RESUMO
In terms of the incidence among all tumors, skin cancer is on top, with the most deadly among them being melanoma. The search for new therapeutic agents to combat melanoma is very relevant. In our opinion, antisense oligonucleotides (ASO) aimed at suppressing the genes responsible for their viability in cancer cells give hope for treatment, which makes it possible to eliminate cancer cells near the tumor site both before and after surgery. In this article, we describe how Skeen-11 phosphorothioate oligonucleotide significantly decreased the proliferative activity of murine melanoma cells. Injections of Skeen-11 also inhibited tumor growth in mice with inoculated melanoma. A toxicity study showed no side effects with dose adjustments. The results show that the use of ASO Skeen-11 in vivo reduced the tumor size within 7 days, reduced the number of mitoses in the tumor cells, and increased the amount of necrosis compared with the control group.
RESUMO
Insects vastly outnumber us in terms of species and total biomass, and are among the most efficient and voracious consumers of plants on the planet. As a result, to preserve crops, one of the primary tasks in agriculture has always been the need to control and reduce the number of insect pests. The current use of chemical insecticides leads to the accumulation of xenobiotics in ecosystems and a decreased number of species in those ecosystems, including insects. Sustainable development of human society is impossible without useful insects, so the control of insect pests must be effective and selective at the same time. In this article, we show for the first time a natural way to regulate the number of insect pests based on the use of extracellular double-stranded DNA secreted by the plant Pittosporum tobira. Using a principle similar to one found in nature, we show that the topical application of artificially synthesized short antisense oligonucleotide insecticides (olinscides, DNA insecticides) is an effective and selective way to control the insect Coccus hesperidum. Using contact oligonucleotide insecticide Coccus-11 at a concentration of 100 ng/µL on C. hesperidum larvae resulted in a mortality of 95.59 ± 1.63% within 12 days. Green oligonucleotide insecticides, created by nature and later discovered by humans, demonstrate a new method to control insect pests that is beneficial and safe for macromolecular insect pest management.
Assuntos
Hemípteros , Inseticidas , Animais , Humanos , Inseticidas/farmacologia , Oligonucleotídeos/farmacologia , Ecossistema , Resistência a Inseticidas , Insetos/genética , Controle de Insetos/métodos , Hemípteros/genética , Agricultura/métodos , Produtos Agrícolas/genética , DNA/farmacologia , Controle Biológico de VetoresRESUMO
The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund's adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Oligonucleotídeos Antissenso/uso terapêutico , Fator de Necrose Tumoral alfa/genética , Animais , Inativação Gênica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Morphological data on heart damage and its mechanisms due to extremely severe course of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are limited, as well as data on the correlation of damage and expression of vitamin D receptors (VDRs). In this study, we analyzed a series of myocardial samples obtained during postmortem autopsy of 48 critically ill patients with COVID-19 who died with SARS-CoV-2-associated pneumonia. The purpose of the study was to evaluate immunohistochemical VDR expression in the myocardium. The results showed the only minimal or no immunohistochemical expression of VDR in the nuclei of cardiomyocytes in most cases, along with the persisted strong expression in lymphoid cells. To the best of our knowledge, it is the first study and data provided were regarding myocardial VDR expression in COVID-19 patients. The results are of interest in terms of further study of the effects of ligand-associated VDR activation on the cardiovascular system.