Studie zaměřené na hledání příčin obezity ukazují v posledních letech stále častěji na možnou roli nadměrného příjmu sodíku, i když sám o sobě nemá žádnou energetickou hodnotu. Tato souvislost může být vysvětlena z mnoha úhlů pohledu. Nadměrně slané potraviny mají obvykle vysokou energetickou hodnotu. Jako nejčastěji diskutovaná příčina bývá dále uváděna zvýšená konzumace slazených nápojů po požití stravy s nadměrným obsahem soli. Významnou roli může hrát také vznik závislosti na konzumaci slaných pokrmů, což má za následek jejich zvýšený příjem. Nadměrný příjem energie a sodíku byl zjištěn rovněž při konzumaci ultrazpracovaných potravin, což může být zdůvodněno typicky nižším obsahem bílkovin vzhledem k jejich vysoké energetické denzitě. Kromě toho byla prokázána souvislost vysokého příjmu sodíku a obezity nezávisle na energetickém příjmu. Mechanismus příčiny této souvislosti však nebyl doposud objasněn. Snížení množství soli ve stravě může tedy i pomyslnou oklikou výrazně přispět k účinnosti dietní intervence při prevenci a léčbě obezity.

In recent years, studies aimed at finding the causes of obesity have increasingly pointed to the possible role of excessive sodium intake, even though it has no energy value on its own. This association can be explained from many aspects. Excessively salty foods are usually high in energy. Increased consumption of sweetened beverages after consuming a diet with high in salt is also the most commonly discussed cause. An addiction to salty foods, which leads to their increased intake, may also play an important role. Excessive energy and sodium intake was also found with the consumption of ultra-processed foods, which may be due to their typically lower protein content compared to their high energy density. In addition, high sodium intake has been linked to obesity independently of energy intake. However, the mechanism of the cause of this association is still unclear. Reducing the amount of salt in the diet can therefore make a significant contribution to the effectiveness of dietary intervention in the prevention and treatment of obesity.

• MeSH
• kuchyňská sůl škodlivé účinky   MeSH
• lidé MeSH
• obezita * etiologie   MeSH
• průmyslově zpracované potraviny škodlivé účinky   MeSH
• sodík * škodlivé účinky   MeSH
• strava, jídlo, výživa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Chloride Intracellular Channel (CLIC) family members uniquely transition between soluble and membrane-associated conformations. Despite decades of extensive functional and structural studies, CLICs' function as ion channels remains debated, rendering our understanding of their physiological role incomplete. Here, we expose the function of CLIC5 as a fusogen. We demonstrate that purified CLIC5 directly interacts with the membrane and induces fusion, as reflected by increased liposomal diameter and lipid and content mixing between liposomes. Moreover, we show that this activity is facilitated by acidic pH, a known trigger for CLICs' transition to a membrane-associated conformation, and that increased exposure of the hydrophobic inter-domain interface is crucial for this process. Finally, mutation of a conserved hydrophobic interfacial residue diminishes the fusogenic activity of CLIC5 in vitro and impairs excretory canal extension in C. elegans in vivo. Together, our results unravel the long-sought physiological role of these enigmatic proteins.

• MeSH
• Caenorhabditis elegans * genetika   metabolismus   MeSH
• chloridové kanály metabolismus   MeSH
• chloridy * metabolismus   MeSH
• liposomy MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Cystická fibróza (CF) je autozomálne recesívne genetické ochorenie, ktoré je spôso bené genetickou mutáciou génu pre CFTR (Cystic Fibrosis Transmembrane Conduc tance Regulator), ktorý kóduje proteín – CF transmembránový regulátor vodivosti zabezpečujúci okrem iného aj pohyb chloridových iónov cez bunkovú membránu. Klinický obraz ochorenia je charakterizovaný chronickým zápalom bronchopulmo nálneho systému, pankreatickou insuficienciou a zvýšeným obsahom solí v pote. Cieľom práce bolo zistiť prínos inovatívnej kombinovanej terapie modulátormi CFTR proteínu ivakaftorom/tezakaftorom/elexafaktorom (Kaftrio) v kombinácii s ivakaf torom (Kalydeco) a ivakaftorom/lumakaftorom (Orkambi). Výsledky boli získané prostredníctvom dotazníka, ktorý vyplnilo 26 responden tov s CF užívajúcich tieto modulátory CFTR proteínu. Prieskumu sa zúčastnilo 20 žien a 6 mužov a priemerný vek respondentov bol 27,5 roka. Väčšina pacientov (92 %) bola nastavená na kombináciu ivakaftor/tezakaftor/elexafaktor v kombinácii s ivakaftorom, a to 24 mesiacov a aj 36 mesiacov. Dvaja pacienti (8 %) užívali ivakaf tor/lumakaftor 24 mesiacov a 36 mesiacov. Účinnosť inovatívnej terapie CF bola vyhodnotená hlavne prostredníctvom sledovania FEV1 (exspiračný objem vzduchu za jednu sekundu), chloridov v pote a hmotnosti pacientov, ktorých hodnoty boli zlepšené takmer u všetkých pacientov v porovnaní s obdobím pred indikovanou inovatívnou terapiou. To poukazuje na zmenu a zlepšenie funkcie dýchacích ciest. Z výsledkov možno potvrdiť, že inovatívna terapia modulátormi CFTR proteínu pre pacientov s CF významne zlepšila kvalitu života pacientov.

Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by a genetic mutation of the gene for CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), which encodes a protein - CF transmembrane conductance regulator ensuring, among other things, the movement of chloride ions through the cell membrane. The clinical picture of the disease is characterized by chronic inflammation of the bronchopulmonary system, pancreatic insufficiency and increased salt content in sweat. The aim of the work was to determine the benefit of innovative combined therapy with CFTR protein modulators ivacaftor/tezacaftor/elexafactor (Kaftrio) in combination with ivacaftor (Kalydeco) and ivacaftor/lumakaftor (Orkambi). The results were obtained through a questionnaire filled out by 26 respondents with CF taking these CFTR protein modulators. 20 women and 6 men took part in the survey, and the average age of the respondents was 27.5 years. The majority of patients (92 %) were assigned to the combination of ivacaftor/tezacaftor/elexafactor in combination with ivacaftor for 24 months and 36 months. Two patients (8 %) took ivacaftor/lumacaftor for 24 months and 36 months. The effectiveness of the innovative CF therapy was evaluated mainly by monitoring the values of FEV1 (expiratory volume of air in one second), sweat chloride and weight of the patients, whose values were improved in almost all patients compared to the period before the indicated innovative therapy. This indicates a change and improvement in airway function. From the results, it can be confirmed that the innovative therapy with CFTR protein modulators for CF patients significantly improved the patients' quality of life.

An acidic environment and hypoxia within the tumour are hallmarks of cancer that contribute to cell resistance to therapy. Deregulation of the PI3K/Akt pathway is common in colon cancer. Numerous Akt-targeted therapies are being developed, the activity of Akt-inhibitors is, however, strongly pH-dependent. Combination therapy thus represents an opportunity to increase their efficacy. In this study, the cytotoxicity of the Akt inhibitor perifosine and the Bcl-2/Bcl-xL inhibitor ABT-737 was tested in colon cancer HT-29 and HCT-116 cells cultured in monolayer or in the form of spheroids. The efficacy of single drugs and their combination was analysed in different tumour-specific environments including acidosis and hypoxia using a series of viability assays. Changes in protein content and distribution were determined by immunoblotting and a "peeling analysis" of immunohistochemical signals. While the cytotoxicity of single agents was influenced by the tumour-specific microenvironment, perifosine and ABT-737 in combination synergistically induced apoptosis in cells cultured in both 2D and 3D independently on pH and oxygen level. Thus, the combined therapy of perifosine and ABT-737 could be considered as a potential treatment strategy for colon cancer.

• MeSH
• apoptóza MeSH
• fosfatidylinositol-3-kinasy MeSH
• fosforylcholin * analogy a deriváty   farmakologie   MeSH
• inhibitory proteinkinas farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie účinky léků   MeSH
• nádorové mikroprostředí MeSH
• nádory tračníku * farmakoterapie   MeSH
• protinádorové látky * farmakologie   MeSH
• protoonkogenní proteiny c-akt metabolismus   MeSH
• synergismus léků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is associated with abnormalities of liver lipid metabolism. On the contrary, a diet enriched with n-3 polyunsaturated fatty acids (n-3-PUFAs) has been reported to ameliorate the progression of NAFLD. The aim of our study was to investigate the impact of dietary n-3-PUFA enrichment on the development of NAFLD and liver lipidome. Mice were fed for 6 weeks either a high-fat methionine choline-deficient diet (MCD) or standard chow with or without n-3-PUFAs. Liver histology, serum biochemistry, detailed plasma and liver lipidomic analyses, and genome-wide transcriptome analysis were performed. Mice fed an MCD developed histopathological changes characteristic of NAFLD, and these changes were ameliorated with n-3-PUFAs. Simultaneously, n-3-PUFAs decreased serum triacylglycerol and cholesterol concentrations as well as ALT and AST activities. N-3-PUFAs decreased serum concentrations of saturated and monounsaturated free fatty acids (FAs), while increasing serum concentrations of long-chain PUFAs. Furthermore, in the liver, the MCD significantly increased the hepatic triacylglycerol content, while the administration of n-3-PUFAs eliminated this effect. Administration of n-3-PUFAs led to significant beneficial differences in gene expression within biosynthetic pathways of cholesterol, FAs, and pro-inflammatory cytokines (IL-1 and TNF-α). To conclude, n-3-PUFA supplementation appears to represent a promising nutraceutical approach for the restoration of abnormalities in liver lipid metabolism and the prevention and treatment of NAFLD.

• MeSH
• cholesterol metabolismus   MeSH
• cholin metabolismus   MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• játra metabolismus   MeSH
• kyseliny mastné neesterifikované metabolismus   MeSH
• methionin metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nealkoholová steatóza jater * etiologie   genetika   MeSH
• nenasycené mastné kyseliny metabolismus   MeSH
• omega-3 mastné kyseliny * farmakologie   terapeutické užití   metabolismus   MeSH
• Racemethionin metabolismus   farmakologie   MeSH
• triglyceridy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Farrerol (FA) is a traditional Chinese herbal medicine known for its anti-inflammatory and anti-oxidative properties in various diseases. Ferroptosis is an iron-dependent oxidative stress-induced cell death. It is characterized by lipid peroxidation and glutathione depletion and is involved in neuronal injury. However, the role of FA in inhibiting ferroptosis in hypoxic-ischemic encephalopathy (HIE) and its underlying mechanisms are not yet completely elucidated. This study aimed to investigate whether FA could mediate ferroptosis and explore its function and molecular mechanism in HIE. A neonatal rat model of HIE was used, and rats were treated with FA, ML385 (a specific inhibitor of nuclear factor erythroid 2-related factor 2 [Nrf2]), or a combination of both. Neurological deficits, infarction volume, brain water content, pathological changes, and iron ion accumulation in the brain tissues were measured using the Zea-Longa scoring system and triphenyl tetrazolium chloride (TTC), hematoxylin-eosin (HE), and Perls' staining. The expression levels of GSH-Px, MDA, SOD, and ROS in brain tissues were also evaluated. Western blot analysis was performed to analyze the expression of the Nrf2 pathway and ferroptosis-related proteins. The results showed that FA administration significantly reduced neuronal damage, infarct volume, cerebral edema, and iron ion accumulation and inhibited MDA and ROS levels while promoting GSH-Px and SOD levels. FA also increased the expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), Nrf2, and HO-1. Moreover, the combination of ML385 and FA in HIE abolished the FA protective effects. Therefore, the study concludes that FA exerts a neuroprotective effect after HIE by inhibiting oxidative stress and ferroptosis via the Nrf2 signaling pathway.

• MeSH
• faktor 2 související s NF-E2 MeSH
• ferroptóza * MeSH
• glutathion MeSH
• krysa rodu rattus MeSH
• mozková hypoxie a ischemie * farmakoterapie   MeSH
• novorozená zvířata MeSH
• reaktivní formy kyslíku MeSH
• superoxiddismutasa MeSH
• železo MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The long slender bloodstream form Trypanosoma brucei maintains its essential mitochondrial membrane potential (ΔΨm) through the proton-pumping activity of the FoF1-ATP synthase operating in the reverse mode. The ATP that drives this hydrolytic reaction has long been thought to be generated by glycolysis and imported from the cytosol via an ATP/ADP carrier (AAC). Indeed, we demonstrate that AAC is the only carrier that can import ATP into the mitochondrial matrix to power the hydrolytic activity of the FoF1-ATP synthase. However, contrary to expectations, the deletion of AAC has no effect on parasite growth, virulence or levels of ΔΨm. This suggests that ATP is produced by substrate-level phosphorylation pathways in the mitochondrion. Therefore, we knocked out the succinyl-CoA synthetase (SCS) gene, a key mitochondrial enzyme that produces ATP through substrate-level phosphorylation in this parasite. Its absence resulted in changes to the metabolic landscape of the parasite, lowered virulence, and reduced mitochondrial ATP content. Strikingly, these SCS mutant parasites become more dependent on AAC as demonstrated by a 25-fold increase in their sensitivity to the AAC inhibitor, carboxyatractyloside. Since the parasites were able to adapt to the loss of SCS in culture, we also analyzed the more immediate phenotypes that manifest when SCS expression is rapidly suppressed by RNAi. Importantly, when performed under nutrient-limited conditions mimicking various host environments, SCS depletion strongly affected parasite growth and levels of ΔΨm. In totality, the data establish that the long slender bloodstream form mitochondrion is capable of generating ATP via substrate-level phosphorylation pathways.

• MeSH
• adenosintrifosfát metabolismus   MeSH
• fosforylace MeSH
• mitochondrie metabolismus   MeSH
• Trypanosoma brucei brucei * metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Halotolerant bacteria get adapted to a saline environment through modified physiological/structural characteristics and may provide stress tolerance along with enhanced growth to the host plants by different direct and indirect mechanisms. This study reports on multiple halotolerant plant growth-promoting rhizobacteria isolated from the coastal soils in Bangladesh, in fields where the halophytic wild rice Oryza coarctata is endemic. The aim was to find halotolerant bacteria for potential use as biofertilizer under normal/salt-stressed conditions. In this study, eight different strains were selected from a total of 20 rhizobacterial isolates from the saline-prone regions of Debhata and Satkhira based on their higher salt tolerance. 16S rRNA gene sequencing results of the rhizobacterial strains revealed that they belonged to Halobacillus, Bacillus, Acinetobactor, and Enterobactor genera. A total of ten halotolerant rhizobacteria (the other 2 bacteria were previously isolated and already reported as beneficial for rice growth) were used as both single inoculants and in combinations and applied to rice growing in pots. To investigate their capability to improve rice growth, physiological parameters such as shoot and root length and weight, chlorophyll content at the seedling stage as well as survival and yield at the reproductive stage were measured in the absence or presence (in concentration 40 or 80 mmol/L) of NaCl and in the absence or presence of the rhizobacteria. At the reproductive stage, only 50% of the uninoculated plants survived without setting any grains in 80 mmol/L NaCl in contrast to 100% survival of the rice plants inoculated with a combination of the rhizobacteria. The combined halotolerant rhizobacterial inoculations showed significantly higher chlorophyll retention as well as yield under the maximum NaCl concentration applied compared to application of single species. Thus, the use of a combination of halotolerant rhizobacteria as bioinoculants for rice plants under moderate salinity can synergistically alleviate the effects of stress and promote rice growth and yield.

• MeSH
• Bacteria genetika   MeSH
• chlorid sodný MeSH
• chlorofyl MeSH
• kořeny rostlin mikrobiologie   MeSH
• půdní mikrobiologie MeSH
• RNA ribozomální 16S genetika   MeSH
• rýže (rod) * MeSH
• solný stres MeSH
• Publikační typ
• časopisecké články MeSH

Pancreatic lipase (PNLIP, EC 3.1.1.3) plays a pivotal role in the digestion of dietary lipids, a metabolic pathway directly related to obesity. One of the effective strategies in obesity treatment is the inhibition of PNLIP, which is possible to be achieved by specific phenolic compounds occurring in high abundance in some plants. In this study, a multidisciplinary approach is presented investigating the PNLIP inhibitory effect of 33 plants belonging in the Asteraceae botanical family. In the first stage of the study, a rapid and cost-efficient PNLIP assay in a 96-microwell plate format was developed and important parameters were optimized, e.g., the enzyme substrate. Upon PNLIP assay optimization, aqueous and dichloromethane Asteraceae plant extracts were tested and a cut-off inhibition level was set to further analyze only the samples with a significant inhibitory effect (inhibitory rate > 40%), using an ultra-high-performance liquid chromatography hybrid quadrupole time-of-flight mass spectrometry (UHPLC-q-TOF-MS) method. Specifically, a metabolomic suspect screening was performed and 69 phenolic compounds were tentatively identified, including phenolic acids, flavonoids, flavonoid-3-O-glycosides, and flavonoid-7-O-glycosides, amongst others. In the case of aqueous extracts, phytochemicals known for inducing PNLIP inhibitory effect, e.g., compounds containing galloyl molecules or caffeoylquinic acids, were monitored in Chrysanthemum morifolium, Grindella camporum and Hieracium pilosella extracts. All in all, the presented approach combines in vitro bioactivity measurements to high-end metabolomics to identify phenolic compounds with potential medicinal and/or dietary applications.

• MeSH
• Asteraceae * chemie   MeSH
• chromatografie kapalinová MeSH
• fenoly analýza   MeSH
• flavonoidy chemie   MeSH
• fytonutrienty analýza   MeSH
• glykosidy MeSH
• hmotnostní spektrometrie MeSH
• lipasa MeSH
• lipidy MeSH
• methylenchlorid MeSH
• obezita MeSH
• rostlinné extrakty chemie   farmakologie   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Publikační typ
• časopisecké články MeSH

Obligate symbiotic bacteria associated with the insects feeding exclusively on vertebrate blood are supposed to complement B vitamins presumably lacking in their diet. Recent genomic analyses revealed considerable differences in biosynthetic capacities across different symbionts, suggesting that levels of B vitamins may vary across different vertebrate hosts. However, a rigorous determination of B vitamins content in blood of various vertebrates has not yet been approached. A reliable analytical method focused on B vitamin complex in blood can provide valuable informative background and understanding of general principles of insect symbiosis. In this work, a chromatographic separation of eight B vitamins (thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid, and cyanocobalamine), four B vitamin derivatives (niacinamide, pyridoxal-5-phosphate, 4-pyridoxic acid, and tetrahydrofolic acid), and 3 stable isotope labelled internal standards was developed. Detection was carried out using dual-pressure linear ion trap mass spectrometer in FullScan MS/MS and SIM mode. Except for vitamin B9 (tetrahydrofolic acid), the instrument quantitation limits of all analytes were ranging from 0.42 to 5.0 μg/L, correlation coefficients from 0.9997 to 1.0000, and QC coefficients from 0.53 to 3.2%. Optimization of whole blood sample preparation step was focused especially on evaluation of two types of protein-precipitation agents: trichloroacetic acid and zinc sulphate in methanol. The best results were obtained for zinc sulphate in methanol, but only nine analytes were successfully validated. Accuracy of the procedure using this protein-precipitating agent was ranging from 89 to 120%, precision from 0.5 to 13%, and process efficiency from 65 to 108%. The content of B vitamins in whole blood samples from human and various vertebrates is presented as an application example of this newly developed method.

• MeSH
• chromatografie kapalinová metody   MeSH
• kyselina listová analýza   MeSH
• lidé MeSH
• methanol MeSH
• riboflavin analýza   MeSH
• síran zinečnatý MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• thiamin analýza   MeSH
• vitamin B komplex * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH