In present study, with an hydrazido-based ligand and Cu, Ni metal(II) salts, three new mononuclear and one binuclear end-to-end thiocynate bridged complexes have been synthesized and characterized by ...various physico-chemical techniques.
Display omitted
•Three new mononuclear and one binuclear end-to-end thiocynato bridged complexes have been synthesized and characterized by various physico-chemical techniques.•New complexes were fully structurally characterized using single crystal X-ray diffraction.•The classical image of an O-H⋯π interaction is a T shape with interacting hydrogen atoms approximately directly over the centre of the aromatic ring πc.•The inhibitory effect of the complexes were tested on a cell population with IMR 32 (neuroblastoma), MCF 7 (breast cancer), HepG2 (hepatocellular carcinoma), L132 (lung cells) cell lines by MTT assay.•Antioxidant super oxide dismutase activity measurements show that the complexes behave as superoxide dismutase mimics.
With an hydrazido-based ligand, C14H13N2O and Cu, Ni metal(II) salts, three new mononuclear Ni(HL)(NO3)(H2O)NO3,C14H15N5NiO8, 1, Cu(HL)(H2O)22NO3, C14H17CuN5O4, 2, Ni(HL)22ClO4, C28H30Cl2N6NiO12, 3 and one binuclear end-to-end thiocynate bridged Cu2(μ-SCN)2(L)2, C30H24Cu2N8O2S2, 4 complexes have been synthesized and characterized by physico-chemical techniques. All of the complexes were structurally characterized using single crystal X-ray diffraction. Complexes 1 and 2 have a penta-coordinated environment around the metal(II) centre, whereas complex 3 has a distorted hexa-coordinated geometry. In complex 4 two symmetry related, adjacent copper(II) coordination moieties are joined end-to-end in an unprecedented manner forming a thiocynate bridged, yielding a dicopper entity. The presence of two “symmetric” thiocynate bridges with Cu-SCN and Cu-NCS distances of 2.832 Å and 1.925 Å, respectively, results in a Cu⋯Cu distance of 5.503 Å. Binuclear complex, 4 exhibits a weak antiferromagnetic interaction between adjacent copper(II) centres. These copper(II) mononuclear and binuclear complexes have also been studied by X-band EPR spectroscopy. The crystal packing of these new complexes is stabilized by H-bonding, weak intermolecular interactions, CH⋯π and π⋯π interactions. Electrochemical data (CV and DPV) for the complexes shows MII → MI reduction activity. Electronic spectroscopy and computational features are examined by quantum chemical studies. The inhibitory effect of the complexes were tested on a cell population with IMR 32 (neuroblastoma), MCF 7 (breast cancer), HepG2 (hepatocellular carcinoma), L132 (lung cells) cell lines by MTT assay. Complex 3 showed a prominent cytotoxicity against the all cell lines. Expression levels of the Bax (pro-apoptotic) and Bcl2 (anti-apoptotic) genes were also studied, wherein the genes of interest showed a moderate down regulation after treatment with complexes 1 and 3. Finally, antioxidant superoxide dismutase activity measurements show that the complexes behave as superoxide dismutase mimics.
Exchange of extracellular cystine for intracellular glutamate by the antiporter system xc (-) is implicated in numerous pathologies. Pharmacological agents that inhibit system xc (-) activity with ...high potency have long been sought, but have remained elusive. In this study, we report that the small molecule erastin is a potent, selective inhibitor of system xc (-). RNA sequencing revealed that inhibition of cystine-glutamate exchange leads to activation of an ER stress response and upregulation of CHAC1, providing a pharmacodynamic marker for system xc (-) inhibition. We also found that the clinically approved anti-cancer drug sorafenib, but not other kinase inhibitors, inhibits system xc (-) function and can trigger ER stress and ferroptosis. In an analysis of hospital records and adverse event reports, we found that patients treated with sorafenib exhibited unique metabolic and phenotypic alterations compared to patients treated with other kinase-inhibiting drugs. Finally, using a genetic approach, we identified new genes dramatically upregulated in cells resistant to ferroptosis.DOI: http://dx.doi.org/10.7554/eLife.02523.001.
Two new copper(II) complexes Cu(L
1
)
2
(NO
3
)NO
3
1
and Cu(L
2
)(H
2
O)
2
(NO
3
)
2
2
(L
1
= 2(2-pyridyl)benzimidazole and L
2
= 2-benzoylpyridine) have been prepared and characterized by ...elemental and spectral (UV–visible, FTIR and epr) techniques. Crystal structures of these complexes were determined using single crystal X-ray diffraction analysis. The low value of magnetic moments 1.75 BM for
1
and 1.73 BM for
2
and unusual X-band epr spectral pattern authenticate the antiferromagnetic behavior of complexes. The single crystal X-ray analysis reveals the development of supramolecular architectures through various non-covalent weak interactions such as CH
⋯
π
and lp
⋯
π
interactions. In order to see the stability of complexes, density functional theory (DFT) calculations were carried out. From the energy gap (ΔE) of frontier molecular orbitals (various molecular descriptors were also evaluated. In addition, superoxide dismutase SOD) activities of both complexes were also determined. The enhanced SOD activity of
1
is due to loosely bound nitrate ion.
Graphical Abstract
Two new copper(II) complexes Cu(L
1
)
2
(NO
3
)NO
3
and Cu(L
2
)(H
2
O)
2
(NO
3
)
2
(L
1
= 2(2-pyridyl)benzimidazole and L
2
= 2-benzoylpyridine) have been prepared and characterized by elemental, spectral, and single crystal diffraction techniques
Itch-specific neurons have been sought for decades. The existence of such neurons has been doubted recently as a result of the observation that itch-mediating neurons also respond to painful stimuli. ...We genetically labeled and manipulated MrgprA3(+) neurons in the dorsal root ganglion (DRG) and found that they exclusively innervated the epidermis of the skin and responded to multiple pruritogens. Ablation of MrgprA3(+) neurons led to substantial reductions in scratching evoked by multiple pruritogens and occurring spontaneously under chronic itch conditions, whereas pain sensitivity remained intact. Notably, mice in which TRPV1 was exclusively expressed in MrgprA3(+) neurons exhibited itch, but not pain, behavior in response to capsaicin. Although MrgprA3(+) neurons were sensitive to noxious heat, activation of TRPV1 in these neurons by noxious heat did not alter pain behavior. These data suggest that MrgprA3 defines a specific subpopulation of DRG neurons mediating itch. Our study opens new avenues for studying itch and developing anti-pruritic therapies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
During their late pulsating phase, AGB stars expel most of their mass in the form of massive dusty envelopes, an event that largely controls the composition of interstellar matter. The envelopes, ...however, are distant and opaque to visible and NIR radiation: their structure remains poorly known and the mass-loss process poorly understood. Millimeter-wave interferometry, which combines the advantages of longer wavelength, high angular resolution and very high spectral resolution is the optimal investigative tool for this purpose. Mm waves pass through dust with almost no attenuation. Their spectrum is rich in molecular lines and hosts the fundamental lines of the ubiquitous CO molecule, allowing a tomographic reconstruction of the envelope structure. The circumstellar envelope IRC +10 216 and its central star, the C-rich TP-AGB star closest to the Sun, are the best objects for such an investigation. Two years ago, we reported the first detailed study of the CO(2–1) line emission in that envelope, made with the IRAM 30-m telescope. It revealed a series of dense gas shells, expanding at a uniform radial velocity. The limited resolution of the telescope (HPBW 11″) did not allow us to resolve the shell structure. We now report much higher angular resolution observations of CO(2–1), CO(1–0), CN(2–1) and C4H(24–23) made with the SMA, PdB and ALMA interferometers (with synthesized half-power beamwidths of 3″, 1″ and 0.3″, respectively). Although the envelope appears much more intricate at high resolution than with an 11″ beam, its prevailing structure remains a pattern of thin, nearly concentric shells. The average separation between the brightest CO shells is 16″ in the outer envelope, where it appears remarkably constant. Closer to the star (<40″), the shell pattern is denser and less regular, showing intermediary arcs. Outside the small (r< 0.3′′) dust formation zone, the gas appears to expand radially at a constant velocity, 14.5 km s-1, with small turbulent motions. Based on that property, we have reconstructed the 3D structure of the outer envelope and have derived the gas temperature and density radial profiles in the inner (r< 25′′) envelope. The shell-intershell density contrast is found to be typically 3. The over-dense shells have spherical or slightly oblate shapes and typically extend over a few steradians, implying isotropic mass loss. The regular spacing of shells in the outer envelope supports the model of a binary star system with a period of 700 yr and a near face-on elliptical orbit. The companion fly-by triggers enhanced episodes of mass loss near periastron. The densification of the shell pattern observed in the central part of the envelope suggests a more complex scenario for the last few thousand years.
Abstract
A cobalt‐catalyzed, N,O‐bidentate directing group‐assisted C−H bond functionalization of benzamides with maleimides was developed for the facile access to isoindolone spirosuccinimides in ...good to excellent yields. This C−H bond activation and spirocyclization employing pyridine N‐oxide as directing group provided very good substrate scope and tolerated various functional groups. Furthermore, the mechanistic investigation revealed that the C−H bond activation is the rate‐determining step of this reaction.
Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, is a common dietary component that has histone deacetylase inhibition activity and exciting potential in cancer prevention. The ...mechanisms by which SFN imparts its chemopreventive properties are of considerable interest and little is known of its preventive potential for breast cancer.
We found that SFN significantly inhibits the viability and proliferation of breast cancer cells in vitro while it has negligible effects on normal breast cells. Inhibition of telomerase has received considerable attention because of its high expression in cancer cells and extremely low level of expression in normal cells. SFN treatment dose- and time-dependently inhibited human telomerase reverse transcriptase (hTERT), the catalytic regulatory subunit of telomerase, in both MCF-7 and MDA-MB-231 human breast cancer cells. DNA methyltransferases (DNMTs), especially DNMT1 and DNMT3a, were also decreased in SFN-treated breast cancer cells suggesting that SFN may repress hTERT by impacting epigenetic pathways. Down-regulation of DNMTs in response to SFN induced site-specific CpG demethylation occurring primarily in the first exon of the hTERT gene thereby facilitating CTCF binding associated with hTERT repression. Chromatin immunoprecipitation (ChIP) analysis of the hTERT promoter revealed that SFN increased the level of active chromatin markers acetyl-H3, acetyl-H3K9 and acetyl-H4, whereas the trimethyl-H3K9 and trimethyl-H3K27 inactive chromatin markers were decreased in a dose-dependent manner. SFN-induced hyperacetylation facilitated the binding of many hTERT repressor proteins such as MAD1 and CTCF to the hTERT regulatory region. Depletion of CTCF using siRNA reduced the SFN-induced down-regulation of hTERT mRNA transcription in these breast cancer cells. In addition, down-regulation of hTERT expression facilitated the induction of cellular apoptosis in human breast cancer cells.
Collectively, our results provide novel insights into SFN-mediated epigenetic down-regulation of telomerase in breast cancer prevention and may open new avenues for approaches to SFN-mediated cancer prevention.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Background
The epidemiology of atopic dermatitis (AD) in the U.S.A. has been described largely via US population‐based questionnaire studies. However, the validity of the questions used for ...self‐ and caregiver‐reported eczema has not been previously demonstrated.
Objectives
To validate the assessment of self‐ and caregiver‐reported eczema.
Methods
We performed a prospective multicentre dermatology‐practice‐based study (three sites) to determine the validity of caregiver‐ and self‐reported ever having eczema and 1‐year history of eczema. Questionnaires were administered to unselected patients prior to their encounter. Patients (n = 782) were then evaluated by expert dermatologists trained in utilizing the Hanifin and Rajka criteria for AD. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value were determined.
Results
Caregiver‐reported 1‐year history of childhood eczema was found to have a sensitivity (95% confidence interval) of 0·70 (0·59–0·80), specificity of 0·96 (0·93–0·99) and PPV of 0·87 (0·78–0·96) when compared with a physician's diagnosis of AD at that visit. Similarly, self‐reported 1‐year history of adult eczema was found to have a sensitivity of 0·70 (0·59–0·80), specificity of 0·95 (0·93–0·97) and PPV of 0·76 (0·64–0·85). The specificities and PPVs of a history of ever having caregiver‐ (0·89, 0·82–0·96 and 0·81, 0·70–0·93) and self‐reported eczema (0·97, 0·95–0·99 and 0·91, 0·85–0·97) were high, with a high sensitivity in children (0·83, 0·72–0·95) but not in adults (0·43, 0·37–0·51).
Conclusions
Self‐ and caregiver‐reported diagnosis of eczema ever or in the past year based on a single question demonstrates sufficient validity for the epidemiological study of AD.
What's already known about this topic?
Questions about self‐reported eczema have been used in multiple epidemiological studies.
What does this study add?
A single question about self‐report and caregiver report of healthcare‐diagnosed eczema is valid to assess for atopic dermatitis.
Linked Comment: Ezzedine and Barbarot, Br J Dermatol 2015; 173: 1356–57.
Soft materials that facilitate the three-dimensional (3D) encapsulation, proliferation, and facile local delivery of cells to targeted tissues will aid cell-based therapies, especially those that ...depend on the local engraftment of implanted cells. Herein, we develop a negatively charged fibrillar hydrogel based on the de novo-designed self-assembling peptide AcVES3-RGDV. Cells are easily encapsulated during the triggered self-assembly of the peptide leading to gel formation. Self-assembly is induced by adjusting the ionic strength and/or temperature of the solution, while avoiding large changes in pH. The AcVES3-RGDV gel allows cell–material attachment enabling both two-dimensional and 3D cell culture of adherent cells. Gel–cell constructs display shear-thin/recovery rheological properties enabling their syringe-based delivery. In vivo cellular fluorescence as well as tissue resection experiments show that the gel supports the long-term engraftment of cells delivered subcutaneously into mice.
Two new bridged copper(II) coordination complexes with NNO donor ligands, viz., Cu2(μ-sulfato)(HL)2(H2O)·1.5H2O (1) and Cu2(μ-succinato)(L)(HL)(H2O)ClO4 (2), where ...HL/L = N′-(E)-pyridin-2-ylmethylidenebenzohydrazide, have been synthesized and characterized using various physico-chemical techniques. Both complexes are structurally characterized using single crystal X-ray diffraction studies and belong to the triclinic crystal system having space group P1¯.
Display omitted
In the present study, we use a dual approach comprising experimental and quantum computational studies of two new bridged copper(II) coordination complexes with NNO donor ligands, viz., Cu2(μ-sulfato)(L)2(2H2O)·1.5H2O (1) and Cu2(μ-succinato)(L)(HL)(H2O)ClO4 (2), where HL/L = N′-(E)-pyridin-2-ylmethylidenebenzohydrazide, have been synthesized and characterized using various physico-chemical techniques. Both complexes are structurally characterized using single crystal X-ray diffraction studies. The distances between two copper centers are 3.270(2) Å and 3.178(1) Å, for 1 and 2, respectively. On the basis of quantum computational DFT study, electronic excitations involve transitions mainly from metal-ligand bonding MO’s to the β-LUMO within the dominant Cu atom exhibiting dxy character and to the β-LUMO+1. EPR spectra for these polycrystalline samples were determined for the copper(II) hyperfine structures as well their zero-field splitting which are appropriate for the triplet state of such dimers. Cryomagnetic behavior is consistent with weak antiferromagnetic interactions between the Cu(1)⋯Cu(2) centers in both complexes. The magnetic exchange coupling constant (J) between the Cu(1)⋯Cu(2) centers for 1 and 2 were determined to be J = −1.50(1) and J = −7.7(1)cm−1, respectively. CH⋯π, π⋯π, and lone pair⋯π interactions which have gained attention and their role in bimolecular structure analysis has been recognized. In addition, antioxidant superoxide dismutase activity measurements have showed that homodinuclear complexes give significant scavenging effects against superoxide free radicals. Complex 2 is more antioxidant superoxide dismutase active than 1.
PDF
