The marine environment is considered one of the most important ecosystems with high biodiversity. Microorganisms in this environment are variable and coexist with other marine organisms. The microbes associated with other marine organisms produce compounds with biological activity that may help the host's defense against invading organisms. The symbiotic association of bacteria with marine invertebrates is of ecological and biotechnological importance. Biologically active metabolites isolated from bacteria associated with marine invertebrates are considered potential sources of natural antimicrobial molecules for treating infectious diseases. Many studies have been conducted to screen the antimicrobial activity of metabolites produced by bacteria associated with marine invertebrates. This work provides an overview of the advancements in antimicrobial compound research on bacteria associated with marine invertebrates.

• MeSH
• antibakteriální látky * farmakologie   MeSH
• antiinfekční látky * farmakologie   metabolismus   chemie   MeSH
• Bacteria * metabolismus   izolace a purifikace   chemie   MeSH
• bezobratlí * mikrobiologie   MeSH
• symbióza MeSH
• vodní organismy * mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

INTRODUCTION: Despite being implicated in a wide spectrum of community- and healthcare-acquired infections, anaerobes have not yet been incorporated into systematic surveillance programs in Europe. METHODS: We conducted a multicentre retrospective observational study analysing all anaerobic strains isolated from blood cultures in 44 European Hospital Centres over a 4-y period (2020-2023). Diagnostic approach, epidemiology, and antimicrobial susceptibility according to EUCAST v. 15.0 were investigated. RESULTS: Our study included 14,527 anaerobes, most of which were Gram-positive (45%) or Gram-negative (40%) bacilli. MALDI-TOF coupled to mass spectrometry was the most widely used tool for species identification (98%). Antimicrobial susceptibility testing was performed in the vast majority of centres, using mostly gradient diffusion strip (77%) and disk diffusion (45%) methods according to EUCAST guidelines. The most prevalent species were Cutibacterium acnes (18.7%), Bacteroides fragilis (16.3%), Clostridium perfringens (5.3%), Bacteroides thetaiotaomicron (4.2%), Fusobacterium nucleatum (3.5%), and Parvimonas micra (3.4%). C. acnes showed high resistance to benzylpenicillin (18%), clindamycin (39%), and imipenem (19% and 13% by MIC methods and disk diffusion, respectively). B. fragilis showed high resistance to amoxicillin/clavulanate (24%), piperacillin/tazobactam (22% and 14% by MIC methods and disk diffusion, respectively), clindamycin (22% by both MIC methods and disk diffusion), meropenem (13%), and metronidazole (10%, only by disk diffusion). A similar resistance pattern was observed in B. thetaiotaomicron, Bacteroides ovatus, and Parabacteroides distasonis. C. perfringens showed high resistance to clindamycin (69% and 45% by MIC methods and disk diffusion, respectively), while benzylpenicillin and metronidazole maintained over 90% activity. F. nucleatum showed high resistance to benzylpenicillin (11%), while Fusobacterium necrophorum showed alarming rates of resistance to clindamycin (12%), meropenem (16%) and metronidazole (11%). CONCLUSIONS: This study presented an up-to-date analysis of the diagnostics and epidemiology of anaerobic bacteria in Europe, providing insights for future comparative analyses and the development of antimicrobial diagnostic and management strategies, as well as the optimization of current antibiotic treatments.

• MeSH
• anaerobní bakterie * účinky léků   izolace a purifikace   klasifikace   MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální infekce * epidemiologie   diagnóza   mikrobiologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• Geografické názvy
• Evropa MeSH

OBJECTIVE: To validate the prognostic value of the PAncreatic NeoAdjuvant MAssachusetts (PANAMA) score and to determine its predictive ability for survival benefit derived from adjuvant treatment in patients after resection of pancreatic ductal adenocarcinoma (PDAC) following neoadjuvant FOLFIRINOX. BACKGROUND: The PANAMA score was developed to guide prognostication in patients after neoadjuvant therapy and resection for PDAC. As this score focuses on the risk for residual disease after resection, it might also be able to select patients who benefit from adjuvant after neoadjuvant therapy. METHODS: This retrospective international multicenter study is endorsed by the European-African Hepato-Pancreato-Biliary Association. Patients with PDAC who underwent resection after neoadjuvant FOLFIRINOX were included. Mantel-Cox regression with interaction analysis was performed to assess the impact of adjuvant chemotherapy. RESULTS: Overall, 383 patients after resection of PDAC following neoadjuvant FOLFIRINOX were included of whom 187 (49%), 137 (36%), and 59 (15%) had a low-risk, intermediate-risk, and high-risk PANAMA-score, respectively. Discrimination in median overall survival (OS) was observed stratified by risk groups (48.5, 27.6, and 22.3 months, log-rank Plow-intermediate = 0.004, log-rank Pintermediate-high = 0.027). Adjuvant therapy was not associated with an OS difference in the low-risk group [hazard ratio (HR): 1.50, 95% CI: 0.92-2.50], whereas improved OS was observed in the intermediate (HR: 0.58, 95% CI: 0.34-0.97) and high-risk groups (HR: 0.47, 95% CI: 0.24-0.94; P interaction = 0.008). CONCLUSIONS: The PANAMA 3-tier risk groups (low-risk, intermediate-risk, and high-risk, available through pancreascalculator.com) correspond with differential survival in patients with resected PDAC following neoadjuvant FOLFIRINOX. The risk groups also differentiate between survival benefits associated with adjuvant treatment, with only the intermediate- and high-risk groups associated with improved OS.

• MeSH
• adjuvantní chemoterapie MeSH
• dospělí MeSH
• duktální karcinom slinivky břišní * mortalita   terapie   farmakoterapie   chirurgie   MeSH
• fluoruracil terapeutické užití   MeSH
• hodnocení rizik MeSH
• irinotekan terapeutické užití   MeSH
• leukovorin terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory slinivky břišní * mortalita   terapie   farmakoterapie   chirurgie   MeSH
• neoadjuvantní terapie MeSH
• oxaliplatin terapeutické užití   MeSH
• pankreatektomie * MeSH
• prognóza MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• validační studie 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

A series of new unique acetylene derivatives of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonamide 3a-f and 6a-f were prepared by reactions of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonyl chlorides with acetylene derivatives of amine. A series of new hybrid systems containing quinoline and 1,2,3-triazole systems 7a-h were obtained by reactions of acetylene derivatives of quinoline-5-sulfonamide 6a-d with organic azides. The structures of the obtained compounds were confirmed by 1H and 13C NMR spectroscopy and HR-MS spectrometry. The obtained quinoline derivatives 3a-f and 6a-f and 1,2,3-triazole derivatives 7a-h were tested for their anticancer and antimicrobial activity. Human amelanotic melanoma cells (C-32), human breast adenocarcinoma cells (MDA-MB-231), and human lung adenocarcinoma cells (A549) were selected as tested cancer lines, while cytotoxicity was investigated on normal human dermal fibroblasts (HFF-1). All the compounds were also tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and representatives of multidrug-resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis. Only the acetylene derivatives of 8-hydroxyquinoline-5-sulfonamide 3a-f were shown to be biologically active, and 8-hydroxy-N-methyl-N-(prop-2-yn-1-yl)quinoline-5-sulfonamide (3c) showed the highest activity against all three cancer lines and MRSA isolates. Its efficacies were comparable to those of cisplatin/doxorubicin and oxacillin/ciprofloxacin. In the non-cancer HFF-1 line, the compound showed no toxicity up to an IC50 of 100 μM. In additional tests, compound 3c decreased the expression of H3, increased the transcriptional activity of cell cycle regulators (P53 and P21 proteins), and altered the expression of BCL-2 and BAX genes in all cancer lines. The unsubstituted phenolic group at position 8 of the quinoline is the key structural fragment necessary for biological activity.

• MeSH
• antibakteriální látky * farmakologie   chemie   chemická syntéza   MeSH
• chinoliny * chemie   farmakologie   chemická syntéza   MeSH
• Enterococcus faecalis účinky léků   MeSH
• lidé MeSH
• mikrobiální testy citlivosti * MeSH
• molekulární struktura MeSH
• nádorové buněčné linie MeSH
• protinádorové látky * farmakologie   chemie   chemická syntéza   MeSH
• racionální návrh léčiv MeSH
• Staphylococcus aureus účinky léků   MeSH
• sulfonamidy * farmakologie   chemie   chemická syntéza   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Multiple studies indicate that iron chelators enhance their anti-cancer properties by inducing NDRG1, a known tumor and metastasis suppressor. However, the exact role of NDRG1 remains controversial, as newer studies have shown that NDRG1 can also act as an oncogene. Our group recently introduced mitochondrially targeted iron chelators deferoxamine (mitoDFO) and deferasirox (mitoDFX) as effective anti-cancer agents. In this study, we evaluated the ability of these modified chelators to induce NDRG1 and the role of NDRG1 in breast cancer. We demonstrated that both compounds specifically increase NDRG1 without inducing other NDRG family members. We have documented that the effect of mitochondrially targeted chelators is at least partially mediated by GSK3α/β, leading to phosphorylation of NDRG1 at Thr346 and to a lesser extent on Ser330. Loss of NDRG1 increases cell death induced by mitoDFX. Notably, MDA-MB-231 cells lacking NDRG1 exhibit reduced extracellular acidification rate and grow slower than parental cells, while the opposite is true for ER+ MCF7 cells. Moreover, overexpression of full-length NDRG1 and the N-terminally truncated isoform (59112) significantly reduced sensitivity towards mitoDFX in ER+ cells. Furthermore, cells overexpressing full-length NDRG1 exhibited a significantly accelerated tumor formation, while its N-terminally truncated isoforms showed significantly impaired capacity to form tumors. Thus, overexpression of full-length NDRG1 promotes tumor growth in highly aggressive triple-negative breast cancer.

• Publikační typ
• časopisecké články MeSH

Paclitaxel (PTX) is a chemotherapeutic agent affecting microtubule polymerization. The efficacy of PTX depends on the type of tumor, and its improvement would be beneficial in patients' treatment. Therefore, we tested the effect of slow sulfide donor GYY4137 on paclitaxel sensitivity in two different breast cancer cell lines, MDA-MB-231, derived from a triple negative cell line, and JIMT1, which overexpresses HER2 and is resistant to trastuzumab. In JIMT1 and MDA-MB-231 cells, we compared IC50 and some metabolic (apoptosis induction, lactate/pyruvate conversion, production of reactive oxygen species, etc.), morphologic (changes in cytoskeleton), and functional (migration, angiogenesis) parameters for PTX and PTX/GYY4137, aiming to determine the mechanism of the sensitization of PTX. We observed improved sensitivity to paclitaxel in the presence of GYY4137 in both cell lines, but also some differences in apoptosis induction and pyruvate/lactate conversion between these cells. In MDA-MB-231 cells, GYY4137 increased apoptosis without affecting the IP3R1 protein, changing the morphology of the cytoskeleton. A mechanism of PTX sensitization by GYY4137 in JIMT1 cells is distinct from MDA-MB-231, and remains to be further elucidated. We suggest different mechanisms of action for H2S on the paclitaxel treatment of MDA-MB-231 and JIMT1 breast cancer cell lines.

• MeSH
• apoptóza * účinky léků   MeSH
• chemorezistence účinky léků   MeSH
• lidé MeSH
• morfoliny * farmakologie   MeSH
• nádorové buněčné linie MeSH
• nádory prsu * farmakoterapie   patologie   metabolismus   MeSH
• organothiofosforové sloučeniny * farmakologie   MeSH
• paclitaxel * farmakologie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• sulfidy farmakologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

This study discusses the synthesis and use of a new library of spirooxindole-benzimidazole compounds as inhibitors of the signal transducer and activator of p53, a protein involved in regulating cell growth and cancer prevention. The text includes the scientific details of the [3 + 2] cycloaddition (32CA) reaction between azomethine ylide 7a and ethylene 3a within the framework of Molecular Electron Density Theory. The mechanism of the 32CA reaction proceeds through a two-stage one-step process, with emphasis on the highly asynchronous transition state structure. The anti-cancer properties of the synthesized compounds, particularly 6a and 6d, were evaluated. The inhibitory effects of these compounds on the growth of tumor cells (MDA-MB 231 and PC-3) were quantified using IC50 values. This study highlights activation of the p53 pathway by compounds 6a and 6d, leading to upregulation of p53 expression and downregulation of cyclin D and NF-κB in treated cells. Additionally, we explored the binding affinity of spirooxindole analogs, particularly compound 6d, to MDM2, a protein involved in regulation of p53. The binding mode and position of compound 6d were compared with those of a co-crystallized standard ligand, suggesting its potential as a lead compound for further preclinical research.

• Publikační typ
• časopisecké články MeSH

Fourteen diterpenes were isolated from methanol extracts of the aerial parts ofColeus comosus,Coleus forsteri "Marginatus", and Plectranthus ciliatus. The compounds belong to the abietane (1-4, 9-11, and 13), ent-clerodane (5-8), and ent-kaurane (14, 15) classes. Three new compounds were isolated from C. comosus, including 3-O-acetylornatin G (2), 3,12-di-O-acetylornatin G (3), ornatin B methyl ester (5), and ornatin F (4), for which we proposed a revised structure. The structures of the compounds were determined by comprehensive spectroscopic data analysis. The isolated diterpenes were examined in silico for their physicochemical and early ADME properties. Their antiproliferative effects were determined in vitro using human breast (MDA-MB-231 and MCF-7), cervical (HeLa), and glioblastoma (U-87 MG) cancer cell lines. The royleanone- and hydroquinone-type abietane diterpenes (9-13)exhibited the most potent antiproliferative activity against all cancer cell lines tested, particularly against glioblastoma cells, with IC50 values ranging from 1.1 to 15.6 μM.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: This paper brings new information about the genome and phenotypic characteristics of Pantoea agglomerans strain DBM 3797, isolated from fresh Czech hop (Humulus lupulus) in the Saaz hop-growing region. Although P. agglomerans strains are frequently isolated from different materials, there are not usually thoroughly characterized even if they have versatile metabolism and those isolated from plants may have a considerable potential for application in agriculture as a support culture for plant growth. METHODS: P. agglomerans DBM 3797 was cultured under aerobic and anaerobic conditions, its metabolites were analyzed by HPLC and it was tested for plant growth promotion abilities, such as phosphate solubilization, siderophore and indol-3-acetic acid productions. In addition, genomic DNA was extracted, sequenced and de novo assembly was performed. Further, genome annotation, pan-genome analysis and selected genome analyses, such as CRISPR arrays detection, antibiotic resistance and secondary metabolite genes identification were carried out. RESULTS AND DISCUSSION: The typical appearance characteristics of the strain include the formation of symplasmata in submerged liquid culture and the formation of pale yellow colonies on agar. The genetic information of the strain (in total 4.8 Mb) is divided between a chromosome and two plasmids. The strain lacks any CRISPR-Cas system but is equipped with four restriction-modification systems. The phenotypic analysis focused on growth under both aerobic and anaerobic conditions, as well as traits associated with plant growth promotion. At both levels (genomic and phenotypic), the production of siderophores, indoleacetic acid-derived growth promoters, gluconic acid, and enzyme activities related to the degradation of complex organic compounds were found. Extracellular gluconic acid production under aerobic conditions (up to 8 g/l) is probably the result of glucose oxidation by the membrane-bound pyrroloquinoline quinone-dependent enzyme glucose dehydrogenase. The strain has a number of properties potentially beneficial to the hop plant and its closest relatives include the strains also isolated from the aerial parts of plants, yet its safety profile needs to be addressed in follow-up research.

• Publikační typ
• časopisecké články MeSH