Several novel copper (II) complexes of reduced Schiff bases containing fluoride substituents were prepared and structurally characterized by single-crystal X-ray diffraction. The complexes exhibited diverse structures, with the central atom in distorted tetrahedral geometry. The biological effects of the products were evaluated, specifically their cytotoxicity, antimicrobial, and antiurease activities, as well as affinity for albumin (BSA) and DNA (ct-DNA). The complexes showed marked cytotoxic activities in the HepG2 hepatocellular carcinoma cell line, considerably higher than the standard cisplatin. The cytotoxicity depended significantly on the substitution pattern. The best activity was observed in the complex with a trifluoromethyl group in position 4 of the benzene ring-the dichloro[(±)-trans-N,N'-bis-(4-trifluoromethylbenzyl)-cyclohexane-1,2-diamine]copper (II) complex, whose activity (IC50 28.7 μM) was higher than that of the free ligand and markedly better than the activity of the standard cisplatin (IC50 336.8 μM). The same complex also showed the highest antimicrobial effect in vitro. The affinity of the complexes towards bovine serum albumin (BSA) and calf thymus DNA (ct-DNA) was established as well, indicating only marginal differences between the complexes. In addition, all complexes were shown to be excellent inhibitors of the enzyme urease, with the IC50 values in the lower micromolar region.
- MeSH
- Antineoplastic Agents * pharmacology chemistry MeSH
- Hep G2 Cells MeSH
- DNA metabolism chemistry MeSH
- Fluorine chemistry MeSH
- Coordination Complexes * pharmacology chemistry chemical synthesis MeSH
- Humans MeSH
- Ligands MeSH
- Copper * chemistry MeSH
- Schiff Bases * chemistry pharmacology MeSH
- Serum Albumin, Bovine chemistry MeSH
- Urease antagonists & inhibitors metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Výskum v oblasti ľudskej mikrobioty a jej vplyvu na ľudské zdravie otvoril nové možnosti diagnostiky, prevencie alebo liečby niektorých patologických stavov. Negatívna zmena zloženia črevnej mikrobioty, dysbióza, je asociovaná s ochoreniami, ako sú napr. zápalové ochorenia čreva, obezita, diabetes mellitus či infekcie spôsobené baktériou Clostridium difficile. Pre využitie ľudskej mikrobioty, resp. jej biologicky aktívnych produktov v klinickej praxi je potrebná jej dôkladná identifikácia a charakterizácia vlastností, ktoré môžu byť pre človeka prospešné. Použitie najnovších technológií umožňuje realizovať takýto výskum a v súčasnosti už poznáme viacero potenciálnych kandidátov na tzv. probiotiká ďalšej generácie. Cieľom tohto článku je zhrnúť dostupné informácie o baktériách Akkermansia muciniphila, Bacteroides fragilis a Faecalibacterium prausnitzii, ktoré patria z tohto pohľadu k najperspektívnejším a najštudovanejším.
Research in the field of human microbiota and its impact on human health has opened new possibilities for the diagnosis, prevention or treatment of certain pathological conditions. A negative change in the composition of the intestinal microbiota, dysbiosis, is associated with diseases such as inflammatory bowel diseases, obesity, diabetes mellitus, or Clostridium difficile infections. For the use of human microbiota or its biologically active products in clinical practice, it is necessary to thoroughly identify and characterize properties that may be beneficial to human health. The use of the latest technology enables such research to be carried out, and we are already aware of several potential candidates for the so-called probiotics of the next generation. The aim of this article is to summarize available information on the bacteria Akkermansia muciniphila, Bacteroides fragilis, and Faecalibacterium prausnitzii, which are among the most promising and studied candidates.
Phosphorus-containing heterocyclic cationic surfactants alkyldimethylphenylphospholium bromides with the alkyl chain length 14 to 18 carbon atoms were used for the stabilization of silver nanodispersions. Zeta potential of silver nanodispersions ranges from +35 to +70 mV, which indicates the formation of stable silver nanoparticles (AgNPs). Long-chain heptadecyl and octadecyl homologs of the surfactants series provided the most intensive stabilizing effect to AgNPs, resulting in high positive zeta potential values and smaller diameter of AgNPs in the range 50-60 nm. A comparison with non-heterocyclic alkyltrimethylphosphonium surfactants of the same alkyl chain length showed better stability and more positive zeta potential values for silver nanodispersions stabilized with heterocyclic phospholium surfactants. Investigations of biological activity of phospholium-capped AgNPs are represented by the studies of antimicrobial activity and cytotoxicity. While cytotoxicity results revealed an increased level of HepG2 cell growth inhibition as compared with the cytotoxicity level of silver-free surfactant solutions, no enhanced antimicrobial action of phospholium-capped AgNPs against microbial pathogens was observed. The comparison of cytotoxicity of AgNPs stabilized with various non-heterocyclic ammonium and phosphonium surfactants shows that AgNPs capped with heterocyclic alkyldimethylphenylphospholium and non-heterocyclic triphenyl-substituted phosphonium surfactants have the highest cytotoxicity among silver nanodispersions stabilized by the series of ammonium and phosphonium surfactants.
- Publication type
- Journal Article MeSH
Incidencia nešpecifických zápalových ochorení čreva (IBD) v rozvinutých krajinách každoročne stúpa. Príčiny týchto ochorení dosiaľ nie sú jednoznačne identifikované a práve ich poznanie je kľúčovým predpokladom pre efektívnu profylaxiu a terapiu. Na vzniku IBD sa pravdepodobne podieľa kombinácia viacerých faktorov: environmentálnych, genetických, imunologických a narušenia zloženia črevnej mikrobioty – dysbiózy. Najzávažnejšími environmentálnymi faktormi sa zdajú byť „westernizácia“ životného štýlu a urbanizácia. K patogenéze IBD prispieva tiež nerovnováha medzi TH1 a TH2 bunkovou imunitnou odpoveďou a zmeny v expresii génov zapojených o. i. do T bunkovej odpovede a imunodeficientných stavov. V neposlednom rade celosvetové nadužívanie antimikróbnych liečiv ochudobňuje ľudský mikrobióm, čo má priamy dopad na rozvoj črevnej dysbiózy. Predmetom prehľadového článku je podrobná charakteristika faktorov podieľajúcich sa na vzniku a rozvoji IBD.
The incidence of inflammatory bowel disease (IBD) in developed countries increases every year. The aetiology is still not completely understood and its clarification is a key prerequisite for effective prophylaxis and therapy. IBD is most-likely caused by a combination of several factors: environmental, genetic, immunological, and disruption of intestinal microbiota composition – dysbiosis. “Westernization” of lifestyle and urbanization seem to be among the most serious environmental factors. The pathogenesis is also influenced by the imbalance between the TH1 and TH2 cellular response and the expression of genes involved in T cell response and immunodeficiency. Last but not least, the worldwide overuse of antimicrobial drugs depletes the microbiome, which has a direct impact on the development of the dysbiosis. The subject of this review is a detailed characterization of the above- mentioned factors involved in the onset and development of IBD.
Koexistencia ľudí s mikroorganizmami je známa už dávno. Okrem vzťahu s infekčnými chorobami sa v dnešnej dobe potvrdzuje význam personálnej mikrobioty pre zdravie, resp. niektoré neinfekčné choroby človeka. Osídľovanie ľudského tela vhodnými mikroorganizmami po pôrode je esenciálne napr. pre fyziologický vývoj imunitného systému a má vplyv aj na vývoj centrálneho nervového systému. Zloženie črevnej mikrobioty ovplyvňuje najmä spôsob pôrodu, výživa v ranom detstve a v neposlednom rade aj životný štýl a používanie liekov, najmä antibiotík. Porovnaním črevného mikrobiómu ľudí z rôznych častí sveta sa našli zásadné rozdiely v jeho zložení na základe čoho boli definované konkrétne enterotypy. Zaujímavé bolo zistenie, že druhovo rôzne zloženie mikrobioty pokrýva tie isté, resp. podobné metabolické dráhy. Ukazuje sa, že práve črevná mikrobiota a jej dysbióza môže mať za následok vznik rôznych tzv. civilizačných ochorení, ako napr. diabetes mellitus, obezita, astma, zápalové ochorenia čreva, alergie a autoimunitné ochorenia.
Coexistence of humans with microorganisms is well known for a long time. Besides the association with infectious diseases, personal microbiota is important for human health, possibly for some non-infectious diseases. Colonization of the human body with appropriate microorganisms after delivery is essential for physiological immune system maturation and also has an influence on central nervous system development. The composition of the gut microbiota is affected by the mode of delivery, early life nutrition and last but not least by lifestyle and drug, especially antibiotics intake. A comparison of gut microbiomes between individuals living in different parts of the world showed a cardinal variation in its composition and basic enterotypes were defined. Interestingly, it has been found out that the different microbiota species’ composition covers the same, respectively similar metabolic pathways. It is suggested that gut microbiota composition and its dysbiosis may influence civilization diseases development, e. g. diabetes mellitus, obesity, asthma, inflammatory bowel disease, allergy, and autoimmune diseases.
- Keywords
- civilizační choroby, MAMP,
- MeSH
- Anti-Bacterial Agents adverse effects MeSH
- Autoimmune Diseases etiology MeSH
- Bacteria classification MeSH
- Biodiversity MeSH
- Civilization MeSH
- Diet MeSH
- Dysbiosis therapy MeSH
- Immune System microbiology growth & development MeSH
- Breast Feeding MeSH
- Humans MeSH
- Microbiota * MeSH
- Brain physiology growth & development MeSH
- Parturition physiology MeSH
- Prebiotics MeSH
- Probiotics MeSH
- Receptors, Pattern Recognition agonists antagonists & inhibitors classification MeSH
- Signal Transduction MeSH
- Gastrointestinal Microbiome * genetics immunology drug effects MeSH
- T-Lymphocytes microbiology pathology MeSH
- Age Factors MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Počet predklinických a klinických štúdií, ktoré potvrdzujú účinnosť probiotík v profylaxii a terapii niektorých ochorení, napr. hnačiek rôzneho pôvodu, syndrómu dráždivého čreva, nešpecifickej zápalovej choroby čreva, alergie, hypercholesterolémie, bakteriálnej vaginózy, kolorektálneho karcinómu a i. stále rastie. Tieto zdraviu prospešné účinky sú často druhovo a kmeňovo špecifické. V práci podávame prehľad dostupných poznatkov o predpokladaných mechanizmoch účinku probiotických mikroorganizmov, pričom sa zameriavame najmä na interakciu probiotických buniek s bunkami hostiteľa. Jedným z výsledkov tejto interakcie je navodenie pro- alebo protizápalovej imunitnej odpovede makroorganizmu. Detailné poznanie signálnych dráh, ktorými prebieha komunikácia medzi bakteriálnymi a ľudskými bunkami môže nájsť uplatnenie pri selekcii vhodných probiotík pre cielenú liečbu vybraných ochorení. Ďalšie možnosti využitia probiotických mikroorganizmov v klinickej praxi poskytujú genetické manipulácie a metódy génového inžinierstva.
The number of preclinical and clinical studies showing efficacy of probiotics in the treatment and prophylaxis of certain diseases, e.g. diarrhoea of various origin, irritable bowel syndrome, inflammatory bowel disease, allergies, hypercholesterolemia, bacterial vaginosis, and colorectal cancer, is increasing. These health benefits are often species and strain specific. This article provides an overview of available knowledge about the supposed mechanisms of probiotic microorganism’s action focusing in particular on the interaction between probiotic and host cells. One of the results of this interaction is induction of pro- or anti-inflammatory immune response in the macroorganism. Detailed knowledge of the signalling pathways involved in the communication between bacterial and human cells can find application in the selection of optimal probiotics for the targeted treatment of selected diseases. Additional possibilities for their use in clinical practice are provided by genetic manipulation of probiotic microorganisms.
- MeSH
- Bacteria immunology MeSH
- Epithelial Cells MeSH
- Organisms, Genetically Modified MeSH
- Immunomodulation * MeSH
- Humans MeSH
- Lymphoid Tissue MeSH
- PPAR gamma MeSH
- Probiotics * classification therapeutic use MeSH
- Signal Transduction drug effects MeSH
- Intestinal Mucosa MeSH
- Toll-Like Receptors MeSH
- Inflammation * immunology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Five new strains of lactobacilli isolated from goatling's stomach were identified by molecular-biological approaches. Profiles of fermentable saccharides, Gram staining, and cell morphology were also determined. They were identified as Lactobacillus reuteri (strains KO4b, KO4m, KO5) and as Lactobacillus plantarum (strains KG1z, KG4). In DNA samples of all newly isolated L. reuteri strains as well as in L. reuteri E (Lreu E; originated from lamb), the part of gldC gene, coding large subunit of glycerol dehydratase, that is necessary for 3-hydroxypropionaldehyde (3-HPA; reuterin) production, was amplified using two designed primer sets. However, the 3-HPA production was revealed only in the strain Lreu E. It produced five- or ten-fold lower amount of 3-HPA in comparison with probiotic L. reuteri ATCC 55730 in aerobic or anaerobic conditions, respectively. Moreover, Lreu E completely lost its production ability after ca. five passages in MRS medium. The co-incubation of Lreu E, but not other L. reuteri isolates, with Escherichia coli re-induced 3-HPA production. In the case of L. reuteri ATCC 55730, the 3-HPA production increased more than four times after co-incubation with E. coli.
Elicitácia rastlinných in vitro kultúr predstavuje biotechnologický nástroj na zvýšenie produkcie sekundárnych metabolitov. V tejto práci bol sledovaný vplyv elicitácie dusičnanom strieborným a chloridom kademnatým na produkciu sanguinarínu suspenznou kultúrou slncovky kalifornskej. Elicitory boli ku kultúram pridané na 14. deň subkultivácie a ich vplyv na tvorbu sanguinarínu bol vyhodnotený po 48 h pôsobení. AgNO3 v koncentrácii 0,075 mmol.l-1 a CdCl2 v koncentrácii 4 mmol.l-1 indukovali približne 5,2-, resp. 5,6-násobné zvýšenie tvorby sanguinarínu. Toto zvýšenie pravdepodobne predstavuje maximálny nárast, pretože zvýšenie koncentrácie elicitorov už k ďalšiemu nárastu produkcie sanguinarínu neviedlo. Použitie obidvoch elicitorov viedlo k zvýšeniu špecifickej aktivity polyfenoloxidázy. Polyfenoloxidáza je pravdepodobne zapojená do biosyntézy sanguinarínu na úrovni tvorby dopamínu, ktorý je prekurzorom S-norkoklaurínu, prvého intermediátu s benzylizochinolínovou štruktúrou.
Elicitation of plant in vitro cultures represents a biotechnological tool to improve the production of secondary metabolites. In this study, the effect of AgNO3 and CdCl2 on the sanguinarine production by the suspension culture of Eschscholtzia californica CHAM. was investigated. Elicitors were added to the cultures at the 14th day of subcultivation and their effect on the sanguinarine production was evaluated after a 48 h exposure. AgNO3 at the concentration of 0.075 mmol.l-1 and CdCl2 at the concentration of 4 mmol.l-1 induced a ca. 5.2- and 5.6-multiple increase in sanguinarine synthesis, respectively. This amount represents probably the maximal production, because a further increase in the elicitors concentrations did not increase sanguinarine production. Both abiotic elicitors induced a polyphenol oxidase specific activity increase. Polyphenol oxidase is probably involved in the biosynthesis of sanguinarine at the level of dopamine formation. Dopamine is a precursor of (S)-norcoclaurine, the first intermediate with the benzylisoquinoline structure.
- MeSH
- Anti-Bacterial Agents MeSH
- Benzophenanthridines * pharmacology chemistry isolation & purification MeSH
- Biotechnology methods instrumentation trends MeSH
- Chemistry Techniques, Analytical methods utilization MeSH
- Chemistry, Pharmaceutical * MeSH
- Eschscholzia * chemistry MeSH
- Technology, Pharmaceutical MeSH
- Phenols analysis MeSH
- Analytic Sample Preparation Methods MeSH
- Plants MeSH
- Suspensions MeSH
- In Vitro Techniques MeSH
- Tissue Culture Techniques * MeSH
Niektoré kmene laktobacilov sú vďaka svojim probiotickým vlastnostiam využívané v potravinárstve a vo výživových doplnkoch. Na našom pracovisku je testovaných 8 kmeňov laktobacilov, pochádzajúcich zo žalúdočných slizníc jahňaťa a kozľaťa, na potenciálne využitie v probiotických prípravkoch pre humánnu, a/alebo veterinárnu medicínu. Sanguinarín je majoritným alkaloidom in vitro kultúr rastlín čeľade Papaveraceae. Vďaka svojmu antimikróbnemu, antimykotickému, antiplakovému a protizápalovému účinku našiel uplatnenie v stomatologických prípravkoch. Spolu s ďalšími alkaloidmi je obsiahnutý aj v prípravku na zvýšenie apetítu hospodárskych zvierat. V tejto práci sme sa zamerali na sledovanie antibakteriálneho vplyvu sanguinarínu, vyizolovaného zo suspenzných kultúr maku siateho, na vybrané kmene laktobacilov. Z nami testovaných laktobacilov bol voči sanguinarínu najmenej citlivý L. reuteri KO5 s MIC 0,6 mg.ml-1. Nasledovali L. murinus C, L. mucosae D a L. plantarum KG4, zhodne s MIC 0,3 mg.ml-1. V prípade použitia kombinácie dvoch a viacerých kmeňov mikroorganizmov v jednom prípravku je potrebné poznať ich vzájomnú schopnosť ovplyvňovať svoj rast a prežívanie. Na testovanie vzájomného vplyvu laktobacilov bola použitá prúžková metóda na agarových platniach. Zo získaných výsledkov vyplýva, že pre použitie v kombinovaných prípravkoch sú najvhodnejšie kmene L. reuteri E, L. plantarum KG1 a L. reuteri KO4m. Kľúčové slová: Lactobacillus spp. • probiotiká • výživové doplnky • sanguinarín
Some lactobacilli strains are used as probiotics in food industry and in dietary supplements. Eight lactobacilli strains, originated from the stomach of the lamb and goatling, are tested for their potential use in human and/or veterinary medicine in our department. Sanguinarine is a major alkaloid of Papaveraceae suspension cultures. For its antimicrobial, antifungal, anti-plaque and anti-inflammatory properties sanguinarine found application in dental preparations. A mixture of sanguinarine with other alkaloids is used for appetite stimulation of livestock. This paper is focused on testing of selected lactobacilli sensitivity to sanguinarine, isolated from the opium poppy suspension cultures. L. reuteri KO5 demonstrated the lowest sensitivity (MIC 0.6 mg.l-1). Other less sensitive strains were L. murinus C, L. mucosae D and L. plantarum KG4 (MIC 0.3 mg.l-1). For a combination of more strains of microorganisms in one preparation it is necessary to know their ability to influence their growth and survival. To test the mutual influence of lactobacilli, the streak line method on agar plates was used. The results show that the strains L. reuteri E, L. plantarum KG1 a L. reuteri KO4m are the most suitable ones for the use in combinations. Keywords: Lactobacillus spp. • probiotics • food supplements • sanguinarine
Intaktné rastliny čeľade Papaveraceae sú schopné produkovať celý rad benzylizochinolínových alkaloidov, ktoré majú využitie vo farmaceutickej praxi. In vitro kultúry odvodené z rastlín tejto čeľade si nezachovávajú schopnosť produkcie širokého spektra alkaloidov – aktívna je v nich iba biosyntetická dráha, vedúca k sanguinarínu. V rámci tejto práce boli odvodené in vitro kultúry z rastlín Papaver somniferum, Eschscholtzia californica, Chelidonium majus a Macleaya cordata a porovnaná ich schopnosť produkcie sanguinarínu. Najnižšie množstvá sanguinarínu vyprodukovali kultúry maku siateho (0,45–0,55 μg . g-1 čerstvej hmoty). Kultúry Eschscholtzia californica, Chelidonium majus a Macleaya cordata produkovali navzájom porovnateľné množstvá (18,0–22,7 μg; 20,5–26,3 μg; resp. 15,4 až 20,3 μg na 1 g č. hm.). Po elicitácii kultúr hydrolyzátom z Botrytis cinerea bola vo všetkých vzorkách zaznamenaná zvýšená produkcia sanguinarínu. K relatívne najvyššiemu zvýšeniu produkcie došlo v kultúrach maku siateho, avšak tieto kultúry ani po elicitácii nedosiahli úroveň produkcie ostatných troch kultúr bez ovplyvnenia. Kľúčové slová: Papaver somniferum • Eschscholtzia californica • Chelidonium majus • Macleaya cordata • suspenzné kultúry • elicitácia • sanguinarín
Intact plants of the Papaveraceae family are producers of a whole range of benzylisoquinoline alkaloids, which are used in pharmaceutical industry. In vitro cultures derived from plants of the Papaveraceae do not have the ability to produce such a broad spectrum of alkaloids, only the biosynthetic pathway leading to sanguinarine is active. This study deals with the preparation of in vitro cultures of Papaver somniferum, Eschscholtzia californica, Chelidonium majus and Macleaya cordata. Their sanguinarine production abilities were tested and compared. The lowest amounts of sanguinarine from all cultures tested were accumulated in suspension cultures of the opium poppy (0.45–0.55 μg in 1 g of fresh weight). Eschscholtzia californica, Chelidonium majus and Macleaya cordata cultures produced similar amounts of sanguinarine (18.0–22.7 μg; 20.5–26.3 μg; 15.4–20.3 μg in 1 g of fresh weight, resp.). The elicitation study used a biotic stressor, Botrytis cinerea hydrolysate. In all cultures treated, an increase in sanguinarine accumulation was observed. Of all cultures tested, the most intensive response was observed in the opium poppy cultures, although the amount of sanguinarine in the elicited poppy cultures was lower than in the non-elicited samples of the other cultures. Key words: Papaver somniferum • Eschscholtzia californica • Chelidonium majus • Macleaya cordata • suspension cultures • elicitation • sanguinarine Received 25 October 2012 / Accepted 17 November 2012
