This study aimed to establish a rat model of chronic wounds to observe the effects of hyperbaric oxygen (HBO) on chronic wound repair and pyroptosis and explore the potential role of pyroptosis in the pathogenesis of chronic wounds. Sprague-Dawley (SD) rats were randomly divided into acute wound group (control group), chronic wound group (model group), chronic wound + HBO treatment group (HBO group), and chronic wound + VX-765 (IL-converting enzyme/Caspase-1 inhibitor) treatment group (VX-765 group). After 7 days of respective interventions, the wound healing status was observed, and wound tissue specimens were collected. Hematoxylin and eosin (HE) staining was used to observe the pathological changes in wound tissues. Transmission electron microscopy was used to observe the changes in cellular ultrastructure. Immunofluorescence was used to observe the expression and localization of vascular endothelial growth factor A (VEGF-A) and the N-terminal domain of gasdermin D (GSDMD-N). Western blot was conducted to detect the expression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cysteine-requiring aspartate protease-1 (Caspase-1), VEGF-A, and GSDMD-N proteins in wound tissues. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of NLRP3, Caspase-1, and GSDMD genes. Enzyme-linked immunosorbent assay (ELISA) was performed to observe the expression of the inflammatory cytokines interleukin-1 beta (IL-1beta) and IL-18. The results showed that the HBO group had a faster wound healing rate and better pathology improvement compared to the model group. The expression level of VEGF-A was higher in the HBO group compared to the model group, while the expression levels of NLRP3, Caspase-1, GSDMD, IL-1beta, and IL-18 were lower than those in the model group. HBO can effectively promote the healing of chronic wounds, and the regulation of pyroptosis may be one of its mechanisms of action. Keywords: Hyperbaric oxygen, Pyroptosis, Chronic wounds, Inflammatory.
- MeSH
- chronická nemoc MeSH
- gasderminy MeSH
- hojení ran * fyziologie MeSH
- hyperbarická oxygenace * metody MeSH
- krysa rodu Rattus MeSH
- potkani Sprague-Dawley * MeSH
- protein NLRP3 metabolismus MeSH
- proteiny vázající fosfáty metabolismus MeSH
- pyroptóza * fyziologie MeSH
- vaskulární endoteliální růstový faktor A metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- gasderminy MeSH
- Gsdmd protein, rat MeSH Prohlížeč
- protein NLRP3 MeSH
- proteiny vázající fosfáty MeSH
- vaskulární endoteliální růstový faktor A MeSH
Cardiovascular diseases represent an economic burden for health systems accounting for substantial morbidity and mortality worldwide. Despite timely and costly efforts in drug development, the cardiovascular safety and efficacy of the drugs are not always fully achieved. These lead to the drugs' withdrawal with adverse cardiac effects from the market or in the late stages of drug development. There is a growing need for a cost-effective drug screening assay to rapidly detect potential acute drug cardiotoxicity. The Langendorff isolated heart perfusion technique, which provides cardiac hemodynamic parameters (e.g., contractile function and heart rate), has become a powerful approach in the early drug discovery phase to overcome drawbacks in the drug candidate's identification. However, traditional ex vivo retrograde heart perfusion methods consume a large volume of perfusate, which increases the cost and limits compound screening. An elegant and cost-effective alternative mode for ex vivo retrograde heart perfusion is the constant-flow with a recirculating circuit (CFCC), which allows assessment of cardiac function using a reduced perfusion volume while limiting adverse effects on the heart. Here, we provide evidence for cardiac parameters stability over time in this mode. Next, we demonstrate that our recycled ex vivo perfusion system and the traditional open one yield similar outputs on cardiac function under basal conditions and upon ?-adrenergic stimulation with isoproterenol. Subsequently, we validate the proof of concept of therapeutic agent screening using this efficient method. ?-blocker (i.e., propranolol) infusion in closed circulation countered the positive effects induced by isoproterenol stimulation on cardiac function. Keywords: Drug development, Drug screening, Cardiovascular safety, Langendorff method, Closed circulation.
Animal models are an important tool for studying ischemic mechanisms of stroke. Among them, the middle cerebral artery occlusion (MCAO) model via the intraluminal suture method in rodents is closest to human ischemic stroke. It is a model of transient occlusion followed by reperfusion, thus representing cerebral ischemia-reperfusion model that simulates patients with vascular occlusion and timely recanalization. Although reperfusion is very beneficial for the possibility of preserving brain functions after ischemia, it also brings a great risk in the form of brain edema, which can cause the development of intracranial hypertension, and increasing morbidity and mortality. In this paper, we present the results of our own transient reperfusion model of MCAO in which we tested the permeability of the blood-brain barrier (BBB) using Evans blue (EB), an intravital dye with a high molecular weight (68,500 Da) that prevents its penetration through the intact BBB. A total of 15 animals were used in the experiment and underwent the following procedures: insertion of the MCA occluder; assessment of ischemia by 2,3,5 -Triphenyltetrazolium chloride (TTC) staining; assessment of the BBB permeability using brain EB distribution. The results are presented and discussed. The test of BBB permeability using EB showed that 120 minutes after induction of ischemia, the BBB is open for the entry of large molecules into the brain. We intend to use this finding to time the application of neuroprotective agents via ICA injection in our next stroke model. Keywords: Cerebral ischemia-reperfusion model, Middle cerebral artery occlusion, Blood-brain barrier, 2,3,5 -Triphenyltetrazolium chloride, Evans blue.
- MeSH
- Evansova modř MeSH
- hematoencefalická bariéra * metabolismus MeSH
- infarkt arteria cerebri media * metabolismus MeSH
- ischemie mozku metabolismus MeSH
- kapilární permeabilita MeSH
- krysa rodu Rattus MeSH
- modely nemocí na zvířatech * MeSH
- permeabilita MeSH
- pilotní projekty MeSH
- potkani Sprague-Dawley MeSH
- reperfuzní poškození * metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Evansova modř MeSH
An excessive increase in reactive oxygen species (ROS) levels is one of the main causes of mitochondrial dysfunction. However, when ROS levels are maintained in balance with antioxidant mechanisms, ROS fulfill the role of signaling molecules and modulate various physiological processes. Recent advances in mitochondrial bioenergetics research have revealed a significant interplay between mitochondrial peroxiredoxins (PRDXs) and monoamine oxidase-A (MAO-A) in regulating ROS levels. Both proteins are associated with hydrogen peroxide (H2O2), MAO-A as a producer and PRDXs as the primary antioxidant scavengers of H2O2. This review focuses on the currently available knowledge on the function of these proteins and their interaction, highlighting their importance in regulating oxidative damage, apoptosis, and metabolic adaptation in the heart. PRDXs not only scavenge excess H2O2, but also act as regulatory proteins, play an active role in redox signaling, and maintain mitochondrial membrane integrity. Overexpression of MAO-A is associated with increased oxidative damage, leading to mitochondrial dysfunction and subsequent progression of cardiovascular diseases (CVD), including ischemia/reperfusion injury and heart failure. Considering the central role of oxidative damage in the pathogenesis of many CVD, targeting PRDXs activation and MAO-A inhibition may offer new therapeutic strategies aimed at improving cardiac function under conditions of pathological load related to oxidative damage. Keywords: Mitochondria, Peroxiredoxin, Monoamine oxidase-A, Reactive oxygen species, Cardioprotective signaling.
- MeSH
- lidé MeSH
- monoaminoxidasa * metabolismus MeSH
- oxidační stres MeSH
- peroxiredoxiny * metabolismus MeSH
- reaktivní formy kyslíku * metabolismus MeSH
- signální transdukce * MeSH
- srdeční mitochondrie metabolismus enzymologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- monoaminoxidasa * MeSH
- peroxiredoxiny * MeSH
- reaktivní formy kyslíku * MeSH
Combination of chronic kidney disease (CKD) and heart failure (HF) results in extremely high morbidity and mortality. The current guideline-directed medical therapy is rarely effective and new therapeutic approaches are urgently needed. The study was designed to examine if renal denervation (RDN) will exhibit long-standing beneficial effects on the HF- and CKD-related morbidity and mortality. Fawn-hooded hypertensive rats (FHH) served as a genetic model of CKD and fawn-hooded low-pressure rats (FHL) without CKD served as controls. HF was induced by creation of aorto-caval fistula (ACF). RDN was performed 28 days after creation of ACF and the follow-up period was 70 days. ACF FHH subjected to sham-RDN had survival rate of 34 % i.e. significantly lower than 79 % observed in sham-denervated ACF FHL. RDN did not improve the condition and the final survival rate, both in ACF FHL and in ACF FHH. In FHH basal albuminuria was markedly higher than in FHL, and further increased throughout the study. RDN did not lower albuminuria and did not reduce renal glomerular damage in FHH. In these rats creation of ACF resulted in marked bilateral cardiac hypertrophy and alterations of cardiac connexin-43, however, RDN did not modify any of the cardiac parameters. Our present results further support the notion that kidney damage aggravates the HF-related morbidity and mortality. Moreover, it is clear that in the ACF FHH model of combined CKD and HF, RDN does not exhibit any important renoprotective or cardioprotective effects and does not reduce mortality. Key words Chronic kidney disease, Heart failure, Renal denervation, Fawn-hooded hypertensive rats.
- MeSH
- denervace MeSH
- hypertenze * chirurgie MeSH
- kardiorenální syndrom * etiologie patofyziologie MeSH
- krysa rodu Rattus MeSH
- ledviny * inervace MeSH
- modely nemocí na zvířatech MeSH
- srdeční selhání MeSH
- sympatektomie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Myocardial remodelling involves structural and functional changes in the heart, potentially leading to heart failure. The deoxycorticosterone acetate (DOCA)/salt model is a widely used experimental approach to study hypertension-induced cardiac remodelling. It allows to investigate the mechanisms underlying myocardial fibrosis and hypertrophy, which are key contributors to impaired cardiac function. In this study, myocardial remodelling in rat deoxycorticosterone acetate/salt model was examined over a three-week period. The experiment involved 11 male Sprague-Dawley rats, divided into two groups: fibrosis (n=6) and control (n=5). Myocardial remodelling was induced in the fibrosis group through unilateral nephrectomy, deoxyco-rticosterone acetate administration, and increased salt intake. The results revealed significant structural changes, including increased left ventricular wall thickness, myocardial fractional volume, and development of myocardial fibrosis. Despite these changes, left ventricular ejection fraction was preserved and even increased. ECG analysis showed significant prolongation of the PR interval and widening of the QRS complex in the fibrosis group, indicating disrupted atrioventricular and ventricular conduction, likely due to fibrosis and hypertrophy. Correlation analysis suggested a potential relationship between QRS duration and myocardial hypertrophy, although no significant correlations were found among other ECG parameters and structural changes detected by MRI. The study highlights the advantage of the DOCA/salt model in exploring the impact of myocardial remodelling on electrophysiological properties. Notably, this study is among the first to show that early myocardial remodelling in this model is accompanied by distinct electrophysiological changes, suggesting that advanced methods combined with established animal models can open new opportunities for research in this field. Key words Myocardial fibrosis, Remodelling, Animal model, DOCA-salt, Magnetic resonance imaging.
- MeSH
- deoxykortikosteron-21-acetát * MeSH
- elektrokardiografie * MeSH
- fibróza MeSH
- krysa rodu Rattus MeSH
- kuchyňská sůl škodlivé účinky MeSH
- modely nemocí na zvířatech MeSH
- myokard patologie MeSH
- potkani Sprague-Dawley * MeSH
- remodelace komor * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- deoxykortikosteron-21-acetát * MeSH
- kuchyňská sůl MeSH
The global COVID-19 pandemic, caused by SARS-CoV-2, has led to significant morbidity and mortality, with a profound impact on cardiovascular health. This review investigates the mechanisms of SARS-CoV-2's interaction with cardiac tissue, particularly emphasizing the role of the Spike protein and ACE2 receptor in facilitating viral entry and subsequent cardiac complications. We dissect the structural features of the virus, its interactions with host cell receptors, and the resulting pathophysiological changes in the heart. Highlighting SARS-CoV-2's broad organ tropism, especially its effects on cardiomyocytes via ACE2 and TMPRSS2, the review addresses how these interactions exacerbate cardiovascular issues in patients with pre-existing conditions such as diabetes and hypertension. Additionally, we assess both direct and indirect mechanisms of virus-induced cardiac damage, including myocarditis, arrhythmias, and long-term complications such as 'long COVID'. This review underscores the complexity of SARS-CoV-2's impact on the heart, emphasizing the need for ongoing research to fully understand its long-term effects on cardiovascular health. Key words: COVID-19, Heart, ACE2, Spike protein, Cardiomyocytes, Myocarditis, Long COVID.
- MeSH
- angiotensin konvertující enzym 2 * metabolismus MeSH
- COVID-19 * metabolismus MeSH
- glykoprotein S, koronavirus * metabolismus MeSH
- internalizace viru MeSH
- kardiomyocyty metabolismus virologie patologie MeSH
- lidé MeSH
- myokard metabolismus patologie MeSH
- SARS-CoV-2 * patogenita MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- ACE2 protein, human MeSH Prohlížeč
- angiotensin konvertující enzym 2 * MeSH
- glykoprotein S, koronavirus * MeSH
- spike protein, SARS-CoV-2 MeSH Prohlížeč
An important part of the side effects of combined oral contraceptives (COC) usage is its psychological impact, which includes mood changes, anxiousness and depression. The psychological impacts are expected to be caused by physiological fluctuations of sex hormone levels during the menstrual cycle; this cycling is, however, suppressed in COC users. In our study, we assessed the differences in emotional awareness and anxiousness between women long term users of anti-androgenic COC (AA) and women with no COC use in their medical history (C). We also searched for intraindividual differences by comparing the results of both groups for the follicular and luteal phase of their cycle. A total of 45 women aged 18 to 22 participated in this study. The respondents were given our battery of questionnaires at the beginning of their follicular phase - this battery included two State-Trait Anxiety Inventory questionnaires (STAI-I, STAI-II), as well as a Levels of Emotional Awareness Scale (LEAS) test. The respondents were given only STAI-I in their luteal phase. We also analyzed the hormonal profile of our respondents. Our results show a significant difference in the LEAS analysis, implying the possibility of altered emotional awareness in AA group. STAI-I and STAI-II analysis did not yield any significant results, showing that anxiety levels of COC users probably do not differ from the general female population. We therefore discovered lower emotional awareness in COC using women (AA). Key words LEAS, STAI, Combined oral contraceptives, Anxiety, Hormonal profile.
- MeSH
- dospělí MeSH
- emoce * účinky léků MeSH
- kontraceptiva orální hormonální škodlivé účinky MeSH
- kontraceptiva orální kombinovaná škodlivé účinky MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- pilotní projekty MeSH
- průzkumy a dotazníky MeSH
- uvědomování si MeSH
- úzkost * psychologie chemicky indukované MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kontraceptiva orální hormonální MeSH
- kontraceptiva orální kombinovaná MeSH
Arterial compliance (AC) is an important cardiovascular parameter characterizing mechanical properties of arteries. AC is significantly influenced by arterial wall structure and vasomotion, and it markedly influences cardiac load. A new method, based on a two-element Windkessel model, has been recently proposed for estimating AC as the ratio of the time constant T of the diastolic blood pressure decay and peripheral vascular resistance derived from clinically available stroke volume measurements and selected peripheral blood pressure parameters which are less prone to peripheral distortions. The aim of this study was to validate AC estimation using a virtual population generated by in silico model of the systemic arterial tree. In the second part of study, we analysed causal coupling between AC oscillations and variability of its potential determinants - systolic blood pressure and heart rate in healthy young human subjects. The pool of virtual subjects (n=3818) represented an extensive AC distribution. AC was estimated from the peripheral blood pressure curve and by the standard method from the aortic blood pressure curve. The proposed method slightly overestimated AC set in the model but both ACs were strongly correlated (r=0.94, p<0.001). In real data, we observed that AC dynamics was coupled with basic cardiovascular parameters variability independently of the autonomic nervous system state. In silico analysis suggests that AC can be reliably estimated by noninvasive method. The analysis of short-term AC variability together with its determinants could improve our understanding of factors involved in AC dynamics potentially improving assessment of AC changes associated with atherosclerosis process. Key words Arterial compliance, Cardiovascular model, Arterial blood pressure, Causal analysis, Volume-clamp photoplethysmography.
- MeSH
- arterie * fyziologie MeSH
- cévní rezistence fyziologie MeSH
- dospělí MeSH
- krevní tlak * fyziologie MeSH
- lidé MeSH
- mladý dospělý MeSH
- modely kardiovaskulární * MeSH
- počítačová simulace * MeSH
- poddajnost MeSH
- srdeční frekvence fyziologie MeSH
- tuhost cévní stěny fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- validační studie MeSH
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Therefore, understanding the molecular regulatory mechanisms underlying the pathogenesis of DKD is imperative. In this study, we aimed to explore the molecular mechanisms of tubule region endothelial dysfunction in early DKD. Early-stage DKD model was established in 16-week-old female db/db mice for 16 weeks. Body weight, glucose level, and urine albumin-to-creatinine ratio (UACR) were measured. Hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were performed to evaluate pathological lesions. RNA sequencing data of the kidneys and integrated publicly available single-cell and spatial transcriptome datasets were used to investigate the mechanism of endothelial dysfunction. There was a significant increase in body weight (p = 0.001), glucose levels (p=0.0008), and UACR (p=0.006) in db/db mice compared with db/m mice. H&E and PAS staining showed that vacuolar lesions and protein casts of tubules were the major histopathological changes observed in early-stage DKD mice. The apoptotic pathway in endothelial cells was notably activated in DKD, and Thbs1 was identified as the central gene involved in this apoptotic process. Deconvolution of the cell composition in the RNA sequencing data showed a decrease in the proportion of endothelial cells in the DKD mice. Further analysis of the activity and regulatory network of transcription factors showed that Creb1 was activated in both mouse and human early-stage DKD, suggesting that Creb1 activation may be involved in early kidney injury. The endothelial cell apoptotic pathway is activated in DKD, and the proportion of endothelial cells was reduced in the DKD mice, which is significantly associated with Thbs1. Keywords: Diabetic kidney disease, Endothelial dysfunction, RNA sequencing,Thbs1, Creb1.
- MeSH
- apoptóza MeSH
- diabetické nefropatie * patologie metabolismus patofyziologie genetika MeSH
- endoteliální buňky metabolismus patologie MeSH
- ledvinové kanálky patologie metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- progrese nemoci * MeSH
- protein vázající element responzivní pro cyklický AMP metabolismus genetika MeSH
- thrombospondin 1 metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- protein vázající element responzivní pro cyklický AMP MeSH
- thrombospondin 1 MeSH
