Unique Use of Dibromo-L-Tyrosine Ligand in Building of Cu(II) Coordination Polymer-Experimental and Theoretical Investigations.

Although the crystals of coordination polymer {[CuCl(µ-O,O'-L-Br2Tyr)]}n (1) (L-Br2Tyr = 3,5-dibromo-L-tyrosine) were formed under basic conditions, crystallographic studies revealed that the OH group of the ligand remained protonated. Two adjacent [CuCl(L-Br2Tyr)] monomers, bridged by the carboxylate group of the ligand in the syn-anti bidentate bridging mode, are differently oriented to form a polymeric chain; this specific bridging was detected also by FT-IR and EPR spectroscopy. Each Cu(II) ion in polymeric compound 1 is coordinated in the xy plane by the amino nitrogen and carboxyl oxygen of the parent ligand and the oxygen of the carboxyl group from the symmetry related ligand of the adjacent [Cu(L-Br2Tyr)Cl] monomer, as well as an independent chlorine ion. In addition, the Cu(II) ion in the polymer chain participates in long-distance intermolecular contacts with the oxygen and bromine atoms of the ligands located in the adjacent chains; these intramolecular contacts were also supported by NCI and NBO quantum chemical calculations and Hirshfeld surface analysis. The resulting elongated octahedral geometry based on the [CuCl(L-Br2Tyr)] monomer has a lower than axial symmetry, which is also reflected in the symmetry of the calculated molecular EPR g tensor. Consequently, the components of the d-d band obtained by analysis of the NIR-VIS-UV spectrum were assigned to the corresponding electronic transitions.

Laser Activated and Electroless Metalized Polyurethane Coatings Containing Copper(II) L-Tyrosine and Glass Microspheres.

Polyurethane coatings containing copper(II) L-tyrosine and glass microspheres were laser irradiated and underwent electroless metallization. Various sizes of glass microspheres were incorporated into the polyurethane coating matrix in order to examine their effects on surface activation and electroless metallization. The surface of the coatings was activated by using ArF excimer laser emitting ultraviolet radiation (λ = 193 nm) using different number of laser pulses and their fluence. The effects of surface activation and metallization were evaluated mainly based on optical and scanning electron microcopies (SEM), energy-dispersive X-ray spectroscopy (EDX) and photoelectron spectroscopy (XPS). It was found that the presence of glass microspheres enabled the reduction in copper complex content, intensified the ablation process (higher cone-like structures created) and resulted in higher content of copper metallic seeds. On the other hand, the glass microspheres concentration, which was higher for lower size microspheres, was advantageous for obtaining a fully metallized layer.

Synthesis and Characterization of Magnetic Nanomaterials with Adsorptive Properties of Arsenic Ions.

A new synthesis method of hybrid Fe3O4/C/TiO2 structures was developed using microwave-assisted coprecipitation. The aim of the study was to examine the effect of the addition of glucose and titanium dioxide on adsorptive properties enabling removal of arsenic ions from the solution. The study involved the synthesis of pure magnetite, magnetite modified with glucose and magnetite modified with glucose and titanium dioxide in magnetite: glucose: titanium dioxide molar ratio 1:0.2:3. Materials were characterized by XRD, FT-IR, and BET methods. Magnetite and titanium dioxide nanoparticles were below 20 nm in size in obtained structures. The specific surface area of pure magnetite was approximately 79 m2/g while that of magnetite modified with titanium dioxide was above 190 m2/g. Obtained materials were examined as adsorbents used for removal As(V) ions from aqueous solutions. Adsorption of arsenic ions by pure magnetite and magnetite modified with titanium dioxide was very high, above 90% (initial concentration 10 mg/L), pH in the range from 2 to 7. The preparation of magnetic adsorbents with a high adsorption capacity of As(V) ions was developed (in the range from 19.34 to 11.83 mg/g). Magnetic properties enable the easy separation of an adsorbent from a solution, following adsorption.

Prospective, Randomized, Investigator-Blinded, Split-Face Evaluation of a Topical Crosslinked Hyaluronic Acid Serum for Post-Procedural Improvement of Skin Quality and Biomechanical Attributes.

BACKGROUND: This split-face, controlled study investigated the ability of a topical crosslinked hyaluronic acid formulation (RHA serum) to enhance clinical results from fillers, microneedling, or chemical peeling of aging skin. Previous comparative skin explant studies demonstrated greater efficacy of RHA serum than topical non-crosslinked high or low molecular weight hyaluronic acid in decreasing trans-epidermal water loss, increasing epidermal hydration, and improving corneocyte microstructure. METHODS: 24 female subjects aged 35 to 55 were enrolled. 8 received intradermal hyaluronic acid filler injection, 8 received microneedling, and 8 received superficial mandelic acid chemical peeling. Subjects initiated twice-daily, standardized application of RHA serum to one side of the face 2 days after the procedure. Topographical imaging, bioinstrumental, and blinded clinical evaluations were performed at days 0, 14, and 28. RESULTS: Areas treated with RHA serum showed statistically significant improvements in skin surface topography and hydration compared to untreated areas. Blinded investigator scoring showed greater improvement of RHA serum-treated skin in moisture, tone/complexion, radiance, texture, uniformity, and global appearance. Subjects' questionnaire responses correlated with these findings. Subjects expressed greater satisfaction with appearance of the treated hemiface. No adverse events were observed during the study. CONCLUSIONS: When initiated post-procedurally, topical RHA serum was well-tolerated and enhanced biomechanical properties, quality, and clinical appearance of the skin. Based on these data, RHA serum may be of value in improving patient outcomes and satisfaction following minimally invasive aesthetic procedures. The availability of the same hyaluronic acid technology also as a cohesive, tissue-integrating injectable filler enables synergistic, multi-level treatment plans to be devised.

J Drugs Dermatol. 2018;17(4):442-450.

Dinuclear Metallacycles with Single M-X-M Bridges (X = Cl-, Br-; M = Fe(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II)): Strong Antiferromagnetic Superexchange Interactions.

A series of monochloride-bridged, dinuclear metallacycles of the general formula [M2(µ-Cl)(µ-L)2](ClO4)3 have been prepared using the third-generation, ditopic bis(pyrazolyl)methane ligands L = m-bis[bis(1-pyrazolyl)methyl]benzene (Lm), M = Cu(II), Zn(II), and L = m-bis[bis(3,5-dimethyl-1-pyrazolyl)methyl]benzene (Lm*), M = Fe(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II). These complexes were synthesized from the direct reactions of M(ClO4)2·6H2O, MCl2, and the ligand, Lm or Lm*, in the appropriate stoichiometric amounts. Three analogous complexes of the formula [M2(µ-Cl)(µ-L)2](BF4)3, L = Lm, M = Cu(II), and L = Lm*, M = Co(II), Cu(II), were prepared from the reaction of [M2(µ-F)(µ-L)2](BF4)3 and (CH3)3SiCl. The bromide-bridged complex [Cu2(µ-Br)(µ-Lm*)2](ClO4)3 was prepared by the first method. Three acyclic complexes, [Co2(µ-Lm)µ-Cl4], [Co2(µ-Lm*)Cl4], and [Co2(µ-Lm*)Br4], were also prepared. The structures of all [M2(µ-X)(µ-L)2]3+ (X = Cl-, Br-) complexes have two ditopic bis(pyrazolyl)methane ligands bridging two metals in a metallacyclic arrangement. The fifth coordination site of the distorted trigonal bipyramidal metal centers is filled by a bridging halide ligand that has an unusual linear or nearly linear M-X-M angle. The NMR spectra of [Zn2(µ-Cl)(µ-Lm*)2](ClO4)3 and especially [Cd2(µ-Cl)(µ-Lm*)2](ClO4)3 demonstrate that the metallacycle structure is maintained in solution. Solid state magnetic susceptibility data for the copper(II) compounds show very strong antiferromagnetic exchange interactions, with -J values of 536 cm-1 for [Cu2(µ-Cl)(µ-Lm)2](ClO4)3·xCH3CN, 720 cm-1 for [Cu2(µ-Cl)(µ-Lm*)2](ClO4)3, and 945 cm-1 for [Cu2(µ-Br)(µ-Lm*)2](ClO4)3·2CH3CN. Smaller but still substantial antiferromagnetic interactions are observed with other first row transition metals, with -J values of 98 cm-1 for [Ni2(µ-Cl)(µ-Lm*)2](ClO4)3, 55 cm-1 for [Co2(µ-Cl)(µ-Lm*)2](ClO4)3, and 34 cm-1 for [Fe2(µ-Cl)(µ-Lm*)2](ClO4)3. EPR spectra of [Cu2(µ-Cl)(µ-Lm*)2](BF4)3 confirm the dz2 ground state of copper(II). In addition, the sign of the zero-field splitting parameter D was determined to be positive for [Cu2(µ-F)(µ-Lm*)2](BF4)3. Electronic spectra of the copper(II) complexes as well as Mössbauer spectra of the iron(II) complexes were also studied in relation with the EPR spectra and magnetic properties, respectively. Density functional theory calculations were performed using ORCA, and exchange integral values were obtained that parallel but are slightly higher than the experimental values by about 30%.

Amorolfine vs. ciclopirox - lacquers for the treatment of onychomycosis.

Amorolfine 5% and ciclopirox 8% nail lacquers are commonly used in topical treatment of onychomycosis. These formulations may be used alone or in combination with oral antifungal agents. Amorolfine and ciclopirox are valuable therapeutic options, however, their usage in monotherapy should be limited. Proper amorolfine and ciclopirox penetration through the nail plate is provided by transungual drug delivery systems. Although amorolfine and ciclopirox have a different mode of action, they both exhibit a broad antifungal activity. The use of antifungal nail lacquers in combination with oral agents, such as terbinafine and itraconazole, improves efficacy of antifungal therapy.

The Effect of Leukocyte Removal and Matrix Metalloproteinase Inhibition on Platelet Storage Lesions.

The reasons for unfavorable changes in platelet concentrate (PC) quality during storage are not fully understood yet. We aimed to evaluate whether leukocytes and matrix metalloproteinases (MMPs) lead to a decrease in the quality of PCs and examine whether MMP inhibition will slow down the platelets' aging. Nine PCs were divided into three parts: (1) leukocyte-depleted (F) PCs, (2) PCs with no additional procedures (NF), and (3) PCs with the addition of an MMP inhibitor-doxycycline (D). Each PC was stored for 144 h, and a sample for testing was separated from each part on the day of preparation and after 24, 48, 72 and 144 h of storage. Blood morphological analysis, platelet aggregation, and the expression of activation markers were evaluated. MMP-2 and MMP-9 concentration, activity, and gene expression were assessed. Platelet aggregation decreased, and platelet activation marker expression increased during the storage. D concentrates showed the lowest level of platelet activation. In turn, leukocyte-depleted PCs showed the highest level of platelet activation in general. MMP-9 platelet activity was higher in leukocyte-containing concentrates at the end of the storage period. We concluded that the filtration process leads to a higher platelet activation level. The presence of doxycycline in PCs reduces the expression of the activation markers as compared to leukocyte-depleted concentrates.

RhoA/ROCK Pathway Is Upregulated in Experimental Autoimmune Myocarditis and Is Inhibited by Simvastatin at the Stage of Myosin Light Chain Phosphorylation.

Many studies have proven the involvement of the RhoA/ROCK pathway in autoimmune and cardiovascular diseases and the beneficial effects of its downregulation. Here, we examined whether the effect of simvastatin on experimental autoimmune myocarditis (EAM) may be through targeting the Ras homolog family member A/Rho-associated coiled-coil containing kinases (RhoA/ROCK) pathway and whether previously shown downregulation of metalloproteinase 9 (MMP-9) could be associated with MLC phosphorylation. Two doses of simvastatin were administered to experimental rats with autoimmune myocarditis by gastric gavage for 3 weeks, at the stage of development of the inflammatory process. Immunohistochemical staining for RhoA and ROCK1 was evaluated semi-quantitatively with H-score. The RhoA staining showed no significant differences in expression between the groups, but the ROCK1 expression was significantly upregulated in the hearts of the EAM group and was not downregulated by simvastatin. The Western blotting analysis of the last downstream product of the RhoA/ROCK axis, phosphorylated myosin light chain (phospho-MYL9), revealed that protein content increased in EAM hearts and it was prevented by the highest dose of simvastatin. Our findings suggest that the RhoA/ROCK pathway is upregulated in EAM, and simvastatin in EAM settings inhibits the RhoA/ROCK pathway at the stage of phosphorylation of myosin light chains and provides a new insight into the molecular pathology of autoimmune myocarditis.

L-tyrosinatonickel(II) complex: synthesis and structural, spectroscopic, magnetic, and biological properties of 2{[Ni(L-Tyr)2(bpy)]}·3H2O·CH3OH.

The complex 2{[Ni(L-Tyr)2(bpy)]}·3H2O·CH3OH [1, where L-Tyr = L-tyrosine; bpy = 2,2'-bipyridine (2,2'-bpy)] was obtained in crystalline form and characterized by X-ray and spectroscopic (FT-IR, NIR-vis-UV, and HFEPR) and magnetic methods. The complex crystallized in the hexagonal system with a = b = 12.8116(18) Å, c = 30.035(6) Å, and space group P3221. The six-coordination sphere around the Ni(2+) ion is formed by two N and two O L-tyrosinato atoms and completed by two N atoms of the 2,2'-bpy molecule. Neighboring [Ni(L-Tyr)2(bpy)] units are joined via weak hydrogen bonds, which create a helical polymeric chain. The coordinated atoms form a strongly distorted cis-NiN2N2'O2 octahedral chromophore. The solid-state electronic spectrum of complex 1 was analyzed assuming D2h symmetry, and the observed bands were assigned to (3)B1g → (3)Ag, (3)B1g → (3)B3g, (3)B1g → (3)B2g, (3)B1g → (3)B3g, (3)B1g → (3)B1g, and (3)B1g → (3)B2g transitions for the I and II d-d bands, respectively. The crystal-field parameters found for D2h symmetry are Dq = 1066 cm(-1), Ds = 617 cm(-1), Dt = -93 cm(-1), B22 = 7000 cm(-1), and Racah B = 812 cm(-1). Magnetic studies revealed the occurrence of hydrogen-bonded metal pairs. The spin Hamiltonian parameters D = -3.262 cm(-1) and E = -0.1094 cm(-1), determined from high-field, high-frequency electron paramagnetic resonance spectra, together with a weak antiferromagnetic exchange parameter J = -0.477 cm(-1), allowed us to reproduce the powder magnetic susceptibility and field-dependent magnetization of the complex. The biological activity of 1 has been tested by using the Fusarium solani, Penicillium verrucosum, and Aspergillus flavus fungi strains and Escherichia coli, Pseudomonas fluorescens, Serratia marcescens, and Bacillus subtilis bacterial strains.

TiO2-Modified Magnetic Nanoparticles (Fe3O4) with Antibacterial Properties.

This paper presents the synthesis and characteristics of Fe3O4/C/TiO2 hybrid magnetic nanomaterials with antibacterial properties. The materials used were obtained using a microwave-assisted two-stage precipitation method. In the first stage, magnetite nanoparticles (Fe3O4) were prepared with the precipitation method, during which an additional glucose layer was placed on them. Next, the surface of Fe3O4 nanoparticles was covered by TiO2. It was observed that the addition of carbon and titanium dioxide caused a decrease in the average size of magnetite crystallites from 15.6 to 9.2 nm. Materials with varying contents of anatase phase were obtained. They were characterized in terms of phase composition, crystallite size, specific surface area, surface charge and the kinds of function groups on the surface. The results show a successful method of synthesizing hybrid magnetic nanoparticles, stable in a solution, with antibacterial properties under direct solar light irradiation. Compared to classical materials based on TiO2 and used for water disinfection, the obtained photocatalytic nanomaterials have magnetic properties. Owing to this fact, they can be easily removed from water once their activity under direct irradiance in a given process has completed.

The Protective Effect of Simvastatin on the Systolic Function of the Heart in the Model of Acute Ischemia and Reperfusion Is Due to Inhibition of the RhoA Pathway and Independent of Reduction of MMP-2 Activity.

The present study investigated whether Rho-associated protein kinase (RhoA/ROCK) signaling pathway inhibitor simvastatin inhibits matrix metalloproteinase 2 (MMP-2) activity in a rat ischemia-reperfusion injury (I/Ri) model by inhibiting the RhoA/ROCK pathway and reducing MMP-2 mRNA levels. Isolated rat hearts were subjected to aerobic perfusion or I/Ri control. The effect of simvastatin was assessed in hearts subjected to I/Ri. We determined cardiac mechanical function, the content of RhoA, phosphorylated myosin light chain subunit 1 (phospho-MYL9), troponin I, MMP-2, and MMP-2 mRNA in the heart homogenates, as well as MMP-2 activity in heart tissue. We showed that treatment with simvastatin caused improvement in the contractile function of the heart subjected to I/Ri which was accompanied by a decrease of MMP-2 activity in heart tissue along with inhibition of RhoA pathway, expressed in a reduction in both RhoA and its downstream product-phosphorylated myosin light chain (phospho-MYL9) in hearts treated with simvastatin. MMP-2 inactivation is not due to inhibition of MMP-2 m-RNA synthesis caused by inhibition of RhoA/ROCK pathway and is due, at least in part, to the direct drug action. The protective effect of simvastatin on systolic function in the acute ischemia-reperfusion model does not appear to be related to reduced MMP-2 activation, but other mechanisms related with the inhibition RhoA/ROCK pathway.

Synthesis, crystal structure, spectroscopic, magnetic, theoretical, and microbiological studies of a nickel(II) complex of L-tyrosine and imidazole, [Ni(Im)2(L-tyr)2]·4H2O.

The [Ni(Im)(2)(L-tyr)(2)]·4H(2)O (1) complex was obtained in crystalline form as a product of interaction of L-tyrosine sodium salt, imidazole, and NiSO(4). The X-ray structure was determined, and the spectral (IR, FIR, NIR-vis-UV, HF EPR) and magnetic properties were studied. The Ni(2+) ion is hexacoordinated by the N and O atoms from two L-tyrosine molecules and by two N atoms of imidazole, resulting in a slightly distorted octahedral [NiN(2)N(2)'O(2)] geometry with a tetragonality parameter T = 0.995. The bands observed in the electronic spectra were ascribed to the six spin-allowed electronic transitions (3)B(1g) → (3)E(g) and (3)B(2g), (3)B(1g) → (3)A(2g) and (3)E(g), and (3)B(1g) → (3)A(2g) and (3)E(g). The spin Hamiltonian parameters g, D, and E, which were determined from high-field HF EPR spectra, excellently reproduced the magnetic properties of the complex. Calculation of the zero-field splitting in the S = 1 state of nickel(II) using DFT and UHF was attempted. The biological activity of the complexes has been tested for antifungal and antibacterial effects against Aspergillus flavus, Fusarium solani, Penicillium verrucosu, Bacillus subtilis, Serratia marcescens, Pseudomonas fluorescens, and Escherichia coli.

Prognostic Value of Tie2-Expressing Monocytes in Chronic Lymphocytic Leukemia Patients.

Tie2-expressing monocytes (TEMs) are associated with tumor progression and metastasis. This unique subset of monocytes has been identified as a potential prognostic marker in several solid tumors. However, TEMs remain poorly characterized in hematological cancers, including chronic lymphocytic leukemia (CLL). This study analyzed, for the first time, the clinical significance of TEM population in CLL patients. Flow cytometry analysis of TEMs (defined as CD14+CD16+Tie2+ cells) was performed at the time of diagnosis on peripheral blood mononuclear cells from 104 untreated CLL patients. Our results revealed an expansion of circulating TEM in CLL patients. These monocytes express high levels of VEGF and suppressive IL-10. A high percentage of TEM was associated closely with unfavorable prognostic markers (ZAP-70, CD38, 17p and 11q deletion, and IGHV mutational status). Moreover, increased percentages of circulating TEMs were significantly higher in patients not responding to the first-line therapy as compared to responding patients, suggesting its potential predictive value. High TEM percentage was also correlated with shorter overall survival (OS) and shorter time to treatment (TTT). Importantly, based on multivariate Cox regression analysis, TEM percentage was an independent predictor for TTT. Thus, we can suggest the adverse role of TEMs in CLL.

Isothiocyanate l-argininato copper(II) complexes - Solution structure, DNA interaction, anticancer and antimicrobial activity.

l-argininato copper(II) complexes have been intensively investigated in a variety of diseases due to their therapeutic potential. Here we report the results of comprehensive structural studies (ESI-MS, NIR-VIS-UV, EPR) on the complexes arising in aqueous solutions of two ternary copper(II) complexes with molecular formulas from crystal structures, [Cu(l-Arg)2(NCS)](NCS)·H2O (1) and [Cu(l-Arg)(NCS)2] (2) (l-Arg = l-arginine). Reference systems, the ternary Cu(II)/l-Arg/NCS- as well as binary Cu(II)/NCS- and Cu(II)/l-Arg, were studied in parallel in aqueous solutions by pH-potentiometric titration, EPR and VIS spectroscopy to characterize stability, structures and speciation of the formed species over the broad pH range. Comparative analysis of the obtained results showed that at a pH close to 7.0 mononuclear [Cu(l-Arg)2(NCS)]+ is the only species in water solution of 1, while equilibrium between [Cu(l-Arg)(SCN)]+ and binary [Cu(l-Arg)2]2+ was detected in water solution of 2. According to DNA binding studies, the [Cu(l-Arg)2(NCS)]+, [Cu(l-Arg)(SCN)]+ and [Cu(l-Arg)2]2+ species could be considered as strong minor groove binding agents causing, in the presence of H2O2, the involvement of ROS in plasmid damage. The human carcinoma cells (A549 cell line) were generally significantly more sensitive to cytotoxic and antiproliferative effect of compounds 1 and 2 than human normal cells. The studied compounds shown antimicrobial activity against bacteria belonging to Enterobacteriaceae family.

HMG-CoA Reductase Inhibitor, Simvastatin Is Effective in Decreasing Degree of Myocarditis by Inhibiting Metalloproteinases Activation.

BACKGROUND: Acute myocarditis often progresses to heart failure because there is no effective, etiology-targeted therapy of this disease. Simvastatin has been shown to be cardioprotective by decreasing matrix metalloproteinases' (MMPs) activity. The study was designed to determine whether simvastatin inhibits MMPs activity, decreases the severity of inflammation and contractile dysfunction of the heart in experimental autoimmune myocarditis (EAM). METHODS: Simvastatin (3 or 30 mg/kg/day) was given to experimental rats with EAM by gastric gavage for 21 days. Then transthoracic echocardiography was performed, MMPs activity and troponin I level were determined and tissue samples were assessed under a light and transmission electron microscope. RESULTS: Hearts treated with simvastatin did not show left ventricular enlargement. As a result of EAM, there was an enhanced activation of MMP-9, which was significantly reduced in the high-dose simvastatin group compared to the low-dose group. It was accompanied by prevention of myofilaments degradation and reduction of severity of inflammation. CONCLUSIONS: The cardioprotective effects of simvastatin in the acute phase of EAM are, at least in part, due to its ability to decrease MMP-9 activity and subsequent decline in myofilaments degradation and suppression of inflammation. These effects were achieved in doses equivalent to therapeutic doses in humans.

Matrix Metalloproteinase-2 Inhibition in Acute Ischemia-Reperfusion Heart Injury-Cardioprotective Properties of Carvedilol.

Matrix metalloproteinase 2 (MMP-2) is activated in hearts upon ischemia-reperfusion (IR) injury and cleaves sarcomeric proteins. It was shown that carvedilol and nebivolol reduced the activity of different MMPs. Hence, we hypothesized that they could reduce MMPs activation in myocytes, and therefore, protect against cardiac contractile dysfunction related with IR injury. Isolated rat hearts were subjected to either control aerobic perfusion or IR injury: 25 min of aerobic perfusion, followed by 20 min global, no-flow ischemia, and reperfusion for 30 min. The effects of carvedilol, nebivolol, or metoprolol were evaluated in hearts subjected to IR injury. Cardiac mechanical function and MMP-2 activity in the heart homogenates and coronary effluent were assessed along with troponin I content in the former. Only carvedilol improved the recovery of mechanical function at the end of reperfusion compared to IR injury hearts. IR injury induced the activation and release of MMP-2 into the coronary effluent during reperfusion. MMP-2 activity in the coronary effluent increased in the IR injury group and this was prevented by carvedilol. Troponin I levels decreased by 73% in IR hearts and this was abolished by carvedilol. Conclusions: These data suggest that the cardioprotective effect of carvedilol in myocardial IR injury may be mediated by inhibiting MMP-2 activation.

High M-MDSC Percentage as a Negative Prognostic Factor in Chronic Lymphocytic Leukaemia.

In the current study, we analysed the role and prognostic value of myeloid-derived suppressor cells (MDSC) in chronic lymphocytic leukaemia (CLL). The frequency of circulating monocytic MDSC (M-MDSC; defined as CD14+CD11b+CD15-HLA-DR-/low cells) was assessed in correlation with clinical and laboratory parameters characterising the disease activity and patient immune status. Samples of peripheral blood from untreated CLL patients and healthy volunteers were stained with monoclonal antibodies for flow cytometry analysis. CLL patients with M-MDSC percentages above 9.35% (according to the receiver operating characteristic (ROC) analysis) had a shorter time-to-treatment and shorter survival time than the group with a lower percentage of M-MDSC. The M-MDSC percentage was higher in patients with adverse prognostic factors (i.e., 17p and 11q deletion and CD38 and ZAP-70 expression). A high M-MDSC percentage was linked to significantly lower expression of the CD3ζ in T cells. Furthermore, an analysis of immune regulatory molecules (arginase 1 (ARG1), nitric oxide synthase (NOS2), indoleamine 2,3-dioxygenase (IDO), transforming growth factor beta (TGF-ß), and interleukin (IL)-10) was performed. By the means of flow cytometry and RT-qPCR, we showed an overexpression of three of them in M-MDSC of CLL patients. M-MDSC cells seem to be an important factor in the immunosuppressive microenvironment of CLL and seem to be a good and novel prognostic factor.

Extracellular Matrix Remodeling Factors as Markers of Carotid Artery Atherosclerosis.

MATERIALS AND METHODS: 20 patients undergoing routine carotid endarterectomy and 40 healthy volunteers were enrolled in this study. MMPs activity and OPG and FN concentrations were measured in atherosclerotic plaques and nonchanged contiguous tissue after homogenization as well as in plasma from patients and reference group. The activity of MMPs was evaluated by gelatin zymography, and the concentration of OPG and FN was assessed by ELISA. RESULTS: OPG concentration and MMP-9 activity showed differences between plaque and nonchanged tissue; OPG was higher in adjacent tissue (P=0.0009), whereas MMP-9 was higher in plaque (proMMP-9 P=0.0003; MMP-9 P < 0.0001). The OPG plasma concentration and both MMPs plasma activity were higher in patients (OPG P < 0.001; proMMP-2 P=0.0292; and proMMP-9 P=0.0374), while FN plasma concentration was lower in patients than in the reference group (P=0.0004). The ROC curves analysis showed the highest AUC for OPG (0.943) with 85.0% sensitivity and 92.1% specificity. CONCLUSIONS: The atherosclerotic plaque and the contiguous artery wall are biochemically different. OPG shows the highest potential to be a marker of advanced carotid atherosclerosis.

Low pH constructed Co(ii) and Ni(ii) 1D coordination polymers based on Cα-substituted analogues of zoledronic acid: structural characterization, and spectroscopic and magnetic properties.

Three novel coordination compounds based on α,α-disubstituted analogues of zoledronic acid with a cyclopropane (cpp) or cyclobutane (cbt) ring on the Cα carbon, isomorphous [Co(H2cppZol)(H2O)]·H2O (1a), [Ni(H2cppZol)(H2O)]·H2O (1b) and [Co(H2cbtZol)(H2O)]·H2O (2a), were synthesized under hydrothermal conditions at low pH. Single-crystal X-ray diffraction analysis revealed that all the compounds had a 1D double zig-zag chain architecture with an 8 + 8 ring motif formed by alternately arranged symmetrical (-O-P-O-)2 bridges linking equivalent octahedral metal centres. Both the ligand coordination mode and chain architecture displayed by 1a, 1b and 2a are unique among 1D [M(H2L)(H2O) x ]·yH2O coordination polymers based on nitrogen-containing bisphosphonates reported so far. All the compounds exhibit similar decomposition pathways upon heating with thermal stabilities decreasing in the order 1b > 1a > 2a. The IR spectra revealed that lattice water release above 227, 178 and 97 °C, respectively, does not change the chain architecture leaving them intact up to ca. 320, 280 and 240 °C. Magnetic behaviour investigations indicated that 1a, 2a and 1b exhibit weak alternating antiferromagnetic-ferromagnetic exchange interactions propagated between the magnetic centres through double (-O-P-O-)2 bridges. The boundary between antiferro- and ferromagnetic couplings for the Co-O⋯O-Co angle in 1a and 2a was estimated to be ca. 80°. This value is also applicable for recently reported [M3(HL)2(H2O)6]·6H2O (M = Co, Ni) complexes based on α,α-disubstituted analogues of zoledronic acid and can be used to the explain magnetic behaviour of 1b.

Landscape structure affects the prevalence and distribution of a tick-borne zoonotic pathogen.

BACKGROUND: Landscape structure can affect pathogen prevalence and persistence with consequences for human and animal health. Few studies have examined how reservoir host species traits may interact with landscape structure to alter pathogen communities and dynamics. Using a landscape of islands and mainland sites we investigated how natural landscape fragmentation affects the prevalence and persistence of the zoonotic tick-borne pathogen complex Borrelia burgdorferi (sensu lato), which causes Lyme borreliosis. We hypothesized that the prevalence of B. burgdorferi (s.l.) would be lower on islands compared to the mainland and B. afzelii, a small mammal specialist genospecies, would be more affected by isolation than bird-associated B. garinii and B. valaisiana and the generalist B. burgdorferi (sensu stricto). METHODS: Questing (host-seeking) nymphal I. ricinus ticks (n = 6567) were collected from 12 island and 6 mainland sites in 2011, 2013 and 2015 and tested for B. burgdorferi (s.l.). Deer abundance was estimated using dung transects. RESULTS: The prevalence of B. burgdorferi (s.l.) was significantly higher on the mainland (2.5%, 47/1891) compared to island sites (0.9%, 44/4673) (P < 0.01). While all four genospecies of B. burgdorferi (s.l.) were detected on the mainland, bird-associated species B. garinii and B. valaisiana and the generalist genospecies B. burgdorferi (s.s.) predominated on islands. CONCLUSION: We found that landscape structure influenced the prevalence of a zoonotic pathogen, with a lower prevalence detected among island sites compared to the mainland. This was mainly due to the significantly lower prevalence of small mammal-associated B. afzelii. Deer abundance was not related to pathogen prevalence, suggesting that the structure and dynamics of the reservoir host community underpins the observed prevalence patterns, with the higher mobility of bird hosts compared to small mammal hosts leading to a relative predominance of the bird-associated genospecies B. garinii and generalist genospecies B. burgdorferi (s.s.) on islands. In contrast, the lower prevalence of B. afzelii on islands may be due to small mammal populations there exhibiting lower densities, less immigration and stronger population fluctuations. This study suggests that landscape fragmentation can influence the prevalence of a zoonotic pathogen, dependent on the biology of the reservoir host.