25 research outputs found
Dual-Band Binary Metamaterial Absorber Based on Low-Permittivity All-Dielectric Resonance Surface
Kynurenineâ3âmonooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis
Acute pancreatitis (AP) is a common and devastating inflammatory condition of the pancreas that is considered to be a paradigm of sterile inflammation leading to systemic multiple organ dysfunction syndrome (MODS) and death1,2 Acute mortality from AP-MODS exceeds 20%3 and for those who survive the initial episode, their lifespan is typically shorter than the general population4. There are no specific therapies available that protect individuals against AP-MODS. Here, we show that kynurenine-3-monooxygenase (KMO), a key enzyme of tryptophan metabolism5, is central to the pathogenesis of AP-MODS. We created a mouse strain deficient for Kmo with a robust biochemical phenotype that protected against extrapancreatic tissue injury to lung, kidney and liver in experimental AP-MODS. A medicinal chemistry strategy based on modifications of the kynurenine substrate led to the discovery of GSK180 as a potent and specific inhibitor of KMO. The binding mode of the inhibitor in the active site was confirmed by X-ray co-crystallography at 3.2 Ă
resolution. Treatment with GSK180 resulted in rapid changes in levels of kynurenine pathway metabolites in vivo and afforded therapeutic protection against AP-MODS in a rat model of AP. Our findings establish KMO inhibition as a novel therapeutic strategy in the treatment of AP-MODS and open up a new area for drug discovery in critical illness
Studying Different Binding and Intracellular Delivery Efficiency of ssDNA Single-Walled Carbon Nanotubes and Their Effects on LC3-Related Autophagy in Renal Mesangial Cells via miRNA-382
Studying Different Binding and Intracellular Delivery Efficiency of ssDNA Single-Walled Carbon Nanotubes and Their Effects on LC3-Related Autophagy in Renal Mesangial Cells via miRNA-382
Single-walled
carbon nanotubes (SWCNTs) have been used to deliver
single-stranded (ssDNA). ssDNA in oligonucleotide can act as an inhibitor
of microRNA to regulate cellular functions. However, these ssDNA are
difficult to bind carbon nanotubes with low transferring efficiency
to cells. To this end, we designed ssDNA with regulatory and functional
units to form ssDNA-SWCNT hybrids to study their binding effects and
transferring efficiency. The functional unit on ssDNA mimics the inhibitor
(MI) of miRNA-382, which plays a crucial role in the progress of many
diseases such as renal interstitial fibrosis. After verification of
overexpression of miRNA-382 in a coculture system, we designed oligonucleotide
sequences (GCG)<sub>5</sub>-MI, (TAT)<sub>5</sub>-MI, and N<sub>23</sub>-MI as regulatory units added to the 5âČ-terminal end of the
functional DNA fragment, respectively. These regulatory units lead
to different secondary structures and thus exhibit different affinity
ability to SWCNTs, and finally decide their deliver efficacy to cells.
Autophagy, apoptosis and necrosis were observed in renal mesangial
cells
Magnetic properties and magnetoresistance of Co x C1âx granular films prepared by magnetron sputtering
Pollen distribution in large freshwater lake of arid region: a case study on the surface sediments from Bosten Lake, Xinjiang, China
Serum carbohydrate antigen 242 expression exerts crucial function in the diagnosis of pancreatic cancer
An injectable self-healing coordinative hydrogel with antibacterial and angiogenic properties for diabetic skin wound repair
In this work, an injectable, self-healing hydrogel with antibacterial and angiogenic abilities was prepared based on the coordination of multi-arm thiolated polyethylene glycol (SH-PEG) with antibacterial silver ions (Ag+). The injectable and self-healing properties derive from the dynamic nature of the Ag-S coordination bonds. After incorporation of an angiogenic drug desferrioxamine (DFO), we could obtain a multifunctional hydrogel with manageable, resistant to external stress, antibacterial and angiogenic properties. Such unique multifunctional hydrogel thus shows potential to accelerate the healing of some exposed wounds (e.g., diabetic skin wound) under disturbed physiological functions, high risk of bacterial infections, and external mechanical irritation