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Organic compounds originating from plant metabolism and reaching the environment may inhibit or stimulate germination and early developmental processes of other plants grown in the vicinity. The aim of this study was to investigate the allelopathic interactions of brown mustard with four other aromatic plants (summer savoury, coriander, caraway and common sage). While health-promoting metabolites of brown mustard are thoroughly investigated and the plant receives an increasing interest from cultivators of aromatic and medicinal plants, its allelopathic interactions with other aromatic plants are poorly documented. The experiments were performed in closed germination vessels, under controlled conditions. The influence of the presence or absence of light, as well as of a sufficient or reduced water supply on the co-germination of brown mustard seeds with each of the other four aromatic plants was also evaluated. The presence of brown mustard reduced the germination velocity of caraway, coriander, sage and savoury. It inhibited stem elongation, but stimulated root growth of savoury. Shoot growth of coriander seedlings was enhanced by the vicinity of brown mustard plantlets. Caraway slowed down the germination of brown mustard seeds, but it stimulated root and stem elongation of the seedlings. The presence of savoury enhanced the fresh biomass production of brown mustard. Common sage inhibited root growth, but stimulated stem elongation of brown mustard plantlets. Most of the allelopathic effects were more pronounced under water shortage than under sufficient water supply. Positive interspecific influences on biomass production were, in most cases, more pronounced in the presence of light. The findings may contribute to optimization of brown mustard cultivation in small parcels, in the vicinity of other aromatic plants, some allelopathic interactions being able to stimulate growth and developmental processes in an environmental-friendly and cost-effective manner.

The goal of this work was to prepare modified titanium dioxide catalysts applicable for self-cleaning and disinfecting surfaces, possessing both antibacterial and photocatalytic activity in the visible-light region, via green and affordable synthesis. For this purpose, silverization was chosen due to its antibacterial and electron-capturing effects, and to achieve efficient visible-light excitation, urea was used as a precursor for nitrogen doping. Mechanochemical activation with grinding, as an environmentally friendly process, was applied for the catalyst modification under various conditions, such as the amounts of the modifying substances, the milling time, the ratio of the weights of the material to be ground, and the grinding balls. The photocatalytic activity in the UV and visible range was tested in suspensions with oxalic acid and coumarin as model compounds. The antibacterial effect was measured by the bioluminescence of Vibrio fischeri bacteria. The highest photocatalytic activity in the visible range was observed with the nitrogen-doped titanium dioxide (N-TiO2) prepared with 10% urea. Silveration of N-TiO2 (up to 0.2%) decreased photocatalytic activity while improving the antibacterial efficiency. To maximize both effects, mechanical mixtures of the separately modified catalysts (N-TiO2 and Ag-TiO2) were also examined in different ratios. The 1:1 mixture provided the optimum combination.

The goal of this work was to prepare modified titanium dioxide catalysts applicable for self-cleaning and disinfecting surfaces, possessing both antibacterial and photocatalytic activity in the visible-light region, via green and affordable synthesis. For this purpose, silverization was chosen due to its antibacterial and electron-capturing effects, and to achieve efficient visible-light excitation, urea was used as a precursor for nitrogen doping. Mechanochemical activation with grinding, as an environmentally friendly process, was applied for the catalyst modification under various conditions, such as the amounts of the modifying substances, the milling time, the ratio of the weights of the material to be ground, and the grinding balls. The photocatalytic activity in the UV and visible range was tested in suspensions with oxalic acid and coumarin as model compounds. The antibacterial effect was measured by the bioluminescence of Vibrio fischeri bacteria. The highest photocatalytic activity in the visible range was observed with the nitrogen-doped titanium dioxide (N-TiO[sub.2]) prepared with 10% urea. Silveration of N-TiO[sub.2] (up to 0.2%) decreased photocatalytic activity while improving the antibacterial efficiency. To maximize both effects, mechanical mixtures of the separately modified catalysts (N-TiO[sub.2] and Ag-TiO[sub.2]) were also examined in different ratios. The 1:1 mixture provided the optimum combination.

Background Cpf1 nucleases have recently been repurposed for site-specific genome modification. Two members of the Cpf1 family, the AsCpf1 from Acidaminococcus sp. and the LbCpf1 from Lachnospiraceae bacterium were shown to induce higher indel frequencies than SpCas9 when examining four randomly-selected target sequences for each type of nuclease. Whether they are a real match for Cas9 nucleases, however, remains to be verified. Results Here, we used AsCpf1 and LbCpf1 to induce homology directed repair, either single strand annealing (SSA) or homologous recombination (HR), in N2a mouse neuroblastoma cells. Exploiting a plasmid that contains two GFP halves with overlapping sequences and exploring 20 targets, on all but one both nucleases consistently performed with above 10 % efficiency. Several Cas9 nucleases have been previously characterised in order to find an orthogonal counterpart for the most widely used promiscuous SpCas9. Here, we found that AsCpf1 and LbCpf1 might be better candidates than three of the best such counterparts: Cas9 from Staphylococcus aureus , from Streptococcus thermophilus and from Neisseria meningitidis , when assessed for inducing efficient SSA mediated repair in N2a cells. When tested on genomic targets exploiting HR, both nucleases were able to induce the integration of a donor cassette with 1000 bp-long homologous arms. We also generated plasmids that express these Cpf1 nucleases together with their cognate crRNAs and that are equipped with type IIS restriction enzyme sites to facilitate spacer cloning. Conclusions Our results suggest that employing As- or LbCpf1 nuclease to induce homology directed repair in N2a cells, although is less effective at present than employing SpCas9, it is an equally or more effective tool than the most frequently used orthogonal Cas9 counterparts of SpCas9. These findings support the position of Cpf1 nucleases on the side of SpCas9 on the palette of effective genome engineering tools. Reviewers This article was reviewed by Eugene Koonin, Haruhiko Siomi and Jean-Yves Masson.

The phenolic drug molecules can be metabolized, among others, by the small intestine’s enterocytes. The conjugation reactions (glucuronidation and sulfation) show great importance in these transformations, although the oxidation reactions can be significant. These processes are dependent on the substituents of the phenolic compounds or the reacting functional groups (hydroxyl or carboxyl). Pathologic conditions, e.g., permanent hyperglycemia and diabetes, can alter the activities of the conjugative and possibly the oxidative enzymes, thus forming a change in the metabolic pattern and eventually provoking oxidative stress. A rat intestinal perfusion model was used to investigate the way in which experimental hyperglycemia affects the paracetamol’s intestinal elimination and metabolism. Hyperglycemia was induced by the administration of streptozotocin. Two hundred and fifty µM paracetamol was used in the intestinal perfusion solution. For the quantitation of the paracetamol and its major metabolites in the intestinal perfusate, an isocratic high-performance liquid chromatography method with UV-Vis detection was developed. The results revealed that quantities of all of the measured metabolites (glucuronide, sulfate, cysteine, and mercapturic acid conjugates) increased as the effect of the streptozotocin-induced hyperglycemia also did. In the small intestine’s homogenate, the glutathione levels showed that there was a decrease in the hyperglycemia levels after the paracetamol administration. In contrast, the tissue levels of the cysteine were lower in the streptozotocin-induced hyperglycemia and increased after the administration of the paracetamol. The changes in the activity of the intestinal CYP 3A4, CYP 2E1, and cyclooxygenase (COX) enzymes were determined in the control and the hyperglycemic cases. Still, there was a significant observable enzyme activity elevation in the intestinal COX enzymes, but there was a decrease in the amount of activity of the intestinal CYP3A4 enzymes, and the CYP2E1 enzyme activity was practically changeless. The results on the cysteine levels in the intestinal homogenate, at least partly, can be explained by the regulation function of the cysteine during the occurrence of oxidative stress.

Background Umin was discovered in Curcuma longa L. and/or Curcuma domestica L. C 5 -curcumin and its derivatives, like synthetic cyclic C 5 -curcuminoids, are promising anticancer compounds with exceptional pharmacokinetic profiles compared to curcumin. Methods To demonstrate their anticancer activities, we tested six novel synthetic cyclic C 5 -curcuminoids on HeLa, HEC-1A, and T24 tumor cell lines. This investigation focused on ferroptosis and apoptosis, two types of programmed cell death. Ferroptosis-related genes were investigated using real-time polymerase chain reaction (PCR) and Western blotting. The total iron content, reactive oxygen species (ROS) levels, glutathione peroxidase activity, and thiol concentrations were measured to determine ferroptosis. Cytochrome c levels and caspase-3 activity were measured to monitor the apoptosis. Results The study of six synthetic cyclic C 5 -curcuminoids revealed that their effects on HeLa cells differed from those on HEC-1A and T24 cells, indicating distinct mechanisms of action. Compound 4 notably increased iron accumulation and reactive oxygen species (ROS) production, while decreasing antioxidant defenses in all three carcinoma cell lines, suggesting a ferroptotic response. In contrast, compound 9 was successful in activating caspase-3 in carcinoma cells and inducing apoptosis in the COS-1 control cell line. Notably, compound 4 did not enhance caspase-3 activity in the control cell line. These results highlight compound 4 as a possible synthetic cyclic C 5 -curcuminoid for the three cancerous cell lines tested. Conclusion Regarding the distinct effects of the examined synthetic cyclic C 5 -curcuminoids on the three cancer cell types, we hypothesize that their mechanisms of action are different and that divergent target molecules and/or signaling pathways may be involved. However, compounds 4 and 9 were efficient against the three carcinoma cell lines. Further examination of the possible targets could help elucidate which compounds are more suitable for consideration as potential antitumor drug candidates.

Background Mitochondrial dysfunction, oxidative stress and their interplay are core pathological features of Parkinson’s disease. In dopaminergic neurons, monoamines and their metabolites provide an additional source of reactive free radicals during their breakdown by monoamine oxidase or auto-oxidation. Moreover, mitochondrial dysfunction and oxidative stress have a supraadditive impact on the pathological, cytoplasmic accumulation of dopamine and its subsequent release. Here we report the effects of a novel series of potent and selective MAO-B inhibitory (hetero)arylalkenylpropargylamine compounds having protective properties against the supraadditive effect of mitochondrial dysfunction and oxidative stress. Results The (hetero)arylalkenylpropargylamines were tested in vitro, on acute rat striatal slices, pretreated with the complex I inhibitor rotenone and in vivo, using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced acute, subchronic, and chronic experimental models of Parkinson’s disease in mice. The compounds exhibited consistent protective effects against i) in vitro oxidative stress induced pathological dopamine release and the formation of toxic dopamine quinone in the rat striatum and rescued tyrosine hydroxylase positive neurons in the substantia nigra after rotenone treatment; ii) in vivo MPTP-induced striatal dopamine depletion and motor dysfunction in mice using acute and subchronic, delayed application protocols. One compound (SZV558) was also examined and proved to be protective in a chronic mouse model of MPTP plus probenecid (MPTPp) administration, which induces a progressive loss of nigrostriatal dopaminergic neurons. Conclusions Simultaneous inhibition of MAO-B and oxidative stress induced pathological dopamine release by the novel propargylamines is protective in animal models and seems a plausible strategy to combat Parkinson’s disease.

The procedure described here allows the cloning of PCR fragments containing a recognition site of the restriction endonuclease (Type IIP) used for cloning in the sequence of the insert. A Type IIS endonuclease--a Body Double of the Type IIP enzyme--is used to generate the same protruding palindrome. Thus, the insert can be cloned to the Type IIP site of the vector without digesting the PCR product with the same Type IIP enzyme. We achieve this by incorporating the recognition site of a Type IIS restriction enzyme that cleaves the DNA outside of its recognition site in the PCR primer in such a way that the cutting positions straddle the desired overhang sequence. Digestion of the PCR product by the Body Double generates the required overhang. Hitherto the use of Type IIS restriction enzymes in cloning reactions has only been used for special applications, the approach presented here makes Type IIS enzymes as useful as Type IIP enzymes for general cloning purposes. To assist in finding Body Double enzymes, we summarised the available Type IIS enzymes which are potentially useful for Body Double cloning and created an online program (http://group.szbk.u-szeged.hu/welkergr/body_double/index.html) for the selection of suitable Body Double enzymes and the design of the appropriate primers.

BACKGROUND: Umin was discovered in Curcuma longa L. and/or Curcuma domestica L. C5-curcumin and its derivatives, like synthetic cyclic C5-curcuminoids, are promising anticancer compounds with exceptional pharmacokinetic profiles compared to curcumin. METHODS: To demonstrate their anticancer activities, we tested six novel synthetic cyclic C5-curcuminoids on HeLa, HEC-1A, and T24 tumor cell lines. This investigation focused on ferroptosis and apoptosis, two types of programmed cell death. Ferroptosis-related genes were investigated using real-time polymerase chain reaction (PCR) and Western blotting. The total iron content, reactive oxygen species (ROS) levels, glutathione peroxidase activity, and thiol concentrations were measured to determine ferroptosis. Cytochrome c levels and caspase-3 activity were measured to monitor the apoptosis. RESULTS: The study of six synthetic cyclic C5-curcuminoids revealed that their effects on HeLa cells differed from those on HEC-1A and T24 cells, indicating distinct mechanisms of action. Compound 4 notably increased iron accumulation and reactive oxygen species (ROS) production, while decreasing antioxidant defenses in all three carcinoma cell lines, suggesting a ferroptotic response. In contrast, compound 9 was successful in activating caspase-3 in carcinoma cells and inducing apoptosis in the COS-1 control cell line. Notably, compound 4 did not enhance caspase-3 activity in the control cell line. These results highlight compound 4 as a possible synthetic cyclic C5-curcuminoid for the three cancerous cell lines tested. CONCLUSION: Regarding the distinct effects of the examined synthetic cyclic C5-curcuminoids on the three cancer cell types, we hypothesize that their mechanisms of action are different and that divergent target molecules and/or signaling pathways may be involved. However, compounds 4 and 9 were efficient against the three carcinoma cell lines. Further examination of the possible targets could help elucidate which compounds are more suitable for consideration as potential antitumor drug candidates.

Introduction Our purpose was to analyze the long-term evolution of wide neck cerebral aneurysms treated with stent assistance. Methods Data of consecutive patients treated with the Neuroform stent over 9 years were retrospectively analyzed with emphasis on periprocedural complications, aneurysm occlusion grade evolution, and in-stent stenosis rates. Results Altogether, 113 patients with 117 unruptured and ruptured aneurysms were subject of analysis. Mean aneurysm size was 9.4 mm, and mean neck size was 4.7 mm. Procedural thromboembolic and hemorrhagic complications affected eight (6.8 %) and four cases (3.4 %), respectively. Immediate complete occlusion and occlusion with residual neck was achieved in 85 % of cases, which at the first follow-up of 6 months, changed to 77 and 76 % at 36 months. Aneurysms ≥10 mm showed a higher tendency of recurrence. During the overall follow-up time ranging from 1 to 9 years, an in-stent stenosis of ≥50 % was observed only in three cases, all of them being asymptomatic. Conclusions Stent-assisted coiling of wide neck aneurysms provided stable occlusion over the long-term follow-up, with very low and silent in-stent stenosis rates. Some incompletely occluded aneurysms showed a tendency of progressive occlusion; however, this was counterbalanced by the regrowth of others.