Organofluorine Hydrazone Derivatives as Multifunctional Anti-Alzheimer's Agents with CK2 Inhibitory and Antioxidant Features

A set of novel hydrazone derivatives were synthesized and analyzed for their biological activities. The compounds were tested for their inhibitory effect on the phosphorylating activity of the protein kinase CK2, and their antioxidant activity was also determined in three commonly used assays. The hydrazones were evaluated for their radical scavenging against the DPPH, ABTS and peroxyl radicals. Several compounds have been identified as good antioxidants as well as potent protein kinase CK2 inhibitors. Most hydrazones containing a 4-N(CH₃)₂ residue or perfluorinated phenyl rings showed high activity in the radical-scavenging assays and possess nanomolar IC₅₀ values in the kinase assays.     

Cell-Permeable Succinate Rescues Mitochondrial Respiration in Cellular Models of Statin Toxicity

Statins are the cornerstone of lipid-lowering therapy. Although generally well tolerated, statin-associated muscle symptoms (SAMS) represent the main reason for treatment discontinuation. Mitochondrial dysfunction of complex I has been implicated in the pathophysiology of SAMS. The present study proposed to assess the concentration-dependent ex vivo effects of three statins on mitochondrial respiration in viable human platelets and to investigate whether a cell-permeable prodrug of succinate (complex II substrate) can compensate for statin-induced mitochondrial dysfunction. Mitochondrial respiration was assessed by high-resolution respirometry in human platelets, acutely exposed to statins in the presence/absence of the prodrug NV118. Statins concentration-dependently inhibited mitochondrial respiration in both intact and permeabilized cells. Further, statins caused an increase in non-ATP generating oxygen consumption (uncoupling), severely limiting the OXPHOS coupling efficiency, a measure of the ATP generating capacity. Cerivastatin (commercially withdrawn due to muscle toxicity) displayed a similar inhibitory capacity compared with the widely prescribed and tolerable atorvastatin, but did not elicit direct complex I inhibition. NV118 increased succinate-supported mitochondrial oxygen consumption in atorvastatin/cerivastatin-exposed platelets leading to normalization of coupled (ATP generating) respiration. The results acquired in isolated human platelets were validated in a limited set of experiments using atorvastatin in HepG2 cells, reinforcing the generalizability of the findings.     

Spinal Excitatory Dynorphinergic Interneurons Contribute to Burn Injury-Induced Nociception Mediated by Phosphorylated Histone 3 at Serine 10 in Rodents

The phosphorylation of serine 10 in histone 3 (p-S10H3) has recently been demonstrated to participate in spinal nociceptive processing. However, superficial dorsal horn (SDH) neurons involved in p-S10H3-mediated nociception have not been fully characterized. In the present work, we combined immunohistochemistry, in situ hybridization with the retrograde labeling of projection neurons to reveal the subset of dorsal horn neurons presenting an elevated level of p-S10H3 in response to noxious heat (60 °C), causing burn injury. Projection neurons only represented a small percentage (5%) of p-S10H3-positive cells, while the greater part of them belonged to excitatory SDH interneurons. The combined immunolabeling of p-S10H3 with markers of already established interneuronal classes of the SDH revealed that the largest subset of neurons with burn injury-induced p-S10H3 expression was dynorphin immunopositive in mice. Furthermore, the majority of p-S10H3-expressing dynorphinergic neurons proved to be excitatory, as they lacked Pax-2 and showed Lmx1b-immunopositivity. Thus, we showed that neurochemically heterogeneous SDH neurons exhibit the upregulation of p-S10H3 shortly after noxious heat-induced burn injury and consequential tissue damage, and that a dedicated subset of excitatory dynorphinergic neurons is likely a key player in the development of central sensitization via the p-S10H3 mediated pathway.     

Energy-efficient and fault-tolerant drone-BS placement in heterogeneous wireless sensor networks

Wireless Networks - This paper introduces a distributed and energy-aware algorithm, called Minimum Drone Placement (MDP) algorithm, to determine the minimum number of base stations mounted on...     

Evaluation of the potential use of discard species for fish silage and assessment of its oils for human consumption

Waste or by-products contains a substantial amount of nutrients. Fish silage is an alternative way for assessment of fish discards and waste generated in the fish processing industries. The aim of the study was to evaluate the potential use of discard species (Equulites klunzingeri, marine fish and Carassius gibelio, freshwater fish) for fish silage and chemical quality of fish oil extracted from fish silages prepared with acid and fermented methods. Lipid quality of fish oils extracted from fish silages with LAB strains was evaluated in terms of thiobarbituric acid (TBA), peroxide value (PV), p-Anisidine (AV), totox values and fatty acid composition. The results showed that PV, TBA, AV and totox values of all extracted fish oils were within the acceptable limits for edible oils. Recovered fish oils from silage contained high level of polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), serving as a source of good quality fish oil for human consumption.     

Fabrication and characterization of in-situ Al3Ni intermetallic and CeO2 particulate-reinforced aluminum matrix composites

Al-xNi-yCeO₂ (x = 6, 10, 15, 20 and y = 0, 5, 10 wt%) composites were produced by a powder metallurgical production route. Powder mixtures of Al, Ni and CeO₂ were fabricated via mechanical alloying (MA) for 4 h in a Spex-type high-energy ball mill. Both the mechanically alloyed (MAed) and non-MAed (as-blended mixtures) powders were pre-compacted in a hydraulic press under 650 MPa and then pressurelessly consolidated at 630 °C for 2 h under an inert atmosphere. The effects of MA process and the amounts of Ni and CeO₂ on the microstructural, mechanical and tribological properties of the sintered composites were determined. Based on the SEM and XRD investigations, the MAed powders illustrated a homogenous structure, comprising flaky particles with smaller crystallite sizes and greater lattice strain. According to the XRD analysis, Ni formed Al–Ni intermetallic compounds in the matrix of sintered composites that act as secondary reinforcement phases. The SEM observations conducted on the MAed samples demonstrated more uniformly and finely distributed Al₃Ni and CeO₂ phases in the microstructure of the MAed samples, unlike the non-MAed ones. The hardness values of sintered composites increased due to the MA process and increasing Ni and CeO₂ amounts, and the hardness value of the MAed Al20Ni–10CeO₂ sample reached 179 HV. The ultimate compressive strength and failure strain of the MAed Al6Ni–10CeO₂ sample were 441 MPa and 11.3%. In the Al20Ni–10CeO₂ sample, the compressive strength and failure strain were 391 MPa and 5.5%, respectively. Additionally, the reciprocating wear test results illustrated that both wear resistance and hardness values of the composites increased as the amounts of Ni and CeO₂ increased, and the Al20Ni–10CeO₂ sample exhibited the highest wear resistance as 0.175 × 10^-3 mm³/Nm.