Cure synergism in XNBR vulcanization in presence of thiophosphoryl disulfides and amine disulfide/thiazole accelerators

The study deals with the vulcanization of carboxylated nitrile butadiene rubber (XNBR) having synergistic combinations of accelerators comprising thiophosphoryl disulfide as one of the components. Other constituent accelerators employed in the present investigation are 2-mercaptobenzothiazole (MBT), 2-mercaptobenzothiazyl disulfide (MBTS), bis(N-oxydiethylene)disulfide (ODDS), N-oxydiethylene 2-benzothiazole sulfenamide (OBTS), etc. The binary combinations of thiophosphoryl disulfides with OBTS exhibited the highest mutual activity in the respective areas, so far as the physical properties are concerned. Structural characterization of different thiophosphoryl disulfide-accelerated XNBR vulcanizates, including those formed from the synergistic combinations with OBTS, were studied using a methyl iodide probe. It was found that the amount of sulfidic crosslinks arising from the reaction between  COOH groups of XNBR and thiophosphoryl disulfides, actually controls the network structure as wellas the physical properties of the vulcanizates. © 1996 John Wiley & Sons, Inc.     

EAPB0503, an Imidazoquinoxaline Derivative Modulates SENP3/ARF Mediated SUMOylation,and Induces NPM1c Degradation in NPM1 Mutant AML

Nucleophosmin-1 (NPM1) is a pleiotropic protein involved in numerous cellular processes. NPM1 shuttles between the nucleus and the cytoplasm, but exhibits a predominant nucleolar localization, where its fate and functions are exquisitely controlled by dynamic post-translational modifications (PTM). Sentrin/SUMO Specific Peptidase 3 (SENP3) and ARF are two nucleolar proteins involved in NPM1 PTMs. SENP3 antagonizes ARF-mediated NPM1 SUMOylation, to promote ribosomal biogenesis. In Acute Myeloid Leukemia (AML), NPM1 is frequently mutated, and exhibits an aberrant cytoplasmic localization (NPM1c). NPM1c mutations define a separate AML entity with good prognosis in some AML patients, rendering NPM1c as a potential therapeutic target. SENP3-mediated NPM1 de-SUMOylation induces resistance to therapy in NPM1c AML. Here, we demonstrate that the imidazoquinoxaline EAPB0503 prolongs the survival and results in selective reduction in the leukemia burden of NPM1c AML xenograft mice. Indeed, EAPB0503 selectively downregulates HDM2 expression and activates the p53 pathway in NPM1c expressing cells, resulting in apoptosis. Importantly, we unraveled that NPM1c expressing cells exhibit low basal levels of SUMOylation paralleled with high SENP3 and low ARF basal levels. EAPB0503 reverted these molecular players by inducing NPM1c SUMOylation and ubiquitylation, leading to its proteasomal degradation. EAPB0503-induced NPM1c SUMOylation is concurrent with SENP3 downregulation and ARF upregulation in NPM1c expressing cells. Collectively, these results provide a strong rationale for testing therapies modulating NPM1c post-translational modifications in the management of NPM1c AML.     

A Novel Sprague-Dawley Rat Model Presents Improved NASH/NAFLD Symptoms with PEG Coated Vitexin Liposomes

Chronic liver disease (CLD) is a global threat to the human population, with manifestations resulting from alcohol-related liver disease (ALD) and non-alcohol fatty liver disease (NAFLD). NAFLD, if not treated, may progress to non-alcoholic steatohepatitis (NASH). Furthermore, inflammation leads to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Vitexin, a natural flavonoid, has been recently reported for inhibiting NAFLD. It is a lipogenesis inhibitor and activates lipolysis and fatty acid oxidation. In addition, owing to its antioxidant properties, it appeared as a hepatoprotective candidate. However, it exhibits low bioavailability and low efficacy due to its hydrophobic nature. A novel rat model for liver cirrhosis was developed by CCL4/Urethane co-administration. Vitexin encapsulated liposomes were synthesized by the ‘thin-film hydration’ method. Polyethylene glycol (PEG) was coated on liposomes to enhance stability and stealth effect. The diseased rats were then treated with vitexin and PEGylated vitexin liposomes, administered intravenously and orally. Results ascertained the liposomal encapsulation of vitexin and subsequent PEG coating to be a substantial strategy for treating liver cirrhosis through oral drug delivery.     

A cation exchange resin from poly(N-vinyl carbazole)

Poly(N-vinyl carbazole) was sulfonated with different sulfonating agents and ion exchange capacities of the resins produced were evaluated. A maximum capacity of 4.5 meq · g^?1 of dry resin was realized when sulfonation was done with 98.8% H₂SO⁴ at 30°C for 10 h. The pH titration curves reveal the nature of a strong monofunctional cation exchanger with a pK value of 2.2. The resin exhibits a moderate rate of exchange with NaCl and is thermally stable up to ca. 250°C.     

Crosslinked polymer from N-vinylcarbazole and formalin

A crosslinked polymer has been synthesized from the reaction of N-vinylcarbazole and formalin in toluene in the presence of dry HCl gas. The copolycondensate is insoluble in all common solvents for poly-N-vinylcarbazole, and exhibits higher thermal stability than the unmodified poly-N-vinylcarbazole. However, this polymer is less thermally stable than the corresponding furfural modified poly-N-vinylcarbazole. A mechanism for the overall reaction has been suggested and the factors affecting the synthesis have been discussed.