Photochemical Targeting of Mitochondria to Overcome Chemoresistance in Ovarian Cancer †

Ovarian cancer is the most lethal gynecologic malignancy with a stubborn mortality rate of ~65%. The persistent failure of multiline chemotherapy, and significant tumor heterogeneity, has made it challenging to improve outcomes. A target of increasing interest is the mitochondrion because of its essential role in critical cellular functions, and the significance of metabolic adaptation in chemoresistance. This review describes mitochondrial processes, including metabolic reprogramming, mitochondrial transfer and mitochondrial dynamics in ovarian cancer progression and chemoresistance. The effect of malignant ascites, or excess peritoneal fluid, on mitochondrial function is discussed. The role of photodynamic therapy (PDT) in overcoming mitochondria-mediated resistance is presented. PDT, a photochemistry-based modality, involves the light-based activation of a photosensitizer leading to the production of short-lived reactive molecular species and spatiotemporally confined photodamage to nearby organelles and biological targets. The consequential effects range from subcytotoxic priming of target cells for increased sensitivity to subsequent treatments, such as chemotherapy, to direct cell killing. This review discusses how PDT-based approaches can address key limitations of current treatments. Specifically, an overview of the mechanisms by which PDT alters mitochondrial function, and a summary of preclinical advancements and clinical PDT experience in ovarian cancer are provided.     

The ultraviolet photochemistry of phenylacetylene and the enthalpy of formation of 1,3,5-hexatriyne.

The ultraviolet photochemistry of phenylacetylene was studied in a molecular beam at 193 nm. The only primary photofragments observed were HCCH (acetylene) and C(6)H(4). Some of the C(6)H(4) molecules were found to decompose to 1,3,5-hexatriyne and molecular hydrogen. An enthalpy of formation of DeltaH(f) < or = 160 +/- 4 kcal mol(-1) was determined for 1,3,5-hexatriyne from the energetic threshold for this process. This experimentally determined value agrees well with our ab initio calculations performed at the G2 level of theory. Angular distribution measurements for the HCCH + C(6)H(4) channel yielded an isotropic distribution and were attributed to a long-lived intermediate and ground-state dissociation. An exhaustive search yielded no evidence for the phenyl + ethynyl or the atomic hydrogen elimination channels even though these were observed in the pyrolytic studies of phenylacetylene [Hofmann, J.; Zimmermann, G.; Guthier, K.; Hebgen, P.; Homann, K. H. Liebigs Ann. 1995, 631, 1995. Guthier, K.; Hebgen, P.; Hofmann, K. H.; Zimmermann, G. Liebigs Ann. 1995, 637, 1995].     

Structural and electrical properties of doped polypyrrole and its composite with montmorillonite clay

Polypyrrole is synthesized and doped with Dodecylbenzenesulphonic acid. The doped Polypyrrole with Dodecylbenzenesulphonic acid is intercalated into the layers of Montmorillonite clay successfully by in situ polymerization. The structural properties of synthesized doped Polypyrrole and intercalated doped Polypyrrole were studied by XRD analysis. The crystallinity of intercalated doped Polypyrrole into the layers of Montmorillonite clay is confirmed by means of X-rays diffraction studies, which is more than the doped Polypyrrole. Enhanced d-spacing of Montmorillonite confirmed that doped Polypyrrole is interclated into the layers of Montmorillonite clay at nanoscale. The scanning electron micrographs also confirm the formation of dual phase of platelet as well as of flaky structure of intercalated doped Polypyrrole. Temperature dependant conductivity showed three dimensional variable ranges hopping model. Activation energy, density of states and hopping length are calculated and found to be influenced by intercalating Doped Polypyrole into the layers of Montmorillonite clay.     

Elemental fingerprint profile of beer samples constructed using 14 elements determined by inductively coupled plasma–mass spectrometry (ICP-MS): multivariation analysis and potential application to forensic sample comparison

Determination of elemental fingerprint profile of 40 commercial beer samples was performed using inductively coupled plasma–mass spectrometry combined with principal component analysis and receiver operating characteristic (ROC) analysis. Fourteen trace elements, ⁵¹V, ⁵²Cr, ⁵⁹Co, ⁶⁰Ni, ⁷⁵As, ⁸²Se, ⁹⁵Mo, ¹¹¹Cd, ¹¹⁵In, ¹²¹Sb, ¹³³Cs, ²⁰⁸Pb, ²⁰⁹Bi, and ²³⁸U, were monitored. All 40 beer samples are distinguishable by using the proposed method. ROC analysis showed that individual beer samples can be correctly identified via the magnitude of its correlation coefficient with respect to the other beers with low false positive rate. The obtained results suggested that the elemental fingerprint technique is feasible for sample differentiation and comparison.     

A multivariate quantification of Box‐Behnken design assisted method development and validation of dextromethorphan hydrobromide and desloratadine simultaneously by reverse‐phase HPLC in in‐house syrup formulation

An innovative high‐performance liquid chromatography assay method was developed and validated for quantification of dextromethorphan hydrobromide and desloratadine simultaneously in monophasic liquid formulation by preparing syrup containing 30 mg/5 mL of dextromethorphan hydrobromide and 1.2 mg/mL of desloratadine. The chromatographic severance was executed by gradient solution A and B. The composition of buffer solution A contained 0.05 M monobasic potassium, then 1 mL triethylamine was added to it and the pH was adjusted to 2.3 with orthophosphoric acid. Methanol was used as solution B. The gradient elution was executed with Kromasil C8 (250 mm × 4.6 mm) column having 1.5 mL/min flow rate and 20 µL injection volume with UV‐estimation at 254 nm for dextromethorphan hydrobromide and DES. The present research was planned according to Box‐Behnken design by utilizing design expert software, using four factors such as column temperature (A), flow rate (B), mobile phase–organic phase (C), and pH (D); correspondingly the selected response variables were resolution between A and B, that is, desloratadine and methyl paraben (Y1), tailing of dextromethorphan hydrobromide (Y2), and tailing of desloratadine (Y3). The parameters such as system suitability, linearity, accuracy, precision, robustness, limit of detection, limit of quantitation, and ruggedness were analyzed to validate the developed method in accordance with current regulatory guidelines.     

Anti-oxidative action of resveratrol: Implications for human health

Resveratrol, the red-wine polyphenol, is intensively studied polyphenols for its pleiotropic biological effects. A plethora of health beneficial effects of this stilbene has been reported including cardio-protective, neuro-protective, anti-cancer, anti-diabetic and interesting anti-aging. Though it has been proposed that these effects of resveratrol arise from its capacity to interact with multiple molecular targets involved in diverse intracellular pathways including activation of sirtuins, the antioxidant property of this compound is the most described one to attribute its diverse health beneficial effects. In the present review we have explained the biological activities of resveratrol with the latest laboratory evidences towards its antioxidant effects.     

Liposome fusion rates depend upon the conformation of polycation catalysts

Cryo-TEM and NaCl-leakage experiments demonstrated that the cationic polymer polylysine induces fusion of anionic liposomes but that the cationic polymer poly(N-ethyl-4-vinylpyridinium bromide) (PEVP) does not, although both polymers bind strongly to the liposomes. The difference was traced to the thickness of the coatings at constant charge coverage. Polylysine is believed to form planar β-sheets that are sufficiently thin to allow membrane fusion. In contrast, looping and disorganization among adsorbed PEVP molecules physically prevent fusion. A similar effect is likely to be applicable to important polycation-induced fusion of cell membranes.     

On 𝒦-Nonsingular Modules and Applications

We introduce the notion of 𝒦-nonsingularity of a module and show that the class of 𝒦-nonsingular modules properly contains the classes of nonsingular modules and of polyform modules. A necessary and sufficient condition is provided to ensure that this property is preserved under direct sums. Connections of 𝒦-nonsingular modules to their endomorphism rings are investigated. Rings for which all modules are 𝒦-nonsingular are precisely determined. Applications include a type theory decomposition for 𝒦-nonsingular extending modules and internal characterizations for 𝒦-nonsingular continuous modules which are of type I, type II, and type III, respectively.     

Iterative algorithms for generalized mixed equilibrium problems

In this paper, we consider a generalized mixed equilibrium problem in real Hilbert space. Using the auxiliary principle, we define a class of resolvent mappings. Further, using fixed point and resolvent methods, we give some iterative algorithms for solving generalized mixed equilibrium problem. Furthermore, we prove that the sequences generated by iterative algorithms converge weakly to the solution of generalized mixed equilibrium problem. These results require monotonicity (θ-pseudo monotonicity) and continuity (Lipschitz continuity) for mappings.     

Investigation of the influence of incomplete fusion on complete fusion of <Superscript>12</Superscript>C-induced reactions at ≈ 4–7.2 MeV/nucleon

In this paper, we present the results of our investigation of reaction dynamics leading to incomplete fusion of heavy ions at moderate excitation energies, especially the influence of incomplete fusion on complete fusion of ¹²C -induced reactions at specific energies ≈ 4–7.2M eV/nucleon. Excitation functions of various reaction products populated via complete and/or incomplete fusions of a ¹²C projectile with ⁹³Nb, ⁵⁹Co and ⁵²Cr targets were measured at several specific energies ≈ 4–7.2 MeV/nucleon, using a recoil catcher technique, followed by off-line γ-ray spectrometry. The measured excitation functions were compared with theoretical values obtained using the PACE4 statistical model code. For representative non-α-emitting channels in the ¹²C + ⁹³Nb system, the experimentally measured excitation functions were, in general, found to be in good agreement with the theoretical predictions. However, for α-emitting channels in the ¹²C + ⁹³Nb, ¹²C + ⁵⁹Co, and ¹²C + ⁵²Cr systems, the measured excitation functions were higher than the predictions of the theoretical model code, which may be credited to incomplete fusion reactions at these energies. An attempt was made to estimate the incomplete fusion fraction for the present systems, which revealed that the fraction was sensitive to the projectile energy and mass asymmetry of the entrance channel.