Anthracyclines, such as doxorubicin (adriamycin), daunorubicin, or epirubicin, rank among the most effective agents in classical anticancer chemotherapy. However, cardiotoxicity remains the main limitation of their clinical use. Topoisomerase IIβ has recently been identified as a plausible target of anthracyclines in cardiomyocytes. We examined the putative topoisomerase IIβ selective agent XK469 as a potential cardioprotective and designed several new analogs. In our experiments, XK469 inhibited both topoisomerase isoforms (α and β) and did not induce topoisomerase II covalent complexes in isolated cardiomyocytes and HL-60, but induced proteasomal degradation of topoisomerase II in these cell types. The cardioprotective potential of XK469 was studied on rat neonatal cardiomyocytes, where dexrazoxane (ICRF-187), the only clinically approved cardioprotective, was effective. Initially, XK469 prevented daunorubicin-induced toxicity and p53 phosphorylation in cardiomyocytes. However, it only partially prevented the phosphorylation of H2AX and did not affect DNA damage measured by Comet Assay. It also did not compromise the daunorubicin antiproliferative effect in HL-60 leukemic cells. When administered to rabbits to evaluate its cardioprotective potential in vivo, XK469 failed to prevent the daunorubicin-induced cardiac toxicity in either acute or chronic settings. In the following in vitro analysis, we found that prolonged and continuous exposure of rat neonatal cardiomyocytes to XK469 led to significant toxicity. In conclusion, this study provides important evidence on the effects of XK469 and its combination with daunorubicin in clinically relevant doses in cardiomyocytes. Despite its promising characteristics, long-term treatments and in vivo experiments have not confirmed its cardioprotective potential.
- MeSH
- antibiotika antitumorózní toxicita MeSH
- antracykliny * toxicita terapeutické užití MeSH
- chinoxaliny * MeSH
- daunomycin toxicita terapeutické užití MeSH
- DNA-topoisomerasy typu II metabolismus terapeutické užití MeSH
- doxorubicin toxicita MeSH
- inhibitory topoisomerasy II * toxicita terapeutické užití MeSH
- kardiotoxicita MeSH
- králíci MeSH
- krysa rodu rattus MeSH
- poškození DNA MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Throughout human evolutionary history, snakes have been associated with danger and threat. Research has shown that snakes are prioritized by our attentional system, despite many of us rarely encountering them in our daily lives. We conducted two high-powered, pre-registered experiments (total N = 224) manipulating target prevalence to understand this heightened prioritization of threatening targets. Target prevalence refers to the proportion of trials wherein a target is presented; reductions in prevalence consistently reduce the likelihood that targets will be found. We reasoned that snake targets in visual search should experience weaker effects of low target prevalence compared to non-threatening targets (rabbits) because they should be prioritized by searchers despite appearing rarely. In both experiments, we found evidence of classic prevalence effects but (contrasting prior work) we also found that search for threatening targets was slower and less accurate than for nonthreatening targets. This surprising result is possibly due to methodological issues common in prior studies, including comparatively smaller sample sizes, fewer trials, and a tendency to exclusively examine conditions of relatively high prevalence. Our findings call into question accounts of threat prioritization and suggest that prior attention findings may be constrained to a narrow range of circumstances.
Background: After injuries, infections, or tumor removal, endogenous healing depends on bone repair. Disorders of bone healing are difficult to treat in clinical settings. There are numerous induced methods for correcting bone abnormalities, such as the induced membrane technique, allogenic bone grafting, synthetic bone grafting, artificial joint replacement, and autologous bone grafting. However, the delivery of the bone graft and bone filling materials necessitates surgical implantation at the fracture site, which could cause edema, infection, and the development of heterotopic bone locally. Therefore, systemically administered osteogenic drugs will provide an excellent method for bone lesion healing. Aim of the study: to evaluate the systemic effect of metformin on bone healing after surgical induction of bony defect and to determine the amount of newly formed bone using histological, histomorphometric analysis, and the surface area measurement of newly formed bone. Also to study the safety of metformin administration at the administered dose for this purpose. Materials and methods: Twenty mature male New Zealand rabbits were separated into two groups, each including ten rabbits for the study. The same surgical procedure was performed on all rabbits. Two holes were made at the femur (3 mm in diameter and 3 mm in depth) and left empty. Metformin tablets were ground into a fine powder and the resultant powder was dissolved in 10ml of water to prepare a liquid dosage containing 50 mg /1ml of metformin. Metformin is administered orally to the rabbits through a feeding tube at a dose of 50 mg/kg body weight. Animals were euthanized at two-time intervals, 14 and 28 days. The femur was separated, sectioned preserved, and sent for histological analysis and histomor-phometry. Results: The results revealed that there is an increase in new bone formation and bone-forming cells in the metformin-treated group. Conclusion: Metformin increases bone healing by increasing the number of bone-forming cells and the surface area of newly formed bone tissues and causes less inflammatory response at the site of a bone lesion. So it possesses an osteogenic effect.
Background: Gingiva is a delicate tissue that protects alveolar bone against external stimuli. Gingival breaks expose alveolar bone, and the fast wounds heal the betterment of the teeth frame. We aimed to compare the influence of omega-3 on the gingival healing period after trauma and the potential involvement of cytokeratin-19 protein expression.Methods: A total of 18 rabbits were used, after trauma-induced, these rabbits were subdivided into three groups of 6 each. Group 1 is the control group that received normal saline only, the second group received omega 3 for 10 days before the trauma, while the third group received omega 3 supplements for 10 days before the gingival injury and continued receiving them for an additional 10 days afterwards. For each time point (third and seventh day of healing), 3 rabbits were sacrificed, and tissue was collected for total antioxidant capacity and malondialdehyde measurement. Tissue fixed for histopathology and immunohistochemistry analysis.Results: Omega 3 has shown improvement in the healing process regarding the period of healing, antioxidant parameters, and intensity of cytokeratin-19 expression compared to the control group. Moreover, rabbit groups exposed to omega 3 before trauma has shown better healing response compared to those initiated therapy with trauma.Conclusion: Omega 3 is notably beneficial when used for both prevention and treatment since it reduces oxidative stress and improves healing processes measured by increased expression of cytokeratin-19 in epithelial tissue. Omega 3 can therefore be thought of as a possible choice for the treatment of gingival wounds and gingivitis.
BACKGROUND: The objective of this systematic review is to summarize the available animal models of ischemic limbs, and to provide an overview of the advantages and disadvantages of each animal model and individual method of limb ischemia creation. METHODS: A review of literature was conducted using the PubMed and Web of Science pages. Various types of experimental animals and surgical approaches used in creating ischemic limbs were evaluated. Other outcomes of interest were the specific characteristics of the individual experimental animals, and duration of tissue ischemia. RESULTS: The most commonly used experimental animals were mice, followed by rabbits, rats, pigs, miniature pigs, and sheep. Single or double arterial ligation and excision of the entire femoral artery was the most often used method of ischemic limb creation. Other methods comprised single or double arterial electrocoagulation, use of ameroid constrictors, photochemically induced thrombosis, and different types of endovascular methods. The shortest duration of tissue ischemia was 7 days, the longest 90 days. CONCLUSIONS: This review shows that mice are among the most commonly used animals in limb ischemia research. Simple ligation and excision of the femoral artery is the most common method of creating an ischemic limb; nevertheless, it can result in acute rather than chronic ischemia. A two-stage sequential approach and methods using ameroid constrictors or endovascular blinded stent grafts are more suitable for creating a gradual arterial occlusion typically seen in humans. Selecting the right mouse strain or animal with artificially produced diabetes or hyperlipidaemia is crucial in chronic ischemic limb research. Moreover, the observation period following the onset of ischemia should last at least 14 days, preferably 4 weeks.
- MeSH
- arteria femoralis * chirurgie MeSH
- ischemie * MeSH
- králíci MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- modely u zvířat MeSH
- myši MeSH
- ovce MeSH
- prasata MeSH
- stenty MeSH
- teoretické modely MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- systematický přehled MeSH
Determining the most appropriate cannula diameter for lipoaspirate harvesting is important, both in terms of the quality and composition of the material obtained, and the ease of practical use of the cannula. The size of the cannula is one of the main factors affecting the qualitative characteristics of the obtained lipoaspirate sample for further use of adipose tissue. The purpose of the investigation was to clinically and histomorphometrically determine the optimal cannula diameter for lipoaspirate samples collection from rabbit inguinal fat pad in an experimental study. The methods of Animal models, Surgical procedures, Macroscopic examination, Histological examination, and Morphometric study were applied. There is a direct correlation between the percentage of connective tissue fibres in the lipoaspirate and the diameter of the cannula. The lack of clear criteria for selecting a lipoaspiration cannula is one of the limitations to obtaining generally accepted lipoaspiration protocols with subsequent use of adipose tissue. In this study, the animal experiment determined the most ideal cannula diameter suitable for collecting the largest amount of lipoaspirate for subsequent use.
- MeSH
- kanyla * MeSH
- králíci MeSH
- lipektomie * metody MeSH
- modely u zvířat MeSH
- odběr tkání a orgánů MeSH
- tuková tkáň MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Seminal plasma (SP) provides essential nutrients, transport, and protection to the spermatozoa during their journey through the male and female reproductive tracts. Extracellular vesicles (EVs) are one of the main components of the SP with several biomolecular cargoes, including miRNAs, that can influence spermatozoa functions and interact with the cells of the female reproductive tract. This study aimed to isolate, characterize, and identify the miRNA expression profiles in the SP-EVs isolated from fertile (F) and subfertile (S) rabbit bucks that could serve as fertility biomarkers. In this study, the methods to isolate and identify EVs including exosomes, from SP of 3 F and S bucks have been developed. Ultracentrifugation and size exclusion chromatography analysis were using to isolate EVs from SP of F and S males that were qualitative and quantitively characterised using transmission electron microscopy, nanoparticle tracking analysis and western blotting. In addition, total RNA, including miRNA, was isolated, sequenced and identified from SP-EVs samples. Different SP-EVs concentrations (8.53 × 1011 ± 1.04 × 1011 and 1.84 × 1012 ± 1.75 × 1011 particles/mL of SP; P = 0.008), with a similar average size (143.9 ± 11.9 and 115.5 ± 2.4 nm; P = 0.7422) in F and S males, respectively was observed. Particle size was not significantly correlated with any kinetic parameter. The concentration of SP-EVs was positively correlated with the percentage of abnormal forms (r = 0.94; P < 0.05) and with the percentage of immotile spermatozoa (r = 0.88; P < 0.05). Small-RNA-seq analysis identified a total of 267 and 244 expressed miRNAs in the F and S groups, respectively. Two miRNAs (let-7b-5p and let-7a-5p) were the top most abundant miRNAs in both groups. Differential expression analysis revealed that 9 miRNAs including miR-190b-5p, miR-193b-5p, let-7b-3p, and miR-378-3p, and another 9 miRNAs including miR-7a-5p, miR-33a-5p, miR-449a-5p, and miR-146a-5p were significantly up- and downregulated in the F compared to the S group, respectively. The SP from F and S rabbit males contains EVs with different miRNA cargo correlated with spermatogenesis, homeostasis, and infertility, which could be used as biomarkers for male fertility and potential therapies for assisted reproductive technologies.
NMDA receptors (NMDARs) are ionotropic glutamate receptors that play a key role in excitatory neurotransmission. The number and subtype of surface NMDARs are regulated at several levels, including their externalization, internalization, and lateral diffusion between the synaptic and extrasynaptic regions. Here, we used novel anti-GFP (green fluorescent protein) nanobodies conjugated to either the smallest commercially available quantum dot 525 (QD525) or the several nanometer larger (and thus brighter) QD605 (referred to as nanoGFP-QD525 and nanoGFP-QD605, respectively). Targeting the yellow fluorescent protein-tagged GluN1 subunit in rat hippocampal neurons, we compared these two probes to a previously established larger probe, a rabbit anti-GFP IgG together with a secondary IgG conjugated to QD605 (referred to as antiGFP-QD605). The nanoGFP-based probes allowed faster lateral diffusion of the NMDARs, with several-fold increased median values of the diffusion coefficient (D). Using thresholded tdTomato-Homer1c signals to mark synaptic regions, we found that the nanoprobe-based D values sharply increased at distances over 100 nm from the synaptic edge, while D values for antiGFP-QD605 probe remained unchanged up to a 400 nm distance. Using the nanoGFP-QD605 probe in hippocampal neurons expressing the GFP-GluN2A, GFP-GluN2B, or GFP-GluN3A subunits, we detected subunit-dependent differences in the synaptic localization of NMDARs, D value, synaptic residence time, and synaptic-extrasynaptic exchange rate. Finally, we confirmed the applicability of the nanoGFP-QD605 probe to study differences in the distribution of synaptic NMDARs by comparing to data obtained with nanoGFPs conjugated to organic fluorophores, using universal point accumulation imaging in nanoscale topography and direct stochastic optical reconstruction microscopy.SIGNIFICANCE STATEMENT Our study systematically compared the localization and mobility of surface NMDARs containing GFP-GluN2A, GFP-GluN2B, or GFP-GluN3A subunits expressed in rodent hippocampal neurons, using anti-green fluorescent protein (GFP) nanobodies conjugated to the quantum dot 605 (nanoGFP-QD605), as well as nanoGFP probes conjugated with small organic fluorophores. Our comprehensive analysis showed that the method used to delineate the synaptic region plays an important role in the study of synaptic and extrasynaptic pools of NMDARs. In addition, we showed that the nanoGFP-QD605 probe has optimal parameters for studying the mobility of NMDARs because of its high localization accuracy comparable to direct stochastic optical reconstruction microscopy and longer scan time compared with universal point accumulation imaging in nanoscale topography. The developed approaches are readily applicable to the study of any GFP-labeled membrane receptors expressed in mammalian neurons.
- MeSH
- hipokampus metabolismus MeSH
- imunoglobulin G metabolismus MeSH
- jednodoménové protilátky * metabolismus MeSH
- králíci MeSH
- krysa rodu rattus MeSH
- neurony metabolismus MeSH
- receptory N-methyl-D-aspartátu * metabolismus MeSH
- savci MeSH
- synapse fyziologie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The purpose of this study was to evaluate the impact of 1% and 2% topical nifedipine ointments on TGF-β and the acceleration of facial skin wound healing in rabbits. Nifedipine ointments of 1% and 2% were prepared. Fifty healthy male rabbits were involved and distributed into two groups according to the study period: group A (7 days) and group B (14 days). Each group was subdivided into five groups (5 rabbits/group): Group I (Normal): rabbits did not undergo a surgical procedure and did not receive treatment; group II (negative control): rabbits had surgical wounds without treatment; group III (positive control): rabbits had surgical wounds with white petroleum treatment; group IV(nifedipine 1%): rabbits had surgical wounds with nifedipine 1% ointment treatment; and group V(nifedipine 2%): rabbits had surgical wounds with nifedipine 2% ointment treatment. Following euthanasia, blood samples (5 ml) were collected from all animals for TGF-β analysis using an ELISA kit. The TGF-β level in NFD 1% group was significantly higher on the 7th and14th day of the study associated with a higher rate of wound closure in comparison to other groups. Conclusions: Nifedipine 1% ointment has beneficial value for improving wound healing, while nifedipine NFD 2% has no such effect.
Growth hormone (GH) the most abundant hormone secreted by the anterior pituitary gland could have a role with other growth factors in wound healing because they can help in the physiological wound healing process.Aims: To investigate the effects of GH on facial skin wound healing in rabbits and to evaluate its effect on "insulin-like growth factor (IGF-1)" and "transforming growth factor- β (TGF-β)" in serum. Material and Method: Thirty healthy male rabbits included in this study were classified into two groups according to the day of euthanization 7 and 14 days of study, each group was subdivided into three groups; negative control group, positive control group, and treatment group, full-thickness circle 1 cm wounds were excised in the skin of the forehead for each rabbit without any medication.3-(treated group) full-thickness circle 1 cm wounds will excise in the skin of the forehead for each rabbit, 0.1ml [contain 1.2mg /3.6 IU] of growth hormone injected subcutaneously around the incision, the injection process is every other day.Result: showed a highly significant difference among all study groups in serum TGF-β (ng/L) and IGF (ng/ml) during the first and second weeks. the serum TGF-β at the end of the first and second weeks showed a significant elevation in the treatment group when compared to the other study groups. There is no significant difference between the two control groups. The serum IGF at the end of the first and second weeks showed a significant difference in IGF levels among all study groups.Conclusions: Topical GH has a role in skin wound healing since it can increase the serum level of TGF-β. GH also causes a decrease in serum IGF. Topical GH may have a positive impact on skin wound healing.
- MeSH
- aplikace lokální MeSH
- experimenty na zvířatech MeSH
- hojení ran * fyziologie účinky léků MeSH
- injekce subkutánní MeSH
- insulinu podobný růstový faktor I analýza fyziologie metabolismus MeSH
- králíci MeSH
- kůže zranění MeSH
- obličej MeSH
- růstový hormon aplikace a dávkování terapeutické užití MeSH
- studie případů a kontrol MeSH
- transformující růstový faktor beta analýza fyziologie metabolismus MeSH
- Check Tag
- králíci MeSH
