Настоящая работа посвящена изучению эффектов лейтрагина, аналога эндогенного гексапептида динорфина 1-6, на экспрессию провоспалительных цитокинов и интерферонов I типа в экспериментальной фатальной модели острого респираторного дистресс-синдрома (ОРДС) у мышей C57BL/6Y. Экспрессию интерлейкина-1β (IL-1β), интерлейкина-6 (IL-6), фактора некроза опухоли (TNF-α), интерферонов α (IFN-α) и β (IFN-β) в легких оценивали методом ПЦР в реальном времени. Индукция ОРДС α-галактозилцерамидом и липополисахаридом E. coli приводила к многократному повышению экспрессии цитокинов в легких. Введение лейтрагина в сочетанном режиме, внутримышечная инъекция плюс ингаляция, приводило к статистически значимому снижению уровней мРНК цитокинов в легких уже через 3 ч после начала введения. При этом средний уровень мРНК IL-6, ключевого цитокина в развитии тяжелого ОРДС, снижался в 4,7 раза (p<0,01) до значений, близких к наблюдаемым у интактных животных. С учетом особой роли повышенных концентраций IL-6 в развитии тяжелых форм COVID-19 использование лейтрагина для подавления «цитокинового шторма» может быть эффективным подходом к лечению коронавирусной инфекции.
With the advent of endonuclease methods of genome editing, particularly CRISPR/Cas9, it has become possible to obtain genetically modified rabbits by microinjection of zygotes. These highly effective human disease models can be used for various purposes. The present review aims to consider modern achievements in the creation of rabbit biomodels of human diseases using the technologies of genetic editing. It is concluded that Russian laboratories should intensify research in the development of genetically modified rabbits that can be used for various biomedical studies and biomodelling.
Health and productivity of ruminants directly depend on the state of rumen and digestion in intestinal tract. Normal microflora protects the body from pathogenic microbes, stimulates the immune system, participates in metabolic reactions and plays an important role in energy metabolism. Disturbance of species composition of microflora in rumen under effect of various factors leads to a state of dysbiosis, disorders of products digestibility, changes in enzymatic processes and other disorders. Biologically active substances of an adaptogenic nature can show immunomodulatory and antimicrobial activity. Adaptogen lithium ascorbate has stress-protective, neurotrophic, neuroprotective, antioxidant, immunomodulatory properties. In this paper, using molecular genetic methods, the effect of lithium ascorbate on composition of rumen microbiota of sheep was studied for the first time. Composition of microbiota was determined by NGS sequencing method. In total, 37 phylums, 76 classes, 98 orders, 225 families and 894 species of microorganisms were identified. It has been determined that introduction of lithium ascorbate at a dose of 10 mg/kg of body weight into the main diet of sheep contributed to increase in proportion of cellulolytic bacteria from 73.6±1.6% to 75.4±0.9% and over 40% decrease in total number of infusoria in rumen content. Cellulolytic activity of rumen fluid in sheep of the experimental group increased by 38% compared to the animals of the control group. The number of pathogenic bacteria decreased from 2.7% in sheep of the control group to 1.6% in animals of the experimental group, while the content of beneficial bacilli increased from 0.3% to 0.5%, respectively. Content of undesirable and conditionally pathogenic microflora decreased in the sheep of experimental group. The obtained data confirm positive effect of adaptogen lithium ascorbate, introduced into diet at a dosage of 10 mg/kg of body weight, on qualitative and quantitative composition of microbiota in sheep rumen. Therefore, lithium ascorbate, a broad-spectrum adaptogen, can be recommended as a feed additive to the main diet of sheep to improve rumen digestion and increase productivity.
The survival rate of rabbit embryos microinjected by the plasmid form of CRISPR/Cas9 components specific to the sour whey protein gene was evaluated. At high concentrations of plasmid components, embryo survival decreased slightly, possibly because the WAP gene does not belong to the housekeeping genes. After microinjection of a genetic construct with a sequence of green fluorescent protein under a cytomegalovirus promoter, the embryo survival significantly decreased. This is most likely due to the superexpression of GFP at the 2-16 cell stage of development.
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