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Objective Muscle unloading leads to its atrophy development. The MuRF-1 and MAFbx E3-ligases expression is increasing under this condition. FOXO3 was considered to be the only transcription factor that triggers E3-ligases expression. Beharry A.W. et al pinpoints HDAC1 as a primary regulator of FoxO in skeletal muscle that is both sufficient and required for skeletal muscle atrophy. We aimed to determine the role of histone deacetylase 1 (HDAC1) proteins in activation of MuRF-1 and MAFbx E3-ligases expression at the early stage of muscle unloading. Methods We investigate it by CI-994 (inhibitor of HDAC1) administration in male Wistar rats (180-200 g) upon 3-day hindlimb suspension. The method of hindlimb suspension was described in Morey-Holton E & Globus R (2002). 24 animals were divided into 3 groups (n=8 in each): C-control, CI - hindlimb suspension with CI-994 (i.p. 1 mg/kg/day), or placebo (HS group) administration. The animals were anaesthetized with an i.p. injection of tribromoethanol (240 mg/kg), soleus muscles were surgically excised, frozen in liquid nitrogen. The Western blot and RT-PCR analyzes were done. The statistical analysis was performed using REST 2009 v.2.0.12 and Bio-Rad CFX Manager programs at the significance level set at 0.05. The significant differences between groups were statistically analyzed using Mann-Whitney test. Results The evaluation of the levels of mRNA expression of MuRF-1 and MAFbx showed that CI-994 treatment inhibited unloading induced up-regulation of MAFbx in CI group but had no effect on mRNA expression of MuRF-1. After unloading, mRNA expression of MAFbx increased 2.12-fold (p < 0.05) in HS group. There were statistically significant differences in MAFbx mRNA expression between HS and CI groups. When compared with the control, unloading increased MuRF-1 mRNA expression 1.67- and 1.56-fold in HS and CI groups, respectively. CI-994 treatment also inhibited unloading-induced upregulation of mRNA expression of ubiquitin. The levels of ubiquitin mRNA expression when compared with the control were 4.21- and 2.32-fold in HS and CI groups, respectively. We did not find any differences in the content of phosphorylated anabolic signaling system components (Akt/mTOR/S6k) between both suspended groups (CI and HS). Conclusions Therefore, HDAC1 inhibiting prevented hindlimb suspension-induced up-regulation of MAFbx and ubiquitin, but did not any effect MuRF-1expression. This work was supported by Russian Science Foundation (grant № 18-15-00062).

Objective Unloading causes rapid skeletal muscle atrophy mainly due to the increased protein degradation. Muscle proteolysis results from the activation of ubiquitin-proteasome systems. The ubiquitination proteins are carried out by muscle-specific E3 ubiquitin ligases – MuRF-1 and MAFbx. It is known that MuRF-1 and MAFbx expression significantly increases on the third day of muscle unloading. We tested the hypothesis that p38 MAPK participates in the regulation of E3 ligases expression and the development of skeletal muscle atrophy during unloading. To check this idea we inhibited p38 MAPK by VX-745. Methods 21 male Wistar rats were divided into 3 groups (7 rats in each group): intact control (C), rats suspended for 3 days (HS) and rats suspended and injected i.p. with VX-745 (10 mg/kg/day) (VX). The hindlimb suspension was carried out according to Morey-Holton technique. The animals were anaesthetised with an i.p. injection of tribromoethanol (240 mg/kg). Under anesthesia, the m.soleus were excised, frozen in liquid nitrogen, and stored at -80°C until further analysis. All procedures with the animals were approved by the Biomedicine Ethics Committee of the Institute of Biomedical Problems of the Russian Academy of Sciences/Physiology section of the Russian Bioethics Committee. The statistical analysis was performed using the REST 2009 v.2.0.12 and Origin Pro programs at the significance level set at 0,05. The results are given as median in percent and interquartile range (0.25-0.75). Results The muscle weight in HS group was significantly reduced (72,3±2,5 mg) compared to C (83,0±3 mg), p

BACKGROUND: The house dust mites (HDM) Dermatophagoides farinae and D. pteronyssinus are important environmental allergens implicated in the pathogenesis of human and canine atopic dermatitis. Sensitization to HDM measured by allergen‐specific IgE is common in Finnish atopic dogs. Studies on HDM prevalence in Finland are few but suggest that HDM are scarce. OBJECTIVE: The aim of the present study was to evaluate the prevalence of HDM in the home environments of atopic dogs in Finland. METHODS: Dust samples were obtained from the homes of 50 atopic dogs. Samples were collected by vacuuming the owners’ mattresses and each dog's bed. In each case, an area of 21 × 30 cm was vacuumed for 2 min. Samples weighing 100 mg or more were considered sufficient for determination of HDM allergen concentrations (Der f 1 and Der p 1) using standardized ELISA. Samples sufficient for further analysis were also examined by direct microscopy for the presence of mites and by multiplex PCR for HDM DNA. RESULTS: Eighty one samples were sufficient for analysis by ELISA, 59 by PCR and 29 by direct microscopy. A single sample was analysed from four homes in which the dog shared the owner's bed. Der f 1 was detected in three samples (3.7%). Der p 1 was not detected in any sample. No mites were identified on microscopy. Five samples were positive for HDM on multiplex PCR (8.4%). CONCLUSION: House dust mites seem to be uncommon in the home environment of atopic dogs in Finland despite reported frequent allergen‐specific IgE antibodies.

Hypersensitivity dermatitides (HD) are commonly seen in cats, and they are usually caused by environmental, food and/or flea allergens. Affected cats normally present with one of the following clinical reaction patterns: head and neck excoriations, usually symmetrical self-induced alopecia, eosinophilic skin lesions or miliary dermatitis. Importantly, none of these clinical presentations is considered to be pathognomonic for HD skin diseases, and the diagnosis of HD is usually based on the exclusion of other pruritic diseases and on a positive response to therapy. The objectives of this study were to propose sets of criteria for the diagnosis of nonflea-induced HD (NFHD). We recruited 501 cats with pruritus and skin lesions and compared clinical parameters between cats with NFHD (encompassing those with nonflea, nonfood HD and those with food HD), flea HD and other pruritic conditions. Using simulated annealing techniques, we established two sets of proposed criteria for the following two different clinical situations: (i) the diagnosis of NFHD in a population of pruritic cats; and (ii) the diagnosis of NFHD after exclusion of cats with flea HD. These criteria sets were associated with good sensitivity and specificity and may be useful for homogeneity of enrolment in clinical trials and to evaluate the probability of diagnosis of NFHD in clinical practice. Finally, these criteria were not useful to differentiate cats with NFHD from those with food HD.