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1.
Medicina (Kaunas) ; 60(3)2024 Mar 19.
Article En | MEDLINE | ID: mdl-38541225

Background and Objectives: Workplace burnout syndrome is often as sociated with particular aspects of certain job positions, especially those that entail working with people with special needs. The burnout syndrome in healthcare jobs is a serious problem that has grown into an epidemic among healthcare workers and associates. The aim of this research is to assess the presence of stress and burnout syndrome at work with healthcare workers, expert workers, professional associates, and associates in social service institutions in Belgrade. Materials and Methods: This research was conducted in the form of a cross-sectional study of a representative sample in social institutions in Belgrade. It was conducted from March to the end of June of 2023. The sample of the study had 491 participants. The questionnaires used were a structured instrument with social-demographic and social-economic characteristics, workplace characteristics, lifestyle characteristics, and the following questionnaires: DASS-21, Copenhagen, Brief Resilience Scale, and Brief Resilient Coping Scale. Results: The end results indicate the following to be significant risk factors for the occurrence of workplace burnout syndrome: overtime (OR = 2.62; CI = 1.50-4.56), BRS average score (OR = 0.28; CI = 0.17-0.44), DASS21 D heightened depression (OR = 2.09; CI = 1.1-4.04), DASS21 A heightened anxiety (OR = 2.38; CI = 1.34-4.21), and DASS21 S heightened stress (OR = 2.08; CI = 1.11-3.89). The only protective risk factor that stood out was the self-assessment of health levels (OR = 0.60; CI = 0.42-0.85). Conclusion: Overtime is a significant factor associated with workplace burnout. Apart from it, other significant factors associated with workplace burnout were heightened depression, anxiety, and stress levels.


Burnout, Professional , Health Personnel , Humans , Cross-Sectional Studies , Burnout, Professional/epidemiology , Burnout, Professional/etiology , Workplace , Surveys and Questionnaires , Social Work
2.
Polymers (Basel) ; 15(15)2023 Jul 26.
Article En | MEDLINE | ID: mdl-37571062

Electrochemical crosslinking of alginate strands by in situ iron oxidation was explored using a potentiostatic regime. Carbon-based materials co-doped with iron, nitrogen, and/or sulfur were prepared via electrolyte composition variation with a nitrogen-rich compound (rivanol) or through post-treatments with sodium sulfide. Nanometer-sized iron particles were confirmed by transmission and field emission scanning electron microscopy in all samples as a consequence of the homogeneous dispersion of iron in the alginate scaffold and its concomitant growth-limiting effect of alginate chains. Raman spectra confirmed a rise in structural disorder with rivanol/Na2S treatment, which points to more defect sites and edges known to be active sites for oxygen reduction. Fourier transform infrared (FTIR) spectra confirmed the presence of different iron, nitrogen, and sulfur species, with a marked difference between Na2S treated/untreated samples. The most positive onset potential (-0.26 V vs. saturated calomel electrode, SCE) was evidenced for the sample co-doped with N, S, and Fe, surpassing the activity of those with single and/or double doping. The mechanism of oxygen reduction in 0.1 M KOH was dominated by the 2e- reduction pathway at low overpotentials and shifted towards complete 4e- reduction at the most negative explored values. The presented results put forward electrochemically formed alginate gels functionalized by homogeneously dispersed multivalent cations as an excellent starting point in nanomaterial design and engineering.

3.
Article En | MEDLINE | ID: mdl-37453120

Introduction: Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus and the leading cause of visual impairment and blindness. The aim of the study was to estimate and compare the prevalence of DR and to determine an association between DR and systemic risk factors in hospitalized type 1 (DMT1) and type 2 (DMT2) diabetic patients. Material and methods: We analyzed 260 patients with diabetes, 43 with DMT1 and 217 with DMT2. The following data were collected: age, gender, type and duration of diabetes, glycemic control, blood pressure, estimated glomerular filtration rate, ophthalmologic examinations and routine biochemical parameters. Results: Out of the total number of 260 patients, 77 (29.6%) had non-proliferative DR (NPDR), 21 (8.1%) had proliferative DR (PDR), 29 (11.1%) had diabetic macular edema (DME), and 69 (23.5%) had diabetic cataracts. Forty-three (16.5%) patients were previously diagnosed with DMT1 and 217 (83.5%) with DMT2. The duration of diabetes was not significantly longer in DMT1 (12.8±11.2 years) in comparison to DMT2 (11.07±8.1 years). The prevalence of NPDR and PDR did not differ statistically in either groups. DME was more prevalent in DMT2 than in DMT1 (P<0.05). Diabetic cataract was found in 26.7% vs. 6.7% of patients with DMT2 and DMT1, respectively (p<0.01). The duration of diabetes significantly correlated with NPDR and PDR in DMT1 (r=o.31, p<0.05; r=0.55, p<0.001, respectively). In DMT2, significant correlations were found between the duration of diabetes and cataract, NPDR, PDR and DME (r=0.31, p<0.001; r=0.43 p<0.01, r=0.16 p<0.05 and r=0.20 p<0.01, respectively). Fasting plasma glucose (FPG) significantly correlated with PDR (r=0.258, p<0.05), while HbA1c with DME (r= 0.15 p<0.05). Conclusion: The duration of diabetes and hyperglycemia were associated with DR in both types of diabetes.


Diabetes Mellitus, Type 2 , Diabetic Retinopathy , Macular Edema , Humans , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/epidemiology , Prevalence , Tertiary Healthcare , Macular Edema/complications , Macular Edema/epidemiology , Risk Factors
4.
Spectrochim Acta A Mol Biomol Spectrosc ; 301: 122987, 2023 Nov 15.
Article En | MEDLINE | ID: mdl-37327500

Herein we unequivocally identify the mechanism of zeolite-catalysed thermal degradation of pesticide, employing Fourier-transform infrared spectroscopy (FTIR), Raman and mass spectrometry following temperature decomposition (TPDe/MS). We demonstrate that Y zeolite can effectively adsorb a significant amount of acetamiprid both in a single trial (168 mg/g) and in 10 cycles (1249 mg/g) with intermittent thermal regeneration at 300 °C. Sectional vibrational analysis of acetamiprid two-stage thermal degradation is performed for pristine and supported pesticide. The acetamiprid Raman spectral changes appear at 200 °C, while partial carbonization occurs at 250 °C. The gradual disappearance of the FTIR bands of acetamiprid is seen up to 270 °C when two Raman signature bands for carbonised material emerged. The TPDe/MS profiles reveal the evolution of mass fragments - in the first step, cleavage of the CC bond occurs between the aromatic core of the molecule and its tail-end, followed by cleavage of the CN bond. The mechanism of adsorbed acetamiprid degradation follows the same step, at significantly lower temperatures, as the process is catalysed by the interaction of acetamiprid nitrogens and zeolite support. Reduced temperature degradation allows for a quick recovery process that leaves 65% efficacy after 10 cycles. After numerous cycles of recovery, a subsequent one-time heat treatment at 700 °C completely restores initial efficacy. The efficient adsorption, novel details on degradation mechanism and ease of regeneration procedure place the Y zeolite at the forefront of future all-encompassing environmental solutions.


Pesticides , Zeolites , Zeolites/chemistry , Neonicotinoids , Temperature
5.
J Pharm Sci ; 111(12): 3215-3223, 2022 12.
Article En | MEDLINE | ID: mdl-36162493

Due to their promising effects, gold(III) complexes recently drew increasing attention in the design of new metal-based anticancer therapeutics. Two gold(III) complexes, square-planar [Au(DPP)Cl2]+ - Complex 1 and distorted square-pyramidal [Au(DMP)Cl3] - Complex 2 (where DPP=4,7-diphenyl-1,10-phenanthroline and DMP=2,9-dimethyl-1,10-phenanthroline) were previously synthetized, described and approved as complexes with pronounced cytotoxic effects on colorectal HCT-116 and breast MDA-MB-231 cancer cells. This study investigated the type of cell death by AO/EB double staining, and identification of possible targets responsible for their cytotoxicity, monitored by immunofluorescence and qPCR methods. Both complexes induced apoptosis in all applied concentrations. In the HCT-116 cells apoptosis was activated by external apoptotic pathway, via increase of Fas receptor protein expression and Caspase 8 gene expression. Also, the mitochondrial pathway was triggered by affecting the Bcl-2 members of regulatory proteins and increased caspase 9 protein expression. In MDA-MB-231 cells, apoptosis was initiated from the mitochondria, due to disbalance between expressions of pro- and anti-apoptotic Bcl-2 family members and caspase 9 activation. Complex 1 shows better activity compared to Complex 2, which is in accordance with its structural characteristics. The results deal weighty data about proapoptotic activity of gold(III) complexes and highlighted potential targets for cancer therapy.


Breast Neoplasms , Colorectal Neoplasms , Humans , Female , Phenanthrolines/pharmacology , Phenanthrolines/chemistry , Caspase 9/pharmacology , Gold/pharmacology , Gold/chemistry , Breast Neoplasms/drug therapy , Cell Line, Tumor , Apoptosis , Proto-Oncogene Proteins c-bcl-2/pharmacology , Ligands , Colorectal Neoplasms/drug therapy
6.
Food Technol Biotechnol ; 60(2): 213-224, 2022 Jun.
Article En | MEDLINE | ID: mdl-35910272

Research background: Acquisition of migratory potential is pivotal for cancer cells, enabling invasion and metastasis of colorectal carcinoma. Royal jelly and its bioactive component trans-10-hydroxy-2-decenoic acid (10H2DA) showed remarkable antimetastatic potential, but the molecular mechanism underlying this activity is unclear. Experimental approach: Identification and quantification of 10H2DA in royal jelly originating from Serbia was done by HPLC method. Cytotoxicity of 10H2DA was measured by tetrazolium dye MTT test in concentration range 1-500 µg/mL after 24 and 72 h. Its effect on the collective and single-cell migration was measured by wound healing and transwell migration assays. Invasive potential of cancer cells was evaluated by a transwell method modified with collagen. Immunofluorescence was used for migratory and invasive protein expression, while the gene expression of these markers was evaluated by quantitative real time polymerase chain reaction (qRT-PCR). All assays were applied on human colorectal carcinoma HCT-116 and SW-480 cell lines and, except for MTT, evaluated after 24 h of treatment with two selected concentrations of royal jelly and 10H2DA. Results and conclusions: According to HPLC, the mass fraction of 10H2DA in royal jelly was 0.92% (m/m). Treatment with 10H2DA showed no cytotoxic effect; however, significant inhibitory potential of royal jelly and 10H2DA on the motility and invasiveness of colorectal cancer cells was observed. More pronounced effect was exerted by 10H2DA, which significantly suppressed collective cell migration and invasiveness of SW-480 cells, as well as single- and collective cell migration and invasive potential of HCT-116 cell line. Treatments increased epithelial markers E-cadherin and cytoplasmic ß-catenin in HCT-116 cells, thus stabilizing intercellular connections. In SW-480 cells, 10H2DA increased E-cadherin on protein and gene level, and suppressed epithelial-mesenchymal transition (EMT) markers. In both cell lines, treatments induced significant suppression of promigratory/proinvasive markers: N-cadherin, vimentin and Snail on protein and gene level, which explains decreased migratory and invasive potential of HCT-116 and SW-480 cells. Novelty and scientific contribution: Our study presents new findings and elucidation of royal jelly and 10H2DA molecular mechanism that underlies their antimigratory/antiinvasive activity on colorectal cancer cells. These findings are shown for the first time indicating that these natural products are a valuable source of anticancer potential and should be reconsidered for further antitumour therapy.

7.
Article En | MEDLINE | ID: mdl-35451297

Background: Evidence for disturbances in HPA activation and abnormal HPA regulatory mechanisms in schizophrenia is accumulating. Aim: To compare serum levels of cortisol, DHEA-S and their ratio between patients with schizophrenia and healthy controls and among patients before and after treatment with different types of antipsychotics. Material and methods: In this clinical prospective study, 60 patients with schizophrenia and 40 healthy age and sex matched control subjects were included. All patients experienced an acute exacerbation of the illness (PANSS: P1 and P3 ≥ 4). Clinical evaluation of patients was performed using the Positive and Negative Symptom Scale. A questionnaire for socio-demographic and clinical data collection was used. Serum levels of cortisol, DHEA-S and their ratio were measured at baseline in all participants and after 3 and 6 weeks, respectively, of the antipsychotic treatment with different types of antipsychotics in patients with schizophrenia. Results: Patients with schizophrenia had significantly higher serum cortisol and DHEA-S levels in comparison to the control group. There was no significant difference in serum levels of cortisol, DHEA-S and their ratio between patients treated with different types of antipsychotics (typical/atypical). Serum levels of the analyzed hormones significantly reduce during the 6-week period of examination in both subgroups treated with different types of antipsychotics. Conclusion: Elevated serum cortisol and DHEA-S in schizophrenic patients might be associated with their role in the pathophysiology of the disorder. There is no significant difference in serum levels of cortisol, DHEA-S and their ratio among the patients treated with different types of antipsychotics.


Antipsychotic Agents , Schizophrenia , Antipsychotic Agents/adverse effects , Dehydroepiandrosterone Sulfate/therapeutic use , Humans , Hydrocortisone/therapeutic use , Prospective Studies , Schizophrenia/diagnosis , Schizophrenia/drug therapy
8.
J Ethnopharmacol ; 284: 114758, 2022 Feb 10.
Article En | MEDLINE | ID: mdl-34688797

ETHNOPHARMACOLOGICAL RELEVANCE: Pseudevernia furfuracea (L.) Zopf is common lichen species, traditionally used worldwide in treating various medical conditions, among which are intestinal issues and cancer. Most studies are focused mainly on cytotoxic potential of lichens, whilst their antimigratory and antiinvasive properties are often disregarded. Migration and invasion of cancer cells are pivotal processes in cancer metastasis, wherein cancer cells are able to migrate individually or in form of a coherent mass. One of successful strategies in anticancer treatments is targeting Wnt/ß-catenin signal pathway, that is aberrantly activated in colorectal carcinoma, as well as lowering level of migratory/invasive markers. AIM OF THE STUDY: Present study aimed to show antimigratory/invasive potential of Pseudevernia furfuracea methanol extract on HCT-116 and SW-480 colorectal carcinoma cell lines and to elucidate possible mechanism of its action. MATERIALS AND METHODS: Collective cell migration was assessed by Wound healing assay and single cell migration in real time by RTCA method. Analysis of anti- and promigratory protein expression was performed using immunofluorescent staining. Additionally, gene expression of antimigratory/promigratory and invasive (E-cadherin, ß-catenin, N-cadherin, Vimentin, Snail and MMP-9) markers were investigated by qRT-PCR method. Concentration of MMP-9 was determined colorimetrically by ELISA test. RESULTS: P. furfuracea extract was able to suppress both collective and single cancer cell migration, by inhibiting expression of promigratory/invasive markers and possibly re-establishing cell-cell adhesions. The present study indicates at P. furfuracea as effective antimigratory treatment, and HCT-116 cells were proved to be a more sensitive cell line to applied treatment. CONCLUSIONS: This lichen species is a promising candidate for application in treatment of cancer in order to prevent metastasis.


Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Colorectal Neoplasms/metabolism , Lichens , Cell Line, Tumor , Cell Movement , Chemical Fractionation , Colorectal Neoplasms/genetics , Humans , Medicine, Traditional , Wound Healing
9.
Oxid Med Cell Longev ; 2021: 6670135, 2021.
Article En | MEDLINE | ID: mdl-33628375

Mineral components of dental composites are used in many medical and dental applications, including preventive, restorative, and regenerative dentistry. To evaluate the behavioural alterations induced by nanosized particles of novel dental composites, by means of depressive level and cognitive functions, experimental groups of rats were chronically administered with nanosized hydroxyapatite (HA), tricalcium phosphate (TCP), and amorphous calcium phosphate (ACP) with or without simultaneous application of Filipendula ulmaria L. (FU) methanolic extract. The significant prodepressant action was observed in groups solely treated with HA and ACP. Besides, prolonged treatment with ACP also resulted in a significant decline in cognitive functions estimated in the novel object recognition test. The adverse impact of calcium phosphates on estimated behavioural functions was accompanied by increased oxidative damage and apoptotic markers in the prefrontal cortex, as well as diminished specific neurotrophin (BDNF) and gabaergic expression. The results of our investigation showed that simultaneous antioxidant supplementation with FU extract prevented calcium phosphate-induced behavioural disturbances, as well as prooxidative and apoptotic actions, with the simultaneous restoration of BDNF and GABA-A receptors in the prefrontal cortex. These findings suggest that FU may be useful in the prevention of prodepressant impact and cognitive decline as early as the manifestation of calcium phosphate-induced neurotoxicity.


Calcium Phosphates/toxicity , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/prevention & control , Depression/drug therapy , Depression/prevention & control , Filipendula/chemistry , Nanoparticles/toxicity , Plant Extracts/therapeutic use , Animals , Apoptosis/drug effects , Apoptosis/genetics , Brain-Derived Neurotrophic Factor/metabolism , Cognitive Dysfunction/complications , Cognitive Dysfunction/genetics , Depression/complications , Depression/genetics , Gene Expression Regulation/drug effects , Hindlimb Suspension , Male , Open Field Test , Oxidative Stress/drug effects , Oxidative Stress/genetics , Plant Extracts/pharmacology , Rats, Wistar , gamma-Aminobutyric Acid/metabolism
10.
Environ Sci Process Impacts ; 22(11): 2199-2211, 2020 Nov 01.
Article En | MEDLINE | ID: mdl-32975257

This study investigated the environmental application of FAU type zeolites modified with cationic surfactants (cetylpyridinium chloride, tetrapropylammonium chloride and benzalkonium chloride). Adsorbent characterization was conducted using Fourier-transform infrared and Raman spectroscopy, thermogravimetry and differential thermal analysis, atomic force microscopy and X-ray powder diffraction. The efficiency for tannic acid adsorption from aqueous solution on the surface of prepared composites is studied and the adsorption process was modelled with different isotherm equations. Surfactant modifications of zeolites led to improved adsorption properties compared to FAU zeolites alone. The proposed mechanism controlling the adsorption of tannic acid onto surfactant modified zeolites mainly relies on π-π and hydrophobic interactions. The investigated materials are promising adsorbents for tannic acid and similar phenolics and may be important for environmental and dietary aspects of polyphenol persistence and usage. Further on, functionalized zeolites were studied for insecticide acetamiprid removal, prior to and after tannic acid retention. Promising findings of insecticide co-adsorption with tannic acid led to cytotoxicity evaluation. The cytotoxicity modulation effect of zeolites and tannic acid on acetamiprid points to the essential role of both components in insecticide toxicity reduction.


Pesticides , Zeolites , Adsorption , Pesticides/toxicity , Spectroscopy, Fourier Transform Infrared , Surface-Active Agents/toxicity , Tannins
11.
Sci Total Environ ; 735: 139530, 2020 Sep 15.
Article En | MEDLINE | ID: mdl-32473436

Novel composites of BEA zeolite and silver tungstophosphate were prepared by different procedures: two-step impregnation, ion-exchange, and as physical mixtures with varying component mass ratios. Composites were characterized using Atomic force microscopy, Infrared, Raman and Atomic absorption spectroscopy, and results were related to adsorption properties and antimicrobial efficiencies of the composites. Prepared samples were tested as antimicrobial agents for fungal and different bacterial strains, as well as for adsorbents for pesticide nicosulfuron in aqueous solutions by using High-performance liquid chromatography. Experimental conditions for batch adsorption testing were optimized in order to efficiently eliminate nicosulfuron from aqueous solutions, while enabling antimicrobial activity of these advanced materials. Antimicrobial efficiency of composites was verified, and indicated that silver ion persistence in the solid phase is of utmost significance for the antimicrobial activity. Spectroscopic investigation revealed interaction of the silver tungstophosphate active phase and the zeolite framework, giving evidence of uniform distribution of active sites in the synthesized materials that proved to be essential for adsorption application. The best obtained adsorption capacity, as well as highest antimicrobial efficiency, is found for composite samples prepared by two-step impregnation with (BEA: silver tungstophosphate) mass ratio 2:1. The amount of nicosulfuron removed from water suspension was 38.2 mg per gram of composite, and the minimum inhibitory concentration determined for all investigated gram-negative bacteria was 125 µg mL-1.


Anti-Infective Agents , Pesticides , Zeolites , Adsorption , Silver
12.
EXCLI J ; 19: 442-457, 2020.
Article En | MEDLINE | ID: mdl-32398969

It is known that many edible mushrooms have important medicinal properties, including effects on different types of cancers. This is the first report regarding the neuroprotective, antimicrobial, antioxidative and anticancer activities of the acetone extract of edible mushroom Hygrophorus eburneus. Neuroprotective potential was evaluated by measuring the capacity of the extract to inhibit acetylcholinesterase. In this assay, the tested extract showed activity against acetylcholinesterase in a dose-dependent manner where the percentage of inhibition ranged from 13.19 to 46.44 %. The antimicrobial potential was determined by the microdilution method against five species of bacteria and eight species of fungi and the results of this method exhibited moderate antimicrobial activity of H. eburneus with MIC values ranging from 6.25 to 25 mg/mL. Antioxidant activity was evaluated by measuring the scavenging capacity of the tested sample on DPPH and superoxide anion radicals, by the reducing power assay and by measuring the amounts of total phenolics in extract. As a result of the study, H. eburneus extract showed a potent antioxidant activity (IC50 were 102.93 µg/mL for DPPH radical scavenging activity and 123.27 µg/mL for superoxide anion radicals scavenging) while absorbances for reducing power assay were from 0.0235 to 0.1161. The total phenolic content in the extract was 9.27 µg PE/mg. Finally, anticancer effects were evaluated by MTT test for cytotoxicity, acridine orange/ethidium bromide staining for detection of the type of cell death and wound healing assay for antimigratory effects on human colorectal cancer cell line (HCT-116) and human breast cancer cell line (MDA-MB-231). The results for cytotoxicity and apoptosis were measured after 24 and 72 h and for anti-migratory effect after 12 and 24 h. The tested H. eburneus mushroom extract expressed cell selectivity, with notable cytotoxic effects observed on HCT-116 cells, with a strong proapoptotic potential. The migration of HCT-116 cells was significantly inhibited, while MDA-MB-231 cells were less sensitive to the treatment. The results of this study revealed that the tested extract had relatively strong neuroprotective, antimicrobial, antioxidant, and anticancer effects. It suggests that this mushroom can be proposed as a novel source of nutraceuticals and pharmaceuticals.

13.
Anim Biotechnol ; 31(3): 195-202, 2020 Jun.
Article En | MEDLINE | ID: mdl-30795724

Insect silk has been widely studied for its application in regenerative medicine. However, the data about Plodia interpunctella silk as a biomaterial and its anticancer properties are insufficient. Thus, the aim of this study was to investigate native silk as a substrate for growing normal human fibroblasts MRC-5, and test potential cytotoxic effects of the two silk extracts (with DMSO and Trypsin for sericin isolation) on HCT-116 colorectal carcinoma cells and MRC-5 fibroblasts as a control. Fifth-instar larval silk, collected for 15 and 30 days, was used for testing of proliferation and adhesion of MRC-5, 24 h and 72 h after seeding. Light- and fluorescence-microscope showed cell adhesion and spread on silk, as well as enhanced number of cells after 72 compared to 24 h and nonsignificant percentage of apoptotic cells on the silk. Although insoluble, P. interpunctella silk showed remarkable cytotoxic activity on HCT-116 cells, without significant cytotoxity on normal fibroblasts after 24 h and weak effects after 72 h. This study provides significant information about P. interpunctella silk as a potential biomaterial and shows the presence of some active constituents with anticancer properties, thus pointing to the possibility for exploitation of this worldwide pest insect in biomedical application.


Antineoplastic Agents , Biocompatible Materials , Silk , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Cell Adhesion/drug effects , Cell Line , Cell Survival/drug effects , Fibroblasts/cytology , Fibroblasts/drug effects , HCT116 Cells , Humans , Moths , Sericins , Silk/chemistry , Silk/pharmacology
14.
J Biol Inorg Chem ; 24(7): 1057-1076, 2019 10.
Article En | MEDLINE | ID: mdl-31489480

In this study, we have synthesized a series of dinuclear and trinuclear gold(III) complexes of the general formula [Au2(N-N)Cl6] (1-3) for dinuclear and [Au3(N-N)2Cl8]+ (4-6) for trinuclear compounds, respectively, in which N-N is a bidentate ligand (1,4-diaminobutane; 1,6-diaminohexane or 1,8-diaminooctane). These complexes were characterized by elemental analysis, molar conductivity, and spectroscopic techniques (IR, UV-Vis, 1H NMR, ESI-MS). We performed DFT calculations to get insight into the geometry of the studies complexes. DNA-binding studies were performed by UV-Vis spectrophotometry and fluorescence spectroscopy. The results of competitive reactions between gold(III) complexes and ethidium bromide (EB) towards DNA have shown that selected complexes can displace EB from DNA-EB adduct. In addition, these experiments confirm that polynuclear gold(III) complexes interact with DNA covalently or via intercalation. Furthermore, high values of binding constants of gold(III) complexes towards bovine serum albumin (BSA) protein indicate good binding affinity. In addition, redox stability of complexes in the presence of DNA/BSA was confirmed by cyclic voltammetry. Results of the interactions between gold(III) complexes with DNA/BSA were discussed in reference to molecular docking data obtain by Molegro virtual docker. The cytotoxic activity of synthesized gold(III) complexes was evaluated on human breast cancer cell line (MDA-MB-231), human colorectal cancer cell line (HCT-116), and normal human lung fibroblast cell line (MRC-5). All complexes dose-dependently reduced cancer and normal cells viabilities, with significant cytotoxic effects (IC50 < 25 µM) for trinuclear gold(III) complexes (4, 5) on HCT-116 cells.


DNA/metabolism , Density Functional Theory , Gold/chemistry , Organogold Compounds/chemical synthesis , Organogold Compounds/pharmacology , Serum Albumin, Bovine/metabolism , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Chemistry Techniques, Synthetic , DNA/chemistry , Electrochemistry , Humans , Molecular Docking Simulation , Nucleic Acid Conformation , Organogold Compounds/chemistry , Organogold Compounds/metabolism
15.
J Ethnopharmacol ; 240: 111951, 2019 Aug 10.
Article En | MEDLINE | ID: mdl-31085226

ETHNOPHARMACOLOGICAL RELEVANCE: Teucrum chamaedrys L. is one of the known medicinal plants, useful for treatment of various health problems, especially digestive. In this study, we investigated methanol, ethyl-acetate and acetone extracts of T. chamaedrys in respect to their anticancer properties in SW480 colorectal cancer cells. MATERIALS AND METHODS: Cytotoxicity and proapoptotic potential were assessed by MTT cell viability assay and AO/EB double staining. Molecular mechanisms of induced apoptosis were determined by monitoring Fas receptor protein expression through immunofluorescence, Caspase 8 and 9 activity, as well as concentrations of O2.- spectrophotometrically. Additionally, mRNA expression of biotransformation enzymes (CYP1A1, CYP1B1, GSTP1) and membrane transporters (MRP1 and MRP2) involved in drug resistance were investigated by qPCR method. Qualitative analysis of individual phenolic compounds was performed by reversed phase HPLC-MS analysis. RESULTS: Methanol extract shows the best cytotoxicity and selectivity compared to ethyl-acetate and acetone extracts, mainly causing apoptosis of SW480 cells, without affecting normal HaCaT keratinocytes. The increased expression of Fas receptor protein and caspase 8 activity indicate that the death receptor-mediated pathway plays a crucial role in the observed apoptosis. The increased caspase 9 activity and O2.- concentration suggest that mitochondria are also involved in the apoptosis. T. chamaedrys methanol extract inhibits mRNA expression of CYP1A1, CYP1B1, GSTP1, MRP1 and MRP2 in SW480 cells. CONCLUSIONS: Induction of apoptosis and inhibition of CYP1A1, CYP1B1, GSTP1, MRP1 and MRP2 mRNA expression implies that T. chamaedrys can serve as a valuable source of bioactive compounds as dietary supplements or selective anticancer agents, with the ability to induce apoptosis and modulate drug resistance in colorectal cancer cells.


Antineoplastic Agents, Phytogenic/pharmacology , Plant Extracts/pharmacology , Teucrium , Apoptosis/drug effects , Biotransformation/drug effects , Cell Line , Cell Survival/drug effects , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Cytochrome P-450 CYP1A1/genetics , Cytochrome P-450 CYP1B1/genetics , Flowers , Gene Expression Regulation, Neoplastic/drug effects , Glutathione S-Transferase pi/genetics , Humans , Multidrug Resistance-Associated Protein 2 , Multidrug Resistance-Associated Proteins/genetics
16.
Food Technol Biotechnol ; 56(3): 421-430, 2018 Sep.
Article En | MEDLINE | ID: mdl-30510485

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.

17.
Nat Prod Res ; 32(22): 2712-2716, 2018 Nov.
Article En | MEDLINE | ID: mdl-28882053

In the present study, five root extracts of Onosma visianii Clem were investigated for their in vitro cytotoxic activity. On the basis of HPLC-PDA analysis, these extracts have proved to be a rich source of naphthoquinones as natural colourants for food and cosmetic industry. All investigated root extracts contain acetylshikonin, isobutyrylshikonin and α-methylbutyrylshikonin as major compounds. As the most abundant source of active compounds for antitumour therapy, acetone, chloroform and ethyl acetate extracts showed strong cytotoxic activity towards HCT-116 and MDA-MB-231 cancer cell lines. Also, these extracts induced apoptosis and cell cycle arrest in HCT-116 and MDA-MB-231 cancer cell lines.


Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis , Boraginaceae/chemistry , Cell Cycle Checkpoints , Naphthoquinones/pharmacology , Plant Extracts/pharmacology , Anthraquinones , Cell Line, Tumor , Humans , Molecular Structure , Phytochemicals/pharmacology , Plant Roots/chemistry
18.
Clin Exp Hypertens ; 40(3): 281-286, 2018.
Article En | MEDLINE | ID: mdl-28920713

In this study, we tested a hypothesis that a short-term estradiol therapy may reduce blood pressure in preeclampsia by modulating plasma oxidative stress. The intramuscular injections of 10 mg 17-beta-estradiol were prescribed to preeclamptic pregnant women during the 3-day therapy before a labor induction. The analyses of mean arterial pressure (MAP), serum estradiol concentrations, plasma superoxide anion (O2.), hydrogen peroxide (H2O2), nitrites (NO2-), and peroxynitrite (ONOO-) were conducted before and during the therapy. We found that the plasma concentrations of oxidative stress markers, such as O2- and H2O2, are higher in preeclampsia and positively correlated with the MAP value. Moreover, it was shown that the plasma concentration of NO2- as an indicator of NO levels is higher in preeclampsia. A short-term intramuscular application of estradiol decreases the MAP value and the plasma concentration of O.-, H2O2, NO2-, and ONOO- in preeclampsia. A positive correlation between the decrease of MAP values and the decrease of plasma concentrations of O2-, H2O2, and ONOO- was found in preeclampsia during a short-term estradiol therapy. We conclude that the short-term estradiol therapy decreases the MAP value in preeclampsia by modulating the plasma oxidative stress. We speculate that the estradiol metabolism in preeclampsia is an important mechanism that contributes to vascular dysfunction.


Arterial Pressure/drug effects , Estradiol/therapeutic use , Estrogens/therapeutic use , Oxidative Stress/drug effects , Pre-Eclampsia/drug therapy , Adult , Biomarkers/blood , Estradiol/blood , Female , Humans , Hydrogen Peroxide/blood , Hypertension , Nitrites/blood , Oxidation-Reduction , Peroxynitrous Acid/blood , Pre-Eclampsia/blood , Pregnancy , Superoxides/blood , Young Adult
19.
Reprod Biol ; 17(2): 120-125, 2017 Jun.
Article En | MEDLINE | ID: mdl-28336198

There is established association between oxidative stress, infections of genital tract and fertility. Genital tract infections may provoke increased production of free radicals and generate oxidative stress that can be involved in pathophysiology of a number of reproductive diseases and complications during pregnancy. The aim of this study was to determine connection between oxidative stress and infertility associated with persistent chlamydial infection. Serum samples of infertile women with tubal factor infertility (TFI), women with multiple spontaneous abortions (MSA) and fertile women was screened for C. trachomatis MOMP specific IgG and IgA antibodies and cHSP60 specific igG antibodies using ELISA. The levels of superoxide anion radical, nitric oxide and reduced glutathione were determined spectrophotometricaly. Serum levels of testosterone, luteinizing hormone and follicle stimulating hormone were determined by enzyme-linked fluorescent immunoassay method. Our results showed that persistent infection was more prevalent in TFI than in MSA group, whereas seropositivity was higher in MSA than in TFI group of patients. We also found that superoxide anion was significantly lower, while LH was markedly higher in TFI and MSA group of patients. However, when our results were analyzed according to the serological status of chlamydial infection, we found that parameters of oxidative stress, superoxide anion and index of oxidative stress, defined as relative ratio between superoxide anion and nitrites sum and glutathione ((O2-+NO2-)/GSH) were significantly elevated in infertile patients with persistent chlamydial infection compared to seropositive and seronegative patients. Our findings point to the possible impact of Chlamydia trachomatis infection on prooxidative-antioxidative balance that can influence fertility potential in women with persistent chlamydial infection.


Chlamydia Infections/pathology , Infertility, Female , Oxidative Stress , Abortion, Habitual/microbiology , Adult , Chaperonin 60/metabolism , Chlamydia trachomatis/immunology , Enzyme-Linked Immunosorbent Assay , Fallopian Tube Diseases/microbiology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Mitochondrial Proteins/metabolism
20.
Gen Physiol Biophys ; 36(2): 187-196, 2017 Apr.
Article En | MEDLINE | ID: mdl-28150586

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.


Cell Movement/drug effects , Cell Survival/drug effects , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/physiopathology , Palladium/administration & dosage , Selenium/administration & dosage , Antineoplastic Agents/administration & dosage , Dose-Response Relationship, Drug , Drug Compounding/methods , HCT116 Cells , Humans , Hydantoins/chemistry , Neoplasms, Experimental/pathology , Oxidants/administration & dosage , Palladium/chemistry , Reactive Oxygen Species/metabolism , Selenium/chemistry , Treatment Outcome
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