GENETICS AND EPIGENETICS OF ANIMALS-BIOMODELS
The containment of lethal acute lung injuries, acute respiratory distress syndrome (ARDS) and cytokine storm arising from severe interstitial pathology, including COVID-19, requires an efficient design and therapeutic implementation of new drugs and biomedical technologies. This demand calls for adequate biomodels in preclinical research and trial. Genetic variations between ethnic groups condition the specific mechanisms of drug efficiency. Modelling this population-specific genetic polymorphism allows a comprehensive research into the molecular bases of pharmacological action, also in immune biology. The engineered chimeric molecule encodes a MHC class I product that combines human ß2-microglobulin, the α1 and α2 domains of Russian ethnic allelic variant HLA-A*02:01:01:01 and murine H2-K complex α3 domain. The linear chimeric gene fragment will be used to obtain humanised lineages of transgenic mice.
METHODS AND TECHNOLOGIES OF BIOMEDICAL RESEARCH
The musk deer possesses an exceptional value for producing high-quality musk, which warrants the development of appropriate veterinary strategies for its captive breeding. The main profile of musk deer health monitoring is assessed: the presence of infectious and protozoan diseases, helminthiases and gastrointestinal disorders. We present a strategy for non-invasive health monitoring and criteria for phytotherapeutic and drug prophylaxis and treatment in open-cage captivity of musk deer for further research into their impact on musk quality.
I Ion channels are complex protein structures comprising the molecular systems of opening, closing, selectivity, inactivation and regulation. This review article aims to generalize and systematize literature data on the structural and functional characteristics of ion channels and methods for investigating their activity. Violations of the activity of ion channels may alter the functioning of both individual cells and the entire organism. Therefore, further research into the structural and physiological characteristics of ion channels can be considered promising and relevant.
The work presents a comparative assessment of the effects of delta-sleep-inducing peptide (DSIP), kiss-peptin-10 and PT-141 neuropeptides on the copulatory behaviour in male rats with natural sexual activity.
A single intraperitoneal injection of DSIP (1 mg/kg) promotes the motivational and copulatory components of sexual male rat behaviour in courtship of a receptive female. The neuropeptide application significantly boosts sexual activity in males, rises the copulation rate, mean number of ejaculations towards sexual exhaustion and reduces rest periods in animals. Kisspeptin-10 (1 mg/kg) promotes high arousal in the middle (increased copulation rate in copulatory series 6) and end of the courtship cycle (increased ratio of sexually active males in copulatory series 8-9). PT-141 (0.13 mg/kg) facilitates sexual activity in male rats only in the onset and middle of the courtship cycle. The transience of DSIP and PT-141 stimulating effect warrants adjustments in the neuropeptide dosage and application regimens.
The study experimentally modelled the functional state in laboratory animals under haemic hypoxia combined with thermal exposure (hyper- or hypothermia) by estimating their physical capacity with the forced swim test. Trimetazidine has been proved an effective drug agent for the correction of hypoxic hyperthermal response in a two-factor model due to its marked antihypoxic effect observed under haemic hypoxia and hypoxia combined with hyperthermia. Relative to haemic hypoxia and hypothermia, the drugs studied can be separated between three groups by corrective efficiency: weak protectors (150-200% of control level, Flamenco 250 mg/kg, trimetazidine), moderate protectors (200-300%, polypeptide mix, Flamenco 50 and 75 mg/kg, Hypoxen) and effective protectors (>300%, course intake of specialised “MioActive Sport” nutrition additive).
RELEVANT AND ALTERNATIVE BIOMODELLING
Retinal degenerations comprise a large heterogeneous class of diseases (dystrophies) of retina leading to a progressive vision loss. The emergence of new experimental therapies (gene and cell therapy, regenerative ophthalmic surgery) generates a demand for new experimental models. The review tackles various animal models of human retinal degenerative diseases. Pros and contras of induced and genetic experimental models are highlighted. An adequate experimental model choice may condition a pathogenetic approach to retinal disease therapy.
The work aimed to investigate the impact of chronic formalin-induced inflammation on the remote malignancy development and longevity in white outbred tumour-bearing rats.
Experiments were conducted with 29 white outbred mature male rats divided in three groups: a control, water-injection and main formalin-injection group. Aqueous formaldehyde or same water volume were injected into left ankle joint thrice prior to Guerin’s carcinoma transplantation, 4 weeks past the first injection. The tumour size dynamics, longevity, oedema severity, blood leucocyte count and overall motor activity were estimated with an Open Field test. Statistical analysis was performed with Statistica 6 using the Kruskal—Wallis and Dunn’s test criteria.
Formalin administration accelerated the tumour growth in most animals. Nevertheless, longevity increased relative to the control’s maximum in 50% cases. Lethality in such cases was often registered with larger tumours relative to the control group. The pre-tumour traits of inflammatory response and motor dynamics in longer-lived animals have been revealed. A similar trend was registered in water administration trials at a less pronounced inflammatory and algetic response relative to the formalin trials. Putative chronic inflammation-associated mechanisms of anti-tumour resistance have been proposed.
A multidirectional effect of formalin-induced inflammation on tumourigenesis is shown for the first time: a prevailing tumour growth acceleration at higher longevity with seldom tumour inhibition cases in white outbred male rats. The mechanisms of inflammation-associated anti-tumour resistance require further research. The results relate to the known effect of musculoskeletal inflammatory conditions on tumourigenesis.
ISSN 2713-0428 (Online)