Selective deletion of PPARβ/δ in fibroblasts causes dermal fibrosis by attenuated LRG1 expression.

Connective tissue diseases of the skin are characterized by excessive collagen deposition in the skin and internal organs. Fibroblasts play a pivotal role in the clinical presentation of these conditions. Nuclear receptor peroxisome-proliferator activated receptors (PPARs) are therapeutic targets for dermal fibrosis, but the contribution of the different PPAR subtypes are poorly understood.

Development of high accuracy methods for the certification of calcium, iron, magnesium and potassium in human serum.

High accuracy methods were developed for the measurements of calcium, potassium, iron and magnesium in human serum using standard addition and isotope dilution mass spectrometry methods. The results were comparable to those obtained by other national metrology institutes and designated institutes as demonstrated in an inter-laboratory comparison. The methods were then adopted for the assignment of reference values in a human serum material and the uncertainties associated with the certified values were obtained by combining the uncertainty components from the characterisation, homogeneity and long-term stability of the materials.

Early controlled release of peroxisome proliferator-activated receptor β/δ agonist GW501516 improves diabetic wound healing through redox modulation of wound microenvironment.

Diabetic wounds are imbued with an early excessive and protracted reactive oxygen species production. Despite the studies supporting PPARβ/δ as a valuable pharmacologic wound-healing target, the therapeutic potential of PPARβ/δ agonist GW501516 (GW) as a wound healing drug was never investigated. Using topical application of polymer-encapsulated GW, we revealed that different drug release profiles can significantly influence the therapeutic efficacy of GW and consequently diabetic wound closure.

Inorganic-base-mediated hydroamination of alkenyl oximes for the synthesis of cyclic nitrones.

A method based on hydroamination mediated by inorganic base was developed for the synthesis of cyclic nitrones from alkenyl oximes. DFT calculations of the reaction pathway suggested that this hydroamination could proceed through an unprecedented nucleophilic amination of the unactivated alkene by the oxime nitrogen atom. The transition state of this reaction is stabilized by an ionic interaction between a metal cation such as K(+) and the oxime oxygen and negatively charged alkene moiety.

Formal [4 + 1]- and [5 + 1]-annulation by an S(N)2-conjugate addition sequence: stereoselective synthesis of highly substituted carbocycles.

K(2)CO(3)-mediated reactions of 6-bromo-2-hexenoates and 7-bromo-2-heptenoate with active methylene compounds deliver highly substituted cyclopentane and cyclohexane derivatives, respectively via a sequence of S(N)2-conjugate addition reactions (formal [4 + 1]- and [5 + 1]-annulation) in a diastereoselective manner.

Diamine-catalyzed conjugate addition to acrylate derivatives.

Diamines were found to promote catalytic conjugate addition of α-cyano active methine nucleophiles to various acrylate derivatives.