RESUMO
The neuritogenic and neuroprotective activities of six starfish polar steroids, asterosaponin Ð 1, (25S)-5α-cholestane-3ß,4ß,6α,7α,8,15α,16ß,26-octaol, and (25S)-5α-cholestane-3ß,6α,7α,8,15α,16ß,26-heptaol (1-3) from the starfish Patiria pectinifera and distolasterosides D1-D3 (4-6) from the starfish Distolasterias nipon were analyzed using the mouse neuroblastoma (NB) C-1300 cell line and an organotypic rat hippocampal slice culture (OHSC). All of these compounds enhanced neurite outgrowth in NB cells. Dose-dependent responses to compounds 1-3 were observed within the concentration range of 10-100 nM, and dose-dependent responses to glycosides 4-6 were observed at concentrations of 1-50 nM. All the tested substances exhibited notable synergistic effects with trace amounts of nerve growth factor (NGF, 1 ng/mL) or brain-derived neurotrophic factor (BDNF, 0.1 ng/mL). Using NB cells and OHSCs, it was shown for the first time that starfish steroids 1-6 act as neuroprotectors against oxygen-glucose deprivation (OGD) by increasing the number of surviving cells. Altogether, these results suggest that neurotrophin-like neuritogenic and neuroprotective activities are most likely common properties of starfish polyhydroxysteroids and the related glycosides, although the magnitude of the effect depended on the particular compound structure.
Assuntos
Neuritos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estrelas-do-Mar/química , Esteroides/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Glucose/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Camundongos , Fator de Crescimento Neural/farmacologia , Neuritos/metabolismo , Neuroblastoma/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Oxigênio/metabolismo , Ratos , Esteroides/química , Esteroides/isolamento & purificaçãoRESUMO
The comparison of the development of the SARS-CoV-2 epidemic in several neighboring regions can help researchers to assess the risks and develop more effective strategies and approaches in the field of preventive medicine. We analyzed the infection and mortality statistics for the 2020-2022 period in ten individual regions of the Siberian Federal District of Russia. We also sequenced complete genomes, which allowed us to analyze the genetic diversity of SARS-CoV-2 circulated in each of the ten regions and to build a phylogenetic dendrogram for the virus variants. The ParSeq v.1.0 software was developed to automate and speed up the processing and analysis of viral genomes. At the beginning of the pandemic, in the first two waves, the B.1.1 variant (20B) dominated in all regions of the Siberian Federal District. The third and fourth waves were caused by the Delta variant. Mortality during this period was at a maximum; the incidence was quite high, but the number of deposited genomes with GISAID during this period was extremely low. The maximum incidence was at the beginning of 2022, which corresponds to the arrival of the Omicron variant in the region. The BA.5.2 variant became the dominant one. In addition, by using NextClade, we identified three recombinants in the most densely populated areas.