Role of HMOX1 Promoter Genetic Variants in Chemoresistance and Chemotherapy Induced Neutropenia in Children with Acute Lymphoblastic Leukemia

Whilst the survival rates of childhood acute lymphoblastic leukemia (ALL) have increased remarkably over the last decades, the therapy resistance and toxicity are still the major causes of treatment failure. It was shown that overexpression of heme oxygenase-1 (HO-1) promotes proliferation and chemoresistance of cancer cells. In humans, the HO-1 gene (HMOX1) expression is modulated by two polymorphisms in the promoter region: (GT)n-length polymorphism and single-nucleotide polymorphism (SNP) A(−413)T, with short GT repeat sequences and 413-A variants linked to an increased HO-1 inducibility. We found that the short alleles are significantly more frequent in ALL patients in comparison to the control group, and that their presence may be associated with a higher risk of treatment failure, reflecting the role of HO-1 in chemoresistance. We also observed that the presence of short alleles may predispose to develop chemotherapy-induced neutropenia. In case of SNP, the 413-T variant co-segregated with short or long alleles, while 413-A almost selectively co-segregated with long alleles, hence it is not possible to determine if SNPs are actually of phenotypic significance. Our results suggest that HO-1 can be a potential target to overcome the treatment failure in ALL patients.     

Effect of Aminated Chitosan-Coated Fe3O4 Nanoparticles with Applicational Potential in Nanomedicine on DPPG,DSPC, and POPC Langmuir Monolayers as Cell Membrane Models

An adsorption process of magnetite nanoparticles functionalized with aminated chitosan (Fe₃O₄-AChit) showing application potential in nanomedicine into cell membrane models was studied. The cell membrane models were formed using a Langmuir technique from three selected phospholipids with different polar head-groups as well as length and carbon saturation of alkyl chains. The research presented in this work reveals the existence of membrane model composition-dependent regulation of phospholipid-nanoparticle interactions. The influence of the positively charged Fe₃O₄-AChit nanoparticles on a Langmuir film stability, phase state, and textures is much greater in the case of these formed by negatively charged 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG) than those created by zwitterionic 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC). The adsorption kinetics recorded during penetration experiments show that this effect is caused by the strongest adsorption of the investigated nanoparticles into the DPPG monolayer driven very likely by the electrostatic attraction. The differences in the adsorption strength of the Fe₃O₄-AChit nanoparticles into the Langmuir films formed by the phosphatidylcholines were also observed. The nanoparticles adsorbed more easily into more loosely packed POPC monolayer.     

Analytical and experimental analysis of deep drawing process for bimetal elements

The paper presents the concepts of solving of deep drawing process for bimetal elements of sheet materials. The inertia forces, plastic hardening behaviour of the deformed material and dynamic stress are utilized in the problems of plasticity. The experimental results and general conclusion are presented at the end of the paper.     

Potential of Silver Nanoparticles in Overcoming the Intrinsic Resistance of Pseudomonas aeruginosa to Secondary Metabolites from Carnivorous Plants

Carnivorous plants are exemplary natural sources of secondary metabolites with biological activity. However, the therapeutic antimicrobial potential of these compounds is limited due to intrinsic resistance of selected bacterial pathogens, among which Pseudomonas aeruginosa represents an extreme example. The objective of the study was to overcome the intrinsic resistance of P. aeruginosa by combining silver nanoparticles (AgNPs) with secondary metabolites from selected carnivorous plant species. We employed the broth microdilution method, the checkerboard titration technique and comprehensive phytochemical analyses to define interactions between nanoparticles and active compounds from carnivorous plants. It has been confirmed that P. aeruginosa is resistant to a broad range of secondary metabolites from carnivorous plants, i.e., naphthoquinones, flavonoids, phenolic acids (MBC = 512 µg mL⁻¹) and only weakly sensitive to their mixtures, i.e., extracts and extracts’ fractions. However, it was shown that the antimicrobial activity of extracts and fractions with a significant level of naphthoquinone (plumbagin) was significantly enhanced by AgNPs. Our studies clearly demonstrated a crucial role of naphthoquinones in AgNPs and extract interaction, as well as depicted the potential of AgNPs to restore the bactericidal activity of naphthoquinones towards P. aeruginosa. Our findings indicate the significant potential of nanoparticles to modulate the activity of selected secondary metabolites and revisit their antimicrobial potential towards human pathogenic bacteria.     

Anti-Inflammatory Activity of Oat Beta-Glucans in a Crohn’s Disease Model: Time- and Molar Mass-Dependent Effects

Background: The incidence of Crohn’s disease (CD) is increasing worldwide, and it has currently become a serious public health issue in society. The treatment of CD continues throughout a patient’s lifetime, and therefore, it is necessary to develop new, effective treatment methods, including dietotherapy. The present study aimed to determine the effects of consumption of oat beta-glucans with different molar mass on colon inflammation (colitis) in the early stages of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD in an animal model. Methods: Sprague–Dawley rats (control and TNBS-induced CD) were divided into three dietary groups and fed for 3 days (reflecting acute inflammation) or 7 days (reflecting remission) with a feed containing 1% low (βGl) or high (βGh) molar mass oat beta-glucan or a feed without this polysaccharide. The level of colon inflammatory markers and the expression of cytokines and their receptor genes were measured by ELISA and RT-PCR methods, respectively. Results: Acute inflammation or remission (3 or 7 days after TNBS administration, respectively) stages of experimentally induced CD were characterized by an increase in the level of inflammatory markers (IL-1, IL-6, IL-10, IL-12, TNF-α, CRP, MPO, COX, and PGE2) and the disruption of some cytokine signaling pathways as well as macro- and microscopic changes of colon tissue. The consumption of oat beta-glucans reduced the level of inflammatory markers and recovered the signaling pathways and histological changes, with stronger effects of βGl after 7 days of colitis. Conclusions: Dietary oat beta-glucans can reduce colitis at the molecular and organ level and accelerate CD remission.     

Polymorphisms in EGFR Gene Predict Clinical Outcome in Unresectable Non-Small Cell Lung Cancer Treated with Radiotherapy and Platinum-Based Chemoradiotherapy

For non-small cell lung cancer (NSCLC), radiotherapy (RT) and platinum-based chemotherapy (CHT) are among the main treatment options. On the other hand, radioresistance and cytotoxic drug resistance are common causes of failure. The epidermal growth factor receptor (EGFR) plays an important role in radioresponse and therapy resistance. We hypothesized that single nucleotide polymorphisms (SNPs) in the EGFR gene might affect individual sensitivity to these treatments, and thus, therapy outcome and prognosis. The association between functional EGFR SNPs and overall (OS), locoregional recurrence-free (LFRS), and metastasis-free (MFS) survival was examined in 436 patients with unresectable NSCLC receiving RT and platinum-based CHTRT. In a multivariate analysis, the rs712830 CC homozygotes showed reduced OS in the whole group (p = 0.039) and in the curative treatment subset (p = 0.047). The rs712829 TT genotype was strongly associated with decreased LRFS (p = 0.006), and the T-C haplotype was a risk factor for locoregional recurrence in our patients (p = 0.003). The rs2227983 GG alone and in combination with rs712829 T was an indicator of unfavorable LRFS (p = 0.028 and 0.002, respectively). Moreover, significant independent effects of these SNPs on OS, LRFS, and MFS were observed. Our results demonstrate that inherited EGFR gene variants may predict clinical outcomes in NSCLC treated with DNA damage-inducing therapy.     

Microstructure and Mechanical Properties of the Ductile Al–Ti–Mo–Nb–V Refractory High Entropy Alloys

Metallurgical and Materials Transactions A - A number of non-equimolar refractory high entropy alloys (RF HEAs) from the Al–Ti–Mo–Nb–V system are synthesized, with the...     

Detecting Fixed Patterns in Chordal Graphs in Polynomial Time

The Contractibility problem takes as input two graphs G and H, and the task is to decide whether H can be obtained from G by a sequence of edge contractions. The Induced Minor and Induced Topological Minor problems are similar, but the first allows both edge contractions and vertex deletions, whereas the latter allows only vertex deletions and vertex dissolutions. All three problems are NP-complete, even for certain fixed graphs H. We show that these problems can be solved in polynomial time for every fixed H when the input graph G is chordal. Our results can be considered tight, since these problems are known to be W[1]-hard on chordal graphs when parameterized by the size of H. To solve Contractibility and Induced Minor, we define and use a generalization of the classic Disjoint Paths problem, where we require the vertices of each of the k paths to be chosen from a specified set. We prove that this variant is NP-complete even when k=2, but that it is polynomial-time solvable on chordal graphs for every fixed k. Our algorithm for Induced Topological Minor is based on another generalization of Disjoint Paths called Induced Disjoint Paths, where the vertices from different paths may no longer be adjacent. We show that this problem, which is known to be NP-complete when k=2, can be solved in polynomial time on chordal graphs even when k is part of the input. Our results fit into the general framework of graph containment problems, where the aim is to decide whether a graph can be modified into another graph by a sequence of specified graph operations. Allowing combinations of the four well-known operations edge deletion, edge contraction, vertex deletion, and vertex dissolution results in the following ten containment relations: (induced) minor, (induced) topological minor, (induced) subgraph, (induced) spanning subgraph, dissolution, and contraction. Our results, combined with existing results, settle the complexity of each of the ten corresponding containment problems on chordal graphs.     

Upgrading a Granular Computing Based Data Mining Framework to a Relational Case

One of the popular methods to develop an algorithm for mining data stored in a relational structure is to upgrade an existing attribute‐value algorithm to a relational case. Current approaches to this problem have some shortcomings such as (1) a dependence on the upgrading process of the algorithm to be extended, (2) complicated redefinitions of crucial notions (e.g., pattern generality, pattern refinement), and (3) a tolerant limitation of the search space for pattern discovery. In this paper, we propose and evaluate a general methodology for upgrading a data mining framework to a relational case. This methodology is defined in a granular computing environment. Thanks to our relational extension of a granular computing based data mining framework, the three above problems can be overcome.