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•Four octahedral Co(III) complexes were synthesized and characterized.•Partial intercalation with DNA and static quenching with BSA was established.•MTT assay on A549 and MCF-7 cells ...revealed their anticancer activity•The complexes showed significant microbial activity.•Complex 3 possessed better biological activity than the ligands and other complexes.
The present work deals with the synthesis and characterization of four Co(III) complexes derived from 7-hydroxy-4-oxo-4H-chromene-3-carbaldehyde-4(N)-substituted thiosemicarbazones. Structural confirmation of the complexes 2 and 3 were aided by X-ray crystallographic analysis, which revealed the coordination of azomethine nitrogen, ring carbonyl oxygen and thiol sulfur atoms of the ligands. DNA and Bovine serum albumin (BSA) binding studies brought about the binding ability of the complexes to biomolecules. The binding constant values calculated for the complexes were in the range (0.30–1.19) × 106 M−1 and the mode of interaction was found to be partially intercalative. The mechanism of quenching with BSA was static with quenching constants in the order 1012 M−1s−1. Their antimicrobial profile has been established by testing against four pathogenic bacterial and fungal species. The cytotoxic potential of the complexes were examined against MCF-7 and A549 cells by MTT assay. The IC50 values of the complexes were less than cisplatin, which indicated their greater activity over the standard drug. In addition, testing on human normal keratinocyte cells HaCaT indicated their non toxic nature. Lactate dehydrogenase (LDH) and Nitric oxide (NO) release assays supported the cytotoxic ability and suggested apoptotic mode of cell death induced by the complexes.
Stress affects the hippocampus, a brain region crucial for memory. In rodents, acute stress may reduce density of dendritic spines, the location of postsynaptic elements of excitatory synapses, and ...impair long-term potentiation and memory. Steroid stress hormones and neurotransmitters have been implicated in the underlying mechanisms, but the role of corticotropin-releasing hormone (CRH), a hypothalamic hormone also released during stress within hippocampus, has not been elucidated. In addition, the causal relationship of spine loss and memory defects after acute stress is unclear. We used transgenic mice that expressed YFP in hippocampal neurons and found that a 5-h stress resulted in profound loss of learning and memory. This deficit was associated with selective disruption of long-term potentiation and of dendritic spine integrity in commissural/associational pathways of hippocampal area CA3. The degree of memory deficit in individual mice correlated significantly with the reduced density of area CA3 apical dendritic spines in the same mice. Moreover, administration of the CRH receptor type 1 (CRFR₁) blocker NBI 30775 directly into the brain prevented the stress-induced spine loss and restored the stress-impaired cognitive functions. We conclude that acute, hours-long stress impairs learning and memory via mechanisms that disrupt the integrity of hippocampal dendritic spines. In addition, establishing the contribution of hippocampal CRH–CRFR₁ signaling to these processes highlights the complexity of the orchestrated mechanisms by which stress impacts hippocampal structure and function.
Our goal was to investigate the neuroprotective effects of galantamine in a mouse model of blast-induced indirect traumatic optic neuropathy (bITON). Galantamine is an FDA-approved ...acetylcholinesterase inhibitor used to treat mild-moderate Alzheimer's disease. We exposed one eye of an anesthetized mouse to repeat bursts of over-pressurized air to induce traumatic optic neuropathy. Mice were given regular or galantamine-containing water (120 mg/L) ad libitum, beginning immediately after blast and continuing for one month. Electroretinograms and visual evoked potentials were performed just prior to endpoint collection. Histological and biochemical assessments were performed to assess activation of sterile inflammation, axon degeneration, and synaptic changes. Galantamine treatment mitigated visual function deficits induced by our bITON model via preservation of the b-wave of the electroretinogram and the N1 of the visual evoked potential. We also observed a reduction in axon degeneration in the optic nerve as well as decreased rod bipolar cell dendritic retraction. Galantamine also showed anti-inflammatory and antioxidant effects. Galantamine may be a promising treatment for blast-induced indirect traumatic optic neuropathy as well as other optic neuropathies.
•Galantamine is an FDA approved acetylcholinesterase inhibitor used for the treatment of mild Alzheimer’s disease.•Post-injury galantamine mitigated ERG b-wave deficits and biopolar cell dendrite retraction.•Post-injury galantamine mitigated optic nerve damage and VEP deficits.•Post-injury galantamine mitigated increases in IL-1a, IL-1b, glutamate, nitrotyrosine, and SOD2.
Transcatheter aortic valve implantation (TAVI) is becoming a valuable alternative to surgical aortic valve replacement in patients with severe aortic stenosis that are at high surgical risk or deemed ...inoperable. The optimal anesthesia technique for TAVI is still undecided. We performed a systematic review and metaanalysis to compare the safety of locoregional anesthesia (LRA) with or without conscious sedation and general anesthesia (GA) for the TAVI-procedure.
We searched PUBMED, MEDLINE, EMBASE and the Cochrane central register of controlled trials from January 1st 2002 to February 15th 2015. The primary outcome parameters searched were 30-days mortality, hospital length of stay, procedure time, use of adrenergic support, stroke rate, incidence of myocardial infarction, incidence of acute kidney injury, rate of procedural succes.
Ten studies, including 5919 patients, fulfilled the inclusion criteria. None of these studies was randomized resulting in a considerable risk of bias. The choice for a specific anesthesia technique did neither affect the average 30-day mortality rate RR 0.91 (95% CI: 0.53 to 1.56), p=0.72 nor a wide variety of safety endpoints. LRA for TAVI was associated with a significantly shorter procedure time when compared to GA, and a reduction in hospital length of stay. However, LRA significantly increased the risk for implantation of a permanent pacemaker (RR 1.23, p=0.02) and for paravalvular leakage (RR 1.31, p=0.006.).
Neither mortality nor the incidence of major adverse cardiac and cerebrovascular events after TAVI is affected by the choice for either LRA or GA.
The releasable factor adenosine blocks the formation of long-term potentiation (LTP). These experiments used this observation to uncover the synaptic processes that stabilize the potentiation effect. ...Brief adenosine infusion blocked stimulation-induced actin polymerization within dendritic spines along with LTP itself in control rat hippocampal slices but not in those pretreated with the actin filament stabilizer jasplakinolide. Adenosine also blocked activity-driven phosphorylation of synaptic cofilin but not of synaptic p21-activated kinase (PAK). A search for the upstream origins of these effects showed that adenosine suppressed RhoA activity but only modestly affected Rac and Cdc42. A RhoA kinase (ROCK) inhibitor reproduced adenosine's effects on cofilin phosphorylation, spine actin polymerization, and LTP, whereas a Rac inhibitor did not. However, inhibitors of Rac or PAK did prolong LTP's vulnerability to reversal by latrunculin, a toxin which blocks actin filament assembly. Thus, LTP induction initiates two synaptic signaling cascades: one (RhoA-ROCK-cofilin) leads to actin polymerization, whereas the other (Rac-PAK) stabilizes the newly formed filaments.
Four binuclear Ni(II) complexes Ni2(H-DEAsal-tsc)2(μ-dppm)·2Cl (1), Ni2(DEAsal-mtsc)2(μ-dppm) (2), Ni2(DEAsal-etsc)2(μ-dppm) (3) and Ni2(DEAsal-ptsc)2(μ-dppm) (4) were synthesized from the ligands ...namely 4(N,N)-diethylaminosalicylaldehyde-4(N)-thiosemicarbazone H2-DEAsal-tsc H2L1/4(N,N)-diethylaminosalicylaldehyde-4(N)-methyl thiosemicarbazone H2-DEAsal-mtsc H2L2/4(N,N)-diethylaminosalicylaldehyde-4(N)-ethyl thiosemicarbazone H2-DEAsal-etsc H2L3/4(N,N)diethylaminosalicylaldehyde-4(N)-phenyl thiosemicarbazone H2-DEAsal-ptsc H2L4 and 1,1′-bis(diphenylphosphino)methane (dppm) and characterized by a number of spectro analytical techniques. The molecular structure of complexes Ni2(H-DEAsal-tsc)2(μ-dppm)·2Cl (1) and Ni2(DEAsal-ptsc)2(μ-dppm) (4) have been confirmed by single crystal X-ray diffraction studies. The analysis indicated that in complex 1, the ligand H2-DEAsal-tsc coordinated as monobasic tridentate donor through phenolic oxygen, azomethine nitrogen and thione sulfur atoms. However, in complex 4, the ligand H2-DEAsal-ptsc behaved as dibasic tridentate donor with thiolate sulfur coordination. Their ability to bind with Calf Thymus Deoxyribonucleic acid (CT-DNA) and Bovine Serum Albumin (BSA) were analysed spectrometrically. Intercalative interaction of the complexes with DNA was confirmed by ethidium bromide (EB) displacement studies and DNA viscosity measurements. The interaction mechanism of the complexes with BSA was found as static. In vitro antiproliferative studies of the ligands and complexes in A549 (human lung carcinoma cancer), MCF-7 (human breast cancer) and HeLa (human cervical cancer) cell lines witnessed significant cytotoxic nature of the complexes with low IC50 values (in μM) than the standard metallo-drug cisplatin. Further, the results of Lactate Dehydrogenase (LDH) and Nitric oxide (NO) release assays supported the effectiveness of the complexes on the above said cancer cells.
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•Four binuclear Ni(II) Schiff base complexes were synthesized and characterized.•Molecular structures of complexes 1 and 4 were confirmed by crystallographic studies.•Binding with Calf Thymus Deoxyribonucleic acid and Bovine Serum Albumin were analysed.•IC50 values of complexes were less than cisplatin against A549, MCF-7 and HeLa cells.•Lactate dehydrogenase (LDH) and nitric oxide (NO) release assays were carried out.
New Schiff base ligands are prepared by the condensation of 7-hydroxy-3-formylchromone with semicarbazone and phenyl semicarbazone. The complexation of these ligands with Cu(II) ion is proposed in ...the light of spectral studies (IR, UV–Vis, 1H NMR, 13C NMR, Mass and ESR). In the complexes 1 and 2, the ligands coordinate to the Cu(II) ion in a neutral fashion via ONO donor atoms. The single crystal XRD studies reveal a slightly distorted square-pyramidal geometry for cationic complex (1) and an octahedral geometry for neutral complex (2). Preliminary biological studies such as DNA and Protein binding are carried out by using absorption and emission titration methods. Observation of intercalative mode of binding with Calf Thymus DNA (CT-DNA) is confirmed by means of viscosity measurements. The micro-environmental changes occurring in Bovine Serum Albumin (BSA) and Human Serum Albumin (HSA) are monitored via three dimensional (3D) fluorescence studies. The compounds ability in inhibiting microbial growth is tested against different pathogens. MCF-7 (human breast cancer) and A549 (human lung carcinoma) cell lines are utilized to check the anticancer potential of the synthesized compounds by using MTT, LDH and NO assays. The results show that complexes 1 and 2 exhibited potent cytotoxic activity over standard drug cisplatin.
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•New water soluble copper(II) complexes have been synthesized and characterized.•The DNA/protein interactions of ligands and complexes were studied by a variety of techniques.•The antimicrobial activity against four different bacteria and five fungi has also been examined.•The antiproliferative activity was evaluated against MCF-7 and HeLa cell lines.•Assay on HaCaT cell lines showed that the compounds were non-toxic to those cells.
Estrogen, in addition to its genomic effects in brain, causes rapid and reversible changes to synaptic operations. We report here that these acute actions are due to selective activation of an ...actin-signaling cascade normally used in the production of long-term potentiation (LTP). Estrogen, or a selective agonist of the steroid's beta-receptor, caused a modest increase in fast glutamatergic transmission and a pronounced facilitation of LTP in adult hippocampal slices; both effects were completely eliminated by latrunculin, a toxin that prevents actin filament assembly. Estrogen also increased spine concentrations of filamentous actin and strongly enhanced its polymerization in association with LTP. A search for the origins of these effects showed that estrogen activates the small GTPase RhoA and phosphorylates (inactivates) the actin severing protein cofilin, a downstream target of RhoA. Moreover, an antagonist of RhoA kinase (ROCK) blocked estrogen's synaptic effects. Estrogen thus emerges as a positive modulator of a RhoA>ROCK>LIM kinase>cofilin pathway that regulates the subsynaptic cytoskeleton. It does not, however, strongly affect a second LTP-related pathway, involving the GTPases Rac and Cdc42 and their effector p21-activated kinase, which may explain why its acute effects are reversible. Finally, ovariectomy depressed RhoA activity, spine cytoskeletal plasticity, and LTP, whereas brief infusions of estrogen rescued plasticity, suggesting that the deficits in plasticity arise from acute, as well as genomic, consequences of hormone loss.
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