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The aim of the article is to show the linguistic and cultural image of a woman on the basis of paremiological material preserved in Kashubian, English and Polish. According to Jędrzejko (1994, p. 159) 'views about women, updated and modified by literature and folklore, are expressed in all sorts of general judgements that attribute positive or negative qualities to them'. We can see that the experience of different cultures is habitually collected and fossilised in proverbs. Additionally, as indicated by Mieder (2004, p. xi) (…) ‘there are no signs that proverbs have outlined their usefulness in modern technological societies either’. That is why proverbs make it possible to understand the character, worldview and also the underlying system of values of a given nation. As such, they are an excellent tool for learning about other cultures. The article discusses the history of paremiology and peremiography of the three languages in question. What is more, the notion of linguistic worldview and the studies carried out worldwide will be discussed. Finally, the author attempts to compare proverbs in which a set of features attributed to a woman has been preserved. To this end, she searches the equivalents of the proverbs in order to find an answer to the question of possible convergent observations testifying to the proximity or distinctiveness of the indicated cultures.

Assuming that the information presented in dictionary definitions should indicate that language use depends on the pragmatic situation and the social relationship between speaker and hearer, dictionaries often use special conventions. It is particularly important from the point of view of the language learner that these conventions are not too complicated. Of course, the knowledge of the difference between the semantics of a word and its pragmatic meaning, especially when the dictionary user comes from a different culture, seems to be of prime importance. When consulting dictionaries, the learner of a foreign language needs clear instructions on the formal use of the language, as well as on the use that is not formal, in order to avoid the consequences of a wrong choice.

Comparative research on paremiology seems to be gaining considerable attention in recent times. However, such initiatives should also include those languages which have been subjected to different backgrounds, either social or religious. Conclusions drawn on these grounds seem to be valuable in the field of linguistic, ethnographic and cultural research.

Transfusion of blood and blood components is one of the widely used medical procedures. The responsibility for provision of blood and blood components lies with Polish blood transfusion centers (CKiK) substantively supervised by the Institute of Hematology and Transfusion Medicine. Hospital based blood banks, hospital wards, immunohematology laboratories are supervised by CKiK. Every year approximately 600 thousand people donate blood, more than 75% of which are regular donors. The annual number of donations is maintained at a constant level of about 1.3 million. The aim of this position paper is to present the current status, achievements and advancement in collection, preparation and testing procedures and methods used to obtain the best possible quality blood components dedicated for clinical use. The aim is also to show the structure of blood transfusion service in Poland. Collaboration of all organizational units involved in transfusion medicine is crucial for providing high quality health care for patients. Polish transfusiologists and blood transfusion officers have largely contributed to transfusion science with numerous publications and significant research work. The implementation of novel methods and ongoing research positions Polish blood transfusion service among those of highly developed countries.

The commercial horse feed industry uses palatants to mask undesirable tastes of feeds and enhance product acceptance. However, an unknown odour or taste may also hinder feed intake, due to, inter alia, novelty. The objective of the study was to assess the horses’ response to novel diet: five different herbs added alternately to dry, wet or wet-sweetened oats. Twenty adult horses were given different diet combinations of a feed presentation and a herb: field mint, common yarrow, common chamomile, common sage and common nettle, consecutively, once daily. The response to novelty was assessed regarding traits showing the willingness to consume: times of olfaction and consumption, times and numbers of intervals in consumption and drinking water, and the mass of leftovers. The results show that properties of the herbs studied did not hinder the consumption and only the odour of the dry common sage delayed the intake. Wetting or wetting and sweetening the diet accelerated the intake. In conclusion, herbs in small amounts do not significantly affect the willingness to consume feed. Although wet and wet-sweetened diet presentations may be novel to horses, they increase the feed palatability and can be suggested for use when preparing horse diets.

Background: The extent of morphological and ultrastructural changes in HeLa cells was assessed by optical, fluorescence and electron microscopy after exposure to various concentrations of physcion, taking into account the biological properties of the test compound. Methods: Cell viability was assessed by MTT assay, while the cell cycle, LC3 expression, apoptosis, change of mitochondrial potential, Bcl-2 protein expression level and the level of reactive oxygen species were analyzed by flow cytometry. Results: As a result of physcion encumbrance, concentration-dependent inhibition of HeLa cell viability and the G0/G1 phase of the cell cycle was observed. Activation of the lysosomal system was also revealed, which was expressed by an increased number of lysosomes, autophage vacuoles and increased expression of the LC3 protein, a marker of the autophagy process. Transmission electron microscopy and fluorescence microscopy showed that physcion induced clear changes in cervical cancer cells, especially in the structure of the nucleus and mitochondria, which correlated with the production of reactive oxygen species by the test compound and indicated the induction of the oxidative process. At the same time, the pro-apoptotic effect of physcion was demonstrated, and this mechanism was dependent on the activation of caspases 3/7 and the reduction in Bcl-2 protein expression. Conclusion: The obtained results indicate an antitumor mechanism of action of physcion, based on the induction of oxidative stress, autophagy and apoptosis.

Folate-targeted lipid nanostructures are promising strategies for the development of biocompatible drug delivery systems. The objective of this study was to evaluate the efficacy of drug delivery to cancer cells by folate-targeted lipid mesophases, cubosomes (CUB) and hexosomes (HEX), loaded with doxorubicin (DOX). Three cancer-derived cell lines (KB, HeLa, T98G) exhibiting different expressional levels of folate receptor protein (FR) were used. DOX-loaded folate-targeted CUB and HEX dispersions were characterized via small angle X-ray scattering and dynamic light scattering to assess their physicochemical properties. DOX release characteristics were evaluated by electrochemical methods and demonstrated structure-dependent release capabilities. A slow release rate was observed for hexosomes, while cubosomes offered more rapid drug transport. Analysis of the release kinetics revealed that the total amount of DOX released from cubosomes is linearly dependent on the square root of time, implying that the release process follows the Higuchi diffusion model. Assessment of drug uptake performed on cancer-derived cell lines demonstrated that DOX accumulation in cancer cell depends not only on the release capability of the applied mesophase, but also, on the level of folate receptor protein present in the cancer cells. FR-functionalized CUB and HEX enabled faster drug delivery to cancer cells as a result of receptor-ligand interactions. In addition, doxorubicin encapsulated into FR-cubosomes demonstrated significantly improved anti-tumor activity promoting the necrosis of tumor cells, while DOX-loaded FA-hexosomes acted via induction of the apoptotic state. Overall, our data indicates that folate-modified formulations are promising drug delivery systems and can be considered as potential therapeutic tools in the targeted therapy of FR-positive tumors.

Background Anthraquinones, including emodin, are compounds with numerous pharmacological properties, including anticancer properties. The aim of this study experiment was to examine the effect of emodin, a natural compound present in the roots and rhizomes of Rheum palmatum, on the induction of mitotic catastrophe in cervical cancer cells. Material and methods HeLa celIs were treated with different emodin concentrations for 48 h, and cell growth was measured with 3-(4-,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolyl. The cell-cycle distribution and the level of apoptosis were determined by means of flow cytometry, using annexin V-fluorescein isothiocyanate staining and propidium iodide. Morphological changes in the mitotic apparatus were evaluated using optical and confocal microscopy techniques. Results Emodin induced an increase in the number of polymorphonuclear cells, giant cells, cells with micronuclei, cells with abnormal mitosis and damaged spindle. The reorganization of F-actin depended on the concentration of emodin. With the increase in emodin concentration, inhibition of mitotic activity was demonstrated, which was manifested by a decrease in the mitotic index, mainly in metaphase of the mitotic process and an increase in the number of cells inhibited in the G2/M phase. At the same time, an increase in the number of apoptotic cells was found. Conclusion Emodin leads to death of cervical cancer cells by induction of a mitotic catastrophe.

Multidrug resistance is one of the key barriers suppressing the effectiveness of drug therapies of malignant tumors. Here, we report a study on the effect of a mix of natural extracts (MIX2) prepared from fresh fruits of Prunus spinosa, Crataegus monogyna, Sorbus aucuparia, and Euonymus europaeus on the classic hallmarks of cancer cells and the expression of multidrug resistance proteins. In the studies, HeLa and T98G cell lines, and classic methods of molecular biology, including RT-qPCR, Western blot, flow cytometry, and confocal imaging, were used. Additionally, migration, adhesion, and proliferation assays were performed. The obtained results indicate that the MIX2 cocktail presents strong anti-cancer properties. MIX2 is not toxic, but at the same time significantly alters the migration, proliferation, and adhesion of tumor cells. Furthermore, it was found that cells exposed to the mixture presented a significantly reduced expression level of genes associated with MDR, including ABCB1, which encodes for glycoprotein P. In vitro data showed that MIX2 effectively sensitizes tumor cells to doxorubicin. We postulate that modulation of the multidrug resistance phenotype of tumors with the use of MIX2 may be considered as a safe and applicable tool in sustaining drug delivery therapies of malignancies.

The aim of this study was to determine the influence of different forms of an audience's behavior on the heart work parameters and salivary cortisol level of leisure horses during work. Twelve horses were studied at rest, during standardized work, and at recovery. There was no audience in the arena in the control variant, whereas an audience (10 people) was situated in the middle of the arena in four other variants: standing still and silent in the first variant, standing still and talking in normal voice in the second variant, being silent but walking in both directions along the middle line of the arena in the third variant, and walking as above and simultaneously talking in the fourth variant. Heart rate, heart rate variability parameters: root mean square of successive beat-to-beat differences, low frequency of the power spectrum (LF), high frequency of the power spectrum (HF) and ratio of LF and HF signal (LF/HF), as well as salivary cortisol levels were measured. We found that audience presence and various forms of behavior during horse-riding leisure hours caused a significant decrease (P

Chrysophanol is an anthraquinone with proven antitumor activity against several tumor cell lines. However, its effect on cervical cancer cells is still unknown. Therefore, HeLa cells were exposed to various concentrations of chrysophanol and then subjected to biochemical, ultrastructural, and morphological analysis. It has been shown using flow cytometry and MTT reduction assay that chrysophanol has been shown to inhibit cell viability and arrest cells in the G2/M phase of the cell cycle. Using Annexin V/propidium iodide staining, a significant increase in apoptosis was found after chrysophanol treatment on HeLa cells, and this process was mediated by caspases 3/7 with a clear inactivation of the antiapoptotic Bcl-2 family protein. However, the demonstrated increased number of cells with double-stranded DNA breaks suggests that chrysophanol also causes DNA damage. By means of electron and fluorescence microscopy, a clear effect of chrysophanol on the intensification of degradation processes, on changes in the structure of the nucleus, endoplasmic reticulum and mitochondria was demonstrated. The changes visible in the mitochondria may be related to the increase in the level of free radicals induced by chrysophanol, which induces apoptosis, inter alia, by increasing the permeability of mitochondrial membranes. The range of observed changes depended on the concentration of anthraquinone was tested.

Background Predatory attacks on horses can become a problem in some parts of the world, particularly when considering the recovering gray wolf populations. The issue studied was whether horses transformed by humans and placed in stable-pasture environments had retained their natural abilities to respond to predation risk. The objective of the study was to determine the changes in cardiac activity, cortisol concentrations, and behavior of horses in response to the vocalizations of two predators: the gray wolf (Canis lupus), which the horses of the breed studied had coevolved with but not been exposed to recently, and Arabian leopard (Panthera pardus nimr), from which the horses had been mostly isolated. In addition, we hypothesized that a higher proportion of Thoroughbred (TB) horse ancestry in the pedigree would result in higher emotional excitability in response to predator vocalizations. Nineteen horses were divided into groups of 75%, 50% and 25% TB ancestry. The auditory test conducted in a paddock comprised a 10-min prestimulus period, a 5-min stimulus period when one of the predators was heard, and a 10-min poststimulus period without any experimental stimuli. Results The increase in heart rate and saliva cortisol concentration in response to predator vocalizations indicated some level of stress in the horses. The lowered beat-to-beat intervals revealed a decrease in parasympathetic nervous system activity. The behavioral responses were less distinct than the physiological changes. The responses were more pronounced with leopard vocalizations than wolf vocalizations. Conclusions The horses responded with weak signs of anxiety when exposed to predator vocalizations. A tendency towards a stronger internal reaction to predators in horses with a higher proportion of TB genes suggested that the response intensity was partly innate. The more pronounced response to leopard than wolf may indicate that horses are more frightened of a threatening sound from an unknown predator than one known by their ancestors. The differing response can be also due to differences in the characteristic of the predators’ vocalizations. Our findings suggested that the present-day horses’ abilities to coexist with predators are weak. Hence, humans should protect horses against predation, especially when introducing them into seminatural locations.

The current predation threat of domestic horses is generally low, and horses do not know predators' frightening cues. We studied whether horses still recognise predation threats. The aim of the study was to analyse the emotional response of purebred Arabian horses (Arabian) and Polish Konik horses (Konik) to an Arabian panther (Panthera pardus nimr) (panther) growl and a grey wolf (Canis lupus) (wolf) howl. Panther vocalisation was known to Arabian ancestors, whereas ancestors of Konik knew wolf vocalisation. The response to the howls of golden jackals (Canis aureus) (jackal), which did not prey on equids, was also studied comparatively. Two groups of 10 adult horses of each breed were subject to predator sounds of one predator daily for 5 min during a turn out on pasture. The test was performed for 18 days in total. The sound of each predator was interchangeably featured from one loudspeaker for 3 days followed by four loudspeakers simultaneously to imitate a group of predators for 3 days. The horses' emotional agitation in response to the sounds was measured based on the parameters of heart rate variability (HRV) using telemetric devices. The results showed that the predators' sounds were identified by horses as stressful or neutral. Horses generally retained their anti-predator responses even in the current habitat, which typically lacks predation cues. The results are not always coherent and may demonstrate that the response is somewhat attenuated. The wolf howl elicited a stronger response in Koniks. The panther growl more strongly influenced Arabians, whereas the jackal howl minimally elicited an agitation in the horses. The differentiated response of the two horse breeds to the three predator species suggests that the response is an innate adaptation to the predation risk in the habitat of the breed ancestors. This response occurs regardless of the emotional arousal specific to a breed, and the frightening cue is not the sound per se but the possible attack of predators. Horses display a type of understanding of the sound meaning. Their HRV response seems to be adequate for the threat signalised by the sound.

Melanopsin, a G family coupled receptor, found within the ganglion cell layer in the retina, plays an important role in non-image-forming visual functions, including hormone secretion, entrainment of circadian rhythms, cognitive and affective processes. Diffuse projections of melanopsin-containing cells to many brain areas suggest that different responses may involve different neural projections, thus different melanopsin cells. Considering the complexity of the melanopsin system, its contribution to so many different biological functions is not surprising. In this review, we summarize the current knowledge about melanopsin in terms of its photophysics, photochemistry, mechanisms of activation, cell signaling, morphology, and physiology. In the last part, the role of melanopsin in image and non-image forming processes and cognitive and affective functioning of animals and humans, are discussed. Although in recent years considerable insight has been gained into the melanopsin system, it still remains an open question of how one protein expressed by several thousand cells in the retina, could be responsible for so many diverse functions and what activation mechanism(s) it uses.

Cancer cells, including thyroid cancer cells, suffer from oxidative stress damaging multiple cellular targets, such as DNA and the nucleotide pool. The human MutT homologue 1 (hMTH1) controls the oxidative DNA damage load by sanitizing the nucleotide pool from the oxidized DNA precursor, 8-oxodGTP. It has previously been shown that hMTH1 is essential for cancer cell proliferation and survival, therefore hMTH1 inhibition has been proposed as a novel anticancer therapeutic strategy. Here we show that thyroid cancer cells respond to siRNA mediated hMTH1 depletion with increased DNA damage load and moderately reduced proliferation rates, but without detectable apoptosis, cell-cycle arrest or senescence. Importantly, however, hMTH1 depletion significantly reduced migration and invasion potential of the thyroid cancer cells. Accordingly, our results allow us to propose that hMTH1 may be a therapeutic target in thyroid malignancy, especially for controlling metastasis.

The present paper focuses on the question of how usage is marked within dictionary macrostructure of five most representatives of EFL lexicographic works, namely Collins Cobuild Advanced Dictionary, Longman Dictionary of Contemporary English, Oxford Advanced Learner`s Dictionary, Cambridge Advanced Learner`s Dictionary and Macmillan English Dictionary. What is more, it sets a number of reasons why this particular area of lexicographic enquiry poses problems not only for dictionary users but also for dictionary compilers.

Developmental changes that occur in the prefrontal cortex during adolescence alter behavior. These behavioral alterations likely stem from changes in prefrontal cortex neuronal activity, which may depend on the properties and expression of ion channels. Nav1.9 sodium channels conduct a Na+ current that is TTX resistant with a low threshold and noninactivating over time. The purpose of this study was to assess the presence of Nav1.9 channels in medial prefrontal cortex (mPFC) layer II and V pyramidal neurons in young (20-day old), late adolescent (60-day old), and adult (6- to 7-month old) rats. First, we demonstrated that layer II and V mPFC pyramidal neurons in slices obtained from young rats exhibited a TTX-resistant, low-threshold, noninactivating, and voltage-dependent Na+ current. The mRNA expression of the SCN11a gene (which encodes the Nav1.9 channel) in mPFC tissue was significantly higher in young rats than in late adolescent and adult rats. Nav1.9 protein was immunofluorescently labeled in mPFC cells in slices and analyzed via confocal microscopy. Nav1.9 immunolabeling was present in layer II and V mPFC pyramidal neurons and was more prominent in the neurons of young rats than in the neurons of late adolescent and adult rats. We conclude that Nav1.9 channels are expressed in layer II and V mPFC pyramidal neurons and that Nav1.9 protein expression in the mPFC pyramidal neurons of late adolescent and adult rats is lower than that in the neurons of young rats. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1371-1384, 2017.

Flow cytometry (FC) has been primarily applied to the diagnosis of hematological malignancies, and thereafter, to detection and quantification of CD34+ cells in bone marrow transplants, and granulocytes in neutropenias and paroxysmal nocturnal hemoglobinuria (PNH). In PNH and hereditary spherocytosis, changes in some of the erythrocyte membrane proteins are tested (CD59, CD55, and band 3). The purpose of this paper is to focus on the use of FC in RBC testing. With anti-D, -HbF, and -CA (carbonic anhydrase), we can detect RhD+, HbF+, and CA- fetal RBCs in the maternal RhD-, HbF-, and CA+ blood sample. Obtained results allow to select the appropriate dose of anti-D Ig in the RhD prophylaxis of feto-maternal incompatibility, or to detect the cause of fetal anemia. Expression of antigens and their weak variants, and concentration of specific antibodies, can also be assessed. It is possible to observe changes in selected CD molecules during storage of RBC units. If RBCs for transfusion are unavailable, due to patient's unusual antibody specificity, some of the available RBCs are opsonised, and then phagocytosis with the recipient monocytes is assessed. The microscopic time-consuming and subjective assay is usually used. Stained CD14+ monocytes and CD235a+ erythrocytes are visible on cytograms as well as their interaction. It makes evaluation of phagocytosis easier and objective. Microparticles of RBCs released during storage are also detected. They are 235a+. In differentiation of hemolysis causes, it is important to measure osmotic fragility, and that can be also achieved using FC. Flow cytometry should be applied to immunohematological testing of red blood cells more often than now.

Relaxing massages and playing music in stables may be used to mitigate the high level of stress in race horses. In the study, we compared effects of different frequencies of massages and different hours of music for race horses. Sixty horses were equally divided into one control group and four experimental groups. The experimental groups were treated with various relaxing methods: music for 1 hour a day, music for 3 hours a day, massage on the day preceding a race, and daily massage during the 6 months of the racing season. To evaluate the effects of the methods, horses' heart rate (HR) and parameters of heart rate variability (ratio of low to high frequencies of the power spectrum–LF/HF, and root mean square of successive beat-to-beat difference [RMSSD]) were measured while preparing horses for training sessions. Salivary cortisol concentrations were measured before and after training sessions. Official general handicap and success coefficient in the racing season were considered as performance parameters. In the experimental groups, lowered HR, LF/HF, and salivary cortisol concentrations as well as increased RMSSD were found, however, at various levels. The most positive changes in the parameters under study were found in horses massaged every day, which shows that relaxing massages are beneficial for horses' welfare and performance. Massages only about once every 3 weeks also gave some positive effects. It was shown that playing relaxing music for 3 hours a day had more positive effects on horses' emotional state than for 1 hour.

Introduction: Pregnancy is a physiological state in which the immune system undergoes certain changes. On the one hand, by depleting cell defence mechanisms, it favours development and maintenance of the pregnancy. At the same time cells of the immune system ensure resistance to many risk factors, including infectious agents. Material and Methods: The study was carried out on 24 Polish Konik breed mares which were divided into two equal groups. The first group (group I) included mares living in the reserve. The second group (group II) comprised mares maintained under conventional conditions in the stables. The blood samples were collected for the first time in the perinatal period, i.e. 2 weeks before parturition (trial 0), then within the first 24 h after delivery, and then on 7th and 21st day after foaling. Flow cytometric analysis of lymphocyte expressing TCD4+, TCD8+, CD2+, and MHC class II antigens was performed. Results: Before the delivery, in group I there was a significantly higher CD4:CD8 ratio compared to group II (P ≤0.05). Similarly, significantly increased CD4:CD8 ratio in group I was noted within 24 h after parturition (P ≤0.001) and it was also observed on 7th day (P ≤0.03) and 21st day after foaling (P ≤0.02). In the first 24 h after parturition, a significant decline of lymphocytes CD8+ (P ≤0.02) was noted. No significant differences in terms of lymphocytes CD2+ and CD3+ were observed. Expression of MHC-II molecules before and after the parturition was higher in group I compared to group II; however, the difference between the groups was not significant. Conclusion: The results obtained indicate that mares living in the reserve display higher activity of cell defence mechanisms.

The aim of the study was to evaluate physiological changes in hematological and biochemical parameters in mares in perinatal period. Blood samples were collected from 24 pregnant Polish Konik breed mares which were divided into two groups. The first group (Group – I, n=12) comprised mares living in the wild, in the reserve. The second group (Group – II, n=12) consisted of mares kept in stables. The blood was collected 2 weeks prior to the parturition, then 24 hours after the delivery, and then at the 7th and 21st day after foaling. When comparing the two groups before the parturition, no significant differences in terms of WBC, RBC, and Hb were found, however, there was a significant difference in MCV, MCH, LYM, NEU and SEG NEU (p≤0.05). In Group II, 24 hours after the parturition and at the 21st day after foaling, a significant raise in WBC, NEU and SEG NEU (p≤0.05) was detected. No significant differences in serum concentrations of proteins such as TP, Alb or Glb were observed. As to acute phase proteins, significant rise in SAA and Hp (p≤0.05) was found in the two examined groups 24 hours after the parturition. Yet, this rise remained within physiological range. The study revealed a certain degree of fluctuations in hematological parameters, in serum concentrations of acute-phase proteins and total proteins in the mares in the perinatal period. However, these changes remained still within physiological ranges and thus they do not indicate potential susceptibility to disorders of perinatal period.

The aim of the study was to determine the first reaction of the heart rate (HR) in horses to piping music of different genres into the stable for a short time. The study included 26 saddle horses, mares, stallions and geldings, split into three age groups: 1-5, 6-11 and over 11 years. Three kinds of music were played within three 25-minute tests conducted on three successive days, one test a day. The tests differed in the sequence of music genres: rock, country and relaxing music. The analysis considered the mean HR at rest and during the first two and three minutes of the whole sequence of the three music genres, as well as during particular genres: minimum and maximum HR, difference between maximum HR and HR at rest, as well as the time in which HR decreased from the maximum level to the level before music was played. The data were verified by T-Tukey’s test and by ANOVA (GLM) with regard to sex, age group and music test factors. The results show that music played at 80 dB caused a short HR elevation. The level of emotional excitability measured by HR was different for the three music genres. The relaxation music had the mildest effect, the country music acted more strongly, and the influence of the rock music was the strongest. This finding is based on the mean HR for the first two minutes of a music test, extreme HR, difference between maximum HR and HR at rest, as well as the time in which HR decreased from the maximum level to the level before music was played. Differences in reactions of the horses to music were related to their sex and, to a smaller degree, their age.

The main objective of the study was to determine the genetic diversity in the Polish Konik (PK) population in the context of a currently conducted conservation program. A total of 94 horses of 16 PK dam lines currently distinguished by breeders were considered. Pedigree analyses were carried out for the whole population of PK registered in the studbook. Basic molecular parameters were estimated. The average group linkage clustering method was used based on the Euclidean similarity measurements between the lines. The allele frequency of 17 microsatellites was used to determine Euclidean distances. Inbreeding coefficients were extracted from the additive relationship matrix. Moreover, some pedigree parameters were estimated. The observed heterozygosity ranged from 0.48 to 0.76. The expected heterozygosity estimated for the dam lines was higher. PIC values were higher than 0.6 in all the lines. Fis ranged from –0.19 to 0.28, whereas Fit and Fst varied between 0.12 and 0.41 and 0.12 and 0.29, respectively. Minor dissimilarity distances existed for some dam lines. The inbreeding level was 9.3%. The average number of discrete generation equivalents reached 6.85. The majority of the dam lines are not genetically differentiated. Hence, a revision of the breeding strategy seems to be necessary.

Oxidative stress (OS) is recognized as disturbance of cellular equilibrium between reactive oxygen species (ROS) formation and their elimination by antioxidant defense systems. One example of ROS-mediated damage is generation of potentially mutagenic DNA precursor, 8-oxodGTP. In human cells genomic 8-oxodGTP incorporation is prevented by the MutT homologue 1 (MTH1 or hMTH1 for human MTH1) protein. It is well established that malignant cells, including thyroid cancer cells, require hMTH1 for maintaining proliferation and cancerous transformation phenotype. Above observations led to the development of hMTH1 inhibitors as novel anticancer therapeutics. In the current study we present extensive analysis of oxidative stress responses determining sensitivity to hMTH1 deficiency in cultured thyroid cells. We observe here that hMTH1 depletion results in downregulation of several glutathione-dependent OS defense system factors, including GPX1 and GCLM, making some of the tested thyroid cell lines highly dependent on glutathione levels. This is evidenced by the increased ROS burden and enhanced proliferation defect after combination of hMTH1 siRNA and glutathione synthesis inhibition. Moreover, due to the lack of data on hMTH1 expression in human thyroid tumor specimens we decided to perform detailed analysis of hMTH1 expression in thyroid tumor and peri-tumoral tissues from human patients. Our results allow us to propose here that anticancer activity of hMTH1 suppression may be boosted by combination with agents modulating glutathione pool, but further studies are necessary to precisely identify backgrounds susceptible to such combination treatment.