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

Cíl: Cílem tohoto systematického přehledu bylo ověřit úlohu urgentní mikrochirurgické embolektomie a extrakraniálního-intrakraniálního bypassu jako třetí linie léčby v případech uzávěru velké mozkové cévy po selhání standardní léčby. Soubor a metodika: Provedli jsme rozsáhlou rešerši osmi zdrojů publikované i nepublikované literatury. Dva recenzenti nezávisle na sobě provedli analýzu názvů, abstraktů, plných textů a poté provedli kritické hodnocení a extrakci dat z vybraných studií pomocí standardizovaných nástrojů. Výsledky zahrnutých studií jsme narativně syntetizovali. Výsledky: Vyhledávání identifikovalo osm relevantních článků, zahrnujících 12 pacientů s urgentním uzávěrem velké cévy (terminální krkavice nebo střední mozková tepna) a selháním standardní léčby, kteří podstoupili mikrochirurgický zákrok do 24 hodin od vzniku příznaků. Mikrochirurgická embolektomie byla provedena ve čtyřech případech (33 %), extrakraniální-intrakraniální bypass v pěti případech (42 %), jejich kombinace ve dvou případech (16 %) a manipulační intraoperační rekanalizace v jednom případě (8 %). Skóre na škále National Institutes of Health Stroke Scale se předoperačně pohybovalo v rozmezí 7–25 bodů a pooperačně (1–7 dní po operaci) v rozmezí 1–18 bodů. Funkční nezávislosti (modifikované Rankinovo skóre 0–2) bylo dosaženo u devíti pacientů (75 %) po 3–12 měsících po operaci. Závěr: Urgentní mikrochirurgická embolektomie, extrakraniální-intrakraniální bypass nebo kombinace těchto metod se jeví jako bezpečná a potenciálně účinná třetí linie léčby u pacientů s urgentním uzávěrem velké cévy v přední mozkové cirkulaci.

Aim: This systematic review aimed to verify the role of emergent microsurgical embolectomy and extracranial-intracranial bypass as third-line treatments in cases of intracranial large-vessel occlusion after failure of standard treatment. Materials and methods: We extensively searched eight sources of published and unpublished literature. Two reviewers independently performed titles, abstracts, and full text analyses, and then performed critical appraisal and data extraction from selected studies using standardised tools. We narratively synthesised the findings of the included studies. Results: The search identified eight relevant articles, including 12 patients with emergent large-vessel occlusion (carotid terminus or middle cerebral artery), and standard treatment failure who underwent microsurgery within 24 h from symptom onset. Microsurgical embolectomy was performed in four cases (33%), extracranial-intracranial bypass in five cases (42%), their combination in two cases (16%), and manipulative intraoperative recanalization in one case (8%). National Institutes of Health Stroke Scale score ranged pre-operatively from 7 to 25 points and postoperatively (1–7 days after surgery) from 1–18 points. Functional independence (modified Rankin Scale score 0–2) was achieved in nine patients (75%) at 3–12 months postoperatively. Conclusion: Emergent microsurgical embolectomy, extracranial-intracranial bypass, or a combination of these methods appear to be a safe and potentially effective third-line treatment for patients with emergent occlusion of large vessels in the anterior cerebral circulation

• MeSH
• ischemická cévní mozková příhoda * chirurgie   MeSH
• lidé MeSH
• mikrochirurgie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

The objective of our in vitro study was to quantify the biochemical profile where the total polyphenol, flavonoid and phenolic acid content was determined. The antioxidant potential of microgreen extract from Trigonella foenum-graecum L., was measured molybdenum reducing power assay. Specifically, the study assessed parameters such as metabolic activity (AlamarBlueTM assay), membrane integrity (CFDA-AM assay), mitochondrial potential (JC-1 assay), as well as reactive oxygen species generation (NBT assay). In addition, the steroid hormone release in TM3 murine Leydig cells after 12 h and 24 h exposures were quantified by enzyme-linked immunosorbent assay. The gained results indicate the highest value in total flavonoid content (182.59+/-2.13 mg QE) determination, supported by a significant (108.25+/-1.27 mg TE) antioxidant activity. The effects on metabolic activity, cell membrane integrity, and mitochondrial membrane potential were found to be both time- and dose-dependent. Notably, a significant suppression in reactive oxygen species generation was confirmed at 150, 200 and 250 microg/ml after 24 h exposure. In addition, progesterone and testosterone release was stimulated up to 250 microg/ml dose of Trigonella, followed by a decline in both steroid production at 300 and 1000 microg/ml. Our results indicate, that Trigonella at lower experimental doses (up to 250 microg/ml) may positively affect majority of monitored cell parameters in TM3 Leydig cells. Overleaf, increasing experimental doses may negatively affect the intracellular parameters already after 12 h of in vitro exposure. Key words Microgreens, Trigonella foenum-graecum L., Fenugreek, Leydig cells, Male reproduction.

• MeSH
• antioxidancia farmakologie   MeSH
• buněčné linie MeSH
• fytonutrienty farmakologie   MeSH
• Leydigovy buňky * účinky léků   metabolismus   MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• myši MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• rostlinné extrakty * farmakologie   MeSH
• testosteron metabolismus   MeSH
• Trigonella * chemie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Waterpipe smoking (WPS) has adverse health effects that include endothelial dysfunction with mechanisms involving oxidative stress and inflammation. Nonetheless, there is a scarcity of data on the direct impact of WPS on endothelial function. In this study, we assessed the in vitro effects of waterpipe smoke extract (WPSE) on aortic endothelial cell lines, namely the TeloHAEC. The WPSE markedly caused concentration- and time-dependent decreases in cellular viability. When compared with the control, at a concentration of 20 % and an incubation period of 48 h, the WPSE significantly increased the levels of lactate dehydrogenase, and markers of oxidative stress including thiobarbituric acid reactive substances, superoxide dismutase, catalase, and reduced glutathione. Moreover, the concentrations of proinflammatory cytokine (tumor necrosis factor alpha), and adhesion molecules (E-selectin and intercellular adhesion molecule-1) were also significantly augmented. Likewise, WPSE triggered mitochondrial dysfunction, DNA oxidative damage, as well as apoptosis in TeloHAEC cells. Similarly, cells cultured with WPSE have shown increased expression of phosphorylated nuclear factor-kappaB and hypoxia-inducible factor 1-alpha (HIF-1alpha). In conclusion, our study showed that WPSE triggers endothelial inflammation, oxidative stress, DNA damage, mitochondrial dysfunction, and apoptosis via mechanisms involving the activation of nuclear factor-kappaB and HIF-1alpha. Key words Waterpipe smoking, Aortic endothelial cells, Inflammation, Oxidative Stress.

• MeSH
• aorta * účinky léků   metabolismus   MeSH
• apoptóza účinky léků   MeSH
• buněčné linie MeSH
• endoteliální buňky * účinky léků   metabolismus   MeSH
• kouř * škodlivé účinky   MeSH
• kouření vodní dýmky * škodlivé účinky   metabolismus   MeSH
• lidé MeSH
• oxidační stres * účinky léků   MeSH
• poškození DNA účinky léků   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Coriolus versicolor (CV), known in traditional Chinese medicine for over 2000 years, is currently used in China and Japan to reduce chemotherapy or radiotherapy side effects in cancer patients. Despite extensive research, its effects still need improvement. This study aimed to determine if combining CV extract with LY294002, an inhibitor of the phosphatidylinositol-3-kinase (PI3K) signalling pathway, enhances cancer cell treatment, potentially leading to a novel therapeutic approach. Three human cancer cell lines (MCF-7, HeLa, and A549) were treated with CV extract alone or combined with LY294002. Cell viability was assessed using MTT assays. Then, HeLa and MCF-7 cells most sensitive to the co-treatment were used to evaluate colony formation, apoptosis, cell cycle, cell migration and invasion, and phospho-PI3K expression. The results demonstrated that LY294002 enhanced the CV extract's anti-tumour effects by reducing cell viability and colony formation. The combined treatment with CV extract and LY294002 more effectively induced G0/G1 cell cycle arrest, promoted apoptosis, reduced cell invasion and migration, and inhibited phospho-PI3K expression compared to each agent alone. This study highlights the potent cytotoxic enhancement between CV extract and LY294002 on cancer cells, primarily by inhibiting phospho-PI3K expression. These findings suggest promising avenues for developing novel combination therapies targeting cancer.

• MeSH
• apoptóza * účinky léků   MeSH
• buněčný cyklus účinky léků   MeSH
• buňky A549 MeSH
• chromony * farmakologie   MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• HeLa buňky MeSH
• inhibitory fosfoinositid-3-kinasy * farmakologie   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• morfoliny * farmakologie   MeSH
• nádorové buněčné linie MeSH
• pohyb buněk * účinky léků   MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky farmakologie   MeSH
• rostlinné extrakty farmakologie   chemie   MeSH
• signální transdukce účinky léků   MeSH
• synergismus léků MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

An activity-guided isolation study on the EtOH extract prepared from the bulbs of Prospero autumnale yielded four new phenolic compounds, including a new stilbenoid (1), a new homoisoflavonoid derivative (8), a new homoisoflavonoid dimer (9), and an unprecedented homoisoflavone-stilbene heterodimer (10), together with six known (2-7) analogs. Their chemical structures were elucidated by spectroscopic analysis and theoretical NMR and ECD calculations. Compounds 9 and 10 are unique in their scaffolds. The in vitro cytotoxic activity of purified compounds was evaluated against eight tumor cell lines (HCT116, LoVo, DU145, PC3, HEP3B, HEPG2, MCF7, and MDA-MB-231) and one nontumor cell line (L929) by the MTS assay. Compounds 1, 2, 4, and 10 exhibited inhibition with IC50 values ranging from 8.2 to 37.6 μM. Cytotoxic cell death mechanisms were further investigated, indicating variability in apoptosis, necrosis, or cell cycle arrest.

• MeSH
• apoptóza účinky léků   MeSH
• fytogenní protinádorové látky * farmakologie   chemie   MeSH
• isoflavony farmakologie   chemie   izolace a purifikace   MeSH
• kořeny rostlin chemie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• nádorové buněčné linie MeSH
• screeningové testy protinádorových léčiv MeSH
• stilbeny * farmakologie   chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Mushrooms of the genus Ganoderma are known for diverse biological activities, demonstrated both traditionally and experimentally. Their secondary metabolites have shown cytotoxic potential across different cancer cell lines. Besides exploration of the most active components in different species or genotypes, new formulation techniques are in development. In recent years, there has been a growing interest in the use of nanomaterials because of significant potential for pharmacology applications as substance carriers. Applying nanoparticles may enhance the medicinal effect of the mushroom substances. This study investigated the cytotoxic properties of Ganoderma species methanolic extracts against the HeLa cancer cell line. Notably, the extract obtained from Ganoderma pfeifferi demonstrated the highest activity and was further used for encapsulation within synthesized mesoporous silica nanoparticles MCM-41. Subsequently, the cytotoxic effect of the loaded MCM-41 to the free form of extract was compared. The obtained results indicate successful encapsulation, and similar activity comparing encapsulated form to free extracts (IC50 16.6 μg/mL and 20.5 μg/mL, respectively). In addition, the four unique compounds were identified as applanoxidic acid A, applanoxidic acid G, ganoderone A, and ganoderone B in the G. pfeifferi. This study is an essential prerequisite for further steps like nanoparticle functionalization for sustained or on-command delivery of these natural extracts.

• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Ziziphora clinopodioides subsp. bungeana (Juz.) Rech.f. is used in traditional medicine for various purposes. Previous phytochemical studies focused on phenolic compounds, but triterpenoids were almost overlooked. OBJECTIVE: The study focused on the isolation of compounds with dual antidiabetic activity from the aerial parts of Z. clinopodioides subsp. bungeana. MATERIALS AND METHODS: Separation of CHCl3-soluble fraction by silica gel column chromatography using different mobile phases and purification of compounds by semi-preparative HPLC or preparative TLC. The structures of pure compounds were elucidated by 1D and 2D NMR experiments along with HRMS. Compound 1 was additionally identified by the single crystal X-ray diffraction method. α-Glucosidase inhibitory assay and GLUT4 expression and translocation in C2C12 myotubes were conducted to evaluate antidiabetic potential of isolated compounds. RESULTS: This phytochemical study led to the isolation of 20 compounds, including a unique monoterpene diperoxy dimer (1). Compounds 7 and 9-11 displayed more potent α-glucosidase inhibitory activity (IC50 45.3-135.3 μM) than acarbose used as a positive control (IC50 264.7 μM), while only pomolic acid (5) increased GLUT4 translocation in C2C12 myotubes in a significant manner. CONCLUSION: Extensive chromatographic separation led to the isolation and identification of a unique monoterpene diperoxy dimer (1) from aerial parts of Z. clinopodioides subsp. bungeana. Some triterpenes inhibited α-glucosidase, another increased GLUT4 translocation. Although none of the isolated compounds demonstrated dual antidiabetic activity, selected triterpenes proved to be potent antidiabetic agents in vitro.

• MeSH
• alfa-glukosidasy metabolismus   MeSH
• buněčné linie MeSH
• hluchavkovité * chemie   MeSH
• hypoglykemika * farmakologie   chemie   izolace a purifikace   MeSH
• inhibitory glykosidových hydrolas farmakologie   izolace a purifikace   chemie   MeSH
• myši MeSH
• nadzemní části rostlin chemie   MeSH
• přenašeč glukosy typ 4 metabolismus   MeSH
• rostlinné extrakty chemie   farmakologie   MeSH
• triterpeny * farmakologie   chemie   izolace a purifikace   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Introduction: The use of Cannabis sativa L. in health care requires stringent care for the optimal production of the bioactive compounds. However, plant phenotypes and the content of secondary metabolites, such as phytocannabinoids, are strongly influenced by external factors, such as nutrient availability. It has been shown that phytocannabinoids can exhibit selective cytotoxicity against various cancer cell lines while protecting healthy tissue from apoptosis. Research Aim: This study aimed to clarify the cytotoxic effect of cannabis extracts on colorectal cell lines by identifying the main active compounds and determining their abundance and activity across all developmental stages of medical cannabis plants cultivated under hydroponic conditions. Materials and Methods: Dimethyl sulfoxide extracts of medical cannabis plants bearing the genotype classified as chemotype I were analyzed by high-performance liquid chromatography, and their cytotoxic activity was determined by measuring cell viability by methylthiazolyldiphenyl-tetrazolium bromide assay on the human colon cancer cell lines, Caco-2 and HT-29, and the normal human epithelial cell line, CCD 841 CoN. Results: The most abundant phytocannabinoid in cannabis extracts was tetrahydrocannabinolic acid (THCA). Its maximum concentrations were reached from the 7th to the 13th plant vegetation week, depending on the nutritional cycle and treatment. Almost all extracts were cytotoxic to the human colorectal cancer (CRC) cell line HT-29 at lower concentrations than the other cell lines. The phytocannabinoids that most affected the cytotoxicity of individual extracts on HT-29 were cannabigerol, Δ9-tetrahydrocannabinol, cannabidiol, cannabigerolic acid, and THCA. The tested model showed almost 70% influence of these cannabinoids. However, THCA alone influenced the cytotoxicity of individual extracts by nearly 65%. Conclusions: Phytocannabinoid extracts from plants of the THCA-dominant chemotype interacted synergistically and showed selective cytotoxicity against the CRC cell line, HT-29. This positive extract response indicates possible therapeutic value.

• MeSH
• Caco-2 buňky MeSH
• Cannabis * chemie   MeSH
• hydroponie MeSH
• lidé MeSH
• marihuana pro léčebné účely * MeSH
• tetrahydrokanabinol analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Several Ranunculaceae species are used in folk medicine to eliminate pathologies associated with oxidative stress as well as parasitic infections; however, a number of studies confirming their pharmacological properties is limited. In this study, 19 ethanolic extracts obtained from 16 Ranunculaceae species were assayed for in vitro antioxidant, antiproliferative, and antiparasitic potential. The maximum antioxidant potential in both oxygen radical absorbance capacity (ORAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays was observed for Aconitum toxicum extract [half-maximal inhibitory concentration (IC50) 18.7 and 92.6 μg/mL]. Likewise, Anemone transsilvanica extract exerted the most promising antiproliferative activity against Caco-2 (IC50 46.9 μg/mL) and HT29 (IC50 70.2 μg/mL) cell lines in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Additionally, a dual antioxidant and cytotoxicity effect was demonstrated for Aconitum moldavicum and Caltha palustris extracts. Whilst the efficacy of extracts was modest against Trypanosoma brucei (IC50 ranging from 88.8 to 269.3 μg/mL), several extracts exhibited high potency against Leishmania infantum promastigotes (Aconitum vulparia IC50 18.8 μg/mL). We also tested them against the clinically relevant intracellular stage and found extract of A. vulparia to be the most effective (IC50 29.0 ± 1.1 μg/mL). All tested extracts showed no or low toxicity against FHs 74Int normal cell line (IC50 ranging from 152.9 to >512 μg/mL). In conclusion, we suggest the above-mentioned plant extracts as potential candidates for development of novel plant-based antioxidant and/or antiproliferative and/or antileishmanial compounds.

• MeSH
• antioxidancia * farmakologie   chemie   MeSH
• antiparazitární látky farmakologie   chemie   MeSH
• buňky HT-29 MeSH
• Caco-2 buňky MeSH
• léčivé rostliny chemie   MeSH
• lidé MeSH
• proliferace buněk * účinky léků   MeSH
• Ranunculaceae chemie   MeSH
• rostlinné extrakty * farmakologie   chemie   MeSH
• tradiční lékařství MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Rumunsko MeSH