Adiponectin is one of the most important molecules in the body's compensatory response to the development of insulin resistance. By trying to maintain insulin sensitivity, increase insulin secretion ...and prevent inflammation, adiponectin tries to maintain glucose homeostasis. Interleukin-33, which belongs to the group of alarmins, also promotes insulin secretion. Interleukin-33 might be either pro-inflammatory or anti-inflammatory depending on the disease and the model. However, interleukin-33 has shown various protective effects in CVD, obesity and diabetes. The aim of our study was to investigate the association between adiponectin and interleukin-33 in patients with metabolic syndrome. As expected, all patients with metabolic syndrome had worse parameters that represent the hallmark of metabolic syndrome compared to the control group. In the subgroup of patients with low adiponectin, we observed less pronounced characteristics of metabolic syndrome simultaneously with significantly higher values of interleukin-33 compared to the subgroup of patients with high adiponectin. Our findings suggested that adiponectin might be an early marker of metabolic syndrome that emerges before anthropomorphic, biochemical and clinical parameters. We also suggest that both interleukin-33 and adiponectin may be used to predict the inflammatory status in the early stage of metabolic syndrome.
Abstract The present study compared the photothermal anticancer activity of near-infrared (NIR)-excited graphene nanoparticles and carbon nanotubes (CNT). Despite lower NIR-absorbing capacity, ...suspension of polyvinylpyrrolidone-coated graphene sheets exposed to NIR radiation (808 nm, 2 W/cm2 ) generated more heat than DNA or sodium dodecylbenzenesulfonate-solubilized single-wall CNT under the same conditions. Accordingly, graphene nanoparticles performed significantly better than CNT in inducing photothermal death of U251 human glioma cells in vitro. The superior photothermal sensitivity of graphene sheets could be largely explained by their better dispersivity, which has been supported by a simple calculation taking into account thermodynamic, optical and geometrical properties of the two type of carbon nanoparticles. The mechanisms of graphene-mediated photothermal killing of cancer cells apparently involved oxidative stress and mitochondrial membrane depolarization resulting in mixed apoptotic and necrotic cell death characterized by caspase activation/DNA fragmentation and cell membrane damage, respectively.
The four new ligands, propylenediamine derivatives of phenylalanine (R2-S,S-pddbaˑ2HCl; L1-L4) and their palladium(II) complexes (C1-C4) were synthesized and characterized by elemental analysis, ...infrared, 1H and 13C NMR spectroscopy. The interactions of new palladium(II) complexes with human serum albumin (HSA) were studied by fluorescence spectroscopy. All investigated compounds can be transported to target cells by binding to HSA, but complex C4 interacts most strongly. Molecular docking simulations were applied to comprehend the binding of the complex to the molecular target of HSA. Obtained results are in good correlations with experimental data regarding binding affinity by HSA. In vitro cytotoxicity activities were investigated on four tumor cell lines (mouse mammary (4 T1) and colon (CT26), human mammary (MDA-MD-468) and colon (HCT116)) and mouse mesenchymal stem cells as non-tumor control cells. Cytotoxic capacity was determined by MTT test and according to obtained results ligand L4 stands out as the most active and selective compound and as a good candidate for future in vivo testing. Further examination of the ligand L4 and corresponding complex C4 led to the conclusion that both induced cell death mainly by apoptosis. Ligand L4 facilitated cycle arrest in G0/G1 phase and decreased proliferative capacity of tumor cells. In vitro antimicrobial activity for ligands and corresponding Pd(II) complexes was investigated against eleven microorganisms (eight strains of pathogenic bacteria and three yeast species) using microdilution method. The minimum inhibitory concentration and minimum microbicidal concentration were determined.
The four new ligand and their pallladium(II) complexes were synthesized and characterized by elemental microanalysis, IR, 1H, 13C NMR spectroscopy. The interactions of complexes with HSA were determined and molecular doking simulation were performed. In vitro cytotoxic and antimicrobial activity were tested. Display omitted
•Four new ligand were synthesized by new method.•Four new palladium(II) complexes were synthesized.•Characterization was performed by IR, 1H and 13C NMR spectroscopy.•The interactions of complexes and molecular docking with HSA were investigated.•Cytotoxic and antimicrobial activities of all compaunds were evaluated.
We used a model of a relativistic accretion disk around a supermassive black hole (SMBH), based on ray-tracing method in the Kerr metric, to study the variations of the composite Fe Kα line emitted ...from two accretion disks around SMBHs in a binary system. We assumed that the orbit of such a binary is approximately Keplerian, and simulated the composite line shapes for different orbital elements, accretion disk parameters and mass ratios of the components. The obtained results show that, if observed in the spectra of some SMBH binaries during their different orbital phases, such composite Fe Kα line profiles could be used to constrain the orbits and several properties of such SMBH binaries.
Although separate blockage of either IL33/ST2 or PD-L/PD-1 axes has been shown to be beneficial in many tumors, co-blockage of IL33/ST2 and PD-L/PD-1 hasn't been studied yet.
4T1 breast cancer and ...CT26 colon cancer were inducted in BALB/C wild type (WT) and BALB/C ST2 knockout mice, after which mice underwent anti PD-1 and anti IL-33 treatment.
Co-blockage of IL33/ST2 and PD-L/PD-1 delayed tumor appearance and slowed tumor growth. Enhanced NK cell cytotoxicity against 4T1 tumor cells in ST2 knockout anti-PD-1 treated mice was associated with overexpression of miRNA-150 and miRNA-155, upregulation of NFκB and STAT3, increased expression of activation markers and decreased expression of immunosuppressive markers in splenic and primary tumor derived NK cells. NK cells from ST2 knockout anti-PD-1 treated mice tend to proliferate more and are less prone to apoptosis. Accumulation of immunosuppressive myeloid derived suppressor cells and regulatory T cells was significantly impaired in spleen and primary tumor of ST2 knockout anti-PD-1 treated mice.
Co-blockage of IL3/ST2 and PD-L/PD-1 axes impedes tumor progression more efficiently than single blockage of either axes, thus offering potential new approach to immunotherapy of tumors.
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•Delayed tumor appearance and slowed tumor growth in ST2 knockout anti-PD1 treated mice•IL33/ST2 and PDL/PD1 co-blockage facilitates NK cells’ cytotoxicity and tumoricidal activity•IL33/ST2 and PDL/PD1 co-blockage minimizes the possibility of immune related adverse events linked to anti-PD1 treatment
Four Pt(II) complexes of the general formula Pt(L)(5,6-epoxy-1,10-phen), where L is an anion of either malonic acid (mal, Pt1), 2-methylmalonic acid (Me-mal, Pt2), 2,2-dimethylmalonic acid (Me2-mal, ...Pt3) or 1,1-cyclobutanedicarboxylic acid (CBDCA, Pt4) and 5,6-epoxy-1,10-phen is 5,6-epoxy-5,6-dihydro-1,10-phenanthroline, were synthesized and characterized by elemental microanalysis and different spectroscopic techniques. The crystal structure of anhydrous Pt3 complex was determined by single crystal X-ray diffraction. The in vitro anticancer activity of the platinum(II) complexes was investigated in human and murine cancer cell lines as well as in a normal murine cell line by MTT assay. The results show that the investigated platinum(II) complexes exhibit potent cytotoxic activity against murine breast carcinoma cells (4T1), human (HCT116) and murine (CT26) colorectal carcinoma cells. The Pt3 complex shows stronger selectivity against cancer cells compared to other platinum(II) complexes tested and thus exhibits beneficial antitumor activity, mainly by inducing apoptosis and inhibiting cell proliferation and migration. The Pt3 complex also exhibits significant in vivo antitumor activity in the orthotopical 4T1 tumor model without detected liver, kidney, lung, and heart toxicity. All the results indicate that these novel platinum(II) complexes have good antitumor activity on breast and colorectal cancer and have the potential to become possible candidates for cancer treatment.
Complexes Pt1- Pt4 possess significant in vitro cytotoxicity against murine 4T1, CT26 and human HCT116 cells. Pt3 demonstrates highest selectivity toward cancer cells, triggering apoptosis of 4T1 and CT26 cancer cells with inhibition of cell proliferation and migration. Murine breast cancer growth was inhibited after in vivo application of Pt3. Display omitted
•Pt1- Pt4 possess significant in vitro cytotoxicity against 4T1, HCT116, CT26 cells.•Pt3 complex triggered apoptosis of breast and colorectal cancer cells.•Pt3 complex diminished metastasis capacity of cancer cells.•In vivo application of Pt3 inhibited murine breast cancer growth and progression.•In vivo treatment with Pt3 caused low general toxicity.
Currant fruit extracts were characterized by (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity, 2,2-azinobis-3 ethyl benzothiazoline-6-sulfonic acid cation decolorization activity, total ...reducing power, cupric ion reducing antioxidant power, and ferric ion reducing antioxidant power (FRAP) assays to evaluate their antioxidant activity. All five antioxidant assays revealed the highest antioxidant activity to be present for the black currants. The highest concentrations of phenolics were present in the black currants (1690 ± 10 mg gallic acid equivalents (GAE)/100 g fresh weight), while the lowest value was obtained in the white currants (579 ± 5 mg GAE/100 g fresh weight). The correlation between the total phenolic content and antioxidant activity assays was evaluated using regression analysis. A significant positive correlation was obtained between the total phenols and the cupric ion reducing antioxidant power (r = 0.97, p < 0.05), followed by that between the total phenols and FRAP (r = 0.93, p < 0.05). Hierarchical cluster analysis separated these selected fruit species into two statistically significant clusters with black currants as a distinctive cluster.
This study provides information on plants used for medicinal purposes in Pirot District (southeastern Serbia). The population of 157 villages in four municipalities of Pirot District (631 informants) ...completed questionnaires about the knowledge and use of medicinal herbs; the questionnaires included information about respondents and specific issues related to the applications of medicinal herbs. There were 4817 URs (use reports) on plants used for different ailments classified in various categories. The informant consensus factor (ICF) for the most frequently reported taxa and a comparison of nationality and gender in the use of plants for most frequent medical indications were calculated by ICF analysis. The overlap of plant taxa and URs recorded for three ethnic groups (Serbian, Bulgarian, and Roma) in the study area is also presented. Multivariate correspondence analysis was performed. A total of 182 medicinal plant taxa belonging to 68 families were recorded, of which 53 are included in European Pharmacopoeia 10.2. The most frequently mentioned families were Lamiaceae (1322 URs), and Compositae (899 URs).
Hypericum perforatum
and
Matricaria chamomilla
were the most used plant species. Aerial parts and leaves were the most frequently used plant parts. Infusion and oil extracts were the most reported preparations of medicinal herbs. Among 14 categories, respiratory (1235 URs), and digestive (911 URs) groups of diseases were the most frequently reported. Data on the knowledge and use of medicinal plants in Pirot District could be a good starting point for further ethnopharmacological investigations.
Metformin, an oral anti-diabetic drug, is known to possess a powerful antitumor effect by modulating the tumor-immune interaction. The precise influence of metformin on natural killer (NK) cells, a ...crucial innate immunity player, is not completely understood. In our study, analyses of the effect of metformin on the NK cell functional phenotype were performed, and the potential mechanisms underlying it were investigated.
BALB/C wild type mice were treated with metformin, and the functional phenotype of splenocytes and potential underlying mechanisms were investigated.
Metformin significantly boosts NK cell cytotoxicity and the percentage of NKp46
, FasL
, and interferon (IFN)-γ
NK cells while decreasing interleukin (IL)-10 producing NK cells. Our research also demonstrated that the simultaneous administration of metformin and 1-methyl-DL-tryptophan (1-MT), a specific inhibitor of indoleamine 2,3-dioxygenase (IDO), significantly increased the NK cells synthesis of IFN-γ, IL-17, perforin, and FasL and NKp46 expression. These findings imply that metformin potentiates NK cell cytotoxicity through mechanisms other than IDO blockade. Metformin administration strongly increased the expression of immunostimulatory microRNA (miRNA)-150 and miRNA-155, while decreasing the expression of immunosuppressive miRNA-146a.
These findings suggest that metformin can directly potentiate NK cell activation and cytotoxicity. This research may contribute to dissecting key mechanisms of metformin exerting antitumor activity to advance the use of metformin as an antitumor agent.
Context. We study the photocenter position variability caused by variations in the quasar inner structure. We consider the variability in the accretion disk emissivity and torus structure variability ...caused by the different illumination by the central source. We discuss the possible detection of these effects by Gaia. Observations of the photocenter variability in two AGNs, SDSS J121855+020002 and SDSS J162011+1724327 have been reported and discussed. Aims. For variations in the quasar inner structure, we explore how much this effect can affect the position determination and whether it can (or not) be detected with the Gaia mission. Methods. We use models of (a) a relativistic disk, including the perturbation that can increase the brightness of part of the disk, and consequently offset the photocenter position, and (b) a dusty torus that absorbs and re-emits the incoming radiation from the accretion disk (central continuum source). We estimate the value of the photocenter offset caused by these two effects. Results. We found that perturbations in the inner structure can cause a significant offset to the photocenter. This offset depends on the characteristics of both the perturbation and accretion disk and on the structure of the torus. In the case of the two considered QSOs, the observed photocenter offsets cannot be explained by variations in the accretion disk and other effects should be considered. We discuss the possibility of exploding stars very close to the AGN source, and also that there are two variable sources at the center of these two AGNs that may indicate a binary supermassive black hole system on a kpc (pc) scale. Conclusions. The Gaia mission seems to be very promising, not only for astrometry, but also for exploring the inner structure of AGNs. We conclude that variations in the quasar inner structure can affect the observed photocenter (by up to several mas). There is a chance to observe such an effect in the case of bright and low-redshift QSOs.
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