scholarly journals Maren Pills Improve Constipation via Regulating AQP3 and NF-κB Signaling Pathway in Slow Transit Constipation In Vitro and In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yu Zhan ◽  
Xuegui Tang ◽  
Hong Xu ◽  
Shiyu Tang
Keyword(s):  
Signaling Pathway ◽  
Vital Role ◽  
Slow Transit Constipation ◽  
Dependent Manner ◽  
Water Metabolism ◽  
Laxative Effect ◽  
Irritable Bowel ◽  
Ht 29

Background. Maren pills have been used to treat constipation. Aquaporin 3 (AQP3) plays a vital role in regulating water transfer in the colon. It has been reported that the downregulation of AQP3 can regulate liquid water metabolism and intestinal permeability in irritable bowel syndrome (IBS) rats’ colon via NF-κB pathway. In this study, we investigated whether the laxative effect of Maren pills is associated with the regulation of AQP3 and NF-κB signaling pathway in the colon. Methods. The compound diphenoxylate suspension-induced STC rats received Maren pills intragastrically for 1 consecutive week to evaluate the laxative effect of Maren pills involving the regulation of AQP3 and NF-κB signaling pathway. Moreover, human intestinal epithelial cells (HT-29) were treated with drug serum to obtain in vitro data. Results. Our results revealed that treatment with Maren pills increased the stool number, moisture content of feces, and intestinal transit rate in a dose-dependent manner. Maren pills significantly increased the AQP3, fibrosis transmembrane conductance regulator (CFTR), and protein kinase A (PKA) proteins in the colon of rats and in HT-29 cells. Mechanistically, Maren pills obviously inhibited the activation of NF-κB pathway in the colon of rats and in HT-29 cells. Conclusion. These results suggest that the laxative effect of Maren pills is associated with the increased expression of AQP3 by downregulating NF-κB signal pathway.

Hyperglycemia Promotes Pancreatic Cancer Initiation and Progression by Activating the Wnt/β-Catenin Signaling Pathway

2021 ◽  
Vol 21 ◽  
Author(s):  
Huiming Chen ◽  
Junfeng Zhao ◽  
Ningning Jiang ◽  
Zheng Wang ◽  
Chang Liu
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Precancerous Lesions ◽  
Clinical Specimen ◽  
Ductal Adenocarcinoma ◽  
Dependent Manner ◽  
Pancreatic Cancer Cells ◽  
Cancer Initiation

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, with a 5-year survival rate of less than 10% because of the limited knowledge of tumor-promoting factors and their underlying mechanism. Diabetes mellitus (DM) and hyperglycemia are risk factors for many cancers, including PDAC, that modulate multiple downstream signaling pathways, such as the wingless/integrated (Wnt)/β-catenin signaling pathway. However, whether hyperglycemia promotes PDAC initiation and progression by activating the Wnt/β-catenin signaling pathway remains unclear. Methods: In this study, we used bioinformatics analysis and clinical specimen analysis to evaluate the activation states of the Wnt/βcatenin signaling pathway. In addition, colony formation assays, Transwell assays and wound-healing assays were used to evaluate the malignant biological behaviors of pancreatic cancer cells (PCs) under hyperglycemic conditions. To describe the effects of hyperglycemia and the Wnt/β-catenin signaling pathway on the initiation of PDAC, we used pancreatitis-driven pancreatic cancer initiation models in vivo and pancreatic acinar cell 3-dimensional culture in vitro. Results: Wnt/β-catenin signaling pathway-related molecules were overexpressed in PDAC tissues/cells and correlated with poor prognosis in PDAC patients. In addition, hyperglycemia exacerbated the abnormal activation of β-catenin in PDAC and enhanced the malignant biological behaviors of PCs in a Wnt/β-catenin signaling pathway-dependent manner. Indeed, hyperglycemia accelerated the formation of pancreatic precancerous lesions by activating the Wnt/β-catenin signaling pathway in vivo and in vitro. Conclusion: Hyperglycemia promotes pancreatic cancer initiation and progression by activating the Wnt/β-catenin signaling pathway.

Ulinastatin Activated The ERK5/Mer Signaling Pathway To Promote Macrophage Efferocytosis And Ameliorate Lung Inflammation

2021 ◽  
Author(s):  
Jinju Li ◽  
Rongge Shao ◽  
Qiuwen Xie ◽  
XueKe Du
Keyword(s):  
Lung Injury ◽  
Signaling Pathway ◽  
Lung Inflammation ◽  
Raw264.7 Cells ◽  
Inflammatory Factors ◽  
Inflammatory Factor ◽  
Dependent Manner ◽  
Anti Inflammatory

Abstract Purpose:Ulinastatin (UTI) is an endogenous protease inhibitor with potent anti-inflammatory, antioxidant and organ protective effects. The inhibitor has been reported to ameliorate inflammatory lung injury but precise mechanisms remain unclear. Methods: An in vivo model of lung injury has been constructed by intratracheal infusion of lipopolysaccharide (LPS). The number of neutrophils and the phagocytosis of apoptotic neutrophils were observed by Diff- Quick method. Lung injury was observed by HE staining .BALF cells were counted by hemocytometer and concentrations of protein plus inflammatory factors were measured with a BCA test kit. During in vitro experiments, RAW264.7 cells were pretreated with UTI (1000 and 5000U/ mL), stained with CellTrackerTM Green B0DIPYTM and HL60 cells added with UV-induced apoptosis and PKH26 Red staining. The expression of ERK5\Mer related proteins was detected by western blot and immunofluorescence.Results: An in vivo model of lung injury has been constructed by intratracheal infusion of lipopolysaccharide (LPS). UTI treatment enhanced the phagocytotic effect of mouse alveolar macrophages on neutrophils, alleviated lung lesions, decreased the pro-inflammatory factor and total protein content of BALF and increased levels of anti-inflammatory factors. in vitro experiments ，UTI enhanced the phagocytosis of apoptotic bodies by RAW264.7 cells in a dose-dependent manner. Increased expression levels of ERK5 and Mer by UTI were shown by Western blotting and immunofluorescence.Conclusions: UTI mediated the activation of the ERK5/Mer signaling pathway, enhanced phagocytosis of neutrophils by macrophages and improved lung inflammation. The current study indicates potential new clinical approaches for accelerating the recovery from lung inflammation.

scholarly journals Human milk oligosaccharides reduceEntamoeba histolyticaattachment and cytotoxicityin vitro

2012 ◽  
Vol 108 (10) ◽  
pp. 1839-1846 ◽  
Author(s):  
Evelyn Jantscher-Krenn ◽  
Tineke Lauwaet ◽  
Laura A. Bliss ◽  
Sharon L. Reed ◽  
Frances D. Gillin ◽  
...  
Keyword(s):  
Human Milk ◽  
Protozoan Parasite ◽  
Bacterial Attachment ◽  
Dependent Manner ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
Beneficial Effects ◽  
Ht 29

Human milk oligosaccharides (HMO), complex sugars that are highly abundant in breast milk, block viral and bacterial attachment to the infant's intestinal epithelium and lower the risk of infections. We hypothesised that HMO also prevent infections with the protozoan parasiteEntamoeba histolytica,as its major virulence factor is a lectin that facilitates parasite attachment and cytotoxicity and binds galactose (Gal) andN-acetyl-galactosamine. HMO contain Gal, are only minimally digested in the small intestine and reach the colon, the site ofE. histolyticainfection. The objective of the present study was to investigate whether HMO reduceE. histolyticaattachment and cytotoxicity. Ourin vitroresults show that physiological concentrations of isolated, pooled HMO detachE. histolyticaby more than 80 %. In addition, HMO rescueE. histolytica-induced destruction of human intestinal epithelial HT-29 cells in a dose-dependent manner. The cytoprotective effects were structure-specific. Lacto-N-tetraose with its terminal Gal rescued up to 80 % of the HT-29 cells, while HMO with fucose α1–2-linked to the terminal Gal had no effect. Galacto-oligosaccharides (GOS), which also contain terminal Gal and are currently added to infant formula to mimic some of the beneficial effects of HMO, completely abolishedE. histolyticaattachment and cytotoxicity at 8 mg/ml. Although our results need to be confirmedin vivo, they may provide one explanation for why breast-fed infants are at lower risk ofE. histolyticainfections. HMO and GOS are heat tolerant, stable, safe and in the case of GOS, inexpensive, which could make them valuable candidates as alternative preventive and therapeutic anti-amoebic agents.

Scutellarin Attenuates Human-Neutrophil-Elastase-Induced Mucus Production by Inhibiting the PKC-ERK Signaling Pathway in Vitro and in Vivo

2011 ◽  
Vol 39 (06) ◽  
pp. 1193-1206 ◽  
Author(s):  
De-Peng Jiang ◽  
Qi Li ◽  
Jie Yang ◽  
Juliy M. Perelman ◽  
Victor P. Kolosov ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Erk Signaling ◽  
Control Group ◽  
Human Neutrophil Elastase ◽  
Dependent Manner ◽  
Mucus Production

The aim of this study was to investigate the influence of scutellarin on mucus production induced by human neutrophil elastase (HNE) and the possible in vitro and in vivo mechanisms. To this purpose, cells were incubated with saline, scutellarin or gefitinib for 60 min and exposed to 0.1 μM HNE for 24 h. After being pretreated respectively with saline, scutellarin or gefitinib, rats were challenged intratracheally with HNE by means of nebulization for 30 days. The expression of mucin (MUC) 5AC, protein kinase C (PKC), and extracellular signal-regulated kinase 1/2 (ERK1/2) was assessed by ELISA, RT-PCR or Western blotting. The results showed that scutellarin inhibited MUC5AC mRNA and protein expressions induced by HNE in a concentration-dependent manner in vitro. In the in vivo model, scutellarin significantly attenuated MUC5AC mRNA expression and goblet cell hyperplasia in rats treated with HNE for 30 days, as well as decreased the phosporylation of PKC and ERK1/2 compared to the HNE control group. Therefore, our study showed that scutellarin could prevent mucus hypersecretion by inhibiting the PKC-ERK signaling pathway. Inhalation scutellarin may be valuable in the treatment of chronic inflammatory lung disease.

scholarly journals Effect of Total Flavones from Cuscuta Chinensis on Anti-Abortion via the MAPK Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Hai-wang Wu ◽  
Yi-hui Feng ◽  
Dong-ying Wang ◽  
Wei-yu Qiu ◽  
Qing-ying Yu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Prolactin Receptor ◽  
Chinese Herb ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Dependent Manner ◽  
Active Components ◽  
Cuscuta Chinensis

For centuries, the Chinese herb Cuscuta chinensis has been applied clinically for abortion prevention in traditional Chinese medicine (TCM). Total flavones extracted from Cuscuta chinensis (TFCC) are one of the active components in the herb and also display anti-abortion effect similar to the unprocessed material. However, how TFCC exerts the anti-abortion effect remains largely unknown. In this study, we aim at characterizing the anti-abortion effects of TFCC and its underlying molecular mechanism in vitro and in vivo using human primary decidua cells and a mifepristone-induced abortion model in rat, respectively. The damage to the decidua caused by mifepristone in vivo was reversed by TFCC treatment in a dosage-dependent manner. High dosage of TFCC significantly upregulated the expression of estrogen receptor (ER), progesterone receptor (PR), and prolactin receptor (PRLR) in decidua tissue but downregulated the expression of p-ERK. Furthermore, we detected higher level of p-ERK and p-p38 in primary decidua cells from spontaneous abortion while treatment by TFCC downregulated their expression. Our results suggest TFCC mediates its anti-abortion effect by interfering with MAPK signaling pathway.

scholarly journals Downregulation of Aquaporin 3 Mediated the Laxative Effect in the Rat Colon by a Purified Resin Glycoside Fraction from Pharbitis Semen

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Dongrong Zhu ◽  
Chen Chen ◽  
Lijuan Bai ◽  
Lingyi Kong ◽  
Jianguang Luo
Keyword(s):  
Rat Colon ◽  
Pharbitis Nil ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Resin Glycoside ◽  
Laxative Effect ◽  
Fecal Water ◽  
Cox 2 ◽  
Ht 29

Background. Pharbitis Semen, the seeds ofPharbitis nil, is widely used as a traditional purgative medicine in China, Korea, and Japan. This study investigated the laxative effects of a purified resin glycoside fraction obtained in our previous study from Pharbitis Semen in vivo and in vitro.Materials and Methods. After orally administering a purified resin glycoside fraction from Pharbitis Semen (RFP) to rats, the content of fecal water, AQP3, NF-κB, COX-2 expression, and the prostaglandin E2(PGE2) concentrations in the colon were examined. Moreover, human intestinal epithelial cells (HT-29) were used to investigate the mechanism of RFP decreasing the AQP3 expression.Results. Results obtained showed that treatment with RFP increased the feces excretion and fecal water content of rats in a dose-dependent manner. More interestingly, AQP3 expression was suppressed by RFP treatment both in the rat colons and in HT-29 cells, while the NF-κB pathway-mediated PGE2production was activated. Interestingly, pretreating rats with BAY-11-7082 (NF-κB inhibitor) or indomethacin (COX-2 inhibitor) and RFP neither induced diarrhea nor decreased the AQP3 expression in the colon.Conclusions. The purgative property of the purified resin glycoside fraction was attributed to NF-κB activation in the colon, which increased the COX-2-mediated secretion of PGE2. PGE2decreased AQP3 expression which inhibits water absorbed from the intestine to the blood vessel side, resulting in the laxative effect of RFP.

scholarly journals Lysophosphatidic acid suppresses endothelial cell CD36 expression and promotes angiogenesis via a PKD-1–dependent signaling pathway

Blood ◽  
2011 ◽  
Vol 117 (22) ◽  
pp. 6036-6045 ◽  
Author(s):  
Bin Ren ◽  
James Hale ◽  
Sowmya Srikanthan ◽  
Roy L. Silverstein
Keyword(s):  
Endothelial Cell ◽  
Signaling Pathway ◽  
Lysophosphatidic Acid ◽  
Malignant Tumors ◽  
Transcriptional Level ◽  
Dependent Manner ◽  
Down Regulation ◽  
Thrombospondin 1

Abstract In pathologic settings including retinal ischemia and malignant tumors, robust angiogenesis occurs despite the presence in the microenvironment of antiangiogenic proteins containing thrombospondin structural homology (TSR) domains. We hypothesized that antiangiogenesis mediated by TSR-containing proteins could be blunted by localized down-regulation of their cognate receptor on microvascular endothelial cells (MVECs), CD36. Through screening a panel of endothelial cell agonists, we found that lysophosphatidic acid (LPA) dramatically down-regulated CD36 surface expression on primary MVECs. LPA is a lipid-signaling mediator known to have proangiogenic activity, but the mechanisms are largely unknown. We observed that LPA caused CD36 down-regulation in a dose- and time-dependent manner and was long lasting. Down-regulation occurred at the transcriptional level via a signaling pathway involving specific LPA receptors and protein kinase D. LPA-induced MVEC CD36 repression significantly attenuated in vitro antiangiogenic responses to thrombospondin-1, including blockade of migration, tube formation, and VEGFR-2 signaling in response to fibroblast growth factor-2. In vivo relevance was demonstrated by showing that LPA abrogated thrombospondin-1–mediated inhibition of neovascularization of Matrigel plugs implanted in mice. Our data thus indicate that the proangiogenic mechanism of LPA may in part be via switching off the antiangiogenic switch mediated by TSR proteins and CD36.

scholarly journals Circ_0001367 inhibits glioma proliferation, migration and invasion by sponging miR-431 and thus regulating NRXN3

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Liang Liu ◽  
Peng Zhang ◽  
Xuchen Dong ◽  
Haoran Li ◽  
Suwen Li ◽  
...  
Keyword(s):  
Close Correlation ◽  
Underlying Mechanism ◽  
Vital Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Dependent Manner ◽  
Glioma Growth

AbstractMany studies have reported that circular RNAs play a vital role in the malignant progression of human cancers. However, the role and underlying mechanism of circRNAs in the development of gliomas have not been fully clarified. In this study, we found that circ_0001367 was downregulated in glioma tissues and showed a close correlation with glioma patient survival. Functional assays demonstrated that upregulation of circ_0001367 could suppress the proliferation, migration and invasion of glioma cells in vitro and inhibit glioma growth in vivo. Furthermore, bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation assay indicated that circ_0001367 can serve as a sponge for miR-431 and that miR-431 acts as an oncogene by regulating neurexin 3 (NRXN3). In addition, rescue experiments verified that circ_0001367 could regulate both the expression and function of NRXN3 in a miR-431-dependent manner. In conclusion, circ_0001367 functions as an suppressor in glioma by targeting the miR-431/NRXN3 axis and may be a promising therapeutic target against gliomas.

scholarly journals PSF functions as a repressor of hypoxia-induced angiogenesis by promoting mitochondrial function

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lijie Dong ◽  
Wenbo Li ◽  
Tingting Lin ◽  
Boshi Liu ◽  
Yaru Hong ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Cell Metabolism ◽  
Vital Role ◽  
Retinal Neovascularization ◽  
Vegf Expression ◽  
Oxygen Induced Retinopathy ◽  
Polypyrimidine Tract Binding Protein

Abstract Background Abnormal neovascularization is the most common cause of blindness, and hypoxia alters tissue metabolism, function, and morphology. HIF-1α, the transcriptional activator of VEGF, has intricate mechanisms of nuclear translocation and activation, but its signal termination mechanisms remain unclear. Methods We investigated the role of polypyrimidine tract-binding protein-associated splicing factor (PSF) in cellular energy production, migration, and proliferation by targeting HIF-1α in vivo and in vitro PSF plasmids were transfected with liposome 2000 transfection reagent. Young C57/BL6J mice were kept in a hyperoxia environment, followed by indoor air, resulting in oxygen-induced retinopathy. Oxygen-induced retinopathy (OIR) animals were randomly divided into three groups: OIR group, OIR + vector group (OIR cubs treated with rAAV vector) and OIR + PSF group (OIR cubs treated with rAAV-PSF). Age-matched C57/BL6J mice were used as controls and exposed to constant normoxic conditions. The animals were executed and their pupils were subjected to subsequent experiments. The metabolic spectrum was analyzed by Seahorse XFe96 flux analyzer, and OCR and extracellular acidification rate were quantified at the same time. Results PSF ameliorated retinal neovascularization and corrected abnormal VEGF expression in mice with oxygen-induced retinopathy and reduced intra-retinal neovascularization in Vldlr − / − mice. PSF reprogrammed mitochondrial bioenergetics and inhibited the transition of endothelial cells after hypoxia, suggesting its involvement in pathological angiogenesis.Ectopic PSF expression inhibited hypoxia-induced HIF-1α activation in the nucleus by recruiting Hakai to the PSF/HIF-1α complex, causing HIF-1α inhibition. PSF knockdown increased hypoxia-stimulated HIF-1α reactions. These hypoxia-dependent processes may play a vital role in cell metabolism, migration, and proliferation. Thus, PSF is a potential treatment target in neovascularization-associated ophthalmopathy. Conclusion This is the first study showing that PSF inhibits HIF-1α via recruitment of Hakai, modulates mitochondrial oxidation and glycolysis, and downregulates VEGF expression under hypoxia. We propose a new HIF-1 α/Hakai regulatory mechanism that may play a vital role in the pathogenesis of neovascularization in ophthalmopathy. PSF-Hakai–HIF-1α signaling pathway under hypoxia condition. Schematic diagram showing that the PSF-Hakai–HIF-1α signaling pathway. Under hypoxia condition, PSF-Hakai complex regulate HIF-1α signaling, thus inhibiting downstream target gene VEGF, cell metabolism and angiogenesis eventually.

scholarly journals Pentagalloylglucose Inhibits the Replication of Rabies Virus via Mediation of the miR-455/SOCS3/STAT3/IL-6 Pathway

2019 ◽  
Vol 93 (18) ◽  
Author(s):  
Zhongzhong Tu ◽  
Mengxian Xu ◽  
Jian Zhang ◽  
Ye Feng ◽  
Zhuo Hao ◽  
...  
Keyword(s):  
Viral Replication ◽  
Signaling Pathway ◽  
Rabies Virus ◽  
Antiviral Effect ◽  
Cytokine Signaling ◽  
Dependent Manner ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

ABSTRACT Our previous study showed that pentagalloylglucose (PGG), a naturally occurring hydrolyzable phenolic tannin, possesses significant anti-rabies virus (RABV) activity. In BHK-21 cells, RABV induced the overactivation of signal transducer and activator of transcription 3 (STAT3) by suppressing the expression of suppressor of cytokine signaling 3 (SOCS3). Inhibition of STAT3 by niclosamide, small interfering RNA, or exogenous expression of SOCS3 all significantly suppressed the replication of RABV. Additionally, RABV-induced upregulation of microRNA 455-5p (miR-455-5p) downregulated SOCS3 by directly binding to the 3′ untranslated region (UTR) of SOCS3. Importantly, PGG effectively reversed the expression of miR-455-5p and its following SOCS3/STAT3 signaling pathway. Finally, activated STAT3 elicited the expression of interleukin-6 (IL-6), thereby contributing to RABV-associated encephalomyelitis; however, PGG restored the level of IL-6 in vitro and in vivo in a SOCS3/STAT3-dependent manner. Altogether, these data identify a new miR-455-5p/SOCS3/STAT3 signaling pathway that contributes to viral replication and IL-6 production in RABV-infected cells, with PGG exerting its antiviral effect by inhibiting the production of miR-455-5p and the activation of STAT3. IMPORTANCE Rabies virus causes lethal encephalitis in mammals and poses a serious public health threat in many parts of the world. Numerous strategies have been explored to combat rabies; however, their efficacy has always been unsatisfactory. We previously reported a new drug, PGG, which possesses a potent inhibitory activity on RABV replication. Herein, we describe the underlying mechanisms by which PGG exerts its anti-RABV activity. Our results show that RABV induces overactivation of STAT3 in BHK-21 cells, which facilitates viral replication. Importantly, PGG effectively inhibits the activity of STAT3 by disrupting the expression of miR-455-5p and increases the level of SOCS3 by directly targeting the 3′ UTR of SOCS3. Furthermore, the downregulated STAT3 inhibits the production of IL-6, thereby contributing to a reduction in the inflammatory response in vivo. Our study indicates that PGG effectively inhibits the replication of RABV by the miR-455-5p/SOCS3/STAT3/IL-6-dependent pathway.

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