Autism spectrum disorder (ASD) is a group of developmental disabilities, the aetiology of which remains elusive. The endocannabinoid (eCB) system modulates neurotransmission and neuronal plasticity. Evidence points to the involvement of this neuromodulatory system in the pathophysiology of ASD. We investigated whether there is a disruption to the eCB system in ASD and whether pharmacological modulation of the eCB system might offer therapeutic potential. We examined three major components of the eCB system—endogenous cannabinoids, their receptors and associated enzymes—in ASD children as well as in the valproic acid (VPA) induced animal model in autism. Furthermore, we specifically increased 2-arachidonoylglycerol (2-AG) levels by administering JZL184, a selective inhibitor of monoacylglycerol lipase which is the hydrolytic enzyme for 2-AG, to examine ASD-like behaviours in VPA-induced rats. Results showed that autistic children and VPA-induced rats exhibited reduced eCB content, increased degradation of enzymes and upregulation of CBRs. We found that repetitive and stereotypical behaviours, hyperactivity, sociability, social preference and cognitive functioning improved after acute and chronic JZL184 treatment. The major efficacy of JZL184 was observed after administration of a dosage regimen of 3 mg kg −1 , which affected both the eCB system and ASD-like behaviours. In conclusion, a reduced eCB signalling was observed in autistic children and in the ASD animal model, and boosting 2-AG could ameliorate ASD-like phenotypes in animals. Collectively, the results suggested a novel approach to ASD treatment.

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Deposition of extracellular matrix (ECM) in trabecular meshwork, such as fibronectin, collagen IV, elastin. leads to increased resistance of trabecular meshwork in primary open angle glaucoma (POAG). Connective tissue growth factor (CTGF) is known to regulate the ECM deposits. In this study, we detect the effect of adenovirus conducted CTGF (Adv-CTGF) transfection on either the expression of ECM components or aqueous humor outflow facility. Adv-CTGF was used to transfect rat trabecular meshwork cells in vivo and in vitro. Aqueous humor outflow facility was test by microbeads perfusion. Protein expression of CTGF, fibronectin, and collagen IV was determined using Western blot. In the Adv-CTGF group, the outflow facility displayed a significant decrease from baseline. It appears as though the transfection with Adv-CTGF significantly affects the aqueous humor outflow pattern. A negative correlation between IOP and PEFL indicated that a decrease in the area of bead deposition corresponded to an overall decrease of outflow, leading to an elevated IOP. Adv-CTGF can enhance the expression of CTGF, fibronectin and collagen IV. CTGF is the novel target for treatment of POAG. It is necessary to further study to test inhibition of CTGF expression for treatment of POAG.

Hepatocellular carcinoma (HCC) is a malignant tumor leading cancer-associated high mortality worldwide. Unfortunately, the most commonly used drug therapeutics not only lack of target ability and efficiency, but also exhibit severe systemic toxicity to normal tissues. Thus, effective and targeted nanodrug of HCC therapy is emerging as a more important issue. Here, we design and develop the novel nanomicelles, namely Mannose-polyethylene glycol 600-Nitroimidazole (Man-NIT). This micelle compound with high purity comprise two parts, which can self-assemble into nanoscale micelle. The outer shell is selected mannose as hydrophilic moiety, while the inner core is nitroimidazole as hydrophobic moiety. In the cell experiment, Man-NIT was more cellular uptake by HCCLM3 cells due to the mannose modification. Mannose as a kind of glucose transporter 1 (GLUT1) substrate, can specifically recognize and bind to over-expressed GLUT1 on carcinoma cytomembrane. The nitroimidazole moiety of Man-NIT was reduced by the over-expressed nitroreductase with reduced nicotinamide adenine dinucleotide phosphate (NADPH) as the cofactor, resulting in transient deletion of NADPH and glutathione (GSH). The increase of reactive oxygen species (ROS) in HCCLM3 cells disturbed the balance of redox, and finally caused the death of tumor cells. Additional in vivo experiment was conducted using twenty-four male BALB/c nude mice to build the tumor model. The results showed that nanomicelles were accumulated in the liver of mice. The tumor size and pathological features were obviously improved after nanomicelles treatment. It indicates that namomicelles have a tumor inhibition effect, especially Man-NIT, which may be a potential nanodrug of chemotherapeutics for HCC therapy.