The determination of glutathione-4-hydroxynonenal (GSHNE), E-4-hydroxynonenal (HNE), and E-1-hydroxynon-2-en-4-one (HNO) in mouse liver tissue by LC-ESI-MS

Glutathione (GSH) conjugation of 4-hydroxy-2(E)-nonenal (HNE) is an efficient means of cellular detoxification. HNE is a byproduct of lipid peroxidation which has shown toxicity but also signaling roles. E-1-hydroxynon-2-en-4-one (HNO) is another byproduct of lipid peroxidation which has the same molecular weight as HNE. This study presents the LC-MS detection of GS-HNE, HNE, and HNO in tissue samples without derivatization and with minimal sample preparation. Tissue samples were taken from wild-type mice and knock-out mice, which have been bred without the RLIP76 transfer protein. Extraction procedures were developed to determine GS-HNE and HNE levels in the mouse liver tissue. A gradient elution LC-MS method was developed for GS-HNE analysis using electrospray ionization and selected ion monitoring (SIM). The HNE/HNO method involves isocratic elution due to instability issues. Higher levels of GSHNE, HNE, and HNO were found in the knock-out animals, due to the absence of the RLIP76 transport mechanism.     

Organocatalytic asymmetric synthesis of (−)-δ-coniceine based on sequential proline-catalyzed asymmetric α-amination–HWE olefination

An efficient asymmetric synthesis of (?)-δ-coniceine via sequential proline-catalyzed asymmetric α-amination and Horner–Wadsworth–Emmons olefination of an aldehyde with excellent enantiomeric excess (>99%) and high yields (overall yield 44%) is described.     

Dielectric characterisation of a ferroelectric liquid crystalline material having SmA*–SmC*–SmBh* phase sequence

Thermodynamical, optical and dielectric characterisation of a material possessing ferroelectric SmC* and hexatic SmB* phases has been carried out. Phase identification has been done by miscibility studies. From the dielectric studies, a relaxation mechanism is observed in the low MHz region of the SmA* phase, which is related to the tilt fluctuation (soft mode) of the directors. In the SmC* phase, another collective relaxation mechanism has been observed in the kHz region, which is related to the phase fluctuation (Goldstone mode) of the directors. In the SmB_h* phase, 2-weak relaxation modes are observed in the kHz and MHz frequency range, respectively, due to individual molecular rotations.     

Evaluation of the photosensitizer Tookad for photodynamic therapy on the Syrian golden hamster cheek pouch model: light dose, drug dose and drug-light interval effects

We have evaluated the efficacy of the new photosensitizer (PS) Tookad in photodynamic therapy (PDT) in vivo. This PS is a palladium-bacteriopheophorbide presenting absorption peaks at 762 and 538 nm. The light dose, drug dose and drug injection-light irradiation interval (DLI), ranging between 100 and 300 J/cm2, 1 and 5 mg/kg and from 10 to 240 min, respectively, were varied, and the response to PDT was analyzed by staging the macroscopic response and by the histological examination of the sections of the irradiated cheek pouch. The level of PDT response, macroscopically and histologically, shows a strong dependence on the DLI, light dose and drug dose at the applied conditions in the normal hamster cheek pouch. A decay of the tissular response with increasing DLI is observed corresponding to a time of half-maximum response ranging from 10 to 120 min, depending on drug dose and light dose. The tissues affected at the lowest doses are predominantly the vascularized diffuse connective tissue situated between the inner and outer striated muscle (SM) layers as well as these muscle layers themselves. The highest response at the shortest DLI and the absence of a measurable response at DLI longer than 240 min at 300 J/cm2 and drug dose of 5 mg/kg are characteristics of a predominantly vascular effect of this PS. This observation suggests that Tookad could be effective in PDT of vascularized lesions or pathologies associated with the proliferation of neovessels.     

Synthesis and Characterization of <Emphasis Type="Italic">Sygyzium cumini</Emphasis> Nanoparticles for Its Protective Potential in High Glucose-Induced Cardiac Stress: a Green Approach

There exists a complex and multifactorial relationship between diabetes and cardiovascular disease. Hyperglycemia is an important factor imposing damage (glucose toxicity) on cardiac cell leading to diabetic cardiomyopathy. There are substantial clinical evidences on the adverse effects of conventional therapies in the prevention/treatment of diabetic cardiovascular complications. Currently, green-synthesized nanoparticles have emerged as a safe, efficient, and inexpensive alternative for therapeutic uses. The present study discloses the silver nanoparticle biosynthesizing capability and cardioprotective potential of Syzygium cumini seeds already reported to have antidiabetic properties. Newly generated silver nanoparticles S. cumini MSE silver nanoparticles (SmSNPs) were characterized by UV-visible spectroscopy, scanning electron microscopy (SEM), zeta sizer, X-ray diffraction (XRD), and Fourier transform infrared (FTIR) spectroscopy. Using methanolic extract of S. cumini seeds, an average size of 40–100-nm nanoparticles with 43.02 nm and ?19.6 mV zeta potential were synthesized. The crystalline nature of SmSNPs was identified by using XRD. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assays revealed the antioxidative potential to be 66.87 (±0.7) % and 86.07 (±0.92) % compared to 60.29 (±0.02) % and 85.67 (±1.27) % for S. cumini MSE. In vitro study on glucose-stressed H9C2 cardiac cells showed restoration in cell size, nuclear morphology, and lipid peroxide formation upon treatment of SmSNPs. Our findings concluded that S. cumini MSE SmSNPs significantly suppress the glucose-induced cardiac stress in vitro by maintaining the cellular integrity and reducing the oxidative damages therefore establishing its therapeutic potential in diabetic cardiomyopathy.     

Conformational analysis in diastereoisomer equilibria of square-pyramidal [C5H5(CO)2Mo pyridine-2-imine]PF6 complexes

Synthesis and characterization of sonic new square-pyramidal pyridine-2-imine complexes [C₅,H₅,(CO)₂,MoNC₅,H₄,CX=NCH(R₁)(R₂)]PF₆ with X = CH₃, C₆H₅ and chiral amine, 1-phenyl-isobutylamine and amino acid methyl ester H₂NCH(COOCH₃)(R) with (R) = (CH₂C₆H₅) and (C₂H₅) have been reported. In combination with Mo chirality (R) and (S), mixtures of two diastereoisomeric pairs of enantiomers with racemic amine and amino acids were obtained which were separated by fractional cystallization. The diastereoisomers differ in the chemical shift of most of their ¹H NMR signals and interconvert on heating in acetone-d₆ at 80°C for 80 hr and 40°C for 200 hr. On the basis of three conformational determining effects (i) C-H or C-alkyl of the asymmetric centre eclipses the ligand plane, (ii) MC₅H₅/C₆H₅ attraction and (iii) MC₅H₅/alkyl repulsion in order of decreasing significance, the chemical shifts of the C₅H₅ signals, their differences as well as the diastereoisomer ratio at equilibrium for all the complexes has been rationalised.     

The p53-caspase-2 axis in the cell cycle and DNA damage response

Caspase-2 was discovered almost three decades ago. It was one of the first two mammalian homologs of CED-3, the other being interleukin 1β-converting enzyme (ICE/caspase-1). Despite high similarity with CED-3 and its fly and mammalian counterparts (DRONC and caspase-9, respectively), the function of caspase-2 in apoptosis has remained enigmatic. A number of recent studies suggest that caspase-2 plays an important role in the regulation of p53 in response to cellular stress and DNA damage to prevent the proliferation and accumulation of damaged or aberrant cells. Here, we review these recent observations and their implications in caspase-2-mediated cellular death, senescence, and tumor suppression.Subject terms: Apoptosis, Experimental models of disease