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.
Nonalcoholic fatty liver disease (NAFLD) is relatively associated with comorbidities in obesity and metabolic inflammation. Low-grade inflammation following the highfat 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 NAFLDrat 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-β1), and also recovery to simple stage followed by PAVA suppresses pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, interleukin-6, and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway. Therefore, our findings suggest that
Capsaicinoid nonivamide (PAVA) and rosuvastatin (RSV) have been shown to exert antioxidant and anti‐obesity effects in various animal models, but it is unknown whether their combination would be an effective treatment for obesity‐related endothelial dysfunction. This study aimed to investigate the mechanism of PAVA in synergy with RSV. Male Sprague–Dawley rats were given a high‐fat diet (HFD) or normal diet during a 20‐week period. At 16 weeks, rats in each diet group were divided into subgroups. Normal diet rats were divided into Normal diet control, Normal diet with PAVA, and Normal diet with RSV groups. HFD rats were subdivided into HFD control, HFD with PAVA, HFD with RSV, and HFD with PAVA + RSV groups and evaluated for metabolic parameters, blood pressure, aortic function, and histological change of the aorta in rats. Our results showed the combined therapy had a significantly greater effect than the monotherapy in all measured parameters; this was indicated by improvement in insulin sensitivity and aortic function, decreased blood pressure, lower oxidative stress, and prevention of vascular damage. The synergistic effect of the PAVA and RSV can protect HFD‐induced obesity‐related endothelial dysfunction, suggesting that the combination of PAVA and RSV could be an effective alternative treatment for obesity‐related complications in patients with cardiovascular disease.
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