Abstract. Subfragments of amyloid-beta (Aβ) appear to protect neurons from Alzheimer's disease (AD). The permeability of the blood-brain barrier (BBB) has limited in vivo research. The aim of this study is to explore permeation of the BBB by chitosan nanoparticles loaded with Aβ and to evaluate immunogenicity of these particles. Chitosan microspheres were prepared by mechanical stirring emulsification methods combined with chemical crosslinking. Morphological characteristics of the nanoparticles were examined using high-resolution transmission electron microscopy. The peptide association efficiency was determined by high-performance liquid chromatography. Fluorescently labeled chitosan nanoparticle-intramembranous fragments of Aβ (NP-IF-A) were administered systemically to mice in order to evaluate brain translocation by fluorescence microscopy. The immunogenicity of the nano-vaccine was determined by enzyme-linked immunosorbent assay (ELISA). All nanoparticles analyzed were well-separated, roughly spherical structures with uniform particle size distribution in the range of 15.23±10.97 nm. The peptide association efficiency was 78.4%. The brain uptake efficiency of nano-antigen was 80.6%; uptake efficiency of antigen alone was only 20.6%. ELISA showed that the nano-vaccine had favorable immunogenicity. A chitosan nano-carrier for Aβ allowed permeation of the BBB. These findings indicate that this novel targeted nano-vaccine delivery system can be used as a carrier for Aβ. This system will further research of peptide vaccines for AD.

Background and ObjectivesThe roles of microRNA(miR)‐106b‐5p in hepatocellular carcinoma (HCC) remain unclear. We aimed here to investigate the clinical significance of miR‐106b‐5p expression in HCC and its underlying mechanisms.MethodsExpression levels of miR‐106b‐5p in 108 HCC clinical samples by quantitative real‐time reverse transcription PCR. Associations of miR‐106b‐5p expression with various clinicopathological features and patients' prognosis were evaluated by Chi‐square test, Kaplan‐Meier, and Cox proportional regression analyses, respectively. The target gene of miR‐106b‐5p and their functions in HCC cells were investigated by luciferase reporter, CCK‐8, and Transwell Matrigel invasion assays.ResultsmiR‐106b‐5p expression was markedly higher in HCC tissues than in noncancerous adjacent liver tissues (P < .001). miR‐106b‐5p upregulation was significantly associated with advanced TNM stage (P = .02), short recurrence‐free (P = .005), and overall (P = .001) survivals. Importantly, miR‐106b‐5p expression was an independent predictor of poor prognosis (P < .05). RUNX3 was identified as a direct target gene of miR‐106b‐5p in HCC cells. Functionally, miR‐106b‐5p upregulation promoted the viability and invasion of HCC cells, while enforced RUNX3 expression reversed the oncogenic effects of miR‐106b‐5p overexpression.ConclusionsmiR‐106b‐5p may serve as a potent prognostic marker for tumor recurrence and survival of HCC patients. miR‐106b‐5p may exert an oncogenic role in HCC via regulating its target gene RUNX3.

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Hypertension is an independent risk factor contributing to chronic kidney disease. Buyang Huanwu Decoction (BHD) is a popular traditional Chinese medicine prescription for the treatment of stroke for centuries. Recent studies reported that the use of BHD had been extended to treat various kinds of disorders following traditional Chinese medicine syndrome theory of Treating Different Diseases with the Same Method. Therefore, this study aimed to determine the effects of BHD on renal injury in spontaneously hypertensive rats (SHR). Treatment with BHD at the dose of 12.6 g/kg/day by gavage for 5 weeks had no effect on the increased systolic blood pressure and renal hypertrophy in 17‐week‐old SHR. However, BHD treatment obviously reduced urinary albumin excretion compared with the control SHR (P<0.05). Periodic acid‐Schiff and Masson's trichrome staining showed that obvious glomerulosclerosis and tubulointerstitial injury were found in the kidney in SHR and reduced by BHD treatment (P<0.05). Consistent with the results, renal collagen level determined using hydroxyproline assay was higher in SHR and attenuated by BHD treatment (P<0.05). In addition, the renal monocyte/macrophage infiltration was seen in SHR and inhibited by BHD treatment (P<0.05). Our data showed that treatment with BHD attenuated renal damage in SHR independently of their effects on blood pressure. The results indicate that BHD exhibits a protective effect on renal damage in SHR. This work was supported in part by the National Natural Science Foundation of China (No. 81673734).Support or Funding InformationThis work was supported in part by the National Natural Science Foundation of China (No. 81673734).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Immunotherapy holds great promise for Alzheimer's disease (AD), but meningoencephalitis observed in the first AD vaccination trial, which accompanied T-lymphocytic infiltration, needs to be overcome. This study was aimed to investigate alternative approaches for a safer vaccine to treat AD. We used intramembranous fragment of amyloid-beta (IF-Abeta) to immunize Kunming mice for up to 2.5 months and then evaluated the immunization efficacy and potential adverse effects. Immunization of mice with IF-Abeta plus Freund's adjuvant resulted in moderate levels of Abeta antibodies (IgG), and the anti-sera were able to neutralize Abeta1-42-neurotoxicity in cultured primary cortical neurons. IF-Abeta itself did not show neurotoxicity, and immunization with IF-Abeta did not cause behavioral deficits in Morris water maze or any abnormalities by histological examinations of major organs including the brain. We conclude that vaccination with IF-Abeta may be a potentially safe and effective treatment for AD.