Bioactive potential of Mentha arvensis L. essential oil.

The aim of this study was to evaluate the phytotoxic, genotoxic, cytotoxic and antimicrobial effects of the Mentha arvensis L. essential oil (EO). The biological activity of M. arvensis EO depended on the analyzed variable and the tested oil concentration. Higher concentrations of EO (20 and 30 µg mL-1) showed a moderate inhibitory effect on the germination and growth of seedlings of tested weed species (Bellis perennis, Cyanus segetum, Daucus carota, Leucanthemum vulgare, Matricaria chamomilla, Nepeta cataria, Taraxacum officinale, Trifolium repens and Verbena × hybrida). The results obtained also indicate that the EO of M. arvensis has some genotoxic, cytotoxic and proliferative potential in both plant and human in vitro systems. Similar results were obtained for antimicrobial activity against eight bacteria, including multidrug-resistant (MDR) strains [Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Escherichia coli, extended-spectrum beta-lactamase-producing (ESBL) E. coli, Pseudomonas aeruginosa and Salmonella enterica subsp. enterica serovar Enteritidis], with the effect on multidrug-resistant bacterial strains. Research indicates that the EO of M. arvensis shows phytotoxic, genotoxic, cytotoxic and antimicrobial effects, as well as its potential application as a herbicide and against various human diseases.

In vitro assessment of the antioxidative, toxicological and antimicrobial properties of battery of parabens.

The aim of this study was to evaluate antioxidative features using 2,2-diphenyl-1-pycrylhydrazyl free radical (DPPH•) scavenging method, bovine serum albumin (BSA)-binding properties with usage of spectrofluorimetric method, proliferative and cyto/genotoxic status by use of chromosome aberration test, and antimicrobial potential using broth microdilution method, followed by resazurin assay of benzyl-, isopropyl-, isobutyl and phenylparaben in vitro. Our results showed that all parabens had significant antiradical scavenger activity compared to p-hydroxybenzoic acid (PHBA) precursor. Higher mitotic index for benzyl-, isopropyl and isobutylparaben (250 µg/mL) in comparison with control was demonstrated. An increase in the frequency of acentric fragments in lymphocytes treated with benzylparaben and isopropylparaben (125 and 250 µg/mL), and isobutylparaben (250 µg/mL) was observed. Isobutylparaben (250 µg/mL) induced higher number of dicentric chromosomes. An increased number of minute fragments in lymphocytes exposed to benzylparaben (125 and 250 µg/mL) was found. A significant difference in the frequency of chromosome pulverization, between phenylparaben (250 µg/mL) and control, was detected. Benzylparaben (250 µg/mL) and phenylparaben (62.5 µg/mL) caused an increase in the number of apoptotic cells, while isopropylparaben (62.5, 125 and 250 µg/mL) and isobutylparaben (62.5 and 125 µg/mL) induced higher frequency of necrosis. Minimum inhibitory concentration (MIC) of tested parabens ranged 15.62-250 µg/mL for bacteria, and 125-500 µg/mL for the yeast. Minimum microbiocidal concentration ranged 31.25 to 500 µg/mL, and 250 to 1000 µg/mL in bacteria and fungi respectively. The lowest MICs for bacteria were observed for phenyl- (15.62 µg/mL) and isopropylparaben (31.25 µg/mL) against Enterococcus faecalis.

Evaluation of toxicological and antimicrobial activity of lavender and immortelle essential oils.

Lavender and immortelle essential oils (EOs) are widely used to treat a spectrum of human conditions. The aim of this study was to investigate cyto/genotoxic effects of lavender and immortelle EOs using plant cells (Allium cepa) and human lymphocytes, as well as their antimicrobial potential using nine strains of bacteria and fungi. Our results for lavender and immortelle EOs showed that the frequency of chromosome aberrations (CAs) was increased in comparison with controls. For both oils, increased frequency of apoptosis for all concentrations, as well as the frequency of necrosis (0.10/0.30 µl/ml for lavender/immortelle, respectively) was demonstrated. In human lymphocytes, differences for minute fragments between immortelle oil (0.10 µl/ml) and controls were observed. Increased frequency of apoptosis was detected for immortelle oil (0.20 µl/ml), while both oils (0.20; 0.30 µl/ml lavender, and immortelle at all concentrations) induced higher frequency of necrosis in comparison with controls. Lavender EO was effective against all tested Gram-positive and Gram-negative bacteria, while immortelle EO inhibited only Gram-positive bacteria. Both oils exhibited antifungal effect. Our results demonstrated that lavender and immortelle EOs showed cyto/genotoxic effects in both, plant and human cells, as well as antimicrobial properties. Further studies are needed to strengthen these findings.

Characterization and risk association of polymorphisms in Aurora kinases A, B and C with genetic susceptibility to gastric cancer development.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in genes encoding mitotic kinases could influence development and progression of gastric cancer (GC). METHODS: Case-control study of nine SNPs in mitotic genes was conducted using qPCR. The study included 116 GC patients and 203 controls. In silico analysis was performed to evaluate the effects of polymorphisms on transcription factors binding sites. RESULTS: The AURKA rs1047972 genotypes (CT vs. CC: OR, 1.96; 95% CI, 1.05-3.65; p = 0.033; CC + TT vs. CT: OR, 1.94; 95% CI, 1.04-3.60; p = 0.036) and rs911160 (CC vs. GG: OR, 5.56; 95% CI, 1.24-24.81; p = 0.025; GG + CG vs. CC: OR, 5.26; 95% CI, 1.19-23.22; p = 0.028), were associated with increased GC risk, whereas certain rs8173 genotypes (CG vs. CC: OR, 0.60; 95% CI, 0.36-0.99; p = 0.049; GG vs. CC: OR, 0.38; 95% CI, 0.18-0.79; p = 0.010; CC + CG vs. GG: OR, 0.49; 95% CI, 0.25-0.98; p = 0.043) were protective. Association with increased GC risk was demonstrated for AURKB rs2241909 (GG + AG vs. AA: OR, 1.61; 95% CI, 1.01-2.56; p = 0.041) and rs2289590 (AC vs. AA: OR, 2.41; 95% CI, 1.47-3.98; p = 0.001; CC vs. AA: OR, 6.77; 95% CI, 2.24-20.47; p = 0.001; AA+AC vs. CC: OR, 4.23; 95% CI, 1.44-12.40; p = 0.009). Furthermore, AURKC rs11084490 (GG + CG vs. CC: OR, 1.71; 95% CI, 1.04-2.81; p = 0.033) was associated with increased GC risk. A combined analysis of five SNPs, associated with an increased GC risk, detected polymorphism profiles where all the combinations contribute to the higher GC risk, with an OR increased 1.51-fold for the rs1047972(CT)/rs11084490(CG + GG) to 2.29-fold for the rs1047972(CT)/rs911160(CC) combinations. In silico analysis for rs911160 and rs2289590 demonstrated that different transcription factors preferentially bind to polymorphic sites, indicating that AURKA and AURKB could be regulated differently depending on the presence of particular allele. CONCLUSIONS: Our results revealed that AURKA (rs1047972 and rs911160), AURKB (rs2241909 and rs2289590) and AURKC (rs11084490) are associated with a higher risk of GC susceptibility. Our findings also showed that the combined effect of these SNPs may influence GC risk, thus indicating the significance of assessing multiple polymorphisms, jointly. The study was conducted on a less numerous but ethnically homogeneous Bosnian population, therefore further investigations in larger and multiethnic groups and the assessment of functional impact of the results are needed to strengthen the findings.

Association of the AURKA and AURKC gene polymorphisms with an increased risk of gastric cancer.

Single nucleotide polymorphisms (SNPs) in mitotic checkpoint genes can contribute to susceptibility of human cancer, including gastric cancer (GC). We aimed to investigate the effects of Aurora kinase A (AURKA), Aurora kinase B (AURKB), and Aurora kinase C (AURKC) gene polymorphisms on GC risk in Slovenian population. We genotyped four SNPs in AURKA (rs2273535 and rs1047972), AURKB (rs2241909), and AURKC (rs758099) in a total of 128 GC patients and 372 healthy controls using TaqMan allelic discrimination assays to evaluate their effects on GC risk. Our results showed that genotype frequencies between cases and controls were significantly different for rs1047972 and rs758099 (P < 0.05). Our study demonstrated that AURKA rs1047972 TT and (CC + CT) genotypes were significantly associated with an increased risk of gastric cancer. Our results additionally revealed that AURKC rs758099 TT and (CC + CT) genotypes were also associated with increased GC risk. In stratified analysis, genotypes TT and (CC + CT) of AURKA rs1047972 SNP were associated with increased risk of both, intestinal and diffuse, types of GC. In addition, AURKC rs758099 TT and (CC + CT) genotypes were positively associated with increased intestinal type GC risk, but not with an increased diffuse type GC risk. Based on these results, we can conclude that AURKA rs1047972 and AURKC rs758099 polymorphisms could affect the risk of GC development. Further larger studies are needed to confirm these findings. © 2016 IUBMB Life, 68(8):634-644, 2016.

Assessment of the genotoxicity and cytotoxicity in environmentally exposed human populations to heavy metals using the cytokinesis-block micronucleus cytome assay.

The cytokinesis-block micronucleus cytome (CBMN-Cyt) assay was developed as a system for evaluating DNA damage, cytostasis, and cytotoxicity. The aim of the present study was to estimate levels of micronuclei (MNi), nucleoplasmic bridges (NPBs), nuclear buds (NBUDs), cell death (apoptosis/necrosis), nuclear division index, and nuclear division cytotoxicity index values in the peripheral blood lymphocytes of environmentally exposed subjects to heavy metals from five Bosnian regions, characterized by different exposure to heavy metals. The study was performed using CBMN-Cyt assay, considering factors, such as age, gender and smoking habits and their possible effects on analyzed parameters. In total, 104 healthy subjects were selected (49.04% females and 50.96% males; average age, 35.41 years; 51.92% smokers and 48.08% nonsmokers). There was significant difference between the frequency of NBUDs in Tuzla as compared to the control group. Furthermore, there was observed a statistically significant difference for the frequency of NPBs between Zenica, Olovo, and Kakanj when compared with the controls. Males showed a significantly higher number of apoptotic cells than females in controls. There were significant differences between smokers and nonsmokers in the frequency of NPBs in controls (higher in nonsmokers) and necrotic cells in Olovo (higher in nonsmokers). The pack years of smoking significantly influenced the number of necrotic cells in controls and the frequency of NBUDs in the overall sample. The results of the present study provide evidence of significantly increased frequency of NPBs and NBUDs in exposed subjects, suggesting that these endpoints are highly sensitive markers for measuring genotoxicity.

Biological potential, chemical profiling, and molecular docking study of Morus alba L. extracts.

Morus alba L. is a plant with a long history of dietary and medicinal uses. We hypothesized that M. alba possesses a significant biological potential. In that sense, we aimed to generate the chemical, antimicrobial, toxicological, and molecular profile of M. alba leaf and fruit extracts. Our results showed that extracts were rich in vitamin C, phenols, and flavonoids, with quercetin and pterostilbene concentrated in the leaf, while fisetin, hesperidin, resveratrol, and luteolin were detected in fruit. Extracts exhibited antimicrobial activity against all tested bacteria, including multidrug-resistant strains. The widest inhibition zones were in Staphylococcus aureus ATCC 33591. The values of the minimum inhibitory concentration ranged from 15.62 µg/ml in Enterococcus faecalis to 500 µg/ml in several bacteria. Minimum bactericidal concentration ranged from 31.25 µg/ml to 1000 µg/ml. Extracts impacted the biofilm formation in a concentration-dependent and species-specific manner. A significant difference in the frequency of nucleoplasmic bridges between the methanolic extract of fruit (0.5 µg/ml, 1 µg/ml, 2 µg/ml), as well as for the frequency of micronuclei between ethanolic extract of leaf (2 µg/ml) and the control group was observed. Molecular docking suggested that hesperidin possesses the highest binding affinity for multidrug efflux transporter AcrB and acyl-PBP2a from MRSA, as well as for the SARS-CoV-2 Mpro. This study, by complementing previous research in this field, gives new insights that could be of great value in obtaining a more comprehensive picture of the Morus alba L. bioactive potential, chemical composition, antimicrobial and toxicological features, as well as molecular profile.

PLK2 Single Nucleotide Variant in Gastric Cancer Patients Affects miR-23b-5p Binding.

PURPOSE: Chromosomal instability is a hallmark of gastric cancer (GC). It can be driven by single nucleotide variants (SNVs) in cell cycle genes. We investigated the associations between SNVs in candidate genes, PLK2, PLK3, and ATM, and GC risk and clinicopathological features. MATERIALS AND METHODS: The genotyping study included 542 patients with GC and healthy controls. Generalized linear models were used for the risk and clinicopathological association analyses. Survival analysis was performed using the Kaplan-Meier method. The binding of candidate miRs was analyzed using a luciferase reporter assay. RESULTS: The PLK2 Crs15009-Crs963615 haplotype was under-represented in the GC group compared to that in the control group (Pcorr=0.050). Male patients with the PLK2 rs963615 CT genotype had a lower risk of GC, whereas female patients had a higher risk (P=0.023; P=0.026). The PLK2 rs963615 CT genotype was associated with the absence of vascular invasion (P=0.012). The PLK3 rs12404160 AA genotype was associated with a higher risk of GC in the male population (P=0.015). The ATM Trs228589-Ars189037-Grs4585 haplotype was associated with a higher risk of GC (P<0.001). The ATM rs228589, rs189037, and rs4585 genotypes TA+AA, AG+GG, and TG+GG were associated with the absence of perineural invasion (P=0.034). In vitro analysis showed that the cancer-associated miR-23b-5p mimic specifically bound to the PLK2 rs15009 G allele (P=0.0097). Moreover, low miR-23b expression predicted longer 10-year survival (P=0.0066) in patients with GC. CONCLUSIONS: PLK2, PLK3, and ATM SNVs could potentially be helpful for the prediction of GC risk and clinicopathological features. PLK2 rs15009 affects the binding of miR-23b-5p. MiR-23b-5p expression status could serve as a prognostic marker for survival in patients with GC.

Genetic variations in AURORA cell cycle kinases are associated with glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most frequent type of primary astrocytomas. We examined the association between single nucleotide polymorphisms (SNPs) in Aurora kinase A (AURKA), Aurora kinase B (AURKB), Aurora kinase C (AURKC) and Polo-like kinase 1 (PLK1) mitotic checkpoint genes and GBM risk by qPCR genotyping. In silico analysis was performed to evaluate effects of polymorphic biological sequences on protein binding motifs. Chi-square and Fisher statistics revealed a significant difference in genotypes frequencies between GBM patients and controls for AURKB rs2289590 variant (p = 0.038). Association with decreased GBM risk was demonstrated for AURKB rs2289590 AC genotype (OR = 0.54; 95% CI = 0.33-0.88; p = 0.015). Furthermore, AURKC rs11084490 CG genotype was associated with lower GBM risk (OR = 0.57; 95% CI = 0.34-0.95; p = 0.031). Bioinformatic analysis of rs2289590 polymorphic region identified additional binding site for the Yin-Yang 1 (YY1) transcription factor in the presence of C allele. Our results indicated that rs2289590 in AURKB and rs11084490 in AURKC were associated with a reduced GBM risk. The present study was performed on a less numerous but ethnically homogeneous population. Hence, future investigations in larger and multiethnic groups are needed to strengthen these results.

Single nucleotide polymorphisms rs911160 in AURKA and rs2289590 in AURKB mitotic checkpoint genes contribute to gastric cancer susceptibility.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in mitotic checkpoint genes could confer increased susceptibility to gastric cancer (GC). We investigated the association of Aurora kinase A (AURKA), Aurora kinase B (AURKB), Aurora kinase C (AURKC), Polo-like kinase 1 (PLK1) and Budding uninhibited by benzimidazol 3, yeast (BUB3) gene polymorphisms with GC risk. MATERIALS AND METHODS: Genotyping of 6 SNPs in AURKA (rs911160 and rs8173), AURKB (rs2289590), AURKC (rs11084490), PLK1 (rs42873), and BUB3 (rs7897156) was performed using TaqMan genotyping assays. RESULTS: Our study demonstrated that rs911160 (AURKA) heterozygous genotype was associated with an increased GC risk (OR = 1.50, 95% CI = 1.01-2.22, P = 0.043). Analysis of rs911160 (AURKA) showed significant association with an increased risk for intestinal type GC (OR = 1.80, 95%CI = 1.01-3.21, P = 0.040) and the risk was significantly higher in women than men (OR = 2.65, 95%CI = 1.02-6.87, P = 0.033). SNP rs2289590 in AURKB might contribute to susceptibility for the development of gastric cancer, particularly in women (OR = 2.08, 95% CI = 1.05-4.09, P = 0.032). CONCLUSION: Our findings suggested that AURKA (rs911160) and AURKB (rs2289590) polymorphisms could affect GC risk. Further validation studies in larger and multi-ethnical populations are needed to elucidate their functional impact on the development of GC. Environ. Mol. Mutagen. 58:701-711, 2017. © 2017 Wiley Periodicals, Inc.