In
diabetes, abnormal angiogenesis due to hyperglycemia and endothelial
dysfunction impairs wound healing and results in high risks of diabetic
foot ulcers and mortality. Alternative therapeutic methods were attempted
to prevent diabetic complications through the activation of endothelial
nitric oxide synthase. In this study, direct application of nitric
oxide using dinitrosyl iron complexes (DNICs) to promote angiogenesis
and wound healing under physiological conditions and in diabetic mice
is investigated. Based on in vitro and in vivo studies, DNIC [Fe2(μ-SCH2CH2OH)2(NO)4] (DNIC-1) with a sustainable NO-release reactivity
(t
1/2 = 27.4 ± 0.5 h at 25 °C
and 16.8 ± 1.8 h at 37 °C) activates the NO-sGC-cGMP pathway
and displays the best pro-angiogenesis activity overwhelming other
NO donors and the vascular endothelial growth factor. Moreover, this
pro-angiogenesis effect of DNIC-1 restores the impaired
angiogenesis in the ischemic hind limb and accelerates the recovery
rate of wound closure in diabetic mice. This study translates synthetic DNIC-1 into a novel therapeutic agent for the treatment of
diabetes and highlights its sustainable •NO-release
reactivity on the activation of angiogenesis and wound healing.
Identification
of the distinctive electron paramagnetic resonance signal at g = 2.03 in the yeast cells and liver of mice treated with
carcinogens opened the discovery and investigation of the natural
[Fe(NO)2] motif in the form of dinitrosyliron complexes
(DNICs). In this Viewpoint, a chronological collection of the benchmark
for the study of DNIC demonstrates that the preceding study of its
biological synthesis, storage, transport, transformation, and function
related to NO physiology inspires the biomimetic study of structural and functional models supported
by thiolate ligands to provide mechanistic insight at a molecular
level. During the synthetic, spectroscopic, and theoretical investigations
on the structure-to-reactivity relationship within DNICs, control
of the Fe–NO bonding interaction and of the delivery of NO+/•NO/HNO/NO– by the supporting
ligands and nuclearity evolves into the “redesign of the natural
[Fe(NO)2] motif” as a strategy to develop DNICs
for NO-related biomedical application and therapeutic approach. The
revolutionary transformation of covalent a [Fe(NO)2] motif
into a translational model for hydrogenase, triggered
by the discovery of redox interconversion among [{Fe(NO)2}9-L•] ↔ {Fe(NO)2}9 ↔ {Fe(NO)2}10 ↔ [{Fe(NO)2}10-L•]−, echoes
the preceding research journey on [Fe]/[NiFe]-hydrogenase and completes
the development of an electrodeposited-film electrode for electrocatalytic
water splitting. Through the 50-year journey, bioinorganic chemistry
of DNIC containing the covalent [Fe(NO)2] motif and noninnocent/labile
NO ligands highlights itself as a unique metallocofactor to join the
longitudinal study between biology/chemistry/biomedical application
and the lateral study toward multielectron (photo/electro)catalysis
for industrial application. This Viewpoint discloses the potential
[Fe(NO)2] motif awaiting continued contribution in order
to emerge as a novel application in the next 50 years, whereas the
parallel development of bioinorganic chemistry, guided by inspirational
Nature, moves the science forward to the next stage in order to benefit
the immediate needs for human activity.
1,3-Dioleoyl-2-palmitoylglycerol, an important triacylglycerol in infant formulas, was effectively enriched by a two-step process: (a) dry fractionation of leaf lard and (b) enzymatic acidolysis of the fractionated leaf lard. In step a, the 1,3-dioleoyl-2-palmitoylglycerol content was increased from 16.77 to 30.73% after programmed temperature treatment of the leaf lard at 60 °C for 20 min followed by 34 °C for 10 h. In step b, 43.72% of the 1,3-dioleoyl-2-palmitoylglycerol content was obtained at the optimal conditions of enzymatic acidolysis: a substrate molar ratio of 1:4 (the fractionated leaf lard/camellia oil fatty acids), 6% (w/w) of enzyme loading, and 6 h of reaction time at 45 °C. On the basis of gas chromatography determination and "deducting score" principle, a model was properly established for characterizing the quality of triacylglycerols enriched with 1,3-dioleoyl-2-palmitoylglycerol. This approach would be a valuable contribution in structured lipids industries because only gas chromatography determination was involved.
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