The paper deals with anti-yeast activity of ethanolic extracts from the flowers and bulbs of Lilium candidum L., Liliaceae, as well as some compounds isolated from these extracts. Several different ...methods were used for the determination of anti-yeast activity: Lowry method of protein determination, dilution and cultivation method. The extract from the bulbs was shown to be more active than the extract from the flowers, while isolated compounds were inactive against the tested yeasts.
Antifungal activity of new copper(II) complexes of 2-methylthionicotinate (2-MeSNic) of the composition Cu(2-MeSNic)2(MeNia)2·4H2O (where MeNia isN-methylnicotinamide), and Cu(2-MeSNic)2(Nia)2·2H2O ...(where Nia is nicotinamide) and Cu(2-MeSNic)2L2 (where L is isonicotinamide, iNia, or ethyl nicotinate, EtNic) were tested on various strains of filamentous fungi by the macrodilution method. Most sensitive against copper(II) adducts with bioactive ligands wereRhizopus oryzae andMicrosporum gypseum (IC50 1.5–2.3 mmol/L). The adducts with Nia, MeNia and EtNic at 5 mmol/L induced morphological changes in growing hyphae ofBotrytis cinerea, mainly their intensive branching attached to release of cytoplasm with partial growth inhibition. Inhibition of sporulation (>90%) ofAlternaria alternata by Cu(2-MeSNic)2·H2O was observed as a change in the color of the colonies. The highest resistance was marked byB. cinerea andFusarium moniliforme (average IC50 values 4.25 and 3.13 mmol/L, respectively). The presence of all bioactive ligands in copper(II) complexes caused an increase in the inhibition effect against model fungi (except significant inhibition activity of EtNic onR. oryzae).
Inhibition of the chemokine receptor CXCR4 in combination with blockade of the PD-1/PD-L1 T cell checkpoint induces T cell infiltration and anticancer responses in murine and human pancreatic cancer. ...Here we elucidate the mechanism by which CXCR4 inhibition affects the tumor immune microenvironment. In human immune cell-based chemotaxis assays, we find that CXCL12-stimulated CXCR4 inhibits the directed migration mediated by CXCR1, CXCR3, CXCR5, CXCR6, and CCR2, respectively, chemokine receptors expressed by all of the immune cell types that participate in an integrated immune response. Inhibiting CXCR4 in an experimental cancer medicine study by 1-wk continuous infusion of the small-molecule inhibitor AMD3100 (plerixafor) induces an integrated immune response that is detected by transcriptional analysis of paired biopsies of metastases from patients with microsatellite stable colorectal and pancreatic cancer. This integrated immune response occurs in three other examples of immunemediated damage to noninfected tissues: Rejecting renal allografts, melanomas clinically responding to anti-PD1 antibody therapy, and microsatellite instable colorectal cancers. Thus, signaling by CXCR4 causes immune suppression in human pancreatic ductal adenocarcinoma and colorectal cancer by impairing the function of the chemokine receptors that mediate the intratumoral accumulation of immune cells.
The objective of the paper was to check and compare the sensitivity of four detection systems used parallelly: disk diffusion method, INTEST, DELVOTEST SP and PENZYME S 100 with respect to detection ...of selected beta-lactam antibiotics in milk (penicillin G, amoxycillin, oxacyllin, cefotaxim, cefuroxim, cephamandol). The sensitivity of applied tests was found to be different. High sensitivity and satisfactory correlation of the results (PNC G, amoxycillin, oxacillin) was achieved in most cases by the use of three rapid methods (INTEST, DELVOTEST SP, PENZYME S 100) in comparison with a disk diffusion method of lower sensitivity. Experimentally determined detected limits for cephalosporin antibiotics indicate higher sensitivity of DELVOTEST SP and PENZYME S 100 if used as a diffusion method.
Biological properties of new copper(II) complexes of 2-methylthionicotinate (2-MeSNic) of composition Cu(2-MeSNic)2(MeNia)2·4H2O (where MeNia isN-methylnicotinamide), Cu(2-MeSNic)2(Nia)2·2H2O (where ...Nia is nicotinamide) and Cu(2-MeSNic)2(2 (where L is isonicotinamide (iNia) or ethyl nicotinate (EtNic)) are reported. Gram−-bacteria (Escherichia coli) are more resistant against Cu(II) complexes than Gram+-bacteria (Staphylococcus aureus)—significant antistaphylococcal activity was found with Cu(2-MeSNic)2(MeNia)2·4H2O (IC50 1.3 mmol/L).Caddida parapsilosis was most inhibited by Cu(2-MeSNic)2·H2O and Cu(2-MeSNic)2(MeNia)2·4H2O (IC50 1.4 mmol/L and 1.5 mmol/L, respectively). Biosynthesis of nucleic acids influenced by Cu(2-MeSNic)2-(Nia)2·2H2O indicated by incorporation of14C-adenine (IC50(Ade) 0.31 mmol/L) is more sensitive than biosynthesis of proteins indicated by incorporation of14C-leucine (IC50(Leu) 9.94 mmol/L). Cu(II) complexes with expressed antimicrobial activity showed no mutagenic activity.
Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma ...contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >10
informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to parts per million. This resulted in median area under the curve (AUC) values of 0.98 in advanced cancers and 0.80 in early-stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that INVAR may be applied without requiring personalized sequencing panels so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.
Existing methods to improve detection of circulating tumor DNA (ctDNA) have focused on genomic alterations but have rarely considered the biological properties of plasma cell-free DNA (cfDNA). We ...hypothesized that differences in fragment lengths of circulating DNA could be exploited to enhance sensitivity for detecting the presence of ctDNA and for noninvasive genomic analysis of cancer. We surveyed ctDNA fragment sizes in 344 plasma samples from 200 patients with cancer using low-pass whole-genome sequencing (0.4×). To establish the size distribution of mutant ctDNA, tumor-guided personalized deep sequencing was performed in 19 patients. We detected enrichment of ctDNA in fragment sizes between 90 and 150 bp and developed methods for in vitro and in silico size selection of these fragments. Selecting fragments between 90 and 150 bp improved detection of tumor DNA, with more than twofold median enrichment in >95% of cases and more than fourfold enrichment in >10% of cases. Analysis of size-selected cfDNA identified clinically actionable mutations and copy number alterations that were otherwise not detected. Identification of plasma samples from patients with advanced cancer was improved by predictive models integrating fragment length and copy number analysis of cfDNA, with area under the curve (AUC) >0.99 compared to AUC <0.80 without fragmentation features. Increased identification of cfDNA from patients with glioma, renal, and pancreatic cancer was achieved with AUC > 0.91 compared to AUC < 0.5 without fragmentation features. Fragment size analysis and selective sequencing of specific fragment sizes can boost ctDNA detection and could complement or provide an alternative to deeper sequencing of cfDNA.
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