Novel N-pyrocatechoyl and N-pyrogalloyl hydrazone antioxidants endowed with cytotoxic and antibacterial activity.

Over the years, pharmacological agents bearing antioxidant merits arose as beneficial in the prophylaxis and treatment of various health conditions. Hazardous effects of radical species hyperproduction disrupt normal cell functioning, thus increasing the possibility for the development of various oxidative stress-associated disorders, such as cancer. Contributing to the efforts for efficient antioxidant drug discovery, a thorough in vitro and in silico assessment of antioxidant properties of 14 newly synthesized N-pyrocatechoyl and N-pyrogalloyl hydrazones (N-PYRs) was accomplished. All compounds exhibited excellent antioxidant potency against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. The extensive in silico analysis revealed multiple favorable features of N-PYRs to inactivate harmful radical species, which supported the obtained in vitro results. Also, in silico experiments provided insights into the preferable antioxidant pathways. Prompted by these findings, the cytotoxicity effects and the influence on the redox status of cancer HCT-116 cells and healthy fibroblasts MRC-5 were evaluated. These investigations exposed four analogs exhibiting both cytotoxicity and selectivity toward cancer cells. Furthermore, the frequently uncovered antimicrobial potency of hydrazone-type hybrids encouraged investigations on G+ and G- bacterial strains, which revealed the antibacterial potency of several N-PYRs. These findings highlighted the N-PYRs as excellent antioxidant agents endowed with cytotoxic and antibacterial features.

IFNL3/4 polymorphisms as a two-edged sword: An association with COVID-19 outcome.

Coronavirus Disease 2019 (COVID-19) has been ranked among the most fatal infectious diseases worldwide, with host's immune response significantly affecting the prognosis. With an aim to timely predict the most likely outcome of SARS-CoV-2 infection, we investigated the association of IFNL3 and IFNL4 polymorphisms, as well as other potentially relevant factors, with the COVID-19 mortality. This prospective observational case-control study involved 178 COVID-19 patients, hospitalized at Corona Center or Clinic for Infectious Diseases of University Clinical Centre Kragujevac, Serbia, followed up until hospital discharge or in-hospital death. Demographic and clinical data on all participants were retrieved from the electronic medical records, and TaqMan assays were employed in genotyping for IFNL3 and IFNL4 single nucleotide polymorphisms (SNPs), namely rs12980275, rs8099917, rs12979860, and rs368234815. 21.9% and 65.0% of hospitalized and critically ill COVID-19 patients, respectively, died in-hospital. Multivariable logistic regression analysis revealed increased Charlson Comorbidity Index (CCI), N/L, and lactate dehydrogenase (LDH) level to be associated with an increased likelihood of a lethal outcome. Similarly, females and the carriers of at least one variant allele of IFNL3 rs8099917 were almost 36-fold more likely not to survive SARS-CoV-2 infection. On the other hand, the presence of at least one ancestral allele of IFNL4 rs368234815 decreased more than 15-fold the likelihood of mortality from COVID-19. Our results suggest that, in addition to LDH level, N/L ratio, and CCI, IFNL4 rs368234815 and IFNL3 rs8099917 polymorphisms, but also patients' gender, significantly affect the outcome of COVID-19.

Its all about IFN-λ4: Protective role of IFNL4 polymorphism against COVID-19-related pneumonia in females.

Despite the pivotal role of IFN-λs in the innate immune response, the data on its genetic polymorphism in relation to COVID-19 severity are scarce and contradictory. In the present study, we aimed to determine if the presence of the most frequent functional single nucleotide polymorphisms (SNPs) of the two most important IFN-λs coding genes, namely IFNL3 and IFNL4, alters the likelihood of SARS-CoV-2-infected patients to develop more severe form of the disease. This observational cohort study involved 178 COVID-19 patients hospitalized at the University Clinical Centre Kragujevac, Serbia. Patients' demographics, clinical characteristics, and laboratory parameters were collected at admission. COVID-19 signs and symptoms were assessed during the hospital stay, with the worst condition determining the disease severity. Genotyping for IFNL3 (rs12980275 and rs8099917) and IFNL4 (rs12979860 and rs368234815) SNPs was conducted using TaqMan assays. Our study revealed carriers of IFNL3 and IFNL4 minor alleles to be less likely to progress from mild to moderate COVID-19, that is, to develop COVID-19-related pneumonia. After adjustment for other factors of influence, such as age, sex, and comorbidities, the likelihood of pneumonia development remained significantly associated with IFNL4 polymorphism (odds ratios [ORs] [95% confidence interval (95% CI)]: 0.233 [0.071; 0.761]). When the patients were stratified according to sex, the protective role of IFNL4 minor alleles, controlled for the effect of comorbidities, remained significant only in females (OR [95% CI]: 0.035 [0.003; 0.408]). Our results strongly suggest that IFNL4 rs12979860 and rs368234815 polymorphisms independently predict the risk of COVID-19-related pneumonia development in females.

Effects of direct pulp capping with recombinant human erythropoietin and/or mineral trioxide aggregate on inflamed rat dental pulp.

OBJECTIVE: This study aimed to evaluate the dental pulp responses to recombinant human erythropoietin (rhEPO) and/or mineral trioxide aggregate (MTA) in pulp capping of inflamed dental pulp in vivo. MATERIALS AND METHODS: In accordance with ARRIVE guidelines, pulp inflammation was induced by exposing the maxillary first molars (n = 64) of Wistar rats (n = 32) to the oral environment for two days. The exposed pulps were randomly assigned four groups based on the pulp capping material: rhEPO, MTA, MTA + rhEPO, or an inert membrane. An additional eight rats formed the healthy control group. After four weeks, the animals were euthanized, and histological, qRT-PCR, and spectrophotometric techniques were employed to analyze the left maxillary segments, right first maxillary molars, and blood samples, respectively. Statistical significance was set at p < 0.05 and < 0.001. RESULTS: Pulp capping with rhEPO, MTA, or MTA + rhEPO resulted in lower inflammation and higher mineralization scores compared to untreated control. MTA + rhEPO group exhibited significantly decreased expression of tumor necrosis factor-alpha, and interleukin 1-beta, while MTA group showed substantially reduced expression of interferon-gamma. Both rhEPO and MTA + rhEPO groups presented elevated dentin matrix protein 1 levels compared to untreated control. Furthermore, pulp capping with rhEPO and/or MTA led to increased transforming growth factor-beta 1 expression and reductions of pro-inflammatory/immunoregulatory cytokine ratios and prooxidative markers. Pulp capping with rhEPO also resulted in increase of systemic antioxidative stress markers. CONCLUSION: Capping with rhEPO or MTA + rhEPO resulted in a favorable effect that was similar or even superior to that of MTA.

Sacubitril/valsartan reverses cardiac structure and function in experimental model of hypertension-induced hypertrophic cardiomyopathy.

This study evaluated the effect of sacubtril/valsartan on cardiac remodeling, molecular and cellular adaptations in experimental (rat) model of hypertension-induced hypertrophic cardiomyopathy. Thirty Wistar Kyoto rats, 10 healthy (control) and 20 rats with confirmed hypertension-induced hypertrophic cardiomyopathy (HpCM), were used for this study. The HpCM group was further subdivided into untreated and sacubitril/valsartan-treated groups. Myocardial structure and function were assessed using echocardiography, Langendorff's isolated heart experiment, blood sampling and qualitative polymerase chain reaction. Echocardiographic examinations revealed protective effects of sacubitril/valsartan by improving left ventricular internal diameter in systole and diastole and fractional shortening. Additionally, sacubitril/valsartan treatment decreased systolic and diastolic blood pressures in comparison with untreated hypertensive rats. Moreover, sacubitril/valsartan treatment reduced oxidative stress and apoptosis (reduced expression of Bax and Cas9 genes) compared to untreated rats. There was a regular histomorphology of cardiomyocytes, interstitium, and blood vessels in treated rats compared to untreated HpCM rats which expressed hypertrophic cardiomyocytes, with polymorphic nuclei, prominent nucleoli and moderately dilated interstitium. In experimental model of hypertension-induced hypertrophic cardiomyopathy, sacubitril/valsartan treatment led to improved cardiac structure, haemodynamic performance, and reduced oxidative stress and apoptosis. Sacubitril/valsartan thus presents as a potential therapeutic strategy resulted in hypertension-induced hypertrophic cardiomyopathy.

Pulpal expression of erythropoietin and erythropoietin receptor after direct pulp capping in rat.

This study aimed to evaluate the effect of direct pulp capping on the expression of erythropoietin (Epo) and Epo-receptor (Epor) genes in relation to the expression of inflammatory and osteogenic genes in rat pulp. Dental pulps of the first maxillary molars of Wistar Albino rats were exposed and capped with either calcium hydroxide or mineral trioxide aggregate, or were left untreated. After 4 wk, animals were euthanized, and maxillae were prepared for histological and real-time polymerase chain reaction analysis. Histological scores of pulp inflammation and mineralization, and relative expressions of Epo, Epor, inflammatory cytokines, and pulp osteogenic genes were evaluated. The capped pulps showed higher expressions of Epo, while the untreated pulps had the highest expression of Epor. Both calcium hydroxide and mineral trioxide aggregate downregulated the expression of tumor necrosis factor alpha compared to untreated controls, and upregulated transforming growth factor beta compared to healthy controls. Alkaline phosphatase expression was significantly higher in experimental groups. Relative expression of Epo negatively correlated with pulp inflammation, and positively correlated with pulp mineralization. Pulp exposure promoted expression of Epor and pro-inflammatory cytokines, while pulp capping promoted expression of Epo, alkaline phosphatase, and downregulated Epor and pro-inflammatory cytokines.

The Modified Sublay Technique for the Management of Major Subcostal Incisional Hernia: Long-Term Follow-up Results of 37 Consecutive Patients.

BACKGROUND: The aims of this study were to present the concept of original technique in the management of major incisional subcostal hernias and to evaluate short- and long-term outcome. METHOD: Between January 2010 and January 2020, 280 patients underwent hernia repair surgery for incisional lateral abdominal hernia at Clinic for Digestive Surgery, Clinical Center of Serbia. Among them, 37 patients underwent the modified sublay technique for major incisional subcostal hernia with minimal hernia defect surface of 100 cm2 or greater or minimal hernia defect width or height of 10 cm or greater. The operative techniques are as follows: retromuscular dissection of rectus muscle from posterior sheath on the both sides of hernia defect, external oblique muscle dissection from internal oblique muscle in a circle around hernia defect at the side of the hernia defect, complete reconstruction of the posterior myofascial layer, large heavyweight polypropylene mesh placement in a sublay position, and complete or partial reconstruction of anterior myofascial layer. RESULTS: A median (range) hernia defect surface was 150 (100-500) cm2. A median operative time was 130 (90-330) minutes. The morbidity rate was 18.9%. A median (range) postoperative hospital stay was 7 (2-24) days. After the median follow-up of 50 (1-108) months, 2 patients (5.4%) developed recurrent hernia. CONCLUSIONS: The modified sublay technique using large heavyweight polypropylene mesh provides good results in the management of major subcostal abdominal wall defects.

Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives.

In this contribution, four new compounds synthesized from 4-hydroxycoumarin and tyramine/octopamine/norepinephrine/3-methoxytyramine are characterized spectroscopically (IR and NMR), chromatographically (UHPLC-DAD), and structurally at the B3LYP/6-311++G*(d,p) level of theory. The crystal structure of the 4-hydroxycoumarin-octopamine derivative was solved and used as a starting geometry for structural optimization. Along with the previously obtained 4-hydroxycoumarin-dopamine derivative, the intramolecular interactions governing the stability of these compounds were quantified by NBO and QTAIM analyses. Condensed Fukui functions and the HOMO-LUMO gap were calculated and correlated with the number and position of OH groups in the structures. In vitro cytotoxicity experiments were performed to elucidate the possible antitumor activity of the tested substances. For this purpose, four cell lines were selected, namely human colon cancer (HCT-116), human adenocarcinoma (HeLa), human breast cancer (MDA-MB-231), and healthy human lung fibroblast (MRC-5) lines. A significant selectivity towards colorectal carcinoma cells was observed. Molecular docking and molecular dynamics studies with carbonic anhydrase, a prognostic factor in several cancers, complemented the experimental results. The calculated MD binding energies coincided well with the experimental activity, and indicated 4-hydroxycoumarin-dopamine and 4-hydroxycoumarin-3-methoxytyramine as the most active compounds. The ecotoxicology assessment proved that the obtained compounds have a low impact on the daphnia, fish, and green algae population.

Comparison of Hydroxyapatite/Poly(lactide-co-glycolide) and Hydroxyapatite/Polyethyleneimine Composite Scaffolds in Bone Regeneration of Swine Mandibular Critical Size Defects: In Vivo Study.

Reconstruction of jaw bone defects present a significant problem because of specific aesthetic and functional requirements. Although widely used, the transplantation of standard autograft and allograft materials is still associated with significant constraints. Composite scaffolds, combining advantages of biodegradable polymers with bioceramics, have potential to overcome limitations of standard grafts. Polyethyleneimine could be an interesting novel biocompatible polymer for scaffold construction due to its biocompatibility and chemical structure. To date, there have been no in vivo studies assessing biological properties of hydroxyapatite bioceramics scaffold modified with polyethyleneimine. The aim of this study was to evaluate in vivo effects of composite scaffolds of hydroxyapatite ceramics and poly(lactide-co-glycolide) and novel polyethyleneimine on bone repair in swine's mandibular defects, and to compare them to conventional bone allograft (BioOss). Scaffolds were prepared using the method of polymer foam template in three steps. Pigs, 3 months old, were used and defects were made in the canine, premolar, and molar area of their mandibles. Four months following the surgical procedure, the bone was analyzed using radiological, histological, and gene expression techniques. Hydroxyapatite ceramics/polyethyleneimine composite scaffold demonstrated improved biological behavior compared to conventional allograft in treatment of swine's mandibular defects, in terms of bone density and bone tissue histological characteristics.

Impact of the COVID-19 Pandemic on the Outcomes of Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma: A Single Center Experience from a Developing Country.

Background and Objectives: Treatment of cancer patients during the COVID-19 pandemic has been a challenge worldwide. In accordance with the current recommendations for hepatocellular carcinoma (HCC) management during the COVID-19 pandemic, loco-regional therapy such as transarterial chemoembolization (TACE) was proposed with the purpose of achieving local tumor control and improving overall survival. The aim of this prospective cohort study was to evaluate the outcomes of TACE treatment in patients with HCC during the COVID-19 pandemic in comparison with the outcomes of patients treated in the pre-pandemic period. Materials and Methods: Between September 2018 and December 2021, 154 patients were managed by serial TACE procedures for different liver tumors. Ninety-seven patients met the study criteria and were divided into two groups: the study group n = 49 (patients treated from May 2020 to December 2021); the control group n = 48 (patients treated from September 2018 to May 2020). Results: The mean waiting time for TACE was significantly longer in the study group compared to the control group (p < 0.001). No significant difference in survival between the groups is noted (log-rank test p = 0.823). In multivariate analysis, the MELD score (HR 1.329, 95% CI 1.140−1.548, p < 0.001) remained a significant predictor of mortality. Conclusions: COVID-19 pandemic did not affect the final outcome of TACE treatment.

The effects of offline and online prefrontal vs parietal transcranial direct current stimulation (tDCS) on verbal and spatial working memory.

Working memory (WM) is a limited-capacity system or set of processes that enables temporary storage and manipulation of information essential for complex cognitive processes. The WM performance is supported by a widespread neural network in which fronto-parietal functional connections have a pivotal role. Transcranial direct current stimulation (tDCS) is rapidly emerging as a promising tool for understanding the role of various cortical areas and their functional networks on cognitive performance. Here we comprehensively evaluated the effects of tDCS on WM by conducting three cross-over counterbalanced sham-controlled experiments in which we contrasted the effects and interactions of the anodal (i.e. facilitatory) tDCS across anterior-posterior (i.e. DLPFC vs PPC) and left-right (i.e. the lateralization) axes, and across online and offline protocols using both verbal and spatial WM (3-back) tasks as outcomes. In the offline protocols, left DLPFC stimulation affected neither verbal nor spatial WM, while left PPC stimulation increased spatial WM. When applied offline over right DLPFC, tDCS improved verbal WM task and marginally enhanced spatial WM; while when tDCS was applied over the right PPC, facilitatory effects were observed on verbal WM. In the online protocol, tDCS did not modulate WM regardless of the task modality or stimulation loci. In summary, the study did not replicate the left DLPFC tDCS effect on WM, found in some of the previous studies, but demonstrated positive effects of stimulation of the right DLPFC as well as PPC bilaterally. The observed effects varied across modality of the 3-back task, and tDCS protocol applied. The results of this study argue for moving towards targeting the lesser-explored stimulation sites within the fronto-parietal network, such as PPC, to gain a better understanding of the usefulness of tDCS for WM neuromodulation.

Bis(triazinyl)pyridine complexes of Pt(II) and Pd(II): studies of the nucleophilic substitution reactions, DNA/HSA interactions, molecular docking and biological activity.

Four new complexes of Pt(II) and Pd(II), [Pd(L1)Cl]Cl 1, [Pd(L2)Cl]Cl 2, [Pt(L1)Cl]Cl 3 and [Pt(L2)Cl]Cl 4 (where L1 = 2,6-bis(5,6-diphenyl-1,2,4-triazin-3-yl)pyridine and L2 = 2,6-bis(5,6-dipropyl-1,2,4-triazin-3-yl)pyridine), were synthesized. Characterization of the complexes was performed using elemental analysis, IR, 1H NMR spectroscopy and MALDI-TOF mass spectrometry. The substitution reactions of 1-4 complexes with L-methionine (L-met), L-cysteine (L-cys) and guanosine-5'-monophosphate (5'-GMP), were studied spectrophotometrically at physiological conditions. Complexes with ligand L1 (1 or 3) were more reactive than those with ligand L2 (2 or 4) by a factor ranging up to 1.57 and 3.71, respectively. The order of reactivity of the nucleophiles was: L-met > L-cys > 5'-GMP. The interactions of complexes with calf thymus-DNA (CT-DNA) and human serum albumin (HSA) were studied by Uv-Vis absorption and fluorescence emission spectroscopy. Competitive binding studies with intercalative agent ethidium bromide (EB) and minor groove binder Hoechst 33258 were performed as well. All studied complexes can interact with DNA through the intercalation and minor groove binding, where the latter was preferred. The binding constants (103 and 104 M-1) for the interaction of complexes with HSA indicate the moderate binding affinity of complexes 1-4 to protein. The trends in the experimental results of binding studies between complexes 3 and 4 with DNA and HSA were compared to those obtained from the molecular docking study. Biological evaluation of cytotoxicity of 1 and 2 on HCT-116 and MDA-MB-231 cell lines showed significant cytotoxic and prooxidative character, while 2 also exerted extraordinary selectivity towards colon cancer in comparison to breast cancer cells. The nucleophilic substitution reactions, DNA/HSA interactions, molecular docking and biological activity of bis(triazinyl)pyridine complexes of Pt(II) and Pd(II) were studied.

Variable neuroprotective role of Filipendula ulmaria extract in rat hippocampus.

We evaluated the influence of an antioxidant-rich extract of Filipendula ulmaria L. on anxiety levels induced by nano-sized particles of different calcium phosphates. Rats in experimental groups were administered with either nano-sized hydroxyapatite, tricalcium phosphate, or amorphous calcium phosphate in the presence of Filipendula ulmaria extract. Appropriate behavioral tests were performed to assess anxiety levels, while oxidative status and apoptosis parameters were determined in the hippocampus samples. The applied calcium phosphates increased oxidative stress markers in hippocampal tissue, accompanied by an enhanced pro-apoptotic mechanism. Moreover, the hippocampal immunoreactivity for brain-derived neurotrophic factor and GABAergic-A receptors was significantly lower following calcium phosphate nanoparticles intake. The observed functional and morphological alterations in the rat hippocampus occurred simultaneously with the anxiogenic response estimated in behavioral testing. The neuroprotective effect of Filipendula ulmaria was markedly manifested by the attenuation of oxidative damage induced by amorphous calcium phosphate and enhanced anti-apoptotic action in the rat hippocampus. The increased hippocampal immunoreactivity for brain-derived neurotrophic factor, GABAergic-A receptors and significant anxiolytic-like effects of Filipendula ulmaria may suggest a beneficial role of antioxidant supplementation in preventing anxiogenic response to nano-sized calcium phosphates.

Ambulatory assessment of language use: Evidence on the temporal stability of Electronically Activated Recorder and stream of consciousness data.

The ambulatory assessment offers a wide range of methods enabling researchers to investigate psychological, behavioral, emotional, and biological processes. These methods enable us to gather data on individual differences in language use for psychological research. Two studies were conducted with an aim to evaluate and compare the temporal stability of language measures extracted by LIWC software form data obtained by two frequently used methods for assessment of language use, i.e., Electronically Activated Recorder (EAR) and stream of consciousness (SOC) task. Additionally, we examined the amount of variance in language use (assessed by both methods) that can be attributed to intra-individual variability and stable individual differences. Study 1 was focused on investigating language use obtained from 74 respondents using the EAR for 3 consecutive days. Study 2 was conducted on 250 respondents participating in a SOC task where verbal production was collected at ten time points over a 2-month period. Results show that measures obtained using the SOC task have higher temporal stability and consistency, and to a certain extent enable better detection of individual differences. Taking into account certain situational variations improves the reliability of EAR measures.

Transcranial direct current stimulation (tDCS) over parietal cortex improves associative memory.

Associative memory plays a key role in everyday functioning, but it declines with normal ageing as well as due to various pathological states and conditions, thus impairing quality of life. Associative memory enhancement via neurostimulation over frontal areas resulted in limited success, while posterior stimulation sites seemed to be more promising. We hypothesized that anodal transcranial direct current stimulation (tDCS) of parietal areas would lead to higher performance in associative memory due to high connectivity between posterior parietal cortex (PPC) and hippocampus. Forty-two healthy adults participated in two sham-controlled cross-over experiments. Anodal electrode (20 min, 1.5 mA) was placed over P3 in Experiment 1 and over P4 in Experiment 2. During tDCS participants played a simple computer game. After each stimulation session, participants completed parallel forms of an associative memory task (Experiment 1: face-word memory; Experiment 2: object-location memory) and a control task (verbal fluency). In both experiments, associative memory was improved after anodal stimulation compared to sham stimulation, while no differences were observed in the control task. Additionally, memory performance was higher in the second than in the first trial, but the increase in performance between the two trials did not differ between stimulation conditions. It can be concluded that a single-session anodal tDCS over posterior parietal cortex can improve associative memory performance. The specificity, robustness, and reproducibility of the effect suggest that PPC is a promising target for brain stimulation aiming to enhance memory functions.

Synthesis of Camphor-Derived Bis(pyrazolylpyridine) Rhodium(III) Complexes: Structure-Reactivity Relationships and Biological Activity.

Two novel rhodium(III) complexes, namely, [RhIII(X)Cl3] (X = 2 2,6-bis((4 S,7 R)-7,8,8-trimethyl-4,5,6,7-tetrahydro-1 H-4,7-methanoindazol-3-yl)pyridine or 2,6-bis((4 S,7 R)-1,7,8,8-tetramethyl-4,5,6,7-tetrahydro-1 H-4,7-methanoindazol-3-yl)pyridine), were synthesized from camphor derivatives of a bis(pyrazolylpyridine), tridentate nitrogen-donor chelate system, giving [RhIII(H2L*)Cl3] (1a) and [RhIII(Me2L*)Cl3] (1b). A rhodium(III) terpyridine (terpy) ligand complex, [RhIII(terpy)Cl3] (1c), was also synthesized. By single-crystal X-ray analysis, 1b crystallizes in an orthorhombic P212121 system, with two molecules in the asymmetric unit. Tridentate coordination by the N,N,N-donor localizes the central nitrogen atom close to the rhodium(III) center. Compounds 1a and 1b were reactive toward l-methionine (l-Met), guanosine-5'-monophosphate (5'-GMP), and glutathione (GSH), with an order of reactivity of 5'-GMP > GSH > l-Met. The order of reactivity of the RhIII complexes was: 1b> 1a > 1c. The RhIII complexes showed affinity for calf thymus DNA and bovine serum albumin by UV-vis and emission spectral studies. Furthermore, 1b showed significant in vitro cytotoxicity against human epithelial colorectal carcinoma cells. Since the RhIII complexes have similar coordination modes, stability differences were evaluated by density functional theory (DFT) calculations (B3LYP(CPCM)/LANL2DZp). With (H2L*) and (terpy) as model ligands, DFT calculations suggest that both tridentate ligand systems have similar stability. In addition, molecular docking suggests that all test compounds have affinity for the minor groove of DNA, while 1b and 1c have potential for DNA intercalation.

Pain and executive functions: a unique relationship between Stroop task and experimentally induced pain.

There is a growing body of evidence that a higher level of cognitive inhibition is associated with lower experimental pain sensitivity. However, a systematic examination of the association between executive functions, which include not only inhibition but also updating and shifting, and experimental pain sensitivity is lacking. This study aimed to overcome this limitation by exploring the relationship between a range of executive functions and different measures of experimentally induced cold pain in healthy participants. In a group of 54 healthy participants (age 21-24 years), executive functions (EF) were investigated in a systematic manner following a well-established framework developed by Miyake and collaborators. The investigation included multiple tests of inhibition (Stroop, Stop-signal, and Left-right), updating (Keep-track, Letter-memory, and Spatial n-back), and set-shifting (Plus-minus, Number-letter, and Local-global). The cold pressor test was used to obtain measures of pain threshold (the first sensation of pain), sensitivity to pain (the moment when substantial pain was reported), and pain tolerance (the moment when pain became unbearable). Results showed no relationship between pain measures and measures of updating and shifting. All pain measures were related to Stroop interference inhibition score, but not to other two inhibition tasks. Further analyses confirmed the unique relationship between Stroop-type of inhibition and response to pain. We argue that there is a fundamental relationship between cognitive inhibition and pain experience, which relies on one's ability to suppress automatic processes.

Proapoptotic and Antimigratory Effects of Pseudevernia furfuracea and Platismatia glauca on Colon Cancer Cell Lines.

The aim of this study is to investigate cytotoxic, proapoptotic, antimigratory and pro-antioxidant effects of methanol, acetone and ethyl acetate extracts of lichens Pseudevernia furfuracea and Platismatia glauca on colorectal cancer (HCT-116 and SW-480) cell lines. We compared the cytotoxic effects on colorectal cancer cells with the effects obtained from normal human fibroblast (MRC-5) cell line. Tetrazolium (MTT) test evaluated the cytotoxic effects, Transwell assay evaluated cell migration, acridine orange/ethidium bromide (AO/EB) fluorescent method followed the apoptosis, while prooxidant/antioxidant effects were determined spectrophotometrically through concentration of redox parameters. The tested extracts showed considerable cytotoxic effect on cancer cells with no observable cytotoxic effect on normal cells. Ethyl acetate and acetone extract of P. furfuracea induced the highest cytotoxicity (IC50=(21.2±1.3) µg/mL on HCT-116, and IC50=(51.3±0.8) µg/mL on SW-480 cells, respectively, after 72 h), with noteworthy apoptotic and prooxidant effects, and antimigratory potential of methanol extract. P. glauca extracts induced cytotoxic effects on HCT-116 cells after 72 h (IC50<40 µg/mL), while only methanol and acetone extracts had cytotoxic effects on SW-480 cells after 24 h, with proapoptotic/necrotic activity, as a consequence of induced oxidative stress. In conclusion, lichen extracts changed to a great extent cell viability and migratory potential of colorectal cancer cell lines. HCT-116 cells were more sensitive to treatments, P. furfuracea had better proapoptotic and antimigratory effects, and both investigated lichen species might be a source of substances with anticancer activity.

Novel seleno-hydantoin palladium(II) complex - antimigratory, cytotoxic and prooxidative potential on human colon HCT-116 and breast MDA-MB-231 cancer cells.

Selenium and palladium containing compounds separately exert multifunctional effects on cells. While selenium containing compounds usually exert antioxidative properties, palladium(II) containing compounds are cytotoxic and prooxidative. Here we investigated biological effects of bicyclic seleno-hydantoin cis-7a-ethyl-5-methyl-5-phenylselanylmethyl-tetrahydro-pyrrolo[1,2-c]imidazole-1,3-dione (Hid-Se), and its palladium(II) complex, trans-bis-(cis-7a-ethyl-5-methyl-5-phenylselanylmethyl-tetrahydro-pyrrolo[1,2-c]imidazole-1,3-dionato) palladium(II) chloride ((Hid-Se)2Pd) on human colon HCT-116 and breast MDA-MB-231 cancer cell lines. Hid-Se and (Hid-Se)2Pd showed prooxidative and cytotoxic character. In all performed experiments (Hid-Se)2Pd proved to be more active, i.e. this substance exerted greater prooxidative effect, cytotoxicity and influence on cell migration potential. Even though Hid-Se and (Hid-Se)2Pd enhanced migration of HCT-116 cells, very important feature of these substances is the strong antimigratory potential on metastatic MDA-MB-231 cells.

Antioxidative and antiproliferative evaluation of 2-(phenylselenomethyl)tetrahydrofuran and 2-(phenylselenomethyl)tetrahydropyran.

PURPOSE: To determine the antioxidant and antiproliferative influence of 2-(phenylselenomethyl)tetrahydrofuran (1a) and 2-(phenylselenomethyl)tetrahydropyran (2a) on colon cancer cell line HCT-116 and breast cancer cell line MDA-MB-231. METHODS: Cell viability was monitored in a dose-dependent manner using MTT assay. The concentration of superoxide anion radical (O2 •(-)) was determined spectrophotometrically. Spectrophotometric determination of nitrites (NO2 -) was performed by using the Griess method. Determination of total glutathione (GSH) was also performed spectrophotometrically. RESULTS: HCT-116 cell line was more sensitive to the effects of the investigated substances than MDA-MB-231 cell line. Also, it was noticed that 1a produced greater effect compared to 2a. Moreover, both investigated compounds decreased to a certain degree the oxidative stress by decreasing the O2•(-) and thus the peroxynitrite concentration. At the same time, 1a and 2a acted more efficiently in promoting the endogenous antioxidative capacities (increased GSH concentration) providing better self-defence capabilities for cells. CONCLUSION: Our findings showed that the investigated selenium compounds play an important role in reducing the levels of reactive oxygen species (ROS); therefore, we believe that, as antioxidants, they could prevent the processes arising as a consequence of oxidative stress, including cancer.