Title: Evaluation of the toxicity effects of microplastics and cadmium on earthworms Liang X, Zhou D, Wang J, Li Y, Liu Y, Ning Y Ref: Sci Total Environ, :155747, 2022 : PubMed
Microplastics (MPs) and heavy metal pollution have become research hotspots in recent years. This study focused on the comprehensive evaluation of the toxicity effect on Eisenia fetida under combined exposure to MPs and the heavy metal cadmium (Cd). With Cd concentration, MPs concentration and MPs partical size as stress factors, the TOPSIS model was constructed to explore the toxicity levels of the stress factors. A short-term co-exposure test and a long-term co-exposure test were designed by orthogonal combination tests with equivalent toxicity levels. The activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glutathione peroxidase (GPX), glutathione S transferase (GST), and acetylcholinesterase (AChE) and the contents of protein (TP), glutathione (GSH), and malondialdehyde (MDA) in earthworms were determined. Integrated biological responses version 2 (IBRv2) was used to evaluate the toxicity of MPs and Cd combined exposure on earthworms. The results showed that the toxicity ratio of Cd concentration, MPs concentration and MPs partical size was 46 to 29 to 25. Combined exposure to MPs and Cd enhanced the activities of SOD, POD, CAT, GPX and GST, MDA and GSH contents also increased, while the AChE activities were inhibited. SOD, GPX and GST play important roles in the resistance of earthworms to pollutant stress. During short-term co-exposure, Cd concentration had antagonistic effects with on MPs concentration and MPs partical size, while they showed synergistic effects during long-term co-exposure.
BACKGROUND: Rivastigmine is a cholinesterase inhibitor, approved for the treatment of mild-to-moderate dementia of Alzheimer's type. OBJECTIVE: To explore the efficacy and safety of the maximal tolerated dose of rivastigmine capsules in Chinese patients with mild-to-moderate Alzheimer's disease (AD). METHODS: The study was a multicenter, open-label, single-arm, phase IV clinical study in mild-to-moderate drug-naive AD patients treated with rivastigmine capsules. The primary endpoint was the changes in the total scores of Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) from baseline to week 16. Secondary endpoints included changes in the scores of the following assessment scales and safety: Alzheimer's Disease Cooperative Study; Activities of Daily Living; Mini-Mental Status Examination (MMSE); Neuropsychiatry Index (NPI), and Caregiver Burden Inventory. RESULTS: 222 patients were enrolled. Of these, 136 (75.1%) patients received and maintained the effective dose (>/=6 mg/d) of rivastigmine for at least 4 weeks. The ADAS-Cog scale score improved in rivastigmine-treated patients at week 16 compared with baseline (p < 0.001) by 2.0 (95% CI: -3.0 to -1.1) points, which met the pre-defined superiority criteria. NPI-10 and NPI-12 scores improved by 3.6 and 4.0 points at week 16 (p = 0.001, p < 0.001), respectively. A total of 107 patients (59.1%) experienced adverse effects (AEs) during the study; common AEs included nausea (20.5%), vomiting (16.6%), anorexia (7.8%), dizziness (7.7%), and diarrhea (7.2%). CONCLUSION: This was the first phase IV study on rivastigmine in mainland China. The study preliminarily demonstrated that rivastigmine capsules showed good tolerability and efficacy in mild-to-moderate AD patients with the maximal tolerated dose.
Title: Design, synthesis and evaluation of a novel metal chelator as multifunctional agents for the treatment of Alzheimer's disease Wang Y, Yang Y, Hong KH, Ning Y, Yu P, Ren J, Ji M, Cai J Ref: Bioorg Chem, 87:720, 2019 : PubMed
A series of compounds following the lead compounds including deferasirox and tacrine were designed, synthesized and evaluated as multifunctional agents against Alzheimer's disease (AD). In vitro studies showed that most synthesized compounds exhibited good multifunctional activities in inhibiting acetylcholinesterase (bAChE), and chelating metal ions. Especially, compound TDe demonstrated significant metal chelating property, a moderate acetylcholinesterase (AChE) inhibitory activity and an antioxidant activity. Results from the molecular modeling indicated that TD compounds were mixed-type inhibitor, binding simultaneously to the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of TcAChE. Moreover, TDe showed a low cytotoxicity but a good protective activity against the injury caused by H2O2. These results suggest that TD compounds might be considered as attractive multi-target cholinesterase inhibitor and will play important roles in the treatment of AD.
Title: The Expression Pattern of PLIN2 in Differentiated Adipocytes from Qinchuan Cattle Analysis of Its Protein Structure and Interaction with CGI-58 Li P, Wang Y, Zhang L, Ning Y, Zan L Ref: Int J Mol Sci, 19:, 2018 : PubMed
PLIN2 (Perilipin-2) is a protein that can anchor on the membrane of lipid droplets (LDs), playing a vital role in the early formation of LDs and in the regulation of LD metabolism in many types of cells. However, little research has been conducted in cattle adipocytes. In the present study, we found that the expression of PLIN2 mRNA peaks at Day 2 during cattle adipocyte differentiation (p < 0.01), but PLIN2 protein levels maintain high abundance until Day 4 and then decrease sharply. We first built an interaction model using PyMOL. The results of a pull-down assay indicated that bovine PLIN2 and CGI-58 (ABHD5, α/β hydrolase domain-containing protein 5) had an interaction relationship. Furthermore, Bimolecular Fluorescence Complementation-Flow Cytometry (BiFC-FC) was used to explore the function of the PLIN2-CGI-58 interaction. Interestingly, we found that different combined models had different levels of fluorescence intensity; specifically, PLIN2-VN173+CGI-58-VC155 expressed in bovine adipocytes exhibited the highest level of fluorescence intensity. Our findings elucidate the PLIN2 expression pattern in cattle adipocytes, the protein structure and the function of protein(-)protein interactions (PPI) as well as highlight the characteristics of bovine PLIN2 during the early formation and accumulation of lipid droplets.
We sequenced the genome of Saccharomyces cerevisiae strain YJM789, which was derived from a yeast isolated from the lung of an AIDS patient with pneumonia. The strain is used for studies of fungal infections and quantitative genetics because of its extensive phenotypic differences to the laboratory reference strain, including growth at high temperature and deadly virulence in mouse models. Here we show that the approximately 12-Mb genome of YJM789 contains approximately 60,000 SNPs and approximately 6,000 indels with respect to the reference S288c genome, leading to protein polymorphisms with a few known cases of phenotypic changes. Several ORFs are found to be unique to YJM789, some of which might have been acquired through horizontal transfer. Localized regions of high polymorphism density are scattered over the genome, in some cases spanning multiple ORFs and in others concentrated within single genes. The sequence of YJM789 contains clues to pathogenicity and spurs the development of more powerful approaches to dissecting the genetic basis of complex hereditary traits.
Title: The opdB locus encodes the trypsin-like peptidase activity of Treponema denticola Fenno JC, Lee SY, Bayer CH, Ning Y Ref: Infect Immun, 69:6193, 2001 : PubMed
High levels of Treponema denticola in subgingival dental plaque are associated with severe periodontal disease. T. denticola, along with Porphyromonas gingivalis and Bacteroides forsythus, are the only cultivatable oral microorganisms that produce significant amounts of "trypsin-like" peptidase activity. The ability of subgingival plaque to hydrolyze N-alpha-benzoyl-DL-arginine-2-naphthylamide (BANA) is associated with high levels of one or more of these organisms. The purpose of this study was to identify the gene encoding trypsin-like activity in T. denticola and thus facilitate molecular-level studies of its potential role in disease. Using published peptide sequences of a T. denticola surface-associated oligopeptidase with BANA-hydrolyzing activity, we identified the gene, designated opdB, in an apparently noncoding region of the T. denticola genome unannotated contigs (11/2000; http:\/\/www.tigr.org). The opdB gene begins with a TTG start codon and encodes a 685-residue peptide with high homology to the oligopeptidase B family in prokaryotes and eukaryotes. An isogenic T. denticola opdB mutant was constructed by allelic replacement mutagenesis using an ermF/AM gene cassette. The mutant lacked BANA-hydrolyzing activity and had a slightly slower growth rate than the parent strain. This mutant will be used in future studies of interactions of T. denticola with host cells and tissue.
