The capsaicinoid nonivamide suppresses the inflammatory response and attenuates the progression of steatosis in a NAFLD-rat model.

Nonalcoholic fatty liver disease (NAFLD) is relatively associated with comorbidities in obesity and metabolic inflammation. Low-grade inflammation following the high-fat diet (HFD)-induced NAFLD can promote the development of nonalcoholic steatohepatitis (NASH) through particularly liver-resident immune cell recruitment and hepatic nuclear factor kappa B (NF-κB) pathway. Therefore, inflammatory intervention may contribute to NASH reduction. Pelargonic acid vanillylamide (PAVA) or nonivamide is one of the pungent capsaicinoids of Capsicum species and has been found in chili peppers. Our previous study demonstrated that PAVA improved hepatic function, decreased oxidative stress and reduced apoptotic cell death but the insight role of PAVA on NAFLD is still unclear. Thus, this study aimed to investigate the underlying anti-inflammatory mechanism of PAVA in an NAFLD-rat model. Male Sprague Dawley rats were fed with normal diet or HFD for 16 weeks. Then high-fat rats were given vehicle or PAVA (1 mg/kg/day) for another 4 weeks. We found that PAVA alleviated hepatic inflammation associated with the reducing toll-like receptor 4/NF-κB pathway, showing significantly lower recruitment of cluster of differentiation 44. PAVA also maintained activity of insulin signaling pathway, and attenuated NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome formation. NAFLD progresses to NASH through transforming growth factor (TGF-ß1), and also recovery to simple stage followed by PAVA suppresses pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1ß, interleukin-6, and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway. Therefore, our findings suggest that PAVA provides a novel therapeutic approach for NAFLD and slows the progression to NASH.

Surface-Modified Polypyrrole-Coated PLCL and PLGA Nerve Guide Conduits Fabricated by 3D Printing and Electrospinning.

The efficiency of nerve guide conduits (NGCs) in repairing peripheral nerve injury is not high enough yet to be a substitute for autografts and is still insufficient for clinical use. To improve this efficiency, 3D electrospun scaffolds (3D/E) of poly(l-lactide-co-ε-caprolactone) (PLCL) and poly(l-lactide-co-glycolide) (PLGA) were designed and fabricated by the combination of 3D printing and electrospinning techniques, resulting in an ideal porous architecture for NGCs. Polypyrrole (PPy) was deposited on PLCL and PLGA scaffolds to enhance biocompatibility for nerve recovery. The designed pore architecture of these "PLCL-3D/E" and "PLGA-3D/E" scaffolds exhibited a combination of nano- and microscale structures. The mean pore size of PLCL-3D/E and PLGA-3D/E scaffolds were 289 ± 79 and 287 ± 95 nm, respectively, which meets the required pore size for NGCs. Furthermore, the addition of PPy on the surfaces of both PLCL-3D/E (PLCL-3D/E/PPy) and PLGA-3D/E (PLGA-3D/E/PPy) led to an increase in their hydrophilicity, conductivity, and noncytotoxicity compared to noncoated PPy scaffolds. Both PLCL-3D/E/PPy and PLGA-3D/E/PPy showed conductivity maintained at 12.40 ± 0.12 and 10.50 ± 0.08 Scm-1 for up to 15 and 9 weeks, respectively, which are adequate for the electroconduction of neuron cells. Notably, the PLGA-3D/E/PPy scaffold showed superior cytocompatibility when compared with PLCL-3D/E/PPy, as evident via the viability assay, proliferation, and attachment of L929 and SC cells. Furthermore, analysis of cell health through membrane leakage and apoptotic indices showed that the 3D/E/PPy scaffolds displayed significant decreases in membrane leakage and reductions in necrotic tissue. Our finding suggests that these 3D/E/PPy scaffolds have a favorable design architecture and biocompatibility with potential for use in peripheral nerve regeneration applications.