BACKGROUND AND PURPOSE: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. METHODS: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). RESULTS: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. CONCLUSIONS: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

• Publikační typ
• časopisecké články MeSH

Ideal cardiovascular health (CVH) is defined for the presence of ideal behavioral and health metrics known to prevent cardiovascular disease (CVD). The association of circulatory phospho- and sphingo-lipids to primary reduction in cardiovascular risk is unclear. Our aim was to determine the association of CVH metrics with the circulating lipid profile of a population-based cohort. Serum sphingolipid and phospholipid species were extracted from 461 patients of the randomly selected prospective Kardiovize study based on Brno, Czech Republic. Lipids species were measured by a hyphenated mass spectrometry technique, and were associated with poor CVH scores, as defined by the American Heart Association. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE) species were significantly lower in ideal and intermediate scores of health dietary metric, blood pressure, total cholesterol and blood fasting glucose compared to poor scores. Current smokers presented higher levels of PC, PE and LPE individual species compared to non-smokers. Ceramide (Cer) d18:1/14:0 was altered in poor blood pressure, total cholesterol and fasting blood glucose metrics. Poor cardiovascular health metric is associated with a specific phospho- and sphingolipid pattern. Circulatory lipid profiling is a potential biomarker to refine cardiovascular health status in primary prevention strategies.

• Publikační typ
• časopisecké články MeSH

• Publikační typ
• časopisecké články MeSH

In contrast to the decreasing burden related to cardiovascular disease (CVD), the burden related to dysglycemia and adiposity complications is increasing in Czechia, and local drivers must be identified. A comprehensive literature review was performed to evaluate biological, behavioral, and environmental drivers of dysglycemia and abnormal adiposity in Czechia. Additionally, the structure of the Czech healthcare system was described. The prevalence of obesity in men and diabetes in both sexes has been increasing over the past 30 years. Possible reasons include the Eastern European eating pattern, high prevalence of physical inactivity and health illiteracy, education, and income-related health inequalities. Despite the advanced healthcare system based on the compulsory insurance model with free-for-service healthcare and a wide range of health-promoting initiatives, more effective strategies to tackle the adiposity/dysglycemia are needed. In conclusion, the disease burden related to dysglycemia and adiposity in Czechia remains high but is not translated into greater CVD. This discordant relationship likely depends more on other factors, such as improvements in dyslipidemia and hypertension control. A reconceptualization of abnormal adiposity and dysglycemia into a more actionable cardiometabolic-based chronic disease model is needed to improve the approach to these conditions. This review can serve as a platform to investigate causal mechanisms and secure effective management of cardiometabolic-based chronic disease.

• MeSH
• adipozita etnologie   MeSH
• běloši statistika a číselné údaje   MeSH
• chronická nemoc epidemiologie   etnologie   MeSH
• diabetes mellitus 2. typu epidemiologie   etnologie   MeSH
• dieta škodlivé účinky   etnologie   MeSH
• disparity zdravotního stavu MeSH
• dospělí MeSH
• dyslipidemie epidemiologie   etnologie   MeSH
• hypertenze epidemiologie   etnologie   MeSH
• kardiometabolické riziko MeSH
• kardiovaskulární nemoci epidemiologie   etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolický syndrom epidemiologie   etnologie   MeSH
• obezita epidemiologie   etnologie   MeSH
• porucha glukózové tolerance epidemiologie   etnologie   MeSH
• prediabetes epidemiologie   etnologie   MeSH
• prevalence MeSH
• sedavý životní styl etnologie   MeSH
• sociální determinanty zdraví etnologie   MeSH
• stravovací zvyklosti etnologie   MeSH
• zdravotní gramotnost MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH

Multidrug resistance (MDR) is a common problem when fighting cancer with chemotherapy. P-glycoprotein (P-gp, or MDR1) is an active pump responsible for the efflux of xenobiotics out of the cell, including anti-cancer drugs. It is a validated target against MDR. No crystal structure of the human P-gp is available to date, and only recently several cryo-EM structures have been solved. In this paper, we present a comprehensive computational approach that includes constructing the full-length three-dimensional structure of the human P-gp and its refinement using molecular dynamics. We assessed its flexibility and conformational diversity, compiling a dynamical ensemble that was used to dock a set of lignan compounds, previously reported as active P-gp inhibitors, and disclose their binding modes. Based on the statistical analysis of the docking results, we selected a system for performing the structure-based virtual screening of new potential P-gp inhibitors. We tested the method on a library of 87 natural flavonoids described in the literature, and 10 of those were experimentally assayed. The results reproduced the theoretical predictions only partially due to various possible factors. However, at least two of the predicted natural flavonoids were demonstrated to be effective P-gp inhibitors. They were able to increase the accumulation of doxorubicin inside the human promyelocytic leukemia HL60/MDR cells overexpressing P-gp and potentiate the antiproliferative activity of this anti-cancer drug.

• Publikační typ
• časopisecké články MeSH

Toll-like receptor 3 (TLR3) is a member of the TLR family, which has been extensively studied for its antiviral function. It is highly expressed in the endosomes of antigen-presenting immune cells and epithelial cells. TLR3 binds specifically double-strand RNAs (dsRNAs), leading to the activation of mainly two downstream pathways: the phosphorylation of IRF3, with subsequent production of type I interferon, and the activation of NF-κB, which drives the production of inflammatory cytokines and chemokines. Several studies have demonstrated TLR3 expression in multiple neoplasia types including breast, prostate, and lung cancer. Most studies were focused on the beneficial role of TLR3 activation in tumor cells, which leads to the production of cytotoxic cytokines and interferons and promotes caspase-dependent apoptosis. Indeed, ligands of this receptor were proposed for the treatment of cancer, also in combination with conventional chemotherapy. In contrast to these findings, recent evidence showed a link between TLR3 and tumor progression, metastasis, and therapy resistance. In the present review, we summarize the current knowledge of the mechanisms through which TLR3 can either lead to tumor regression or promote carcinogenesis as well as the potential of TLR-based therapies in resistant cancer.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Existing data have described benefits and drawbacks of alcohol consumption on cardiovascular diseases (CVD), but no research has evaluated its association with the cardiovascular health (CVH) score proposed by the American Heart Association. Here, we conducted a cross-sectional analysis on the Kardiovize cohort (Brno, Czech Republic), to investigate the relationship between alcohol consumption and CVH. We included 1773 subjects (aged 25-64 years; 44.2% men) with no history of CVD. We compared CVD risk factors, CVH metrics (i.e., BMI, healthy diet, physical activity level, smoking status, blood pressure, fasting glucose, and total cholesterol) and CVH score between and within several drinking categories. We found that the relationship between drinking habits and CVH was related to the amount of alcohol consumed, drinking patterns, and beverage choices. Heavy drinkers were more likely to smoke tobacco, and to report diastolic blood pressure, fasting glucose, triglycerides, and low-density lipoprotein (LDL)-cholesterol at higher level than non-drinkers. Among drinkers, however, people who exclusively drank wine exhibited better CVH than those who exclusively drank beer. Although our findings supported the hypothesis that drinking alcohol was related to the CVH in general, further prospective research is needed to understand whether the assessment of CVH should incorporate information on alcohol consumption.

• MeSH
• dospělí MeSH
• ethanol aplikace a dávkování   MeSH
• kardiovaskulární nemoci chemicky indukované   MeSH
• kouření tabáku MeSH
• krevní glukóza MeSH
• krevní tlak MeSH
• lidé středního věku MeSH
• lidé MeSH
• pití alkoholu škodlivé účinky   MeSH
• pivo MeSH
• rizikové faktory MeSH
• víno MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The main objective of this study was to analyze changes in the antiproliferative effect of vitamin D3, in the form of calcitriol and calcidiol, via its combined application with all-trans retinoic acid (ATRA) in osteosarcoma cell lines. The response to treatment with calcitriol and calcidiol alone was specific for each cell line. Nevertheless, we observed an enhanced effect of combined treatment with ATRA and calcitriol in the majority of the cell lines. Although the levels of respective nuclear receptors did not correlate with the sensitivity of cells to these drugs, vitamin D receptor (VDR) upregulation induced by ATRA was found in cell lines that were the most sensitive to the combined treatment. In addition, all these cell lines showed high endogenous levels of retinoic acid receptor α (RARα). Our study confirmed that the combination of calcitriol and ATRA can achieve enhanced antiproliferative effects in human osteosarcoma cell lines in vitro. Moreover, we provide the first evidence that ATRA is able to upregulate VDR expression in human osteosarcoma cells. According to our results, the endogenous levels of RARα and VDR could be used as a predictor of possible synergy between ATRA and calcitriol in osteosarcoma cells.

• MeSH
• alfa receptor kyseliny retinové metabolismus   MeSH
• kalcifediol aplikace a dávkování   MeSH
• kalcitriol aplikace a dávkování   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• osteosarkom farmakoterapie   metabolismus   MeSH
• protinádorové látky aplikace a dávkování   MeSH
• protokoly protinádorové kombinované chemoterapie MeSH
• receptory kalcitriolu metabolismus   MeSH
• screeningové testy protinádorových léčiv MeSH
• tretinoin aplikace a dávkování   MeSH
• vitaminy aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

A better understanding of the interactions between dietary phenolic compounds and the epigenetics of inflammation may impact pathological conditions and their treatment. Phenolic compounds are well-known for their antioxidant, anti-inflammatory, anti-angiogenic, and anti-cancer properties, with potential benefits in the treatment of various human diseases. Emerging studies bring evidence that nutrition may play an essential role in immune system modulation also by altering gene expression. This review discusses epigenetic mechanisms such as DNA methylation, post-translational histone modification, and non-coding microRNA activity that regulate the gene expression of molecules involved in inflammatory processes. Special attention is paid to the molecular basis of NF-κB modulation by dietary phenolic compounds. The regulation of histone acetyltransferase and histone deacetylase activity, which all influence NF-κB signaling, seems to be a crucial mechanism of the epigenetic control of inflammation by phenolic compounds. Moreover, chronic inflammatory processes are reported to be closely connected to the major stages of carcinogenesis and other non-communicable diseases. Therefore, dietary phenolic compounds-targeted epigenetics is becoming an attractive approach for disease prevention and intervention.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Mesenchymal stem cells (MSCs) have become a promising tool in cellular therapy for restoring immune system haemostasis; however, the success of clinical trials has been impaired by the lack of standardized manufacturing processes. This study aims to determine the suitability of source tissues and culture media for the production of MSC-based advanced therapy medicinal products (ATMPs) and to define parameters to extend the set of release criteria. MSCs were isolated from umbilical cord (UC), bone marrow and lipoaspirate and expanded in three different culture media. MSC phenotype, proliferation capacity and immunosuppressive parameters were evaluated in normal MSCs compared to primed MSCs treated with cytokines mimicking an inflammatory environment. Compared to bone marrow and lipoaspirate, UC-derived MSCs (UC-MSCs) showed the highest proliferative capacity, which was further enhanced by media supplemented with bFGF, while the cells maintained their immunosuppressive characteristics. Moreover, UC-MSCs expanded in the bFGF-enriched medium were the least sensitive to undesirable priming-induced changes in the MSC phenotype. Surface markers and secreted factors were identified to reflect the cell response to inflammatory priming and to be variable among MSCs from different source tissues. This study demonstrates that UC is a favorable cell source for manufacturing MSC-based ATMPs for immunosuppressive applications. UC-MSCs are able to use the bFGF-enriched medium for higher cell yields without the impairment of immunosuppressive parameters and undesirable phenotype changes after inflammatory preconditioning of MSCs before transplantation. Additionally, immunosuppressive parameters were identified to help finding predictors of clinically efficient MSCs in the following clinical trials.

• MeSH
• buněčná diferenciace účinky léků   imunologie   MeSH
• fibroblastový růstový faktor 2 imunologie   farmakologie   MeSH
• imunosupresivní léčba * MeSH
• lidé MeSH
• mezenchymální kmenové buňky cytologie   imunologie   MeSH
• proliferace buněk účinky léků   MeSH
• pupečník cytologie   imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH