BACKGROUND: This cross-sectional study investigated the relationship between genetic variations in monocarboxylate transporter genes and blood lactate production and removal after high-intensity efforts in humans. The study was conducted to explore how genetic variations in the MCT1, MCT2, and MCT4 genes influenced lactate dynamics and to advance the field of sports genetics by pinpointing critical genetic markers that can enhance athletic performance and recovery. METHODS: 337 male athletes from Poland and the Czech Republic underwent two intermittent all-out Wingate tests. Before the tests, DNA samples were taken from each participant, and SNP (single nucleotide polymorphism) analysis was carried out. Two intermittent all-out tests were implemented, and lactate concentrations were assessed before and after these tests. RESULTS: Sprinters more frequently exhibited the haplotype TAC in the MCT2 gene, which was associated with an increase in the difference between maximum lactate and final lactate concentration. Additionally, this haplotype was linked to higher maximum lactate concentration and was more frequently observed in sprinters. The genotypic interactions AG/T- and GGxT- (MCT1 rs3789592 x MCT4 rs11323780), TTxTT (MCT1 rs12028967 x MCT2 rs3763979), and MCT1 rs7556664 x MCT4 rs11323780 were all associated with an increase in the difference between maximum lactate concentration and final lactate concentration. Conversely, the AGxGG (MCT1 rs3789592 x MCT2 rs995343) interaction was linked to a decrease in this difference. The relationship between maximum lactate concentration and genotypic interactions can be observed as follows: when ATxTT (MCT2 rs3763980 x MCT4 rs11323780) or CTxCT (MCT1 rs10857983 x MCT2 rs3763979) genotypic combinations are present, it leads to a decrease in maximum lactate concentration. Similarly, the combination of CTxCT (MCT1 rs4301628 x MCT2 rs3763979), CT x TT (MCT1 rs4301628 x MCT4 rs11323780), and CTxTT (MCT1 rs4301628 x MCT2 rs3763979) results in decreased maximum lactate concentration. CONCLUSIONS: The TAC haplotype (rs3763980, rs995343, rs3763979) in the MCT2 gene is associated with altered lactate clearance in sprinters, potentially affecting performance and recovery by elevating post-exercise lactate concentrations. While MCT4 rs11323780 is also identified as a significant variant in lactate metabolism, suggesting its role as a biomarker for sprinting performance, further investigation is necessary to clarify underlying mechanisms and consider additional factors. Based on elite male athletes from Poland and the Czech Republic, the study may not generalize to all sprinters or diverse athletic populations. Although genetic variants show promise as biomarkers for sprinting success, athletic performance is influenced by a complex interplay of genetics, environment, and training extending beyond MCT genes.

• Klíčová slova
• Athletic training, Genetic predisposition, Genetic variants, Genotype, Haplotype, Lactate kinetics, Sprint,
• MeSH
• dospělí MeSH
• genotyp MeSH
• haplotypy * MeSH
• jednonukleotidový polymorfismus * MeSH
• kinetika MeSH
• kyselina mléčná * krev   metabolismus   MeSH
• lidé MeSH
• mladý dospělý MeSH
• přenašeče monokarboxylových kyselin * genetika   metabolismus   MeSH
• průřezové studie MeSH
• sportovci MeSH
• svalové proteiny * genetika   metabolismus   MeSH
• symportéry * genetika   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kyselina mléčná * MeSH
• monocarboxylate transport protein 1 MeSH Prohlížeč
• přenašeče monokarboxylových kyselin * MeSH
• SLC16A2 protein, human MeSH Prohlížeč
• SLC16A4 protein, human MeSH Prohlížeč
• svalové proteiny * MeSH
• symportéry * MeSH

Membrane transporters have a crucial role in compounds' brain drug delivery. They allow not only the penetration of a wide variety of different compounds to cross the endothelial cells of the blood-brain barrier (BBB), but also the accumulation of them into the brain parenchymal cells. Solute carriers (SLCs), with nearly 500 family members, are the largest group of membrane transporters. Unfortunately, not all SLCs are fully characterized and used in rational drug design. However, if the structural features for transporter interactions (binding and translocation) are known, a prodrug approach can be utilized to temporarily change the pharmacokinetics and brain delivery properties of almost any compound. In this review, main transporter subtypes that are participating in brain drug disposition or have been used to improve brain drug delivery across the BBB via the prodrug approach, are introduced. Moreover, the ability of selected transporters to be utilized in intrabrain drug delivery is discussed. Thus, this comprehensive review will give insights into the methods, such as computational drug design, that should be utilized more effectively to understand the detailed transport mechanisms. Moreover, factors, such as transporter expression modulation pathways in diseases that should be taken into account in rational (pro)drug development, are considered to achieve successful clinical applications in the future.

• Klíčová slova
• blood–brain barrier (BBB), brain drug delivery, prodrugs, solute carriers (SLCs),
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Postbiotics are health-promoting microbial metabolites delivered as a functional food or a food supplement. They either directly influence signaling pathways of the body or indirectly manipulate metabolism and the composition of intestinal microflora. Cancer is the second leading cause of death worldwide and even though the prognosis of patients is improving, it is still poor in the substantial part of the cases. The preventable nature of cancer and the importance of a complex multi-level approach in anticancer therapy motivate the search for novel avenues of establishing the anticancer environment in the human body. This review summarizes the principal findings demonstrating the usefulness of both natural and synthetic sources of postbotics in the prevention and therapy of cancer. Specifically, the effects of crude cell-free supernatants, the short-chain fatty acid butyrate, lactic acid, hydrogen sulfide, and β-glucans are described. Contradictory roles of postbiotics in healthy and tumor tissues are highlighted. In conclusion, the application of postbiotics is an efficient complementary strategy to combat cancer.

• Klíčová slova
• GPR81, SCFA, colorectal cancer, functional food, intestinal metabolome, microbiome,
• MeSH
• beta-glukany farmakologie   MeSH
• butyráty farmakologie   MeSH
• kyselina mléčná farmakologie   MeSH
• kyseliny mastné těkavé metabolismus   farmakologie   MeSH
• lidé MeSH
• metabolom MeSH
• nádory dietoterapie   metabolismus   MeSH
• potravní doplňky mikrobiologie   MeSH
• prebiotika mikrobiologie   MeSH
• probiotika metabolismus   farmakologie   MeSH
• střevní mikroflóra účinky léků   MeSH
• sulfan farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• beta-glukany MeSH
• butyráty MeSH
• kyselina mléčná MeSH
• kyseliny mastné těkavé MeSH
• prebiotika MeSH
• sulfan MeSH

BACKGROUND: Morbidity and mortality from COVID-19 caused by novel coronavirus SARS-CoV-2 is accelerating worldwide, and novel clinical presentations of COVID-19 are often reported. The range of human cells and tissues targeted by SARS-CoV-2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS-CoV-2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID-19. METHODS: We performed RNA sequencing and explored available RNA-Seq databases to study gene expression and co-expression of ACE2, CD147 (BSG), and CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4+ and CD8+ T cells, B cells, and plasmablasts. We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID-19 risk factor status. RESULTS: ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA andPPIB), CD26 (DPP4), and related molecules were expressed in both epithelium and in immune cells. We also observed a distinct age-related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2- and CD147-related genes in the bronchial biopsy, BAL, or blood. Additionally, CD147-related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of CD147-related genes in the lesional skin of patients with atopic dermatitis. CONCLUSIONS: Our data suggest different receptor repertoire potentially involved in the SARS-CoV-2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related to age, gender, obesity and smoking, as well as with the disease status, might contribute to COVID-19 morbidity and severity patterns.

• Klíčová slova
• COPD, COVID-19, COVID-19 children, SARS receptor, asthma, hypertension, obesity,
• MeSH
• angiotensin-konvertující enzym 2 genetika   imunologie   MeSH
• basigin genetika   imunologie   MeSH
• bronchiální astma epidemiologie   genetika   imunologie   MeSH
• chronická nemoc epidemiologie   MeSH
• chronická obstrukční plicní nemoc epidemiologie   genetika   imunologie   MeSH
• COVID-19 epidemiologie   genetika   imunologie   MeSH
• dipeptidylpeptidasa 4 genetika   imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• exprese genu genetika   MeSH
• hypertenze epidemiologie   genetika   imunologie   MeSH
• kojenec MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• obezita epidemiologie   genetika   imunologie   MeSH
• předškolní dítě MeSH
• přirozená imunita imunologie   MeSH
• rizikové faktory MeSH
• SARS-CoV-2 genetika   imunologie   MeSH
• senioři MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ACE2 protein, human MeSH Prohlížeč
• angiotensin-konvertující enzym 2 MeSH
• basigin MeSH
• BSG protein, human MeSH Prohlížeč
• dipeptidylpeptidasa 4 MeSH
• DPP4 protein, human MeSH Prohlížeč

The tumor microenvironment (TME) is comprised of many different cell populations, such as cancer-associated fibroblasts and various infiltrating immune cells, and non-cell components of extracellular matrix. These crucial parts of the surrounding stroma can function as both positive and negative regulators of all hallmarks of cancer development, including evasion of apoptosis, induction of angiogenesis, deregulation of the energy metabolism, resistance to the immune detection and destruction, and activation of invasion and metastasis. This review represents a summary of recent studies focusing on describing these effects of microenvironment on initiation and progression of the head and neck squamous cell carcinoma, focusing on oral squamous cell carcinoma, since it is becoming clear that an investigation of differences in stromal composition of the head and neck squamous cell carcinoma microenvironment and their impact on cancer development and progression may help better understand the mechanisms behind different responses to therapy and help define possible targets for clinical intervention.

• Klíčová slova
• Epithelial-mesenchymal transition, Head and neck cancer, Tumor metabolism, Tumor microenvironment,
• MeSH
• lidé MeSH
• nádorové mikroprostředí * MeSH
• nádory hlavy a krku patologie   MeSH
• progrese nemoci MeSH
• spinocelulární karcinom patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• systematický přehled MeSH