One of the main challenges in analyzing chemical messengers in the brain is the optimization of tissue sampling and preparation protocols. Limiting postmortem time and terminating enzyme activity is critical to identify low-abundance neurotransmitters and neuropeptides. Here, we used a rapid and uniform conductive heat transfer stabilization method that was compared with a conventional fresh freezing protocol. Together with a selective chemical derivatization method and an optimized quantitation approach using deuterated internal standards, we spatially mapped neurotransmitters and their related metabolites by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) in rat brain tissue sections. Although the heat stabilization did not show differences in the levels of dopamine, norepinephrine, and serotonin, their related metabolites 3,4-dihydroxyphenylacetaldehyde, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3-methoxy-4-hydroxyphenylacetaldehyde, dihydroxyphenylethyleneglycol, and 5-hydroxyindoleacetic acid were all significantly lower, indicating reduced neurotransmitter postmortem turnover ratios. Heat stabilization enabled detection of an increased number and higher levels of prodynorphin, proenkephalin, and tachykinin-derived bioactive neuropeptides. The low-abundant C-terminal flanking peptide, neuropeptide-γ, and nociceptin remained intact and were exclusively imaged in heat-stabilized brains. Without heat stabilization, degradation fragments of full-length peptides occurred in the fresh frozen tissues. The sample preparation protocols were furthermore tested on rat brains affected by acute anesthesia induced by isoflurane and medetomidine, showing comparable results to non-anesthetized animals on the neurotransmitters level without significant changes. Our data provide evidence for the potential use of heat stabilization prior to MALDI-MSI analyses to improve the examination of the in vivo state of neuronal chemical messengers in brain tissues not impacted by prior acute anesthesia.

• MeSH
• krysa rodu rattus MeSH
• mozek - chemie * fyziologie   MeSH
• mozek * metabolismus   MeSH
• neurony * metabolismus   chemie   MeSH
• neurotransmiterové látky * metabolismus   analýza   MeSH
• potkani Sprague-Dawley MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice * metody   MeSH
• vysoká teplota * MeSH
• zmrazování MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Current antibiotics and chemotherapeutics are becoming ineffective because pathogenic bacteria and tumor cells have developed multiple drug resistance. Therefore, it is necessary to find new substances that can be used in treatment, either alone or as sensitizing molecules in combination with existing drugs. Peptaibols are bioactive, membrane-active peptides of non-ribosomal origin, mainly produced by filamentous fungi such as Trichoderma spp. This study focused on producing peptaibol-rich extracts from Trichoderma atroviride O1, cultivated on malt extract agar (MA) under circadian and constant darkness conditions for 13 days. Peptaibol production was detected by MALDI-TOF mass spectrometry after six days of cultivation. The extracts demonstrated antibacterial activity against Staphylococcus aureus strains, particularly the methicillin-resistant variant, but not against the Gram-negative Pseudomonas aeruginosa. Quorum sensing interference revealed that a peptaibol-rich extract suppressed Vibrio campbellii BAA-1119's AI-2 signaling system to a degree comparable with gentamycin. Beyond antibacterial properties, the extracts exhibited notable antiproliferative activity against human ovarian cancer cells and their adriamycin-resistant subline in both 2D and 3D models. Specifically, MA-derived extracts reduced ovarian cancer cell viability by 70% at 50 μg/mL, especially under light/dark regime of cultivation. Compared to previously published results for PDA-based extracts, MA cultivation shifted the biological effects of peptaibol-containing extracts toward anticancer potential. These findings support the idea that modifying fungal cultivation parameters, the bioactivity of secondary metabolite mixtures can be tailored for specific therapeutic applications.

• MeSH
• agar * chemie   MeSH
• antibakteriální látky * farmakologie   metabolismus   MeSH
• Hypocreales MeSH
• kultivační média chemie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• nádorové buněčné linie MeSH
• peptaiboly * farmakologie   metabolismus   biosyntéza   chemie   MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky * farmakologie   metabolismus   MeSH
• Pseudomonas aeruginosa účinky léků   MeSH
• Staphylococcus aureus účinky léků   MeSH
• Trichoderma * metabolismus   růst a vývoj   chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Food hydrocolloids, derived from natural sources such as plants, algae, and microbes, possess bioactive properties that significantly contribute to cardiovascular health. This review focuses on six key hydrocolloids: alginate, astragalus polysaccharides, carrageenan, fucoidan, lunasin, and psyllium, while also considering other important natural hydrocoloids such as short chain fatty acids (SCFAs), plant-derived food hydrocolloids, plant-derived gums, plant-derived mucilages, pectin, modified citrus pectin, inulin, naringenin, chia seeds, gelatine, whey protein, casein, microbial exopolysaccharides and gums, ulvan, and laminarin. Alginate, from brown seaweed, aids in cardiac tissue regeneration and repair. Astragalus polysaccharides, from the Astragalus plant, provide antioxidant, anti-inflammatory, and immunomodulatory benefits. Carrageenan, sourced from red seaweed, supports lipid profile balance and heart health. Fucoidan, another brown seaweed derivative, offers antihypertensive and lipid-lowering effects. Lunasin, a peptide found in soybeans, oats, and barley, is known for its cholesterol-lowering properties and anti-inflammatory effects. Psyllium, rich in soluble fiber, helps lower LDL cholesterol and improve overall cardiovascular function. These hydrocolloids, along with other mentioned compounds, are utilized in drug formulations, cosmetics, processed foods, and dietary supplements, enhancing food texture and stability while delivering health benefits. Upon consumption, they can be absorbed into the bloodstream or metabolized by gut microbiota into bioactive metabolites. This review examines their effects on cardiovascular function, highlighting their mechanisms in regulating vascular tone, blood pressure, vascular inflammation, and cardiac function. It consolidates current research, emphasizing the potential of these hydrocolloids and related compounds in the prevention and management of cardiovascular diseases (CVDs).

• MeSH
• algináty * chemie   farmakologie   MeSH
• karagenan * chemie   farmakologie   MeSH
• kardiovaskulární nemoci * prevence a kontrola   MeSH
• kardiovaskulární systém * účinky léků   MeSH
• koloidy chemie   farmakologie   MeSH
• lidé MeSH
• polysacharidy * chemie   farmakologie   MeSH
• psyllium * chemie   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

To address the challenge of drug accumulation and penetration at the tumor site(s), herein we describe a first-in-class nanocarrier containing 24 copies each of two bioactive peptides (BAPs) genetically fused in frame to the 24 N-termini of a human ferritin H-type construct, named THE-10. The two BAPs are specific for PD-L1 and integrin αVβ3/αVβ5 plus Neuropilin (iRGD) respectively, conferring immune checkpoint blockade and drug-internalization properties. In turn, the THE-10 backbone brings 48 BAPs contiguous for synergism, prolonged blood half-life, and release into the tumor microenvironment upon conditional cleavage of a metalloprotease-sensitive site. Predicted THE-10 multitasking activity was experimentally supported as follows. Size-exclusion chromatography and surface plasmon resonance demonstrated BAP cleavage/release and receptor binding (nanomolar KD). Live-cell/time-lapse imaging demonstrated 4-fold-increased internalization of naked therapeutic antibodies, mirrored by enhanced cytotoxicity of the corresponding Antibody-Drug Conjugate. Slight antitumor effects were observed in vivo by treating immune checkpoint-sensitive syngeneic mouse colorectal model with THE-10 alone. Drug boosting was instead considerable on colorectal and pancreatic tumor allografts when THE-10 was co-administered with both small and large chemotherapeutic agents, outperforming the original iRGD cyclic peptide. Thus, THE-10 may enhance target therapy, chemotherapy and immunotherapy altogether, e.g. it candidates as a multitasking, all-round, antineoplastic therapy booster.

• MeSH
• ferritiny * chemie   genetika   farmakologie   MeSH
• imunoterapie * MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nanočástice * chemie   MeSH
• nosiče léků * chemie   MeSH
• protinádorové látky farmakologie   chemie   MeSH
• rekombinantní proteiny chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• bioaktivní peptidy ve stravě * fyziologie   imunologie   MeSH
• emoce fyziologie   MeSH
• imunonutriční dieta MeSH
• lidé MeSH
• mitochondriální nemoci etiologie   MeSH
• nemoc etiologie   MeSH
• neuroendokrinologie * MeSH
• nitrosativní stres MeSH
• oxidační stres fyziologie   imunologie   MeSH
• psychický stres imunologie   MeSH
• psychoneuroimunologie * MeSH
• výchova a vzdělávání MeSH
• životní styl MeSH
• Check Tag
• lidé MeSH

Tick saliva injected into the vertebrate host contains bioactive anti-proteolytic proteins from the cystatin family; however, the molecular basis of their unusual biochemical and physiological properties, distinct from those of host homologs, is unknown. Here, we present Ricistatin, a novel secreted cystatin identified in the salivary gland transcriptome of Ixodes ricinus ticks. Recombinant Ricistatin inhibited host-derived cysteine cathepsins and preferentially targeted endopeptidases, while having only limited impact on proteolysis driven by exopeptidases. Determination of the crystal structure of Ricistatin in complex with a cysteine cathepsin together with characterization of structural determinants in the Ricistatin binding site explained its restricted specificity. Furthermore, Ricistatin was potently immunosuppressive and anti-inflammatory, reducing levels of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α and nitric oxide in macrophages; IL-2 and IL-9 levels in Th9 cells; and OVA antigen-induced CD4+ T cell proliferation and neutrophil migration. This work highlights the immunotherapeutic potential of Ricistatin and, for the first time, provides structural insights into the unique narrow selectivity of tick salivary cystatins determining their bioactivity.

• MeSH
• cystatiny * farmakologie   MeSH
• cystein metabolismus   MeSH
• endopeptidasy metabolismus   MeSH
• kathepsiny metabolismus   MeSH
• klíště * chemie   MeSH
• obratlovci MeSH
• proteasy metabolismus   MeSH
• slinné cystatiny chemie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Sepsis has evolved as an enormous health issue amongst critically ill patients. It is a major risk factor that results in multiple organ failure and shock. Acute kidney injury (AKI) is one of the most frequent complications underlying sepsis, which portends a heavy burden of mortality and morbidity. Thus, the present review is aimed to provide an insight into the recent progression in the molecular mechanisms targeting dysregulated immune response and cellular dysfunction involved in the development of sepsis-associated AKI, accentuating the phytoconstituents as eligible candidates for attenuating the onset and progression of sepsis-associated AKI. The pathogenesis of sepsis-mediated AKI entails a complicated mechanism and is likely to involve a distinct constellation of hemodynamic, inflammatory, and immune mechanisms. Novel biomarkers like neutrophil gelatinase-associated lipocalin, soluble triggering receptor expressed on myeloid cells 1, procalcitonin, alpha-1-microglobulin, and presepsin can help in a more sensitive diagnosis of sepsis-associated AKI. Many bioactive compounds like curcumin, resveratrol, baicalin, quercetin, and polydatin are reported to play an important role in the prevention and management of sepsis-associated AKI by decreasing serum creatinine, blood urea nitrogen, cystatin C, lipid peroxidation, oxidative stress, IL-1β, TNF-α, NF-κB, and increasing the activity of antioxidant enzymes and level of PPARγ. The plant bioactive compounds could be developed into a drug-developing candidate in managing sepsis-mediated acute kidney injury after detailed follow-up studies. Lastly, the gut-kidney axis may be a more promising therapeutic target against the onset of septic AKI, but a deeper understanding of the molecular pathways is still required.

• MeSH
• akutní poškození ledvin * farmakoterapie   etiologie   diagnóza   MeSH
• biologické markery MeSH
• lidé MeSH
• lipokaliny terapeutické užití   MeSH
• lipopolysacharidové receptory metabolismus   MeSH
• peptidové fragmenty metabolismus   MeSH
• proteiny akutní fáze analýza   metabolismus   terapeutické užití   MeSH
• sepse * komplikace   farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• antioxidancia MeSH
• antivirové látky MeSH
• bioaktivní peptidy ve stravě imunologie   terapeutické užití   MeSH
• COVID-19 MeSH
• imunomodulační látky MeSH
• kyselina askorbová imunologie   terapeutické užití   MeSH
• lidé MeSH
• mléko * MeSH
• stopové prvky imunologie   terapeutické užití   MeSH
• vitamin B komplex imunologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH

• Publikační typ
• časopisecké články MeSH
• odvolání publikace MeSH

The use of herbal medicinal products and supplements in amateur and professional sports has increased in the last decades. This is because most of these products and supplements contain bioactive compounds with a variety of biological properties that exert a physiological effect on the human body. The aim of this study was to analyze the effect of dietary supplementation with lyophilized black chokeberry extract on the levels of pro-inflammatory cytokines, hepcidin, and selected markers of iron metabolism in a group of young football players. This double-blind study included 22 male football players (mean = 19.96 ± 0.56), divided into two groups: supplemented and placebo. Before and after a 90-day period of training combined with supplementation (6 g of lyophilized black chokeberry extract), participants performed maximal multistage 20-m shuttle run tests at the beginning and at the end of the supplementation period, with blood sampled for analysis at different times before and after exercise. The levels of IL-6, IL-10, ferritin, myoglobin, hepcidin, 8-OHdG, albumin, and TAC were analyzed. The analysis of variance revealed a significant effect of 90-day supplementation with the lyophilized extract on changes in the IL-6 and IL-10 levels, and TAC induced by maximal aerobic effort. In conclusion, supplementation with lyophilized black chokeberry extract improves the performance and antioxidant status of serum in humans and induces protective changes in inflammatory markers.

• MeSH
• dvojitá slepá metoda MeSH
• fotbal MeSH
• hepcidiny MeSH
• interleukin-10 MeSH
• interleukin-6 MeSH
• lidé MeSH
• mladý dospělý MeSH
• Photinia * MeSH
• potravní doplňky * MeSH
• rostlinné extrakty * farmakologie   MeSH
• sportovci MeSH
• zánět MeSH
• železo * metabolismus   MeSH
• Check Tag
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH