| dc.description.abstract | hanges in neuropeptide Y (NPY) levels in the bloodstream can lead to sleep disturbances, disruptions in circadian rhythms, and potentially contribute to emotional disorders. γ-Aminobutyric acid (GABA) is an inhibitory neurotransmitter and has been widely used for reduction of depression, anxiety, and/or psychological stress since it can raise the total or parasympathetic nerve activities in the mammalian central nervous system. In this study, we successfully produced GABA-enriched rice by inoculating grain seeds of Taiwanese rice with Bacillus amyloliquefaciens (B. amyloliquefaciens) during germination, and demonstrated that the B. amyloliquefaciens-inoculated rice (fermented rice) can grow with a normal root/sprout length but significantly increased germination ratio compared to the rice without B. amyloliquefaciens treatment. Based on the animal study in association with the hole board test, our data showed that the level of serum NPY as well as the number of head-dips of the mice treated with the fermented rice for 8 days significantly enhanced 2 folds (P < 0.01) compared to the mice without GABA, but such fermented rice-induced efficacies dramatically vanished as their gastrointestinal GABAB receptor and/or vagus nerves were removed through use of GABA receptor antagonist or vagotomy, respectively. These results manifested the potential of the fermented rice on anxiolytic applications and unveiled likely mediators for GABA-induced anxiolytic activity.
In addition, my other main research is closely related to nanoparticles. Liver fibrosis is generally considered as the beginning of most liver diseases and therefore a liver fibrosis animal model is the cornerstone for the development of therapeutic strategies for most of hepatic diseases. Although administrations of hepatotoxic substances and/or bile duct ligation have been widely used to build up the in vivo model over the last decades, they are seriously hindered with time consuming, high mortality, and instability, indicating that an effective and safe approach for induction of liver fibrosis is still urgently needed nowadays. In this study, we have developed asialoglycoprotein receptor (ASGPR)-target lipopolysaccharide (LPS)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles named ALPNDs for establishing animal models of liver fibrosis. The ALPNDs are characterized as a spherical nanostructure with size of 182.9 ± 8.89 nm and surface charge of −8.3 ± 1.48 mV. The anti-ASGPR-antibodies equipped on the nanoparticles surface with crosslinking efficiency of 95.03% allow the ALPNDs to be hepatocytic binding specific. In comparison to free LPS, the ALPNDs can induce higher aspartate aminotransferase and total bilirubin concentrations in plasma, reduce blood flow rate, and increase vascular resistance in liver, kidney, and collateral shunting vasculature. Based on the histological and RNA-seq analyses, the ALPNDs can provide similar capability on inductions of hepatic inflammation and fibrosis compared to free LPS, but possess higher liver targetability compared to the naked drug. In addition, the ALPNDs are less toxicity in organs other than liver in comparison to free LPS, demonstrating that the ALPNDs did not elicit off-target effects in vivo. Given aforementioned efficacies with other merits such as biocompatibility and drug release controllability provided by PLGA, we anticipate that the developed ALPND is highly applicable for establishing animal models of liver fibrosis in the pre-clinical study. | en_US |