ABSTRACT
Herein, we report an efficient and facile strategy for the preparation of imidazolium-based ionic liquid (IL) monomers ([CnVIm][Br], n = 2, 4, 6, 8, 10, and 12) and their corresponding polymeric ionic liquids (PILs) with potent antimicrobial activities against Gram-negative and Gram-positive bacteria and fungi. The electrospinning technique was utilized to tailor the polymers with the highest antimicrobial potency into porous membranes that can be easily implemented into diverse systems and extend their practical bactericidal application. The antimicrobial mechanism of obtained ILs, polymers, and nanomaterials is considered concerning the bearing chain length, polymerization process, and applied processing technique that provides a unique fibrous structure. The structure composition was selected due to the well-established inherent amphiphilicity that 1-alkylimidazolium ILs possess, coupled with proven antimicrobial, antiseptic, and antifungal behavior. The customizable nature of ILs and PILs complemented with electrospinning is exploited for the development of innovative antimicrobial performances born from the intrinsic polymer itself, offering solutions to the increasing challenge of bacterial resistance. This study opens up new prospects toward designer membranes providing a complete route in their designing and revolutionizing the approach of fabricating multi-functional systems with tunable physicochemical, surface properties, and interesting morphology.
ABSTRACT
S and N-doped carbon dots (S-CDs and N-CDs) and their cisplatin (cis-Pt) derivatives. (S-CDs@cis-Pt and N-CDs@cis-Pt) were tested on two ovarian cancer cell lines: A2780 and A2780 cells resistant to cis-Pt (A2780R). Several spectroscopic techniques were employed to check S-CDs@cis-Pt and N-CDs@cis-Pt: solid- and solution-state nuclear magnetic resonance, matrix-assisted laser desorption, ionization time-of-flight mass spectrometry, and X-ray photoelectron spectroscopy. In addition, synchrotron-based Fourier Transformed Infrared spectro-microscopy was used to evaluate the biochemical changes in cells after treatment with cis-Pt, S-CDs, N-CDs, or S-CDs@cis-Pt and N-CDs@cis-Pt, respectively. Computational chemistry was applied to establish the model for the most stable bond between S-CDs and N-CDs and cis-Pt. The results revealed the successful modification of S-CDs and N-CDs with cis-Pt and the formation of a stable composite system that can be used for drug delivery to cancer cells and likewise to overcome acquired cis-Pt resistance. Nanoparticle treatment of A2780 and A2780R cells led to the changes in their structure of lipids, proteins, and nucleic acids depending on the treatment. The results showed the S-CDs@cis-Pt and N-CDs@cis-Pt might be used in the combination with cis-Pt to treat the adenocarcinoma, thus having a potential to be further developed as drug delivery systems.
Subject(s)
Adenocarcinoma , Ovarian Neoplasms , Carbon , Cell Line, Tumor , Cisplatin/chemistry , Cisplatin/pharmacology , Female , Humans , Ovarian Neoplasms/metabolismABSTRACT
Carbon dots (CDs) and N-carbon dots (N-CDs) loaded with Ru-complex (CDs@RuCN, N-CDs@RuCN, respectively) were investigated as media imposing biochemical changes induced by UV illumination of ovarian cancer, A2780, and osteosarcoma, CAL72, cells. Synchrotron radiation-based Fourier Transform Infrared Spectroscopy was performed, and the spectra were subjected to a Principal Component Analysis. The CDs@RuCN and N-CDs@RuCN effects on cancer cells were analyzed by the theoretical modelling of the stability of the composite systems and a protein database search. Moreover, a detailed evaluation of surface and optical properties of CDs@RuCN and N-CDs@RuCN was carried out. Results demonstrated selective action of the CDs@RuCN and N-CDs@RuCN-based photodynamic therapy, with N-CDs@RuCN being the most active in inducing changes in A2780 and CDs@RuCN in CAL72 cells. We assume that different surface charges of nanoparticles led to direct interactions of N-CDs@RuCN with a Wnt signalling pathway in A2780 and those of CDs@RuCN with PI3-K/Akt in CAL72 cells and that further biochemical changes occurred upon light illumination.
Subject(s)
Nanoparticles , Ovarian Neoplasms , Quantum Dots , Carbon/chemistry , Cell Line, Tumor , Female , Humans , Quantum Dots/chemistryABSTRACT
In the last decade, targeting membrane lipids in cancer cells has been a promising approach that deserves attention in the field of anticancer drug development. To get a comprehensive understanding of the effect of the drug [Ru(η5-Cp)(PPh3)2CN] (RuCN) on cell lipidic components, we combine complementary analytical approaches, matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI TOF MS) and synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectroscopy. Techniques are used for screening the effect of potential metallodrug, RuCN, without and with drug carriers (carbon dots (CDs) and nitrogen-doped carbon dots (N-CDs)) on the lipids of the human ovarian cancer cell line A2780. MALDI TOF MS results revealed that the lysis of ovarian cancer membrane lipids is promoted by RuCN and not by drug carriers (CDs and N-CDs). Furthermore, SR-FTIR results strongly suggested that the phospholipids of cancer cells undergo oxidative stress after the treatment with RuCN that was accompanied by the disordering of the fatty acid chains. On the other hand, using (N-)CDs as RuCN nanocarriers prevented the oxidative stress caused by RuCN but did not prevent the disordering of the fatty acid chain packing. Finally, we demonstrated that RuCN and RuCN/(N-)CDs alter the hydration of the membrane surface in the membrane-water interface region.
ABSTRACT
In this study, C-doped TiO2 nanoparticles (C-TiO2) were prepared and tested as a photosensitizer for visible-light-driven photodynamic therapy against cervical cancer cells (HeLa). X-ray diffraction and Transmission Electron Microscopy confirmed the anatase form of nanoparticles, spherical shape, and size distribution from 5 to 15 nm. Ultraviolet-visible light spectroscopy showed that C doping of TiO2 enhances the optical absorption in the visible light range caused by a bandgap narrowing. The photo-cytotoxic activity of C-TiO2 was investigated in vitro against HeLa cells. The lack of dark cytotoxicity indicates good biocompatibility of C-TiO2. In contrast, a combination with blue light significantly reduced the survival of HeLa cells: illumination only decreased cell viability by 30% (15 min of illumination, 120 µW power), and 60% when HeLa cells were preincubated with C-TiO2. We have also confirmed blue light-induced C-TiO2-catalyzed generation of reactive oxygen species in vitro and intracellularly. Oxidative stress triggered by C-TiO2/blue light was the leading cause of HeLa cell death. Fluorescent labeling of treated HeLa cells showed distinct morphological changes after the C-TiO2/blue light treatment. Unlike blue light illumination, which caused the appearance of large necrotic cells with deformed nuclei, cytoplasm swelling, and membrane blebbing, a combination of C-TiO2/blue light leads to controlled cell death, thus providing a better outcome of local anticancer therapy.
Subject(s)
Carbon/chemistry , Nanoparticles , Phototherapy , Titanium/chemistry , Titanium/pharmacology , Uterine Cervical Neoplasms/pathology , Cell Survival/drug effects , Cell Survival/radiation effects , Combined Modality Therapy , Female , HeLa Cells , HumansABSTRACT
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.
Subject(s)
Antineoplastic Agents/pharmacology , Coordination Complexes/pharmacology , DNA/chemistry , Molecular Docking Simulation , Palladium/pharmacology , Platinum/pharmacology , Pyridines/pharmacology , Serum Albumin, Human/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cells, Cultured , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Drug Screening Assays, Antitumor , Humans , Kinetics , Palladium/chemistry , Platinum/chemistry , Pyridines/chemistryABSTRACT
A binary system composed of carbon dots (CDs) and N-doped CDs (N-CDs) embedded in an organic matrix was used for the analysis of cholesterol by MALDI (matrix-assisted laser desorption and ionization time-of-flight) mass spectrometry, as a model for detection of small, biologically relevant molecules. The results showed that both CDs are sensitive to the cholesterol and can be used either alone or in a binary system with 2,5-dihydroxybenzoic acid (DHB) to enhance the detection process. It was found that both COOH and NH2 groups on CDs surface contributed to the enhancement in the cholesterol detection by MALDI mass spectrometry in the presence of inorganic cations. Nevertheless, in the presence of NaCl, N-CDs led to a better reproducibility of results. It was due to the coexistence of positive and negative charge on N-CDs surface that led to a homogeneous analyte/substrate distribution, which is an important detection parameter. The enhancing effect of carbon dots was linked to a negative Gibbs energy of the complex formation between CDs, Na+, cholesterol and DHB, and it was supported by theoretical calculations. Moreover, upon the addition of CDs/N-CDs, such features as a low ionization potential, vertical excitation, dipole moment and oscillator strength positively affected the cholesterol detection by MALDI in the presence of Na+.
ABSTRACT
Photodynamic therapy (PDT) is a promising cancer treatment that can be implemented using various agents. The conventional photosensitizer Al (III) phthalocyanine chloride tetrasulfonic acid (Pc) has limitations of selectivity in tumor targeting, low affinity to cancer cells, and low two-photon absorption. This study presents a novel photosensitizer FA-TiO2-Pc, which has the TiO2 nanoparticle conjugated with a tumor targeting agent of folic acid (FA), and Pc. FA-TiO2-Pc possessed high targeted photodynamic therapeutic activity and excellent biocompatibility. This promising photosensitizer showed high therapeutic drug efficiency in vitro at a low concentration dose and short incubation time under one-photon excitation (OPE). In vivo, when treated with a low dose of FA-TiO2-Pc and low light irradiation, the tumor growth was depressed in mice bearing HeLa xenograft tumors with minimal side effects. In addition, the two-photon absorption of FA-TiO2-Pc was also enhanced compared to Pc, proving that FA-TiO2-Pc system has a great potential to be used for the therapy of the folate receptor positive cancer cells in both OPE-PDT and two-photon excitation (TPE)-PDT agents.
Subject(s)
Folic Acid/chemistry , Indoles/chemistry , Indoles/pharmacology , Nanoparticles/chemistry , Photochemotherapy/methods , Titanium/chemistry , A549 Cells , Animals , Biological Transport , Female , HeLa Cells , Humans , Indoles/metabolism , Isoindoles , Mice , Photosensitizing Agents/chemistry , Photosensitizing Agents/metabolism , Photosensitizing Agents/pharmacology , Reactive Oxygen Species/metabolismABSTRACT
Altered lipid metabolism has been associated with the progression of various cancers, and aberrant expression of enzymes involved in the lipid metabolism has been detected in different stages of cancer. Breast cancer (BC) is one of the cancer types known to be associated with alterations in the lipid metabolism and overexpression of enzymes involved in this metabolism. It has been demonstrated that inhibition of the activity of certain enzymes, such as that of phospholipase A2 in BC cell lines sensitizes these cells and decreases the IC50 values for forthcoming therapy with traditional drugs, such as doxorubicin and tamoxifen. Moreover, other phospholipases, such as phospholipase C and D, are involved in intracellular signal transduction, which emphasizes their importance in cancer development. Finally, BC is assumed to be dependent on the diet and the composition of lipids in nutrients. Despite their importance, analytical approaches that can associate the activity of phospholipases with changes in the lipid composition and distribution in cancer tissues are not yet standardized. In this review, an overview of various analytical platforms that are applied on the study of lipids and phospholipase activity in BC tissues will be given, as well as their association with cancer diagnosis and tumor progression. The methods that are applied to tissues obtained from the BC patients will be emphasized and critically evaluated, regarding their applicability in oncology.
ABSTRACT
We studied the possibility of detection of [Ru(η5-C5H5)(PPh3)2Cl] (abbreviated by RuCp) complex as a model system for Ru-based metallodrugs in human urine by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) without previous purification or removal of inorganic salts. Inorganic salts might prevent the detection of RuCp by MALDI-TOF MS, most likely through the increased number and intensity of background/organic matrix signals. This problem might be overcome by the acquisition of matrix-free spectra and the addition of nanoparticles, such as carbon dots, to the urine solution. Our results suggest that RuCp is easily detectable by MALDI-TOF MS in all acquisition conditions, with the CHCA matrix being the best for acquisition in phosphate-containing solutions, whereas in urine, DHB and matrix-free approach demonstrated the highest sensitivity, precision, and reproducibility. The sensitivity of matrix-free MALDI detection of RuCp could be increased by the addition of carbon dots to the urine. Based on theoretical calculations for all matrix/analyte combinations, the model for the interaction of RuCp with carbon dots was established, and higher sensitivity explained.
Subject(s)
Carbon , Humans , Reproducibility of Results , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
PURPOSE: One of the hallmarks of cancer cells is the demand of supply for the synthesis of new membranes involved in cell proliferation and lipids have an important role in cellular structure, signaling pathways and progression of cancer. In this sense, lipid studies have become an essential tool allowing the establishment of signatures associated with breast cancer (BC). In this regard, some metabolic processes including proteins, nucleic acids and lipid synthesis are enhanced as part of cancer-associated metabolic reprogramming, as a requirement for cell growth and proliferation. METHODS: Pairwise samples of breast active carcinoma (BAC) and breast cancer-free tissues were collected from n = 28 patients and analyzed by MALDI-TOF MS. RESULTS: Major lipid species are identified in the MALDI-TOF mass spectra, with certain phosphatidylinositols (PIs) detectable only in BAC. Statistical analysis revealed significant differences (p < 0.05) between ratios lysophosphatidylcholine (LPC) 16:0/phosphatidylcholine (PC) 16:0_18:2 between AC and CF groups as well as for BC stages II and III. The ratio PC 16:0_18:2/PC16:0_18:1 was statistically different between AC and CF groups. The one-way ANOVA revealed that there are no statistical differences among BC stages (I, II and III) within AC group. Comparing BC stages, the significance impact increased (p < 0.05) with stage. CONCLUSION: The obtained data revealed MALDI-TOF MS as a powerful tool to explore lipid signatures and the enzyme activity associated with BC and possibly establish novel disease markers.
Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Lipids/analysis , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Female , Humans , Middle Aged , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
Nitrogen and sulphur-doped Carbons Dots (N-CDs and S-CDs) were synthesized by a hydrothermal method and incorporated as surface electrode modifiers to evaluate their properties for electrochemical sensing. The first task was to characterize the synthesized materials, for which different spectroscopies, scanning microscopes, mass spectrometry and elementary analysis were performed. Next, a glassy carbon electrode (GCE) was surface-modified with the doped CDs and applied to check the electrochemical signal of different organic compounds corresponding to different families. Water solubility of the doped carbon dots forced us to incorporate them in a graphite-polystyrene ink to complete the modification of electrodes. This modification needed a first activation to obtain a properly conductive surface. The organic compounds examined were salicylic acid, cysteine and ascorbic acid. The modified GCEs exhibited an enhanced sensitivity, probably caused by the increase of active surface, but in addition, signals of salicylic acid were shifted ca. 200 mV to lower potentials, what is a proof of the increase of the heterogeneous electron transfer rate, and a demonstration of an enhanced catalytic response.
ABSTRACT
Objects of the present study are improved fullerene C60 drug carrier properties trough encapsulation by microbial polysaccharides, levan (LEV), pullulan (PUL), and their hydrophobized cholesterol-derivatives (CHL and CHP), that show better interaction with cancer cells. The zeta potential, polydispersity index, and the diameter of particles were determined, and their cytotoxicity against three cancer cell lines were tested. Biochemical changes in HeLa cells are analyzed by synchrotron radiation (SR) FTIR spectro-microscopy combined with the principal component analysis (PCA). The most significant changes occur in HeLa cells treated with LEV-C60 and correspond to the changes in the protein region, i.e. Amide I band, and the changes in the structure of lipid bodies and membrane fluidity are evident. The highest cytotoxicity was also induced by LEV-C60. In HeLa cells, cytotoxicity could not be strictly associated with biochemical changes in lipids, proteins and nucleic acids, but these findings are significant contribution to the study of the mechanism of interaction of C60-based nanoparticles with cellular biomolecules. In conclusion, LEV, PUL, CHL, and CHP enhanced fullerene C60 potential to be used as target drug delivery system with the ability to induce specific intracellular changes in HeLa cancer cells.
Subject(s)
Cell Culture Techniques/methods , Fructans/chemistry , Glucans/chemistry , Hyaluronic Acid/chemistry , Maleates/chemistry , Adsorption , Cell Adhesion , Cell Proliferation , Diphenhydramine/chemistry , Hep G2 Cells , Humans , Hydrogels , Lidocaine/chemistry , Propranolol/chemistry , Spectroscopy, Fourier Transform Infrared , SynchrotronsABSTRACT
RATIONALE: Changes in lipid composition might be associated with the onset and progression of various neurodegenerative diseases. Herein, we investigated the changes in the plasma phosphatidylcholine (PC)/lysophosphatidylcholine (LPC) ratios in patients with Parkinson's disease (PD) in comparison with healthy subjects and their correlation with clinico-pathological features. METHODS: The study included 10 controls and 25 patients with PD. All patients were assigned to groups based on clinico-pathological characteristics (gender, age at examination, duration of disease and Hoehn and Yahr (H&Y) stage). The analysis of the PC/LPC intensity ratios in plasma lipid extracts was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS: PD patients exhibited an increased PC/LPC intensity ratio in comparison with the control group of healthy subjects. Furthermore, the investigated ratio was shown to be correlated with clinico-pathological parameters, in particular with H&Y stage and disease duration. The PC/LPC intensity ratio in plasma samples of PD patients was found to be elevated in all examined H&Y stages and throughout the disease duration. CONCLUSIONS: To our knowledge, this is the first study examining the PC/LPC ratios in plasma of patients with PD and illustrating their correlation with clinico-pathological features. Although the presented results may be considered as preliminary due to the limited number of participants, the observed alterations of PC/LPC ratios in plasma might be a first step in the characterization of plasma lipid changes in PD patients and an indicator of lipid reconfiguration.
Subject(s)
Lysophosphatidylcholines/blood , Parkinson Disease/blood , Phosphatidylcholines/blood , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , Plasma/chemistry , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
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.
Subject(s)
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/metabolismABSTRACT
Binding of three ruthenium(ii) compounds of general formula mer-[Ru(L3)(N-N)X][Y] (where L3 = 4'-chloro-2,2':6',2''-terpyridine (Cl-tpy); N-N = 1,2-diaminoethane (en), 1,2-diaminocyclohexane (dach) or 2,2'-bipyridine (bipy); X = Cl; Y = Cl) to human serum albumin (HSA) has been investigated by nano-LC/nano-ESI MS and docking studies. A bottom-up proteomics approach has been applied for the structural characterization of metallated proteins and the data were analyzed in both the positive and negative ion mode. The negative ion mode was achieved after the post-column addition of an isopropanol solution of formaldehyde that enabled sample ionization at micro-flow rates. The negative ion mode MS has been proved to be beneficial for the analysis of binding sites on ruthenated protein in terms of ion charge reduction and consequent simplification of target sequence identification based on isotopic differences between ruthenated and non-ruthenated peptides. Moreover, the negative ion mode ESI MS shows the advantage of singly charged ion formation and, unlike MALDI MS, it does not cause complete ligand fragmentation, merging the benefits of each method into a single experiment. Six target sequences were identified for the binding of en and dach compounds, and four sequences for the binding of bipy. All compounds have been found to bind histidine and one aspartate residue. Docking studies showed that the identified sequences are the constituents of five distinct binding sites for en and dach, or two sites for the bipy complex. The selection of binding sites seems to be dependent on the chelate ligand and the form of the complex prior or after hydrolysis of the leaving chloride ligand.
Subject(s)
Angiotensin II/metabolism , Coordination Complexes/metabolism , Molecular Docking Simulation , Nanotechnology/methods , Ruthenium/metabolism , Serum Albumin, Human/metabolism , Spectrometry, Mass, Electrospray Ionization/methods , Angiotensin II/chemistry , Binding Sites , Coordination Complexes/chemistry , Humans , Protein Binding , Ruthenium/chemistry , Serum Albumin, Human/chemistryABSTRACT
BACKGROUND: Biomarkers of oxidative stress are relevant in the evaluation of the disease status and prooxidant-antioxidant balance, advanced oxidation protein products and lipid peroxidation products (malondialdehyde and 4-hydroxynonenal) are being extensively evaluated regarding their relationship with clinical presentation and disease severity. AIM OF THE STUDY: The aim of this study was to evaluate the levels of the above-mentioned parameters in plasma of 39 men and 17 women with Parkinson's disease, originated from the Republic of Serbia and their relation to clinicopathological characteristics (gender, age at examination, duration of the disease, and Hoehn and Yahr score) and oxidative status. RESULTS: The incidence of disease was 2:1 towards males. The investigated oxidative parameters were gender and Hoehn and Yahr related. Significant association of higher Hoehn and Yahr scores was observed for malondialdehyde (p = 0.01) and prooxidant-antioxidant balance (p = 0.02). Relation between oxidant-antioxidant status was further supported by observed positive correlation between 4-hydroxynonenal (p = 0.04) and prooxidant-antioxidant balance (p = 0.03). Finally, the multivariate analysis indicated that prooxidant-antioxidant balance and malondialdehyde were partially determined by gender (10.6% and 7.6%) and Hoehn and Yahr scores (13.6% and 18.8%), while Hoehn and Yahr scores contributed to the variance of advanced oxidation protein products with 13.2%. CONCLUSION: Our results indicate the higher level of oxidative stress (oxidant-antioxidant imbalance) and possible relation of several markers with gender and disease stage in patients with Parkinson's disease. The analyzed markers could be used to specify the severity of oxidative stress; however, their potential value should be analyzed in further studies.
Subject(s)
Advanced Oxidation Protein Products/blood , Antioxidants/metabolism , Lipid Peroxidation/physiology , Oxidants/blood , Parkinson Disease/metabolism , Adult , Aged , Aged, 80 and over , Aldehydes/metabolism , Female , Humans , Male , Malondialdehyde/metabolism , Middle Aged , Oxidants/metabolism , Serbia , Severity of Illness Index , Statistics, NonparametricABSTRACT
[This corrects the article on p. 925 in vol. 8, PMID: 28588570.].
ABSTRACT
In this study the efficacy of two different methods for extracting lipopeptides produced by five Bacillus strains-ethyl acetate extraction, and acid precipitation followed by methanol extraction-was investigated using mass spectrometry. High performance thin layer chromatography (HPTLC) was also used for the simultaneous separation of complex mixtures of lipopeptide extracts and for the determination of antimicrobial activity of their components. The mass spectra clearly showed well-resolved groups of peaks corresponding to different lipopeptide families (kurstakins, iturins, surfactins, and fengycins). The ethyl acetate extracts produced the most favorable results. The extracts of SS-12.6, SS-13.1, and SS-38.4 showed the highest inhibition zones. An iturin analog is responsible for the inhibition of Xanthomonas arboricola and Pseudomonas syringae phytopathogenic strains. HPTLC bioautography effectively identified the active compounds from a mixture of lipopeptide extracts, proving in situ its potential for use in direct detection and determination of antimicrobials. In the test of potential synergism among individual extracts used in different mixtures, stronger antimicrobial effects were not observed. Biochemical and phylogenetic analysis clustered isolates SS-12.6, SS-13.1, SS-27.2, and SS-38.4 together with Bacillus amyloliquefaciens, while SS-10.7 was more closely related to Bacillus pumilus.
ABSTRACT
Ruthenium compounds are highly regarded as metallo-drug candidates. Many studies have focused their attention on the interaction between ruthenium complexes with their possible biological targets. The interaction of ruthenium complexes with transport proteins, enzymes and peptides is of great importance for understanding their biodistribution and mechanism of action, therefore, the development of an anti-cancer therapy involving ruthenium complexes has recently shifted from DNA targeting towards protein targeting. With the aim of gaining insight into possible interactions between ruthenium complexes with biologically relevant proteins, we have studied the interaction of cis-dichlorobis(2,2'-bipyridyl-4,4'-dicarboxylic acid)ruthenium(II) complex [Ru(II)(dcbpy)2Cl2], which previously showed good potency in photo-dynamic chemotherapy, with bovine serum albumin (BSA), phospholipase A2 (PLA2) and glutathione (GSH). Binding constants and possible number of binding sites to mentioned proteins and peptide are investigated by ultraviolet-visible spectroscopy and Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (MALDI TOF MS). The complex binding affinities were in the following order: PLA2 > BSA > GSH. Moreover, genotoxic profile of the complex, tested on peripheral blood lymphocytes as a model system, was also promising.