scholarly journals Oral administration of polystyrene microplastics for 2 weeks induces chronic constipation in ICR mice

2021 ◽  
Author(s):  
Yun Ju Choi ◽  
Jun Woo Park ◽  
Ji Eun Kim ◽  
Su Jin Lee ◽  
Jeong Eun Gong ◽  
...  
Keyword(s):  
Oral Administration ◽  
Signaling Pathway ◽  
Transverse Colon ◽  
Chronic Constipation ◽  
Molecular Mechanisms ◽  
Chloride Ion ◽  
Mucin Secretion ◽  
Icr Mice ◽  
Water Transportation ◽  
Gi Motility

Abstract Objective: Indirect evidence has determined the possibility that microplastics (MP) induce constipation, although direct scientific proof for constipation induction in animals remains unclear. Thus, this study is aimed to investigate whether oral administration of polystyrene MP causes constipation.Methods: An alteration in the constipation parameters and their molecular mechanisms was analyzed in ICR mice treated with 0.5 μm polystyrene (PS)-MP for 2 weeks. Results: Significant alterations in water consumption, stool weight, stool water contents, and stool morphology were detected in MP treated ICR mice, as compared to Vehicle treated group. Also, the gastrointestinal (GI) motility and intestinal length were decreased, while the histopathological structure and cytological structure of the transverse colon were remarkably altered in treated mice. Mice exposed to MP also showed a significant decrease in the GI hormone concentration, muscarinic acetylcholine receptors (mAChRs) expression and their downstream signaling pathway, as well as mucin secretion and transcription of the MUC1, MUC2 and Klf4 genes. Subsequent to MP treatment, concentrations of chloride ion and expressions of its channel (CFTR and CIC-2) were decreased, whereas expressions of AQP3 and 8 for water transportation were downregulated by activation of the MAPK/NF-kB signaling pathway. These regulation on water and chloride transportation were verified in intestinal epithelioid cell line (IEC18) after MP treatment. Conclusion: These results are the first to suggest that oral administration of PS-MP induces chronic constipation through the dysregulation of GI motility, mucin secretion, and chloride ion and water transportation in the transverse colon.

scholarly journals Novel Characterization of Constipation Phenotypes in ICR Mice Orally Administrated with Polystyrene Microplastics

2021 ◽  
Vol 22 (11) ◽  
pp. 5845
Author(s):  
Yun Ju Choi ◽  
Jun Woo Park ◽  
Ji Eun Kim ◽  
Su Jin Lee ◽  
Jeong Eun Gong ◽  
...  
Keyword(s):  
Oral Administration ◽  
Signaling Pathway ◽  
Indirect Evidence ◽  
Chloride Ion ◽  
Muscarinic Acetylcholine Receptors ◽  
Mitogen Activated Protein Kinase ◽  
Icr Mice ◽  
Water Transportation ◽  
Intestinal Length ◽  
Gi Motility

Indirect evidence has determined the possibility that microplastics (MP) induce constipation, although direct scientific proof for constipation induction in animals remains unclear. To investigate whether oral administration of polystyrene (PS)-MP causes constipation, an alteration in the constipation parameters and mechanisms was analyzed in ICR mice, treated with 0.5 μm PS-MP for 2 weeks. Significant alterations in water consumption, stool weight, stool water contents, and stool morphology were detected in MP treated ICR mice, as compared to Vehicle treated group. Also, the gastrointestinal (GI) motility and intestinal length were decreased, while the histopathological structure and cytological structure of the mid colon were remarkably altered in treated mice. Mice exposed to MP also showed a significant decrease in the GI hormone concentration, muscarinic acetylcholine receptors (mAChRs) expression, and their downstream signaling pathway. Subsequent to MP treatment, concentrations of chloride ion and expressions of its channel (CFTR and CIC-2) were decreased, whereas expressions of aquaporin (AQP)3 and 8 for water transportation were downregulated by activation of the mitogen-activated protein kinase (MAPK)/nuclear factor (NF)-κB signaling pathway. These results are the first to suggest that oral administration of PS-MP induces chronic constipation through the dysregulation of GI motility, mucin secretion, and chloride ion and water transportation in the mid colon.

Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells

2020 ◽  
Vol 20 (6) ◽  
pp. 734-750
Author(s):  
Wallax A.S. Ferreira ◽  
Rommel R. Burbano ◽  
Claudia do Ó. Pessoa ◽  
Maria L. Harada ◽  
Bárbara do Nascimento Borges ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Glioma Cell ◽  
Molecular Mechanisms ◽  
Glioma Cells ◽  
Dependent Manner ◽  
M Cell ◽  
Trypan Blue Exclusion ◽  
Cycle Arrest

Background: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown. Objective: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines. Methods: The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect of pisosterol on the distribution of the cells in the cell cycle was performed by flow cytometry. The expression and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite sequencing PCR (BSP-PCR). Results: Here, it has been reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53. Conclusions: It has been, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggests that this compound might be a promising anticancer candidate for further investigation.

scholarly journals A systems biology model of junctional localization and downstream signaling of the Ang–Tie signaling pathway

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yu Zhang ◽  
Christopher D. Kontos ◽  
Brian H. Annex ◽  
Aleksander S. Popel
Keyword(s):  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Reaction Network ◽  
Vascular Growth ◽  
Downstream Signaling ◽  
Signaling Axis ◽  
Agonistic Activity ◽  
Molecular Regulatory Mechanisms

AbstractThe Ang–Tie signaling pathway is an important vascular signaling pathway regulating vascular growth and stability. Dysregulation in the pathway is associated with vascular dysfunction and numerous diseases that involve abnormal vascular permeability and endothelial cell inflammation. The understanding of the molecular mechanisms of the Ang–Tie pathway has been limited due to the complex reaction network formed by the ligands, receptors, and molecular regulatory mechanisms. In this study, we developed a mechanistic computational model of the Ang–Tie signaling pathway validated against experimental data. The model captures and reproduces the experimentally observed junctional localization and downstream signaling of the Ang–Tie signaling axis, as well as the time-dependent role of receptor Tie1. The model predicts that Tie1 modulates Tie2’s response to the context-dependent agonist Ang2 by junctional interactions. Furthermore, modulation of Tie1’s junctional localization, inhibition of Tie2 extracellular domain cleavage, and inhibition of VE-PTP are identified as potential molecular strategies for potentiating Ang2’s agonistic activity and rescuing Tie2 signaling in inflammatory endothelial cells.

scholarly journals Activation of PI3K/Akt Signaling Pathway in Rat Hypothalamus Induced by an Acute Oral Administration of D-Pinitol

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2268
Author(s):  
Dina Medina-Vera ◽  
Juan Antonio Navarro ◽  
Rubén Tovar ◽  
Cristina Rosell-Valle ◽  
Alfonso Gutiérrez-Adan ◽  
...  
Keyword(s):  
Oral Administration ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Insulin Response ◽  
Pharmacological Action ◽  
Akt Signaling ◽  
Insulin Signaling Pathway ◽  
Acute Administration ◽  
Insulin Sensitizer ◽  
Peripheral Tissues

D-Pinitol (DPIN) is a natural occurring inositol capable of activating the insulin pathway in peripheral tissues, whereas this has not been thoroughly studied in the central nervous system. The present study assessed the potential regulatory effects of DPIN on the hypothalamic insulin signaling pathway. To this end we investigated the Phosphatidylinositol-3-kinase (PI3K)/Protein Kinase B (Akt) signaling cascade in a rat model following oral administration of DPIN. The PI3K/Akt-associated proteins were quantified by Western blot in terms of phosphorylation and total expression. Results indicate that the acute administration of DPIN induced time-dependent phosphorylation of PI3K/Akt and its related substrates within the hypothalamus, indicating an activation of the insulin signaling pathway. This profile is consistent with DPIN as an insulin sensitizer since we also found a decrease in the circulating concentration of this hormone. Overall, the present study shows the pharmacological action of DPIN in the hypothalamus through the PI3K/Akt pathway when giving in fasted animals. These findings suggest that DPIN might be a candidate to treat brain insulin-resistance associated disorders by activating insulin response beyond the insulin receptor.

scholarly journals DNA methylation mediated RSPO2 to promote follicular development in mammals

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Xiaofeng Zhou ◽  
Yingting He ◽  
Nian Li ◽  
Guofeng Bai ◽  
Xiangchun Pan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Methylation Level ◽  
Molecular Mechanisms ◽  
Cpg Island ◽  
Wnt Signaling Pathway ◽  
Follicular Development ◽  
Expression Level

AbstractIn female mammals, the proliferation, apoptosis, and estradiol-17β (E2) secretion of granulosa cells (GCs) have come to decide the fate of follicles. DNA methylation and RSPO2 gene of Wnt signaling pathway have been reported to involve in the survival of GCs and follicular development. However, the molecular mechanisms for how DNA methylation regulates the expression of RSPO2 and participates in the follicular development are not clear. In this study, we found that the mRNA and protein levels of RSPO2 significantly increased during follicular development, but the DNA methylation level of RSPO2 promoter decreased gradually. Inhibition of DNA methylation or DNMT1 knockdown could decrease the methylation level of CpG island (CGI) in RSPO2 promoter and upregulate the expression level of RSPO2 in porcine GCs. The hypomethylation of −758/−749 and −563/−553 regions in RSPO2 promoter facilitated the occupancy of transcription factor E2F1 and promoted the transcriptional activity of RSPO2. Moreover, RSPO2 promoted the proliferation of GCs with increasing the expression level of PCNA, CDK1, and CCND1 and promoted the E2 secretion of GCs with increasing the expression level of CYP19A1 and HSD17B1 and inhibited the apoptosis of GCs with decreasing the expression level of Caspase3, cleaved Caspase3, cleaved Caspase8, cleaved Caspase9, cleaved PARP, and BAX. In addition, RSPO2 knockdown promoted the apoptosis of GCs, blocked the development of follicles, and delayed the onset of puberty with decreasing the expression level of Wnt signaling pathway-related genes (LGR4 and CTNNB1) in vivo. Taken together, the hypomethylation of −758/−749 and −563/−553 regions in RSPO2 promoter facilitated the occupancy of E2F1 and enhanced the transcription of RSPO2, which further promoted the proliferation and E2 secretion of GCs, inhibited the apoptosis of GCs, and ultimately ameliorated the development of follicles through Wnt signaling pathway. This study will provide useful information for further exploration on DNA-methylation-mediated RSPO2 pathway during follicular development.

scholarly journals Lactiplantibacillus plantarum as a Potential Adjuvant and Delivery System for the Development of SARS-CoV-2 Oral Vaccines

2021 ◽  
Vol 9 (4) ◽  
pp. 683
Author(s):  
Julio Villena ◽  
Chang Li ◽  
Maria Guadalupe Vizoso-Pinto ◽  
Jacinto Sacur ◽  
Linzhu Ren ◽  
...  
Keyword(s):  
Immune Responses ◽  
Oral Administration ◽  
Molecular Mechanisms ◽  
Spike Protein ◽  
Heterologous Proteins ◽  
Oral Vaccines ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Viral Antigens ◽  
Mucosal Infection

The most important characteristics regarding the mucosal infection and immune responses against the Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) as well as the current vaccines against coronavirus disease 2019 (COVID-19) in development or use are revised to emphasize the opportunity for lactic acid bacteria (LAB)-based vaccines to offer a valid alternative in the fight against this disease. In addition, this article revises the knowledge on: (a) the cellular and molecular mechanisms involved in the improvement of mucosal antiviral defenses by beneficial Lactiplantibacillus plantarum strains, (b) the systems for the expression of heterologous proteins in L. plantarum and (c) the successful expressions of viral antigens in L. plantarum that were capable of inducing protective immune responses in the gut and the respiratory tract after their oral administration. The ability of L. plantarum to express viral antigens, including the spike protein of SARS-CoV-2 and its capacity to differentially modulate the innate and adaptive immune responses in both the intestinal and respiratory mucosa after its oral administration, indicates the potential of this LAB to be used in the development of a mucosal COVID-19 vaccine.

Neuroprotective effect of NDEELNK from sea cucumber ovum against scopolamine-induced PC12 cells damage through enhancing energy metabolism and upregulation of PKA/BDNF/NGF signaling pathway

2021 ◽  
Author(s):  
Yue Zhao ◽  
Yifei Dong ◽  
Qi Ge ◽  
Pengbo Cui ◽  
Na Sun ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Signaling Pathway ◽  
Pc12 Cells ◽  
Sea Cucumber ◽  
Molecular Mechanisms ◽  
Neuroprotective Effect ◽  
Ngf Signaling ◽  
Neuroprotective Function

The aim of study was to evaluate the neuroprotective function of sea cucumber ovum peptides-derived NDEELNK and explore underlying molecular mechanisms. NDEELNK exerted neuroprotective effect by improving the acetylcholine (ACh)...

scholarly journals Neuron-specific activation of necroptosis signaling in multiple sclerosis cortical grey matter

2021 ◽  
Vol 141 (4) ◽  
pp. 585-604 ◽  
Author(s):  
Carmen Picon ◽  
Anusha Jayaraman ◽  
Rachel James ◽  
Catriona Beck ◽  
Patricia Gallego ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Signaling Pathway ◽  
Cortical Neurons ◽  
Grey Matter ◽  
Molecular Mechanisms ◽  
Fold Increase ◽  
Cell Types ◽  
Meningeal Inflammation ◽  
Cortical Grey Matter

AbstractSustained exposure to pro-inflammatory cytokines in the leptomeninges is thought to play a major role in the pathogenetic mechanisms leading to cortical pathology in multiple sclerosis (MS). Although the molecular mechanisms underlying neurodegeneration in the grey matter remain unclear, several lines of evidence suggest a prominent role for tumour necrosis factor (TNF). Using cortical grey matter tissue blocks from post-mortem brains from 28 secondary progressive MS subjects and ten non-neurological controls, we describe an increase in expression of multiple steps in the TNF/TNF receptor 1 signaling pathway leading to necroptosis, including the key proteins TNFR1, FADD, RIPK1, RIPK3 and MLKL. Activation of this pathway was indicated by the phosphorylation of RIPK3 and MLKL and the formation of protein oligomers characteristic of necrosomes. In contrast, caspase-8 dependent apoptotic signaling was decreased. Upregulation of necroptotic signaling occurred predominantly in macroneurons in cortical layers II–III, with little expression in other cell types. The presence of activated necroptotic proteins in neurons was increased in MS cases with prominent meningeal inflammation, with a 30-fold increase in phosphoMLKL+ neurons in layers I–III. The density of phosphoMLKL+ neurons correlated inversely with age at death, age at progression and disease duration. In vivo induction of chronically elevated TNF and INFγ levels in the CSF in a rat model via lentiviral transduction in the meninges, triggered inflammation and neurodegeneration in the underlying cortical grey matter that was associated with increased neuronal expression of TNFR1 and activated necroptotic signaling proteins. Exposure of cultured primary rat cortical neurons to TNF induced necroptosis when apoptosis was inhibited. Our data suggest that neurons in the MS cortex are dying via TNF/TNFR1 stimulated necroptosis rather than apoptosis, possibly initiated in part by chronic meningeal inflammation. Neuronal necroptosis represents a pathogenetic mechanism that is amenable to therapeutic intervention at several points in the signaling pathway.

scholarly journals The OsOXO2, OsOXO3 and OsOXO4 Positively Regulate Panicle Blast Resistance in Rice

Rice ◽  
2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jingfang Dong ◽  
Lian Zhou ◽  
Aiqing Feng ◽  
Shaohong Zhang ◽  
Hua Fu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Blast Resistance ◽  
Aba Signaling ◽  
Leaf Blast ◽  
Expression Levels ◽  
Panicle Blast ◽  
Localization Analysis ◽  
Sa Signaling

Abstract Background Although panicle blast is more destructive to yield loss than leaf blast in rice, the cloned genes that function in panicle blast resistance are still very limited and the molecular mechanisms underlying panicle blast resistance remain largely unknown. Results In the present study, we have confirmed that the three Oxalate oxidase (OXO) genes, OsOXO2, OsOXO3 and OsOXO4 from a blast-resistant cultivar BC10 function in panicle blast resistance in rice. The expression of OsOXO2, OsOXO3 and OsOXO4 were induced by panicle blast inoculation. Subcellular localization analysis revealed that the three OXO proteins are all localized in the nucleus and cytoplasm. Simultaneous silencing of OsOXO2, OsOXO3 and OsOXO4 decreased rice resistance to panicle blast, whereas the OsOXO2, OsOXO3 and OsOXO4 overexpression rice plants individually showed enhanced panicle blast resistance. More H2O2 and higher expression levels of PR genes were observed in the overexpressing plants than in the control plants, while the silencing plants exhibited less H2O2 and lower expression levels of PR genes compared to the control plants. Moreover, phytohormone treatment and the phytohormone signaling related gene expression analysis showed that panicle blast resistance mediated by the three OXO genes was associated with the activation of JA and ABA signaling pathways but suppression of SA signaling pathway. Conclusion OsOXO2, OsOXO3 and OsOXO4 positively regulate panicle blast resistance in rice. The OXO genes could modulate the accumulation of H2O2 and expression levels of PR gene in plants. Moreover, the OXO genes mediated panicle blast resistance could be regulated by ABA, SA and JA, and may be associated with the activation of JA and ABA signaling pathways but suppression of the SA signaling pathway.

Sign in / Sign up

Export Citation Format

Share Document