Dai R

References (9)

Title : In silico identification of novel stilbenes analogs for potential multi-targeted drugs against Alzheimer's disease - Firdoos_2023_J.Mol.Model_29_209
Author(s) : Firdoos S , Dai R , Tahir RA , Khan ZY , Li H , Zhang J , Ni J , Quan Z , Qing H
Ref : J Mol Model , 29 :209 , 2023
Abstract : CONTEXT: Alzheimer's disease (AD) is a chronic progressive neurodegenerative syndrome, which adversely disturbs cognitive abilities as well as intellectual processes and frequently occurs in the elderly. Inhibition of cholinesterase is a valuable approach to upsurge acetylcholine concentrations in the brain and persuades the development of multi-targeted ligands against cholinesterases. METHODS: The current study aims to determine the binding potential accompanied by antioxidant and anti-inflammatory activities of stilbenes-designed analogs against both cholinesterases (Acetylcholinesterase and butyrylcholinesterase) and neurotrophin targets for effective AD therapeutics. Docking results have shown that the WS6 compound exhibited the least binding energy - 10.1 kcal/mol with Acetylcholinesterase and - 7.8 kcal/mol with butyrylcholinesterase. The WS6 also showed a better binding potential with neurotrophin targets that are Brain-derived Neurotrophic Factor, Neurotrophin 4, Nerve Growth Factor, and Neurotrophin 3. The tested compounds particularly WS6 revealed significant antioxidant and anti-inflammatory activities through the comparative docking analysis with Fluorouracil and Melatonin as control drugs of antioxidants while Celecoxib and Anakinra as anti-inflammatory. The bioinformatics approaches including molecular docking calculations followed by the pharmacokinetics analysis and molecular dynamic simulations were accomplished to explore the capabilities of designed stilbenes as effective and potential leads. Root mean square deviation, root mean square fluctuations, and MM-GBSA calculations were performed through molecular dynamic simulations to extract the structural and residual variations and binding free energies through the 50-ns time scale.
ESTHER : Firdoos_2023_J.Mol.Model_29_209
PubMedSearch : Firdoos_2023_J.Mol.Model_29_209
PubMedID: 37314512

Title : Analyses of the autism-associated neuroligin-3 R451C mutation in human neurons reveal a gain-of-function synaptic mechanism - Wang_2022_Mol.Psychiatry__
Author(s) : Wang L , Mirabella VR , Dai R , Su X , Xu R , Jadali A , Bernabucci M , Singh I , Chen Y , Tian J , Jiang P , Kwan KY , Pak C , Liu C , Comoletti D , Hart RP , Chen C , Sudhof TC , Pang ZP
Ref : Mol Psychiatry , : , 2022
Abstract : Mutations in many synaptic genes are associated with autism spectrum disorders (ASD), suggesting that synaptic dysfunction is a key driver of ASD pathogenesis. Among these mutations, the R451C substitution in the NLGN3 gene that encodes the postsynaptic adhesion molecule Neuroligin-3 is noteworthy because it was the first specific mutation linked to ASDs. In mice, the corresponding Nlgn3 R451C-knockin mutation recapitulates social interaction deficits of ASD patients and produces synaptic abnormalities, but the impact of the NLGN3 R451C mutation on human neurons has not been investigated. Here, we generated human knockin neurons with the NLGN3 R451C and NLGN3 null mutations. Strikingly, analyses of NLGN3 R451C-mutant neurons revealed that the R451C mutation decreased NLGN3 protein levels but enhanced the strength of excitatory synapses without affecting inhibitory synapses; meanwhile NLGN3 knockout neurons showed reduction in excitatory synaptic strengths. Moreover, overexpression of NLGN3 R451C recapitulated the synaptic enhancement in human neurons. Notably, the augmentation of excitatory transmission was confirmed in vivo with human neurons transplanted into mouse forebrain. Using single-cell RNA-seq experiments with co-cultured excitatory and inhibitory NLGN3 R451C-mutant neurons, we identified differentially expressed genes in relatively mature human neurons corresponding to synaptic gene expression networks. Moreover, gene ontology and enrichment analyses revealed convergent gene networks associated with ASDs and other mental disorders. Our findings suggest that the NLGN3 R451C mutation induces a gain-of-function enhancement in excitatory synaptic transmission that may contribute to the pathophysiology of ASD.
ESTHER : Wang_2022_Mol.Psychiatry__
PubMedSearch : Wang_2022_Mol.Psychiatry__
PubMedID: 36280753

Title : Human umbilical cord mesenchymal stem cells-derived exosomes for treating traumatic pancreatitis in rats - Han_2022_Stem.Cell.Res.Ther_13_221
Author(s) : Han L , Zhao Z , Chen X , Yang K , Tan Z , Huang Z , Zhou L , Dai R
Ref : Stem Cell Res Ther , 13 :221 , 2022
Abstract : BACKGROUND: The therapeutic and protective effects of human umbilical cord mesenchymal stem cells-exosomes (hucMSC-Exs) on traumatic pancreatitis (TP) remain unknown. Here, we established a rat model of TP and evaluated and compared the therapeutic effects of hUC-MSCs and hucMSC-Exs. METHODS: HucMSC-Exs were obtained by ultracentrifugation and identified using transmission electron microscopy and western blot analysis. TP rats were treated by tail vein injection of hUC-MSCs and hucMSC-Exs. Their homing in rats was observed by performing fluorescence microscopy. The degree of pancreatic tissue damage was assessed by HE staining, the expression levels of amylase, lipase, and inflammatory cytokines were detected by ELISA, apoptosis was detected by TUNEL assay, and the expression levels of various apoptosis-related proteins were detected by western-blot. The expression levels of apoptosis-related molecular markers were detected by RT-qPCR. RESULTS: The colonization of exosomes was observed in pancreatic tissue. Compared to TP group, the histopathological score of pancreas was significantly decreased in the TP + hUC-MSCs group and TP + hucMSC-Exs group (P < 0.05). Compared to TP group, the activity of serum amylase and lipase was significantly decreased (P < 0.05). The expression levels of IL-6 and TNF-alpha were significantly decreased, while those of IL-10 and TGF-beta were significantly increased (P < 0.05). The apoptosis index of the TP group was significantly increased (P < 0.05), whereas that of the TP + hUC-MSCs and TP + hucMSC-Exs groups was significantly decreased (P < 0.05). Compared to TP group, the expression levels of Bax, Bcl-2, and Caspase-3 were significantly decreased in the TP + hUC-MSCs group and TP + hucMSC-Exs group (P < 0.05). CONCLUSION: HucMSC-Exs can colonize injured pancreatic tissue, inhibit the apoptosis of acinar cells, and control the systemic inflammatory response to facilitate the repair of pancreatic tissue.
ESTHER : Han_2022_Stem.Cell.Res.Ther_13_221
PubMedSearch : Han_2022_Stem.Cell.Res.Ther_13_221
PubMedID: 35619158

Title : Anti-Alzheimer's disease potential of traditional chinese medicinal herbs as inhibitors of BACE1 and AChE enzymes - Dai_2022_Biomed.Pharmacother_154_113576
Author(s) : Dai R , Sun Y , Su R , Gao H
Ref : Biomed Pharmacother , 154 :113576 , 2022
Abstract : Alzheimer's disease (AD) is a common neurodegenerative disease that often occurs in the elderly population. At present, most drugs for AD on the market are single-target drugs, which have achieved certain success in the treatment of AD. However, the efficacy and safety of single-target drugs have not achieved the expected results because AD is a multifactorial disease. Multi-targeted drugs act on multiple factors of the disease network to improve efficacy and reduce adverse reactions. Therefore, the search for effective dual-target or even multi-target drugs has become a new research trend. Many of results found that the dual-target inhibitors of the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and acetylcholinesterase (AChE) found from traditional Chinese medicine have a good inhibitory effect on AD with fewer side effects. This article reviews sixty-six compounds extracted from Chinese medicinal herbs, which have inhibitory activity on BACE1 and AChE. This provides a theoretical basis for the further development of these compounds as dual-target inhibitors for the treatment of AD.
ESTHER : Dai_2022_Biomed.Pharmacother_154_113576
PubMedSearch : Dai_2022_Biomed.Pharmacother_154_113576
PubMedID: 36007279

Title : Macrophage ABHD5 Suppresses NFkappaB-Dependent Matrix Metalloproteinase Expression and Cancer Metastasis - Shang_2019_Cancer.Res_79_5513
Author(s) : Shang S , Ji X , Zhang L , Chen J , Li C , Shi R , Xiang W , Kang X , Zhang D , Yang F , Dai R , Chen P , Chen S , Chen Y , Li Y , Miao H
Ref : Cancer Research , 79 :5513 , 2019
Abstract : Metabolic reprogramming in tumor-associated macrophages (TAM) is associated with cancer development, however, the role of macrophage triglyceride metabolism in cancer metastasis is unclear. Here, we showed that TAMs exhibited heterogeneous expression of abhydrolase domain containing 5 (ABHD5), an activator of triglyceride hydrolysis, with migratory TAMs expressing lower levels of ABHD5 compared with the nonmigratory TAMs. ABHD5 expression in macrophages inhibited cancer cell migration in vitro in xenograft models and in genetic cancer models. The effects of macrophage ABHD5 on cancer cell migration were dissociated from its metabolic function as neither triglycerides nor ABHD5-regulated metabolites from macrophages affected cancer cell migration. Instead, ABHD5 deficiency in migrating macrophages promoted NFkappaB p65-dependent production of matrix metalloproteinases (MMP). ABHD5 expression negatively correlated with MMP expression in TAMs and was associated with better survival in patients with colorectal cancer. Taken together, our findings show that macrophage ABHD5 suppresses NFkappaB-dependent MMP production and cancer metastasis and may serve as a prognostic marker in colorectal cancer. SIGNIFICANCE: These findings highlight the mechanism by which reduced expression of the metabolic enzyme ABHD5 in macrophages promotes cancer metastasis.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/21/5513/F1.large.jpg.
ESTHER : Shang_2019_Cancer.Res_79_5513
PubMedSearch : Shang_2019_Cancer.Res_79_5513
PubMedID: 31439546
Gene_locus related to this paper: human-ABHD5

Title : Therapy of Dredging the Bowels Enhanced the Neuroprotective Effect of Nourishing Kidney Herbs on Hippocampal Cholinergic System in Alzheimer's Disease Model Rat Induced by Abeta 1-42 - Feng_2018_Evid.Based.Complement.Alternat.Med_2018_3282385
Author(s) : Feng LD , Tian Y , Wang X , Dai R , Cai S , Cao YJ , Si YC
Ref : Evid Based Complement Alternat Med , 2018 :3282385 , 2018
Abstract : Background: Therapy of nourishing kidney has been used for treating memory deficits of Alzheimer's disease (AD) for thousands of years based on traditional Chinese medicine. However, we found the therapy of dredging the bowels could alleviate both memory deficits and mental symptoms of AD in clinic. Objective: To determine whether the therapy of dredging the bowels could enhance the neuroprotective effect of nourishing kidney herbs for treating AD rats, and to explore the underlying mechanism of the combination of nourishing kidney and dredging the bowels (NKDB) herbs. Methods: 60 rats were randomly divided into sham-operated group (SOG), model group (MG), nourishing kidney group (NKG), dredging the bowels group (DBG), nourishing kidney and dredging the bowels group (NKDBG), and donepezil hydrochloride group (DHG). The model establishment was performed by injecting Abeta 1-42 into the hippocampal CA1 region. Animals received aqueous solution of Chinese herbal medicine or western medicine while SOG received only distilled water. Ability of learning and memory were assessed by Morris water maze. Acetylcholinesterase(AChE) and choline acetyltransferase (ChAT) activity and positive cells in the hippocampus were detected by the biochemical and immunofluorescent assay. Results: All rats were in the same baseline. While after model establishment, ability of learning and memory of MG, NKG, DBG, NKDBG, and DHG were significantly impaired compared with SOG. Whereas after treatment, ability of learning and memory of NKG, DBG, NKDBG, and DHG were significantly improved compared with MG. Additionally, AChE activity of NKG, DBG, and NKDBG was significantly decreased, meanwhile ChAT activity showed an increased tendency. The number of AChE-positive cells and ChAT-positive cells of both NKDBG and DHG were significantly decreased and increased respectively, superior to those when compared with NKG and DBG. What's more, there was no significant difference between NKDBG and DHG. Conclusion: Therapy of dredging the bowels could enhance the neuroprotective effect of nourishing kidney herbs by reversing morphological damage of hippocampal cholinergic system. Furthermore, treatment with NKDB herbs could be effectively against AD, providing a practical therapeutic strategy in clinic.
ESTHER : Feng_2018_Evid.Based.Complement.Alternat.Med_2018_3282385
PubMedSearch : Feng_2018_Evid.Based.Complement.Alternat.Med_2018_3282385
PubMedID: 30298092

Title : Determination of a novel dipeptidyl peptidase IV inhibitor in monkey plasma by HPLC-MS\/MS and its application in a pharmacokinetics study - Deng_2015_J.Pharm.Biomed.Anal_117_99
Author(s) : Deng J , Guo J , Dai R , Zhang G , Xie H
Ref : J Pharm Biomed Anal , 117 :99 , 2015
Abstract : A lot of attention has been given to novel diabetes treatment, which is used to replace injectable insulin. A novel dipeptidyl peptidase IV inhibitor (HWH-10d) for treating type 2 diabetes was previously determined to have comparable efficacy to the marketed drug (alogliptin) in ICR male mice. Therefore, a sensitive and rapid liquid chromatography-tandem mass spectrometric method was developed and validated for the further evaluation of HWH-10d in monkey. The analytes were extracted through a liquid-liquid extraction with ethyl acetate. The linear detection range for HWH-10d in monkey plasma was from 0.5 to 2000ng/mL with the lower limit of quantification of 0.5ng/mL. The relative standard deviation was measured to be less than 10.4% for determination of inter- and intra-day precisions, and the relative error was determined to be within +/-7.2% for all accuracy measurements. The simple and rapid LC-MS/MS method for HWH-10d in monkey plasma could be used for the pharmacokinetics studies of HWH-10d in monkeys. The oral bioavailability of HWH-10d in monkeys is 57.8%.
ESTHER : Deng_2015_J.Pharm.Biomed.Anal_117_99
PubMedSearch : Deng_2015_J.Pharm.Biomed.Anal_117_99
PubMedID: 26344384

Title : Complete genome sequence of Yersinia pestis strain 91001, an isolate avirulent to humans - Song_2004_DNA.Res_11_179
Author(s) : Song Y , Tong Z , Wang J , Wang L , Guo Z , Han Y , Zhang J , Pei D , Zhou D , Qin H , Pang X , Zhai J , Li M , Cui B , Qi Z , Jin L , Dai R , Chen F , Li S , Ye C , Du Z , Lin W , Yu J , Yang H , Huang P , Yang R
Ref : DNA Research , 11 :179 , 2004
Abstract : Genomics provides an unprecedented opportunity to probe in minute detail into the genomes of the world's most deadly pathogenic bacteria- Yersinia pestis. Here we report the complete genome sequence of Y. pestis strain 91001, a human-avirulent strain isolated from the rodent Brandt's vole-Microtus brandti. The genome of strain 91001 consists of one chromosome and four plasmids (pPCP1, pCD1, pMT1 and pCRY). The 9609-bp pPCP1 plasmid of strain 91001 is almost identical to the counterparts from reference strains (CO92 and KIM). There are 98 genes in the 70,159-bp range of plasmid pCD1. The 106,642-bp plasmid pMT1 has slightly different architecture compared with the reference ones. pCRY is a novel plasmid discovered in this work. It is 21,742 bp long and harbors a cryptic type IV secretory system. The chromosome of 91001 is 4,595,065 bp in length. Among the 4037 predicted genes, 141 are possible pseudo-genes. Due to the rearrangements mediated by insertion elements, the structure of the 91001 chromosome shows dramatic differences compared with CO92 and KIM. Based on the analysis of plasmids and chromosome architectures, pseudogene distribution, nitrate reduction negative mechanism and gene comparison, we conclude that strain 91001 and other strains isolated from M. brandti might have evolved from ancestral Y. pestis in a different lineage. The large genome fragment deletions in the 91001 chromosome and some pseudogenes may contribute to its unique nonpathogenicity to humans and host-specificity.
ESTHER : Song_2004_DNA.Res_11_179
PubMedSearch : Song_2004_DNA.Res_11_179
PubMedID: 15368893
Gene_locus related to this paper: yerpe-BIOH , yerpe-IRP1 , yerpe-PIP , yerpe-PLDB , yerpe-PTRB , yerpe-q8zey9 , yerpe-Y0644 , yerpe-y1616 , yerpe-y3224 , yerpe-YPLA , yerpe-YPO0180 , yerpe-YPO0667 , yerpe-YPO0773 , yerpe-YPO0776 , yerpe-YPO0986 , yerpe-YPO1501 , yerpe-YPO1997 , yerpe-YPO2002 , yerpe-YPO2336 , yerpe-YPO2526 , yerpe-YPO2638 , yerpe-YPO2814

Title : Genetics of metabolic variations between Yersinia pestis biovars and the proposal of a new biovar, microtus - Zhou_2004_J.Bacteriol_186_5147
Author(s) : Zhou D , Tong Z , Song Y , Han Y , Pei D , Pang X , Zhai J , Li M , Cui B , Qi Z , Jin L , Dai R , Du Z , Wang J , Guo Z , Huang P , Yang R
Ref : Journal of Bacteriology , 186 :5147 , 2004
Abstract : Yersinia pestis has been historically divided into three biovars: antiqua, mediaevalis, and orientalis. On the basis of this study, strains from Microtus-related plague foci are proposed to constitute a new biovar, microtus. Based on the ability to ferment glycerol and arabinose and to reduce nitrate, Y. pestis strains can be assigned to one of four biovars: antiqua (glycerol positive, arabinose positive, and nitrate positive), mediaevalis (glycerol positive, arabinose positive, and nitrate negative), orientalis (glycerol negative, arabinose positive, and nitrate positive), and microtus (glycerol positive, arabinose negative, and nitrate negative). A 93-bp in-frame deletion in glpD gene results in the glycerol-negative characteristic of biovar orientalis strains. Two kinds of point mutations in the napA gene may cause the nitrate reduction-negative characteristic in biovars mediaevalis and microtus, respectively. A 122-bp frameshift deletion in the araC gene may lead to the arabinose-negative phenotype of biovar microtus strains. Biovar microtus strains have a unique genomic profile of gene loss and pseudogene distribution, which most likely accounts for the human attenuation of this new biovar. Focused, hypothesis-based investigations on these specific genes will help delineate the determinants that enable this deadly pathogen to be virulent to humans and give insight into the evolution of Y. pestis and plague pathogenesis. Moreover, there may be the implications for development of biovar microtus strains as a potential vaccine.
ESTHER : Zhou_2004_J.Bacteriol_186_5147
PubMedSearch : Zhou_2004_J.Bacteriol_186_5147
PubMedID: 15262951
Gene_locus related to this paper: yerpe-YPLA