Antiproliferative Activity and Impact on Human Gut Microbiota of New O-Alkyl Derivatives of Naringenin and Their Oximes.

Naringenin is a 5,7,4'-trihydroxyflavanone naturally occurring mainly in citrus fruits, characterized by a wide spectrum of biological activity. Chemical modifications based on alkylation and oximation in most cases increase its bioactivity. The aim of our research was to evaluate the antiproliferative activity and influence on selected representatives of the human gut microbiota of new synthesized O-alkyl derivatives (A1-A10) and their oximes (B1-B10), which contain hexyl, heptyl, octyl, nonyl and undecyl chains attached to the C-7 or to both the C-7 and C-4' positions in naringenin. To the best of our knowledge, compounds A3, A4, A6, A8-A10 and B3-B10 have not been described in the scientific literature previously. The anticancer activity was tested on human colon cancer cell line HT-29 and mouse embryo fibroblasts 3T3-L1 using the sulforhodamine B (SRB) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays. We also determined the impacts of all compounds on the growth of Gram-positive and Gram-negative bacterial strains, such as Staphylococcus aureus, Enterococcus faecalis and Escherichia coli. The antimicrobial activity was expressed in terms of minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) values. For 7,4'-di-O-hexylnaringenin (A2), 7-O-undecylnaringenin (A9) and their oximes (B2, B9), which were safe for microbiota (MIC > 512 µg/mL) and almost all characterized by high cytotoxicity against the HT-29 cell line (A2: IC50 > 100 µg/mL; A9: IC50 = 17.85 ± 0.65 µg/mL; B2: IC50 = 49.76 ± 1.63 µg/mL; B9: IC50 = 11.42 ± 1.17 µg/mL), apoptosis assays were performed to elucidate their mechanisms of action. Based on our results, new compound B9 induced an apoptotic process via caspase 3/7 activation, which proved its potential as an anticancer agent.

The Identification of the Uncertainty in Soil Strength Parameters Based on CPTu Measurements and Random Fields.

The present paper responds to the challenge of modeling uncertainty in soil strength parameters concerning its spatial variability in a situation of limited soil information. Understanding this uncertainty allows for the management of the risk of geotechnical structure failure. In the present work, this uncertainty is identified based on signals from the cone penetration test (CPT) device. Signals are directly transformed using existing interpretation methods (typically used as a source of mean values of parameters for a given range of depths) to obtain depth-varying effective strength parameters of the soil. The process is performed by incorporating data from two case studies from different locations in similar soil materials. First, Keswick clay from Australia, for which the results of both CPT and laboratory tests are available, is examined. Second, to further verify the obtained results, the soil from Poland called Swierzna clay, for which only CPT signals were available, is also tested. As shown, the variability of the transformed signals can be a good source of information for identifying uncertainty in soil strength. It agrees well with literature data and can be used to identify random fields describing soil parameters.

Development of a Continuous System for 2-Phenylethanol Bioproduction by Yeast on Whey Permeate-Based Medium.

2-Phenylethanol (2-PE) is an alcohol with a rosy scent and antimicrobial activity, and therefore, it is widely used in the food and cosmetic industries as an aroma and preservative. This work was aimed to draw up a technology for 2-PE bioproduction on whey permeate, which is waste produced by the dairy industry, rich in lactase and proteins. Its composition makes it a harmful waste to dispose of; however, with a properly selected microorganism, it could be converted to a value-added product. Herein, two yeast Kluyveromyces marxianus strains and one Kluyveromyces lactis, isolated from dairy products, were tested for 2-PE production, firstly on standard media and then on whey permeate based media in batch cultures. Thereafter, the 2-PE bioproduction in a continuous system in a 4.8 L bioreactor was developed, and subsequently, the final product was recovered from culture broth. The results showed that the yield of 2-PE production increased by 60% in the continuous culture compared to batch culture. Together with a notable reduction of chemical oxygen demand for whey permeate, the present study reports a complete, effective, and environmentally friendly strategy for 2-PE bioproduction with a space-time yield of 57.5 mg L-1 h-1.

Antimicrobial O-Alkyl Derivatives of Naringenin and Their Oximes Against Multidrug-Resistant Bacteria.

New antimicrobial agents are needed to address infections caused by multidrug-resistant bacteria. Here, we are reporting novel O-alkyl derivatives of naringenin and their oximes, including novel compounds with a naringenin core and O-hexyl chains, showing activity against clinical strains of clarithromycin-resistant Helicobacter pylori, vancomycin-resistant Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, and beta-lactam-resistant Acinetobacter baumannii and Klebsiella pneumoniae. The minimum inhibitory concentrations (MICs), which provide a quantitative measure of antimicrobial activity, were in the low microgram range for the selected compounds. Checkerboard assays for the most active compounds in combination with antibiotics revealed interactions that varied from synergistic to neutral.

Effect of Naringenin and Its Derivatives on the Probing Behavior of Myzus persicae (Sulz.).

Substances that alter insect behavior have attracted a lot of attention as potential crop protection agents. Naringenin (5,7,4'-trihydroxyflavanone) is a naturally occurring bioactive flavanone. We evaluated the influence of naringenin on aphid activities during individual phases of probing and feeding and the effect of structural modifications of naringenin on its activity towards aphids. We monitored the probing behavior of Myzus persicae (Sulz.) (Hemiptera: Aphididae) using the Electrical Penetration Graph (EPG) technique. The chemical modifications were the substitution of hydrogen atoms with methyl, ethyl or pentyl groups and the replacement of the carbonyl group in naringenin and its derivatives with an oxime moiety. Depending on the substituents, the activity of naringenin-derived compounds varied in potency and mode of action. Naringenin was an attractant of moderate activity, which enhanced sap ingestion. The naringenin derivative with two methyl groups-7,4'-di-O-methylnaringenin-was a deterrent, which hindered aphid probing in non-phloem tissues. Naringenin oxime derivatives with methyl substituents-7,4'-di-O-methylnaringenin oxime, 7-O-methylnaringenin oxime, and 5,7,4'-tri-O-methylnaringenin oxime-and the derivative with a pentyl substituent-7-O-pentylnaringenin oxime-were strong attractants which stimulated aphid probing in non-phloem tissues and the ingestion of phloem sap.

The role of NEAT1 lncRNA in squamous cell carcinoma of the head and neck is still difficult to define.

INTRODUCTION: Nuclear paraspeckle assembly transcript 1 (NEAT1) is considered an oncogene in various cancers, but the role in head and neck squamous cell carcinomas (HNSCC) is not clear. MATERIAL AND METHODS: Expression of NEAT1 in HNSCC patients' samples and cell lines was analysed using qRT-PCR. The TCGA expression data of NEAT1 were analysed depending on the clinicopathological parameters and tumour localisation. Correlation and gene set enrichment analysis (GSEA) were conducted, and the results were analysed using the REACTOME and GeneMANIA tools. All statistical analyses were carried out using GraphPad Prism 5 and Statistica 13. RESULTS: The NEAT1 was up-regulated in some patients' samples and HNSCC cell lines. Moreover, TCGA data analysis indicated that the expression of NEAT1 was up-regulated in tumour tissue in most of the analysed TCGA cancers, including HNSCC. There were no significant differences in levels of NEAT1 between various tumour localisations. Overall survival of individuals with high expression of NEAT1 was slightly longer than in the low-expression group (p = 0.0553). Analysis of genes that positively and negatively correlated with NEAT1 indicated that they are involved in mRNA metabolism and cellular transport. Moreover, the GSEA revealed that in patients with low NEAT1, the most up-regulated genes were in clusters associated with the cAMP-dependent pathway, the MYC pathway, unfolded protein response, the MTORC1 signalling pathway, oxidative phosphorylation, and DNA repair. CONCLUSIONS: Patients with low expression of NEAT1 display worse overall survival, presumably due to up-regulation of certain oncogenic signalling pathways that are important for cancerogenesis.

Synthesis and Biological Evaluation of Novel Aminochalcones as Potential Anticancer and Antimicrobial Agents.

A series of 18 aminochalcone derivatives were obtained in yields of 21.5-88.6% by applying the classical Claisen-Schmidt reaction. Compounds 4-9, 14 and 16-18 with 4-ethyl, 4-carboxy-, 4-benzyloxy- and 4-benzyloxy-3-methoxy groups were novel, not previously described in the scientific literature. To determine the biological properties of the synthesized compounds, anticancer and antimicrobial activity assays were performed. Antiproliferative potential was evaluated on four different human colon cancer cell lines-HT-29, LS180, LoVo and LoVo/DX -using the SRB assay and compared with green monkey kidney fibroblasts COS7. Anticancer activity was described as the IC50 value. The best results were observed for 2'-aminochalcone (1), 3'-aminochalcone (2) and 4'-aminochalcone (3) (IC50 = 1.43-1.98 µg·mL-1) against the HT-29 cell line and for amino-nitrochalcones 10-12 (IC50 = 2.77-3.42 µg·mL-1) against the LoVo and LoVo/DX cell lines. Moreover, the antimicrobial activity of all derivatives was evaluated on two strains of bacteria: Escherichia coli ATCC10536 and Staphylococcus aureus DSM799, the yeast strain Candida albicans DSM1386 and three strains of fungi: Alternaria alternata CBS1526, Fusarium linii KB-F1 and Aspergillus niger DSM1957. In the case of E. coli ATCC10536 almost all derivatives hindered the bacterial growth (∆OD = 0). Furthermore, the best results were observed in the presence of 4'-aminochalcone (3), that completely limited the growth of all tested strains at the concentration range of 0.25-0.5 mg·mL-1. The strongest bacteriostatic activity was exhibited by novel 3'-amino-4-benzyloxychalcone (14), that prevented the growth of E. coli ATCC10536 with MIC = 0.0625 mg·mL-1.

Novel O-alkyl Derivatives of Naringenin and Their Oximes with Antimicrobial and Anticancer Activity.

In our investigation, we concentrated on naringenin (NG)-a widely studied flavanone that occurs in citrus fruits. As a result of a reaction with a range of alkyl iodides, 7 novel O-alkyl derivatives of naringenin (7a⁻11a, 13a, 17a) were obtained. Another chemical modification led to 9 oximes of O-alkyl naringenin derivatives (7b⁻13b, 16b⁻17b) that were never described before. The obtained compounds were evaluated for their potential antibacterial activity against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. The results were reported as the standard minimal inhibitory concentration (MIC) values and compared with naringenin and its known O-alkyl derivatives. Compounds 4a, 10a, 12a, 14a, 4b, 10b, 11b, and 14b were described with MIC of 25 µg/mL or lower. The strongest bacteriostatic activity was observed for 7-O-butylnaringenin (12a) against S. aureus (MIC = 6.25 µg/mL). Moreover, the antitumor effect of flavonoids was examined on human colon cancer cell line HT-29. Twenty-six compounds were characterized as possessing an antiproliferative activity stronger than that of naringenin. The replacement of the carbonyl group with an oxime moiety significantly increased the anticancer properties. The IC50 values below 5 µg/mL were demonstrated for four oxime derivatives (8b, 11b, 13b and 16b).

Mild hyperbilirubinemia as a marker of oesophageal varices in HCV-related compensated cirrhotic patients.

The natural course of compensated liver cirrhosis caused by chronic hepatitis C virus (HCV) infection is still a very interesting problem in hepatology. The prognostic usefulness of the Child-Pugh and MELD score in compensated liver cirrhosis is still debated. Consequently, several attempts have been made to determine parameters other than included in the Child-Pugh score, which could be helpful in the prognosis of compensated liver cirrhosis assessment. AIM: The aim of study was to identify a clinical or laboratory markers correlated with higher risk of liver decompensation among HCVinfected patients with compensated liver cirrhosis and presence or absence of esophageal varices. MATERIALS AND METHODS: The study included 176 HCV-infected patients with compensated liver cirrhosis (74 women and 102 men) registered in the Clinical Database of Patients with Liver Cirrhosis - e-Hepar. All patients were monitored during 252 weeks for the occurrence of liver failure symptoms and the development of hepatocellular carcinoma (HCC). RESULTS: The presence of esophageal varices was significantly associated with total bilirubin ≥2.0 mg/dl, platelets ≤110.0 G/L and 6 points in Child-Pugh score (p<0.05). The cumulative 252 weeks incidence of clinical decompensation was higher in patients with varices in comparison to patients without them (p<0.05). Variceal hemorrhages were observed in 9 cases (23.1%). During the follow-up period 9 patients died due to HCC complications. CONCLUSIONS: Our findings underline the prognostic value of serum bilirubin (even mild elevation) and platelet count in HCV-infected patients with compensated liver cirrhosis. We have confirmed that liver decompensation is more frequent and more rapid in patients with compensated liver disease and concomitant oesophageal varices.

Significance of Heparin-Binding Protein and D-dimers in the Early Diagnosis of Spontaneous Bacterial Peritonitis.

OBJECTIVES: Ascites and spontaneous bacterial peritonitis (SBP) are among the most important complications of decompensated liver cirrhosis. In clinical practice, new inflammation biomarkers are needed for the early diagnosis of SBP, as well-known biomarkers, such as C-reactive protein (CRP), procalcitonin (PCT), or peripheral blood white blood cell (WBC) count, lack the required specificity and sensitivity. The aim of the study was to evaluate the significance of heparin-binding protein (HBP) in comparison to CRP, PCT, WBC, and D-dimers in the diagnosis of SBP. DESIGN: Cross-sectional descriptive single-center study. SETTING: Department of Infectious and Tropical Diseases and Hepatology, Medical University of Warsaw, Poland. PATIENTS: All patients admitted to the aforementioned department with decompensated liver cirrhosis and ascites between February 1, 2016, and June 30, 2017. INTERVENTION: Several markers (HBP, CRP, PCT, WBC, and D-dimers) were analysed in blood serum in regard to their potential use in the diagnosis of SBP in patients with decompensated liver cirrhosis and ascites. We correlated the levels of the aforementioned markers with an ascitic fluid polymorphonuclear count using simple linear regression and multiple linear regression. Sensitivities, specificities, and positive and negative predictive values for SBP were calculated for the aforementioned makers of inflammation. MEASUREMENTS AND MAIN RESULTS: A total of 63 patients with decompensated liver cirrhosis and ascites participated in the study. The etiology of liver cirrhosis was varied (HCV: n = 40, HBV: n = 13, HCV/HBV: n = 4, AIH: n = 3, PBC: n = 2, and haemochromatosis: n = 1). After the peritoneal tap, 31 patients were determined to have SBP (defined as an ascitic fluid polymorphonuclear count > 250 cells/µL) and 32 patients had no evidence of SBP on peritoneal tap. A very weak, but statistically significant, correlation of HBP, WBC, and D-dimer levels with the peritoneal fluid polymorphonuclear (PMN) count was observed in the simple regression model, but multivariable analysis using the multiple regression model showed that only D-dimers correlated with peritoneal fluid PMNs independently from other inflammation biomarkers. A D-dimer cutoff value of 1500 ng/mL was determined optimal for ruling out SBP due to high sensitivity (96.8%) and a high negative predictive value (92.9%), although predictably, this marker was not useful for confirming SBP due to low specificity (40.6%) and a low positive predictive value (61.2%). The usefulness of D-dimers was limited by the fact that only 22.2% of the studied patients had D-dimer levels below 1500 ng/mL. HBP and WBC showed little to no predictive value in this study. CONCLUSIONS: D-dimers < 1500 ng/mL make the diagnosis of SBP unlikely, although the peritoneal tap is still the reference method in such situations. In the studied group, the determination of HBP was of no diagnostic benefit in the diagnosis of SBP.

Synthesis and Biological Activity of Novel O-Alkyl Derivatives of Naringenin and Their Oximes.

O -Alkyl derivatives of naringenin ( 1a - 10a ) were prepared from naringenin using the corresponding alkyl iodides and anhydrous potassium carbonate. The resulting products were used to obtain oximes ( 1b - 10b ). All compounds were tested for antimicrobial activity against Escherichia coli ATCC10536, Staphylococcus aureus DSM799, Candida albicans DSM1386, Alternaria alternata CBS1526, Fusarium linii KB-F1, and Aspergillus niger DSM1957. The resulting biological activity was expressed as the increase in optical density (ΔOD). The highest inhibitory effect against E. coli ATCC10536 was observed for 7,4'-di- O -pentylnaringenin ( 8a ), 7- O -dodecylnaringenin ( 9a ), naringenin oxime ( NG-OX ), 7,4'-di- O -pentylnaringenin oxime ( 8b ), and 7- O -dodecylnaringenin oxime ( 9b ) (ΔOD = 0). 7- O -dodecylnaringenin oxime ( 9b ) also inhibited the growth of S. aureus DSM799 (ΔOD = 0.35) and C. albicans DSM1386 (ΔOD = 0.22). The growth of A. alternata CBS1526 was inhibited as a result of the action of 7,4'-di- O -methylnaringenin ( 2a ), 7- O -ethylnaringenin ( 4a ), 7,4'-di- O -ethylnaringenin ( 5a ), 5,7,4'-tri- O -ethylnaringenin ( 6a ), 7,4'-di- O -pentylnaringenin ( 8a ), and 7- O -dodecylnaringenin ( 9a ) (ΔOD in the range of 0.49-0.42) in comparison to that of the control culture (ΔOD = 1.87). In the case of F. linii KB-F1, naringenin ( NG ), 7,4'-di- O -dodecylnaringenin ( 10a ), 7- O -dodecylnaringenin oxime ( 9b ), and 7,4'-di- O -dodecylnaringenin oxime ( 10b ) showed the strongest effect (ΔOD = 0). 7,4'-Di- O -pentylnaringenin ( 8a ) and naringenin oxime ( NG-OX ) hindered the growth of A. niger DSM1957 (ΔOD = 0).

Associations of the eNOS G894T gene polymorphism with target organ damage in children with newly diagnosed primary hypertension.

BACKGROUND: The endothelial nitric oxide synthase (eNOS) G894T gene polymorphism is associated with the risk of primary hypertension (PH) and vascular complications in adults with PH. METHODS: We explored the associations of the G894T polymorphism with 24-h ambulatory blood pressure, left ventricular mass (LVM), carotid intima media thickness (cIMT), urinary albumin excretion, oxidative stress and inflammatory parameters in 126 children with newly diagnosed PH and in 83 healthy children. RESULTS: Among the 126 children with PH 92 (73%) had ambulatory hypertension and 34 (27%) had severe ambulatory hypertension. Left ventricular hypertrophy (LVH) was detected in 39 (31%) patients, cIMT of >2 standard deviation scores in 21 (16.6%) patients, albuminuria of >30 mg/24 h in 18 (14.3%) patients and metabolic syndrome (MS) in 22 (17.5%) patients. The frequency of the T allele was 52.4% in the PH group and 54.2% in the control group (not significant), and in both groups the frequency of the T allele was consistent with the Hardy-Weinberg equilibrium. Compared with G allele carriers, hypertensive T allele carriers had increased cIMT (p < 0.05) and more severe albuminuria (not significant, p = 0.1); there was no difference between the groups in hypertension severity and LVM. T and G allele distribution did not differ between patients with and without metabolic syndrome. No significant correlations between the assessed parameters and the eNOS G894T gene polymorphism were found in the controls, although T allele carriers tended to have an increased cIMT (p = 0.09). CONCLUSION: The eNOS T allele is not more prevalent among hypertensive children than among healthy ones, but it is associated with early vascular damage in children with PH, independent of metabolic abnormalities. No associations between the eNOS G894T polymorphism and metabolic abnormalities were found.

[Rapid diagnosis of the most common fetal aneuploidies with the QF-PCR method--a study of 100 cases]. / Szybka diagnostyka najczestszych aneuploidii u plodu meaoda QF-PCR--analiza 100 przypadków.

UNLABELLED: The aim of the study was to assess whether commercial kit QF-PCR can be used as the only method for rapic prenatal dia gnosis of chromosomes 13, 18, 21, X and Y aneuploidies, omitting cell culture and complete cyt6genetik analysis of fetal chromosomes. MATERIAL AND METHODS: DNA from amniocytes (94 cases) and trophoblast cells (6 cases) was analyzed witt QF-PCR according to the manufacturer's protocol. The obtained products were separated using ABI 310 Genetic Analyzer and the resulting data were analyzed using GeneMarker software. RESULTS: The results of QF-PCR were obtained in 95 out of 100 cases (95%). Abnormalities were found in 28 casea (29.5%). All these results were confirmed in subsequent cytogenetic analysis. Normal results were obtained in 62 patients (70.5%). However in that group, we found three chromosomal aberrations other than those analyzed b3 QF-PCR. Additionally two abnormal and three normal karyotypes were found in patients with inconclusive QF-POF results. CONCLUSIONS: QF-PCR is a fast and reliable tool for chromosomal aneuploidy analysis and can be used as the only method without a full analysis of the karyotype, but only in cases of suspected fetal 13, 18, 21 trisomy or numerica aberrations of X chromosome. In other cases, fetal karyotype analysis from cells obtained after cell culture should be offered to the patient.

Analysis of functional efficiency and risk of falls in patients with different types of dementia - preliminary observations.

INTRODUCTION AND OBJECTIVE: Dementia is a multifactorial neurological disease that affects 50 million people worldwide. It is a disorder that impairs cognitive functions, functional efficiency, balance and gait. It contributes to an increased risk of falls, reduces independence in everyday activities and deepens disability. The aim of the study was to investigate the correlation between dementia and independence related to functional efficiency and risk of falls in the elderly. MATERIAL AND METHODS: The eligibility criterion for participation in the study was age over 60, the presence of cognitive disorders, including dementia, and the ability to move with the use of orthopaedic equipment or independently. A total of 51 people participated in the study, including 13 people who underwent rehabilitation procedures. Each subject was evaluated once for cognitive abilities using two types of tests: the ADL scale, MMSE (Mini-Mental state Examination) and three physical fitness tests: SPPB (Short Physical Performance Battery), TUG (Timed Up & Go) and FRT (Functional Reach Test). RESULTS: The average score of the MMSE test was 13.29±6.23 points, the average of the ADL scale was 4.20±1.23 points. A positive correlation was found between the level of dementia and the independence of the examined person, as well as a positive relationship between the MMSE test and the result of the Functional Reach Test, and the relationship between the ADL scale and the SPPB and 'Get-Up and Go' tests. CONCLUSIONS: It has been demonstrated inter alia that static balance and functional efficiency depends on the patient's independence in everyday activities, and the level of dementia may suggest the patient's dynamic balance. In addition, the need for a broader analysis of targeted studies was recognized to confirm the conclusions obtained.

Is Camphor the Future in Supporting Therapy for Skin Infections?

The aim of this review is to present the potential application of camphor-a bicyclic monoterpene ketone-in the prevention of skin infections. Skin diseases represent a heterogeneous group of disorders characterized by prolonged symptoms that significantly diminish the quality of life. They affect the dermis, the epidermis, and even subcutaneous tissue. They very often have a bacterial or fungal background. Therapy for dermatological skin disorders is difficult and long-term. Therefore, it is important to find a compound, preferably of natural origin, that (i) prevents the initiation of this infection and (ii) supports the skin's repair process. Based on its documented anti-inflammatory, antibacterial, antifungal, anti-acne, anesthetic, strengthening, and warming properties, camphor can be used as a preventative measure in dermatological infectious diseases and as a component in medical and cosmetic products. This work discusses the structure and physicochemical properties of camphor, its occurrence, and methods of obtaining it from natural sources as well as through chemical synthesis. The use of camphor in industrial preparations is also presented. Additionally, after a detailed review of the literature, the metabolism of camphor, its interactions with other medicinal substances, and its antimicrobial properties against bacteria and fungi involved in skin diseases are discussed with regard to their resistance.

Interaction of selected alkoxy naringenin oximes with model and bacterial membranes.

Naringenin is a flavonoid found in many fruits and herbs, most notably in grapefruits. In recent years, this compound and its derivatives have been of great interest due to their high biological activity, including fungicidal and bactericidal effects, also in relation to multidrug-resistant bacteria. Membrane interactions of naringenin oxime (NO) and its 7-O-alkyl (7-alkoxy) derivatives, such as methyl (7MENO), ethyl (7ETNO), isopropyl (7IPNO), n-butyl (7BUNO) and n-pentyl (7PENO) were studied. Thermotropic properties of model membranes were investigated via differential scanning calorimetry (DSC), the influence on lipid raft mimicking giant unilamellar vesicles (GUVs) via fluorescence microscopy, and membrane permeability via measuring calcein leakage from liposomes. Molecular calculations supplemented the study. The influence of naringenin oximes on two strains of multidrug resistant bacteria: Staphylococcus aureus KJ and Enterococcus faecalis 37VRE was also investigated. In DSC studies all compounds reduced the temperature and enthalpy of main phase transition and caused disappearing of the pretransition. NO was the least active. The reduction in the area of surface domains in GUVs was observed for NO. Compounds NO and 7BUNO resulted in very low secretion of calcein from liposomes (permeability < 3 %). The highest results were observed for 7MENO (88.4 %) and 7IPNO (78.5 %). When bacterial membrane permeability was investigated all compounds caused significant release of propidium iodide from S. aureus (31.6-87.0 % for concentration 128 µg/mL). In the case of E. faecalis, 7ETNO (75.7 %) and NO (28.8 %) were the most active. The rest of the tested compounds showed less activity (permeability < 13.9 %). The strong evidence was observed that antibacterial activity of the tested compounds may be associated with their interaction with bacterial membrane.

Distribution of HCV genotypes in Poland.

UNLABELLED: Available data on prevalence of HCV genotypes in Poland are insufficient. The aim of the study was the analysis of distribution of HCV genotypes in Poland over the period of recent 10 years regarding the age of patients and the regions of the country. MATERIAL AND METHODS: Analysis of HCV genotypes in Poland was carried out between 2003 and 2012, and included 14 651 patients from 22 centers where patients with chronic viral hepatitis C are diagnosed and treated. Genotypes were analyzed in age groups (< 20 years of age, 20-40 years of age, > 40 years of age) as well as in populations of HBV and HIV co-infections. RESULTS: Genotype (G) 1 infection was demonstrated in 79.4%, G2 -0.1%, G3- 13.8%, G4- 4.9%, G6-0.09% and mixed infections in 1.6%. There was no infection with genotype 5. The highest prevalence of G1 was observed in the Lódzkie voivodship (89.2%) and the Slaskie voivodship (86.7%) while the lowest one in the Warminsko-mazurskie (62.0%) and the Podlaskie voivodships (68.2%). Genotype 3 most commonly occurs in the Warminsko-mazurskie (28.1%), and the Podlaskie voivodships (23.0%) and is least common in the Malopolskie (7.9%) and the Lódzkie voivodships (9.0%). Genotype 4 is more common in the Kujawsko-pomorskie (11.7%) and the Podlaskie voivodships (8.6%) and relatively less common in the Lubelskie (1.1%) and the Lódzkie voivodships (1.8%). Prevalence of G1 infection in 2003-2004 was 72% and increased up to 85.6% in 2011-2012, that was accompanied by decrease of G3 prevalence from 17% to 8% in this period. In HBV co-infected (n = 83), G1 infection was demonstrated in 85.5%, G3 - in 7.2%, G4 -4.8%, and mixed genotypes in 6%. Among HIV co-infected (n = 391), a much lower prevalence of G1 (33.0%) and a high of G3 (40.4%) as well as G4 (24.0%) were observed. CONCLUSIONS: There is a geographic variability of HCV genotypes prevalence in Poland. Increase of HCV G1 infections and decrease of G3 and G4 were observed in the last 10 years. Genotypes G3 and G4 occur more often in HCV/HIV co-infected than in HCV mono-infected patients.

Ether Derivatives of Naringenin and Their Oximes as Factors Modulating Bacterial Adhesion.

Because of the close connection between adhesion and many vital cellular functions, the search for new compounds modulating the adhesion of bacteria belonging to the intestinal microbiota is a great challenge and a clinical need. Based on our previous studies, we discovered that O-lkyl naringenin derivatives and their oximes exhibit antimicrobial activity against antibiotic-resistant pathogens. The current study was aimed at determining the modulatory effect of these compounds on the adhesion of selected representatives of the intestinal microbiota: Escherichia coli, a commensal representative of the intestinal microbiota, and Enterococcus faecalis, a bacterium that naturally colonizes the intestines but has disease-promoting potential. To better reflect the variety of real-life scenarios, we performed these studies using two different intestinal cell lines: the physiologically functioning ("healthy") 3T3-L1 cell line and the disease-mimicking, cancerous HT-29 line. The study was performed in vitro under static and microfluidic conditions generated by the Bioflux system. We detected the modulatory effect of the tested O-alkyl naringenin derivatives on bacterial adhesion, which was dependent on the cell line studied and was more significant for E. coli than for E. faecalis. In addition, it was noticed that this activity was affected by the concentration of the tested compound and its structure (length of the carbon chain). In summary, O-alkyl naringenin derivatives and their oximes possess a promising modulatory effect on the adhesion of selected representatives of the intestinal microbiota.

Assessment of chromosomal imbalances in CIMP-high and CIMP-low/CIMP-0 colorectal cancers.

Data presented in a number of recent studies have revealed a negative correlation between CpG island methylator phenotype (CIMP) and chromosomal instability (CIN) measured by a loss of heterozygosity (LOH) of selected loci, suggesting that CIN and CIMP represent two independent mechanisms in sporadic colorectal cancer (CRC) carcinogenesis. However, CIN is a heterogeneous phenomenon, which may be studied not only by employing LOH analysis but also by observing chromosomal imbalances (gains and deletions). The current study aimed to investigate the relationship between CIMP and chromosomal gains and deletions (assessed by comparative genomic hybridization) in a group of 20 CIMP-high and 79 CIMP-low/CIMP-0 CRCs. Our results revealed that the mean numbers of gains and of total chromosomal imbalances were significantly greater (p = 0.004 and p = 0.007, respectively) in the CIMP-low/CIMP-0 group compared to the CIMP-high group, while no significant difference was observed between the mean numbers of losses (p = 0.056). The analysis of copy number changes of 41 cancer-related genes by multiplex ligation-dependent probe amplification showed that CRK gene was exclusively deleted in CIMP-low/CIMP-0 tumors (p = 0.02). Given that chromosomal losses play an important role in tumor suppressor inactivation and chromosomal gains, in the activation of proto-oncogenes, we hypothesize that tumor suppressor inactivation plays similar roles in both CIMP-high and CIMP-low/CIMP-0 CRCs, while the predominance of chromosomal gains in CIMP-low/CIMP-0 tumors may suggest that the activation of proto-oncogenes is the underlying mechanism of CIMP-low/CIMP-0 CRC progression.

Oxidative stress in hypertensive children before and after 1 year of antihypertensive therapy.

BACKGROUND: The relation between primary hypertension (PH), target organ damage (TOD) and oxidative stress (SOX) is not known. METHODS: We assessed SOX in 86 children with PH before and after 12 months of standard non-pharmacological and pharmacological therapy based on renin-angiotensin system blockade. RESULTS: Patients with left ventricular hypertrophy (LVH) and with carotid intima-media thickness (cIMT) >2SDS had higher thiobarbituric acid reactive substances (TBARS) concentrations in comparison to patients without LVH or with normal cIMT. Patients with metabolic syndrome (MS) had lower activity of gluthatione peroxidase, higher asymmetric dimethyloarginine (ADMA) and oxidized LDL cholesterol (oxyLDL) in comparison to patients without MS. TBARS correlated with left ventricular concentric hypertrophy, cIMT, albuminuria and SBP/24 h. ADMA and oxyLDL correlated with CRP and TG/HDL ratio. After 1 year of antihypertensive treatment blood pressure, TOD and prevalence of MS decreased. TBARS decreased and glutathione concentrations increased. The decrease of TBARS concentration correlated with the decrease of body mass index (BMI). Decrease of oxyLDL and ADMA correlated with increased insulin sensitivity, however markers of SOX did not correlate with BP decrease. CONCLUSION: SOX in children with PH correlates with TOD, metabolic abnormalities, changes in fat amount and improvement of insulin sensitivity, but not with BP decrease.