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We report a simple and rapid microwave-assisted method for the preparation of oligosaccharide-glycosylamines, followed by labelling with tris(2,4,6-trimethoxyphenyl)phosphonium acetic acid N-hydroxysuccinimide ester. The facile strategy introduced a permanent charge at the reducing end of the oligosaccharide. In combination of MALDI-MS, the detection limit for maltoheptaose was as low as 2 fmol μL−1. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate the relationship between the aqueous humor levels of VEGF, TNF-a, IL-10, IL-6, IL-12, MCP-1, and IP-10 with DR/DME. Methods. PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched up to October 2018. Systematic review and meta-analysis were conducted. Results. 18 studies comprising 362 cases with DR (100 with DME) and 620 controls without DR were included in this meta-analysis. There was a significant association between VEGF levels in the aqueous humor and DR (standardized mean difference (SMD) 1.94 (95% CI 1.05-2.83)) and DME (1.07 (0.71, 1.42)). Furthermore, a significant correlation was observed between levels of IL-6 and DR (3.53 (0.37, 6.69)), and similarly correlation with DME (1.26 (0.30, 2.21)). The relationship between MCP-1 and DR and DME was significant, in which the SMD was (0.49 (0.09, 0.89)) and (1.49 (0.78, 2.20)), respectively. However, IL-12, IP-10, and TNF-a had no correlation with DR and DME, whereas there was a significant relationship between IL-8 and DME (1.68 (0.97, 2.40)). Conclusion. Elevated levels of VEGF, IL-6, and MCP-1 in the aqueous humor were associated with the risk for the presence of DR, and levels of VEGF, IL-6, IL-8, and MCP-1 were associated with the risk of DME. Furthermore, these biomarkers may be used as potential predictors or therapeutic targets for DR/DME. [ABSTRACT FROM AUTHOR]

Background: Myelination, degeneration and regeneration are implicated in crucial responses to injury in the peripheral nervous system. Considering the progression of amyotrophic lateral sclerosis (ALS), we used the superoxide dismutase 1 (SOD1)-G93A transgenic mouse model of ALS to investigate the effects of mutant SOD1 on the peripheral nerves. Methods: Changes in peripheral nerve morphology were analyzed in SOD1 mutant mice at various stages of the disease by toluidine blue staining and electron microscopy (EM). Schwann cell proliferation and recruitment of inflammatory factors were detected by immunofluorescence staining and quantitative reverse transcription PCR and were compared between SOD1 mutant mice and control mice. Furthermore, western blotting (WB) and TUNEL staining were used to investigate axonal damage and Schwann cell survival in the sciatic nerves of mice in both groups. Results: An analysis of the peripheral nervous system in SOD1-G93A mice revealed the following novel features: (i) Schwann cells and axons in mutant mice underwent changes that were similar to those seen in the control mice during the early development of peripheral nerves. (ii) The peripheral nerves of SOD1-G93A mice developed progressive neuropathy, which presented as defects in axons and myelin, leading to difficulty in walking and reduced locomotor capacity at a late stage of the disease. (iii) Macrophages were recruited and accumulated, and nerve injury and a deficit in the blood-nerve barrier were observed. (iv) Proliferation and the inflammatory micro-environment were inhibited, which impaired the regeneration and remyelination of axons after crush injury in the SOD1-G93A mice. Conclusions: The mutant human SOD1 protein induced axonal and myelin degeneration during the progression of ALS and participated in axon remyelination and regeneration in response to injury. [ABSTRACT FROM AUTHOR]

By use of the 6-hydroxypyridazinone framework, a new series of potent σ1 receptor ligands associated with pharmacological antineuropathic pain activity was synthesized and is described in this article. In vitro receptor binding studies revealed high σ1 receptor affinity (Ki σ1 = 1.4 nM) and excellent selectivity over not only σ2 receptor (1366-fold) but also other CNS targets (adrenergic, μ-opioid, sertonerigic receptors, etc.) for 2-(3,4-dichlorophenyl)-6-(3-(piperidin-1-yl)propoxy)pyridazin-3(2H)-one (compound 54). Compound 54 exhibited dose-dependent antiallodynic properties in mouse formalin model and rats chronic constriction injury (CCI) model of neuropathic pain. In addition, functional activity of compound 54 was evaluated using phenytoin and indicated that the compound was a σ1 receptor antagonist. Moreover, no motor impairments were found in rotarod tests at antiallodynic doses and no sedative side effect was evident in locomotor activity tests. Last but not least, good safety and favorable pharmacokinetic properties were also noted. These profiles suggest that compound 54 may be a member of a novel class of candidate drugs for treatment of neuropathic pain. [ABSTRACT FROM AUTHOR]

Background: It is important to develop novel antipsychotics that can effectively treat schizophrenia with minor side-effects. The aim of our work is to develop novel antipsychotics that act on dopamine D2 and D3, serotonin 5-HT1A and 5-HT2A receptors with low affinity for the serotonin 5-HT2C and H1 receptors, which can effectively cure positive symptoms, negative symptoms and cognitive impairment without the weight gain side-effect. Methodology/Principal Findings: A series of 2-substituted-5-thiopropylpiperazine (piperidine) -1,3,4-oxadiazoles derivatives have been synthesized and the target compounds were evaluated for binding affinities to D2, 5-HT1A and 5-HT2A receptors. Preliminary results indicated that compounds 14, 16 and 22 exhibited high affinities to D2, 5-HT1A and 5-HT2A receptors among these compounds. Further binding tests showed that compound 22 had high affinity for D3 receptor, and low affinity for serotonin 5-HT2C and H1 receptors. In addition, compound 22 inhibited apomorphine-induced climbing behavior and MK-801-induced hyperactivity with no extrapyramidal symptoms liability in mice. Moreover, compound 22 exhibited acceptable pharmacokinetic properties. Conclusions/Significance: Compound 22 showed an atypical antipsychotic activity without liability for extrapyramidal symptoms. We anticipate compound 22 to be useful for developing a novel class of drug for the treatment of schizophrenia. [ABSTRACT FROM AUTHOR]

In this work, a series of arylpiperazine derivatives were synthesized and screened by in vivo pharmacological trials. Among the tested compounds, 2-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)-1-phenylethanone (18) and 2-(4-(2,3-dimethylphenyl)piperazin-1-yl)-1-phenylethanone (19) exhibited potent analgesic activities in both the mice writhing and mice hot plate tests. They showed more than 70% inhibition relative to controls in the writhing test, and increased latency by 116.0% and 134.4%, respectively, in the hot plate test. Furthermore, compound 18 was also active in the models of formalin pain and neuropathic pain without sedative side effects. [ABSTRACT FROM AUTHOR]