2B subunit of NMDA-receptor (NMDAR) and inositol-3-phosphate receptor (IP3R) is higher in the IL-10 KO mice brain than in the Wt mice brain. Besides, we have found that either glutamate or sigma ligands, separately or together, do not change glutamate-induced NADPH-oxidase (NOX) activity in Wt-type mice brain membrane preparations, whereas in IL-10 KO mice high concentration of glutamate markedly increases the NOX-dependent production of reactive oxygen species (ROS). Glutamate-dependent ROS production was decreased to the normal levels by the action of sigma-agonists CONCLUSIONS: It has been concluded that IL-10 deprivation, at least in part, can lead to the induction of ER-stress, which causes BiP expression and SigR1 redistribution between components of endoplasmic reticulum (ER) and plasma membrane. Moreover, IL-10 deficiency can change the specific organization of NMDAR, increasing the surface expression of SigR1-sensitive NR2B-containing NMDAR. In these conditions, glutamate-dependent ROS production is greatly increased leading to the initiation of apoptosis. In this circumstances, sigma-ligands could play a preventive role against NMDA receptor-mediated excitotoxicit

Synthesis and cytotoxicity of epiandrosterone hydrazones

Two series of hydrazones were synthesized from 3β-hydroxy- and 3β-(1-adamantoate)-5α-androstan-17- one, respectively, to study the structure–activity relationship. Cytotoxicity studies showed that 5α-androstan3β-ol-17-one m-nitrobenzoylhydrazone exhibited pronounced specific activity in a Hoechst experiment against lung carcinoma (A-549) and colorectal adenocarcinoma cell lines (DLD-1)