- MeSH
- bronchopulmonální dysplazie diagnóza komplikace MeSH
- farmakoterapie klasifikace MeSH
- kardiovaskulární nemoci diagnóza klasifikace patofyziologie MeSH
- kazuistiky jako téma MeSH
- lidé MeSH
- novorozenci extrémně nezralí MeSH
- novorozenec MeSH
- růstová retardace plodu diagnóza MeSH
- šok * diagnóza etiologie farmakoterapie klasifikace MeSH
- terlipresin * farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- přehledy MeSH
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
High-intensity interval training (HIIT) is considered an effective therapy strategy for improving chronic pain associated with osteoarthritis (OA). Perineuronal nets (PNNs) are specialized extracellular matrix structures in the cerebral cortex that play a crucial role in regulating chronic pain. However, little is unknown whether HIIT could alleviate OA pain sensitization by reducing PNN levels. This study aimed to determine whether HIIT could reduce sensitivity of the affected joint(s) to pain in a chronic pain model in rats with OA. A rat model of interest was induced by intra-articular injection of monosodium iodoacetate (MIA) into the right knee. Thereafter, the mechanical withdrawal thresholds (MWTs) and PNN levels in the contralateral medial prefrontal cortex (mPFC) were measured in rats in the presence or absence of HIIT alone or in combination with injection of chondroitinase-ABC (ChABC) into the contralateral mPFC (inducing the degradation of PNNs), respectively. Results indicated that rats with OA exhibited significant reductions in MWTs, but a significant increase in the PNN levels; that HIIT reversed changes in MWTs and PNN levels in rats with OA, and that pretreatment of ChABC abolished effects of HIIT on MWTs, with PNN levels not changed. We concluded that pain sensitization in rats with OA may correlate with an increase in PNN levels in the mPFC, and that HIIT may increases OA pain-sensitive threshold by reduction of the PNN levels in the mPFC. Keywords: Osteoarthritis, Chronic pain, Pain sensitization, High-intensity interval training, Perineuronal nets.
- MeSH
- chronická bolest terapie patofyziologie MeSH
- extracelulární matrix metabolismus MeSH
- kondiční příprava zvířat fyziologie metody MeSH
- krysa rodu rattus MeSH
- osteoartróza * terapie MeSH
- potkani Sprague-Dawley * MeSH
- práh bolesti * MeSH
- prefrontální mozková kůra * metabolismus MeSH
- vysoce intenzivní intervalový trénink * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Hemolysis and eryptosis contribute to anemia encountered in patients undergoing chemotherapy. Eicosapentaenoic acid (EPA) is an omega-3 dietary fatty acid that has anticancer potential by inducing apoptosis in cancer cells, but its effect on the physiology and lifespan of red blood cells (RBCs) is understudied. Human RBCs were exposed to anticancer concentrations of EPA (10-100 ?M) for 24 h at 37 °C. Acetylcholinesterase (AChE) activity and hemolysis were measured by colorimetric assays whereas annexin-V-FITC and forward scatter (FSC) were employed to identify eryptotic cells. Oxidative stress was assessed by H2DCFDA and intracellular Ca2+ was measured by Fluo4/AM. EPA significantly increased hemolysis and K+ leakage, and LDH and AST activities in the supernatants in a concentration-dependent manner. EPA also significantly increased annexin-V-FITC-positive cells and Fluo4 fluorescence and decreased FSC and AChE activity. A significant reduction in the hemolytic activity of EPA was noted in the presence extracellular isosmotic urea, 125 mM KCl, and polyethylene glycol 8000 (PEG 8000), but not sucrose. In conclusion, EPA stimulates hemolysis and eryptosis through Ca2+ buildup and AChE inhibition. Urea, blocking KCl efflux, and PEG 8000 alleviate the hemolytic activity of EPA. The anticancer potential of EPA may be optimized using Ca2+ channel blockers and chelators to minimize its toxicity to off-target tissue. Keywords: EPA, Eryptosis, Hemolysis, Calcium, Anticancer.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- cholinesterasové inhibitory * farmakologie MeSH
- eryptóza účinky léků MeSH
- erytrocytární membrána * účinky léků metabolismus MeSH
- erytrocyty účinky léků metabolismus MeSH
- fosfatidylseriny * metabolismus MeSH
- hemolýza * účinky léků MeSH
- kyselina eikosapentaenová * farmakologie MeSH
- lidé MeSH
- vápník metabolismus MeSH
- vápníková signalizace * účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
To evaluate vitamin D levels in children treated with fractures during the healing period. A four-year prospective study, including healthy children treated with diaphyseal fracture of femur or forearm bones. Vitamin D levels were examined four times: at the time of the injury and then one, three, and five months after the injury, together with P1NP, ALP, GGT, and parathormone. In the beginning, patients were blindly divided into two groups, one supplemented with vitamin D3 for the entire follow-up period, the other non-supplemented. Altogether, 107 children underwent examination at the time of their injuries. Of these, 63 were included in the study and examined for the entire follow-up period - 36 supplemented, 27 non-supplemented. At the time of injury, 42 % had a deficit of vitamin D, 36.5 % had insufficiency, only 21.5 % had normal levels. In the children supplemented with cholecalciferol, vitamin D levels increased statistically significantly during the follow-up period (already after 1 month), in contrast with non-supplemented patients, where they did not. When we divided patients according to the initial vitamin D levels (deficit/insufficiency/normal levels) or fracture type (femur/forearm), we also observed significantly better results in supplemented groups. We observed a high prevalence of vitamin D deficit or insufficiency in healthy children at the time of their injuries. Patients supplemented with vitamin D3 had normal levels already after one month and this persisted throughout the follow-up period, in contrast with non-supplemented patients. Therefore, we recommend vitamin D testing and administration for children treated for fractures. Keywords: Vitamin D, Pediatric fracture, Children, Vitamin D supplementation.
- MeSH
- cholekalciferol krev terapeutické užití MeSH
- dítě MeSH
- fraktury femuru krev epidemiologie MeSH
- hojení fraktur * účinky léků MeSH
- lidé MeSH
- mladiství MeSH
- následné studie MeSH
- nedostatek vitaminu D * krev epidemiologie farmakoterapie MeSH
- potravní doplňky MeSH
- předškolní dítě MeSH
- prospektivní studie MeSH
- vitamin D * krev terapeutické užití MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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
Gestational diabetes mellitus (GDM) is a common complication of pregnancy in which women without previously diagnosed diabetes develop chronic hyperglycemia during pregnancy. It is associated with a number of maternal and fetal/neonatal complications. The role of the adipokines retinol binding protein-4, resistin and nesfatin-1 in the development of GDM is relatively poorly understood, but their role in glucose metabolism is suspected and their use as early markers to predict the development of GDM is being sought. The aim of study was to determine the correlation between the levels of selected adipokines (retinol binding protein-4, resistin, nesfatin-1) in women with gestational diabetes mellitus (GDM) and healthy pregnant women and to compare their levels with other clinical and biochemical parameters. Patients with GDM had significantly higher BMI (28.4±4.5 vs. 24.6±4 kg/m2), total cholesterol (6±1.3 vs. 5.3±1.4 mmol/l) and triacylglycerols (1.9±0.8 vs. 1.4±0.7 mmol/l) than women in the control group. RBP4 confirms the significant difference between the groups, it is higher in the control group of healthy pregnant women. The adipokines resistin and nesfatin-1 show no differences between the control and GDM groups, but their ratios with BMI, cholesterol and triacylglycerols, resistin shows elevated levels in the control group. In women with GDM, RBP4 was significantly positively correlated with C-peptide and negatively correlated with total, LDL, and non-HDL cholesterol. Resistin was also negatively correlated with total, LDL, HDL, and non-HDL cholesterol. Nesfatin-1 was only moderately positively correlated with glycated hemoglobin (HbA1C) and fasting glycemia. There is ambiguity in the results of previous studies on the levels of the investigated adipokines in pregnant women with GDM and the interpretation depends on many factors. Keywords: Gestational diabetes, Adipokines, Retinol-binding protein 4, Resistin, Nesfatin-1.
- MeSH
- adipokiny krev MeSH
- biologické markery * krev MeSH
- DNA vazebné proteiny krev MeSH
- dospělí MeSH
- gestační diabetes * krev diagnóza MeSH
- krevní glukóza metabolismus MeSH
- lidé MeSH
- nukleobindiny * krev MeSH
- plazmatické proteiny vázající retinol * metabolismus analýza MeSH
- proteiny nervové tkáně krev MeSH
- proteiny vázající vápník krev MeSH
- resistin * krev MeSH
- studie případů a kontrol MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: patients with type 2 diabetes (T2DM) and obesity are generally known to have increased risk of various types of cancer, though studies addressing associations between T2DM/obesity and thyroid cancer are inconclusive. The aim of our study was to evaluate the risk of thyroid cancer focusing on diabetic patients under conditions of euthyroid status. A retrospective study in 184 patients was performed. Three cohorts were established according to tumor histology: malignant (M), benign (B) and low-risk carcinoma (MB). Fisher's exact test and Kruskal-Wallis one-way ANOVA of ranks were used for statistical analysis. The M (39.1 %), B (57.6 %) and MB (3.3 %) cohorts had comparable age (p=0.4), BMI (p=0.452), glycaemia (p=0.834), Hb1AC (p=0.157) and HOMA-IR (p=0.235). T2DM patients had larger thyroid gland volumes (28.8 vs 17.6 mL;p=0.001) compared to the cohort with normal glucose tolerance. Compared to women, men had more frequently present distal metastases (p=0.017), minimally invasive disease (p=0.027), more advanced staging (p=0.01) and positive pathogenic mutations in the TERT gene (p=0.009);these results were also significant for the diabetic male cohort (p=0.026). Type 2 diabetes and obesity are not risk factors for thyroid cancer, but a subgroup of males seems to have thyroid cancers of poorer prognosis. In general, diabetic patients with insulin resistance and hyperinsulinemia are also prone to have a goiter. KEY WORDS: Thyroid cancer, Type 2 diabetes, Obesity, Thyroid nodule, Insulin resistance.
- MeSH
- diabetes mellitus 2. typu * epidemiologie komplikace MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory štítné žlázy * epidemiologie patologie MeSH
- obezita * komplikace epidemiologie MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články 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 cAMP responzivní element metabolismus genetika MeSH
- thrombospondin 1 metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Acute kidney injury (AKI) is a consequence of several diseases that can severely damage kidney function. It is a frequent complication of hospitalization and very common in critically ill patients because of other serious illnesses, such as septic conditions. New diagnostic options, including renal biomarkers, may help in early diagnosis. Our study included 46 patients, 31 with AKI and 15 without AKI on admission. Blood samples were collected on the first, fourth, and seventh days of treatment, and in addition to basic biochemical parameters, neutrophil gelatinase-associated lipocalin (NGAL) levels in serum were also examined. Data from the first and seventh day were used for statistical analysis. On the first follow-up day, NGAL values were categorized according to an optimal cut-off value of 290 μg/l. We demonstrated that if NGAL levels were higher, the risk of renal injury increased approximately 16 times. Other results showed that NGAL levels were moderately correlated with serum creatinine (r = 0.613, p < 0.0001), procalcitonin (PCT) (r = 0.627, p < 0.0001), and AKI stage (r = 0.589, p < 0.0001). There was also a significant positive correlation with SOFA (Sequential Organ Failure Assessment) score (r = 0.395, p = 0.007). Early diagnosis and treatment are crucial in managing AKI and preventing further kidney damage. NGAL levels can increase within a few hours after injury, making it a useful tool for early AKI detection and diagnosis. Key words: Acute kidney injury, Biomarker, NGAL, Sepsis.
- MeSH
- akutní poškození ledvin * krev diagnóza MeSH
- biologické markery * krev MeSH
- dospělí MeSH
- kritický stav * MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipokalin-2 * krev MeSH
- prediktivní hodnota testů MeSH
- senioři MeSH
- sepse * krev diagnóza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH