Effect of Neuroligin1 and Neurexin1 on the Colonic Motility in a Mouse Model of Neuronal Intestinal Dysplasia

Aim. To investigate the expressions of neuroligin1 (NL1) and neurexin1 (NX1) in a mouse model of neuronal intestinal dysplasia (Tlx2-/- mice) and to explore their effects on colonic motility. Methods. Immunohistochemistry staining was employed to explore the histological appearances of NL1, NX1, the presynaptic marker of glutamatergic synapses VGLUT1, and the subunit of NMDA receptors of NR1 in the colon of mice with or without Tlx2 mutation. Western blotting and qRT-PCR were performed to detect their relative expressions in the colon. Colonic motility was measured by a glass bead technique. Then, the Tlx2-/- mice were intervened by Huperzine A. Variations on expressions of NL1, NX1, VGLUT1, and NR1 and variations on colonic motility were measured. Additionally, serum concentrations of Glu were measured by ELISA. Results. Immunohistochemistry staining reveals that NL1, NX1, VGLUT1, and NR1 were mainly concentrated in the myenteric plexus of ENS. Compared to those in WT and Tlx2+/- mice, expressions of NL1 and NX1 in colon of Tlx2-/- mice were upregulated with increased VGLUT1 and NR1 abundances and impaired colonic motility (P<0.05). After intervention, the upregulated expressions of NL1 and NX1 were decreased with a correlated reduce of VGLUT1 and NR1 and a recovery of the impaired colonic motility (P<0.05). Variations of serum concentrations of Glu measured by ELISA were in concordance with the variations of glutamatergic synapses and colonic motility (P<0.05). Conclusion. NL1 and NX1 are closely related to the colonic motility through their effects of targeting the formation of glutamatergic synapses and may be involved in the pathogenesis of NID. The variations of serum Glu seem to be a potential and less painful auxiliary measure for colonic motility and NID.

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Neuroprotective and immunomodulatory effects of raloxifene in the myenteric plexus of a mouse model of Parkinson's disease

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2016.08.004 ◽

2016 ◽

Vol 48 ◽

pp. 61-71 ◽

Cited By ~ 10

Author(s):

Andrée-Anne Poirier ◽

Mélissa Côté ◽

Mélanie Bourque ◽

Marc Morissette ◽

Thérèse Di Paolo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mouse Model ◽

Myenteric Plexus ◽

Immunomodulatory Effects

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Global microarray profiling identifiedhsa_circ_0064428as a potential immune-associated prognosis biomarker for hepatocellular carcinoma

Journal of Medical Genetics ◽

10.1136/jmedgenet-2018-105440 ◽

2018 ◽

Vol 56 (1) ◽

pp. 32-38 ◽

Cited By ~ 16

Author(s):

Qiaoyou Weng ◽

Minjiang Chen ◽

Maoquan Li ◽

Yong-Fa Zheng ◽

Guoliang Shao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumour Size ◽

Differentially Expressed ◽

Circular Rnas ◽

Tissue Samples ◽

Qrt Pcr ◽

Immunohistochemistry Staining ◽

Microarray Profiling ◽

Spss Software ◽

Infiltrating Lymphocytes

BackgroundIncreasing evidence has shown that circular RNAs (circRNAs) are involved tumourigenesis and metastasis of hepatocellular carcinoma (HCC); however, progression about its function in HCC is relatively slow. Here, we aimed to investigate whether plasma circRNAs could reflect the tumour-infiltrating lymphocytes (TILs) in HCC tumour tissues and serve as prognosis biomarker for HCC.MethodsTissue samples of patients with HCC were subjected to immunohistochemistry staining against CD8 to examine the TILs. Then, we investigated the expression profile of circRNAs by microarray between plasma of patients with HCC with high TILs and low TILs, and the differentially expressed circRNAs were validated with qRT-PCR. Statistical analysis was performed with SPSS software and GraphPad Prism.ResultsWe have demonstrated that patients with HCC with high TILs exhibit a significant better overall survival, suggesting clinical outcome could be predicted by TILs. Global circRNA microarray between plasma of patients with HCC with high TILs and low TILs successfully identified six differentially expressed novel circRNAs. Among them, the expression ofhsa_circ_0064428was significantly reduced in patients with HCC with high TILs but increased in patients with low TILs. Moreover,hsa_circ_0064428was negatively correlated with patient’s survival, tumour size and metastasis.ConclusionThese findings together imply thathsa_circ_0064428could be considered as a potential HCC prognosis biomarker. Future in-depth research is required to further illustrate the involvement ofhsa_circ_0064428in HCC tumourigenesis and metastasis.

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Colonic electrical stimulation promotes colonic motility through regeneration of myenteric plexus neurons in slow transit constipation beagles

Bioscience Reports ◽

10.1042/bsr20182405 ◽

2019 ◽

Vol 39 (5) ◽

Cited By ~ 2

Author(s):

Yongbin Wang ◽

Qian Wang ◽

Kudelaidi Kuerban ◽

Mengxue Dong ◽

Feilong Qi ◽

...

Keyword(s):

Electron Microscopy ◽

Electrical Stimulation ◽

Western Blot ◽

Myenteric Plexus ◽

Pulse Train ◽

Colonic Motility ◽

Slow Transit Constipation ◽

Slow Transit ◽

Transit Constipation ◽

Colonic Electrical Stimulation

Abstract Slow transit constipation (STC) is a common disease characterized by markedly delayed colonic transit time as a result of colonic motility dysfunction. It is well established that STC is mostly caused by disorders of relevant nerves, especially the enteric nervous system (ENS). Colonic electrical stimulation (CES) has been regarded as a valuable alternative for the treatment of STC. However, little report focuses on the underlying nervous mechanism to normalize the delayed colonic emptying and relieve symptoms. In the present study, the therapeutic effect and the influence on ENS triggered by CES were investigated in STC beagles. The STC beagle model was established by oral administration of diphenoxylate/atropine and alosetron. Histopathology, electron microscopy, immunohistochemistry, Western blot analysis and immunofluorescence were used to evaluate the influence of pulse train CES on myenteric plexus neurons. After 5 weeks of treatment, CES could enhance the colonic electromyogram (EMG) signal to promote colonic motility, thereby improving the colonic content emptying of STC beagles. HE staining and transmission electron microscopy confirmed that CES could regenerate ganglia and synaptic vesicles in the myenteric plexus. Immunohistochemical staining showed that synaptophysin (SYP), protein gene product 9.5 (PGP9.5), cathepsin D (CAD) and S-100B in the colonic intramuscular layer were up-regulated by CES. Western blot analysis and immunofluorescence further proved that CES induced the protein expression of SYP and PGP9.5. Taken together, pulse train CES could induce the regeneration of myenteric plexus neurons, thereby promoting the colonic motility in STC beagles.

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Huperzine A Activates Wnt/β-Catenin Signaling and Enhances the Nonamyloidogenic Pathway in an Alzheimer Transgenic Mouse Model

Neuropsychopharmacology ◽

10.1038/npp.2010.245 ◽

2011 ◽

Vol 36 (5) ◽

pp. 1073-1089 ◽

Cited By ~ 47

Author(s):

Chun-Yan Wang ◽

Wei Zheng ◽

Tao Wang ◽

Jing-Wei Xie ◽

Si-Ling Wang ◽

...

Keyword(s):

Mouse Model ◽

Transgenic Mouse ◽

Transgenic Mouse Model ◽

Huperzine A

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RNA Sequencing Reveals Novel LncRNAs/mRNAs Network Associated with Puerarin-mediated Inhibition of Cardiac Hypertrophy in Mice

10.21203/rs.3.rs-788283/v1 ◽

2021 ◽

Author(s):

Shan Ye ◽

Wei-Yang Chen ◽

Caiwen Ou ◽

Min-Sheng Chen

Keyword(s):

Mouse Model ◽

Cardiac Hypertrophy ◽

Protective Effect ◽

Rna Sequencing ◽

Expression Patterns ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Biological Processes ◽

Rna Seq ◽

Qrt Pcr

Abstract Background: Evidence has demonstrated that puerarin is a potential drug for the treatment of cardiac hypertrophy. However, the precise underlying molecular mechanisms of the protective effect of puerarin are still unclear. Here, we aimed to explore the regulatory mechanisms of lncRNAs/mRNAs in a cardiac hypertrophy mouse model after puerarin treatment.Methods: A mouse model of cardiac hypertrophy was established by transverse aortic constriction (TAC). The echocardiography, tissue staining and western blot were used to examine the protective effect of puerarin. Then RNA sequencing (RNA-seq) was carried out to systematically analyze global gene expression. The target lncRNAs were confirmed using qRT-PCR. Moreover, a coding/non-coding gene co-expression (CNC) network was established to find the interaction of lncRNAs and mRNAs. The molecular functions, biological processes, molecular components and pathways of different expression mRNAs targeted by lncRNA were explored using Gene Ontology (GO) analysis and Kyto Encyclopedia of Genes and Genomes (KEGG) pathways analysis.Results: Puerarin exhibited obvious inhibitory effect in cardiac hypertrophy in TAC model. RNA-seq analysis was performed to investigate the lncRNAs and mRNAs expression patterns of cardiomyocytes in sham and TAC groups treated with or without puerarin. RNA-seq identified that TAC upregulated 19 lncRNAs and downregulated 18 lncRNAs, which could be revised by puerarin treatment (Fold change ≥ 3 and P< 0.05). Expression alterations of selected lncRNAs ENSMUST00000125726, ENSMUST00000143044 and ENSMUST00000212795 were confirmed by qRT-PCR. Pearson’s correlation coefficients of co-expression levels suggested that there was interactive relationship between those 3 validated altered lncRNAs and 5,500 mRNAs (r > 0.95 or r < −0.95). Those co-expressed mRNAs were enriched in some important biological processes such as vesicle-mediated transport, sin 3 complex, and translation initiation factor activity. KEGG analyses suggested that those lncRNA-interacted mRNAs were enriched in RNA transport, ribosome biogenesis in eukaryotes and proteasome signaling pathway. Conclusion: Puerarin may exert beneficial effects on cardiac hypertrophy through regulating the ENSMUST00000125726 /ENSMUST00000143044 / ENSMUST00000212795 -mRNAs network.

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Hirschsprung's disease

10.1093/med/9780198569862.003.0039 ◽

2011 ◽

Author(s):

R. Mark Beattie ◽

Anil Dhawan ◽

John W.L. Puntis

Keyword(s):

Myenteric Plexus ◽

High Frequency ◽

Hirschsprung's Disease ◽

Hirschsprung’S Disease ◽

Congenital Abnormalities ◽

Ganglion Cells ◽

Chromosome 10 ◽

Neuronal Intestinal Dysplasia ◽

Intestinal Pseudo Obstruction ◽

Hirschprung's Disease

Hirschprung's disease 280Neuronal intestinal dysplasia 281Intestinal pseudo-obstruction 281Hirschsprung's disease is the absence of ganglion cells in the myenteric plexus of the most distal bowel. Presentation is with constipation. Incidence is 1 in 5000. Long-segment Hirschsprung's disease is familial, with equal sex incidence. The gene is on chromosome 10. It is associated with Down's syndrome and there is a high frequency of other congenital abnormalities....

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The Effects of Dietary Glycine on the Acetic Acid-Induced Mouse Model of Colitis

Mediators of Inflammation ◽

10.1155/2020/5867627 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Xin Wu ◽

Yongmin Zheng ◽

Jie Ma ◽

Jie Yin ◽

Shuai Chen

Keyword(s):

Gene Expression ◽

Amino Acids ◽

Acetic Acid ◽

Amino Acid ◽

Mouse Model ◽

Intestinal Microbiota ◽

Intestinal Inflammation ◽

Serum Concentrations ◽

Intestinal Immunity ◽

Chronic Intestinal Inflammation

Inflammatory bowel disease, a gut disease that is prevalent worldwide, is characterized by chronic intestinal inflammation, such as colitis, and disorder of the gut microbiome. Glycine (Gly) is the simplest amino acid and functions as an anti-inflammatory immune-nutrient and intestinal microbiota regulator. This study aimed at investigating the effect of Gly on colitis induced in mice by intrarectal administration of 5% acetic acid (AA). Bodyweight and survival rates were monitored, and colonic length and weight, serum amino acid concentrations, intestinal inflammation-related gene expression, and colonic microbiota abundances were analyzed. The results showed that Gly dietary supplementation had no effect on the survival rate or the ratio of colonic length to weight. However, Gly supplementation reversed the AA-induced increase in serum concentrations of amino acids such as glutamate, leucine, isoleucine, and valine. Furthermore, Gly inhibited colonic gene expression of interleukin- (IL-) 1β and promoted IL-10 expression in colitis mice. Gly supplementation also reversed the AA-induced reduction in the abundance of bacteria such as Clostridia, Ruminococcaceae, and Clostridiales. This change in the intestinal microbiota was possibly attributable to the changes in colonic IL-10 expression and serum concentrations of valine and leucine. In sum, Gly supplementation regulated the serum concentrations of amino acids, the levels of colonic immune-associated gene expression, and the intestinal microbiota in a mouse model of colitis. These findings enhance our understanding of the role of Gly in regulating metabolism, intestinal immunity, and the gut microbiota in animals afflicted with colitis.

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Hydroxycitric Acid Inhibits Renal Calcium Oxalate Deposition by Reducing Oxidative Stress and Inflammation

Current Molecular Medicine ◽

10.2174/1566524020666200103141116 ◽

2020 ◽

Vol 20 (7) ◽

pp. 527-535 ◽

Cited By ~ 1

Author(s):

Xiao Liu ◽

Peng Yuan ◽

Xifeng Sun ◽

Zhiqiang Chen

Keyword(s):

Oxidative Stress ◽

Mouse Model ◽

Calcium Oxalate ◽

Tubular Injury ◽

Calcium Oxalate Crystals ◽

Calcium Oxalate Crystal ◽

Crystal Deposition ◽

Qrt Pcr ◽

Hydroxycitric Acid ◽

Oxalate Crystals

Objective: The study aimed to evaluate the preventive effects of hydroxycitric acid（HCA） for stone formation in the glyoxylate-induced mouse model. Materials and methods: Male C57BL/6J mice were divided into a control group, glyoxylate(GOX) 100 mg/kg group, a GOX+HCA 100 mg/kg group, and a GOX+HCA 200 mg/kg group. Blood samples and kidney samples were collected on the eighth day of the experiment. We used Pizzolato staining and a polarized light microscope to examine crystal formation and evaluated oxidative stress via the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the expression of monocyte chemotactic protein-1(MCP-1), nuclear factor-kappa B (NF κ B), interleukin-1 β (IL-1 β) and interleukin-6 (IL-6) messenger RNA (mRNA). The expression of osteopontin (OPN) and a cluster of differentiation-44(CD44) were detected by immunohistochemistry and qRT-PCR. In addition, periodic acid Schiff (PAS) staining and TUNEL assay were used to evaluate renal tubular injury and apoptosis. Results: HCA treatment could reduce markers of renal impairment (Blood Urea Nitrogen and serum creatinine). There was significantly less calcium oxalate crystal deposition in mice treated with HCA. Calcium oxalate crystals induced the production of reactive oxygen species and reduced the activity of antioxidant defense enzymes. HCA attenuated oxidative stress induced by calcium oxalate crystallization. HCA had inhibitory effects on calcium oxalate-induced inflammatory cytokines, such as MCP-1, IL- 1 β, and IL-6. In addition, HCA alleviated tubular injury and apoptosis caused by calcium oxalate crystals. Conclusion: HCA inhibits renal injury and calcium oxalate crystal deposition in the glyoxylate-induced mouse model through antioxidation and anti-inflammation.

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