scholarly journals Methylbenzoxime as a therapeutic agent for glucocorticoid-induced osteoporosis in rats

2021 ◽  
Vol 18 (3) ◽  
pp. 563-570
Author(s):  
Mingcong Ding ◽  
Pandeng Wei ◽  
Xuchang Hu ◽  
Tongqun Yang ◽  
Mingxuan Yang ◽  
...  
Keyword(s):  
Normal Control ◽  
Rat Model ◽  
Therapeutic Agent ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
In Vivo Studies ◽  
Type I ◽  
Treatment Groups ◽  
Wnt Signalling Pathway

Purpose: To investigate the effect of methylbenzoxime on dexamethasone-induced rat model of osteoporosis. Methods: Osteoporosis rat model was prepared by administration of dexamethasone to rats for sixty days. The rats were then divided into five groups of five animals each: normal control, untreated, and 2, 5 and 10 mg/kg treatment groups. All rats were administered dexamethasone for 60 days. Thereafter, rats in the three treatment groups received daily doses of 2, 5 or 10 mg/kg methylbenzoxime for 15 days, while rats in normal control and untreated groups were given equivalent volumes of normal saline in place of methylbenzoxime. After treatment, the rats were sacrificed, and the femur removed for histological assessment of pathological changes using H&E staining. Expressions of Wntn signalling pathway proteins in osteoblasts were assayed using reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot assays. Results: Methylbenzoxime inhibited osteoblast proliferation, as revealed from 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It increased the expression of osteoprotegerin and downregulated receptor activator for nuclear factor-kappa B ligand. Dexamethasone decreased the expression of Wnt signalling pathway proteins in osteoblasts. However, treatment of the dexamethasone-exposed osteoblasts with methylbenzoxime reversed the inhibition of expressions of Wnt signalling pathway proteins. In vivo studies showed that methylbenzoxime treatment mitigated dexamethasone-induced pathological features in femur. In osteoporotic rats, methylbenzoxime significantly up-regulated the expression of osteocalcin but down-regulated the level of collagen-type I fragments, relative to the untreated group. The effect was significant in the 5 and 10 mg/kg treatment groups, when compared with 2 mg/kg group. Conclusion: Methylbenzoxime prevents dexamethasone-induced osteoporosis in vitro and in rats. Therefore, it is a potential therapeutic agent for the management of osteoporosis.

scholarly journals The Wnt signalling pathway is upregulated in an in vitro model of acquired tamoxifen resistant breast cancer

BMC Cancer ◽  
2013 ◽  
Vol 13 (1) ◽  
Author(s):  
Yan Ni Loh ◽  
Ellen L Hedditch ◽  
Laura A Baker ◽  
Eve Jary ◽  
Robyn L Ward ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Vitro Model ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Wnt Signalling Pathway ◽  
Tamoxifen Resistant ◽  
Vitro Model

scholarly journals MicroRNA-451 is downregulated in the follicular fluid of women with endometriosis and influences mouse and human embryonic potential

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Xiong Li ◽  
Wenbi Zhang ◽  
Jing Fu ◽  
Yan Xu ◽  
Ruihuan Gu ◽  
...  
Keyword(s):  
Follicular Fluid ◽  
Polymerase Chain Reaction Analysis ◽  
Fertilization Rate ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
University Hospital ◽  
Vitro Fertilization ◽  
Human Oocytes ◽  
Wnt Signalling Pathway

Abstract Background Previous work demonstrated that there are numerous miRNAs in human follicular fluids, some of which are associated with reproductive diseases. In the current study, we sought to determine whether microRNAs (miRNAs) in the follicular fluid (FF) are differentially expressed between women with and without endometriosis and to uncover the association of miRNAs with the oocyte and embryonic development potential. Methods FF was harvested from 30 women with endometriosis and 30 women without who underwent in vitro fertilization treatment at the University Hospital between February and December 2016. The FF samples were subjected to miRNA profiling and validation via quantitative reverse transcription polymerase chain reaction analysis. Mouse/human metaphase-I (MI) oocytes were harvested and micro-injected with an miR-451 inhibitor, and the effects of miR-451 knockdown on Wnt/WNT signalling genes were investigated. Results Oocyte number, fertilization rate, and number of available embryos were decreased significantly in women with endometriosis relative to those without endometriosis. Hsa-miR-451 in FF was downregulated in endometriosis patients relative to control subjects (P < 0.01). Moreover, the proportions of mouse/human MI oocytes that developed into 2-pronuclei (2PN), 2-cell, 8–10-cell and blastocyst-stage embryos were affected by miR-451 knockdown in mouse/human oocytes. Components of the Wnt signalling pathway were aberrantly expressed in the mouse/human oocytes and embryos in the miR-451 inhibitor-injected group. Conclusions miR-451 was downregulated in FF samples from endometriosis patients and was modestly effective in distinguishing endometriosis patients from non-endometriosis patients. miR-451 downregulation in mouse and human oocytes affected pre-implantation embryogenesis by suppressing the Wnt signalling pathway. This miRNA might serve as a novel biomarker of oocyte and embryo quality in assisted reproductive treatment.

scholarly journals Transcriptome Profiling of Toxoplasma gondii-Infected Human Cerebromicrovascular Endothelial Cell Response to Treatment with Monensin

2020 ◽  
Vol 8 (6) ◽  
pp. 842 ◽  
Author(s):  
Mohammad S. R. Harun ◽  
Mica Taylor ◽  
Xing-Quan Zhu ◽  
Hany M. Elsheikha
Keyword(s):  
Endothelial Cells ◽  
Toxoplasma Gondii ◽  
Protein Biosynthesis ◽  
Transcriptome Profiling ◽  
Global Gene Expression ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Response To Treatment ◽  
Wnt Signalling Pathway

Central to the progression of cerebral toxoplasmosis is the interaction of Toxoplasma gondii with the blood-brain barrier (BBB) endothelial cells. In the present work, we tested the hypothesis that inhibition of Wnt pathway signalling by the monovalent ionophore monensin reduces the growth of T. gondii infecting human brain microvascular endothelial cells (hBMECs) or microglial cells. The anti-parasitic effect of monensin (a Wnt signalling inhibitor) on the in vitro growth of T. gondii tachyzoites was investigated using two methods (Sulforhodamine B staining and microscopic parasite counting). The monensin inhibited T. gondii growth (50% inhibitory concentration [IC50] = 0.61 μM) with a selective index = 8.48 when tested against hBMECs (50% cytotoxic concentration [CC50] = 5.17 μM). However, IC50 of monensin was 4.13 μM with a SI = 13.82 when tested against microglia cells (CC50 = 57.08 μM), suggesting less sensitivity of microglia cells to monensin treatment. The effect of T. gondii on the integrity of the BBB was assessed by the transendothelial electrical resistance (TEER) assay using an in vitro human BBB model. The results showed that T. gondii infection significantly decreased hBMECs’ TEER resistance, which was rescued when cells were treated with 0.1 µM monensin, probably due to the anti-parasitic activity of monensin. We also investigated the host-targeted effects of 0.1 µM monensin on global gene expression in hBMECs with or without T. gondii infection. Treatment of hBMECs with monensin did not significantly influence the expression of genes involved in the Wnt signalling pathway, suggesting that although inhibition of the Wnt signalling pathway did not play a significant role in T. gondii infection of hBMECs, monensin was still effective in limiting the growth of T. gondii. On the contrary, monensin treatment downregulated pathways related to steroids, cholesterol and protein biosynthesis and their transport between endoplasmic reticulum and Golgi apparatus, and deregulated pathways related to cell cycle and DNA synthesis and repair mechanisms. These results provide new insight into the host-modulatory effect of monensin during T. gondii infection, which merits further investigation.

PCV2 inhibits the Wnt signalling pathway in vivo and in vitro

2020 ◽  
Vol 247 ◽  
pp. 108787
Author(s):  
Xuejiao Zhu ◽  
Libin Wen ◽  
Wei Wang ◽  
Qi Xiao ◽  
Bin Li ◽  
...  
Keyword(s):  
Wnt Signalling ◽  
Signalling Pathway ◽  
Wnt Signalling Pathway

GSK3 takes centre stage more than 20 years after its discovery

2001 ◽  
Vol 359 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Sheelagh FRAME ◽  
Philip COHEN
Keyword(s):  
Substrate Specificity ◽  
Therapeutic Potential ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Dimensional Structure ◽  
Entire Body ◽  
Wnt Signalling Pathway ◽  
Wnt Proteins

Identified originally as a regulator of glycogen metabolism, glycogen synthase kinase-3 (GSK3) is now a well-established component of the Wnt signalling pathway, which is essential for setting up the entire body pattern during embryonic development. It may also play important roles in protein synthesis, cell proliferation, cell differentiation, microtubule dynamics and cell motility by phosphorylating initiation factors, components of the cell-division cycle, transcription factors and proteins involved in microtubule function and cell adhesion. Generation of the mouse knockout of GSK3β, as well as studies in neurons, also suggest an important role in apoptosis. The substrate specificity of GSK3 is unusual in that efficient phosphorylation of many of its substrates requires the presence of another phosphorylated residue optimally located four amino acids C-terminal to the site of GSK3 phosphorylation. Recent experiments, including the elucidation of its three-dimensional structure, have enhanced our understanding of the molecular basis for the unique substrate specificity of GSK3. Insulin and growth factors inhibit GSK3 by triggering its phosphorylation, turning the N-terminus into a pseudosubstrate inhibitor that competes for binding with the ‘priming phosphate’ of substrates. In contrast, Wnt proteins inhibit GSK3 in a completely different way, by disrupting a multiprotein complex comprising GSK3 and its substrates in the Wnt signalling pathway, which do not appear to require a ‘priming phosphate’. These latest findings have generated an enormous amount of interest in the development of drugs that inhibit GSK3 and which may have therapeutic potential for the treatment of diabetes, stroke and Alzheimer's disease.

scholarly journals Wnt-signalling pathway in ovarian epithelial tumours: increased expression of β-catenin and GSK3β

2003 ◽  
Vol 89 (7) ◽  
pp. 1298-1304 ◽  
Author(s):  
K Rask ◽  
A Nilsson ◽  
M Brännström ◽  
P Carlsson ◽  
P Hellberg ◽  
...  
Keyword(s):  
Wnt Signalling ◽  
Signalling Pathway ◽  
Wnt Signalling Pathway ◽  
Epithelial Tumours

scholarly journals Swertiamarin Contributes to Glucose Homeostasis via Inhibition of Carbohydrate Metabolizing Enzymes

2017 ◽  
Vol 16 (4) ◽  
pp. 125 ◽  
Author(s):  
Javed Ahamad ◽  
Naila Hassan ◽  
Saima Amin ◽  
Showkat R. Mir
Keyword(s):  
Blood Glucose ◽  
Glucose Homeostasis ◽  
In Vivo Studies ◽  
Metabolizing Enzymes ◽  
Treatment Groups ◽  
Whole Plant ◽  
Peak Blood ◽  
Peak Blood Glucose

<strong>Objective:</strong> Swertiamarin is a common secoiridoid found among the members of Gentianaceae. The present study aimed to establish the effectiveness of swertiamarin in achieving glucose homeostasis via inhibition of carbohydrate metabolizing enzymes by in-vitro and in-vivo studies. <strong>Materials and methods:</strong> Swertiamarin was obtained from dried whole plant samples of <em>Enicostemma littorale</em> Blume chromatographic fractionation over the silica gel column. Its effect on carbohydrate metabolizing enzymes viz., α-amylase and α-glucosidase were evaluated at 0.15 to 10 mg/mL in-vitro. The results were supplemented by anti-hyperglycemic studies in carbohydrate challenged mice pretreated with swertiamarin at a dose of 20 mg/kg body weight orally. <strong>Results:</strong> Swertiamarin was effective in inhibiting α-amylase and α-glucosidase with IC<em>50</em> values of 1.29±0.25 mg/mL and 0.84±0.11 mg/mL, respectively. The studies in starch and sucrose challenged mice showed that swertiamarin effectively restricted the increase in the peak blood glucose level (BGL). The increase in peak BGL was 49 mg/dL and 57 mg/dL only in the treatment groups compared to 70 mg/dL and 80 mg/dL in untreated groups after 30 min in starch and sucrose-fed mice, respectively. Acarbose (10 mg/kg b.w.) also produced significant (p&lt;0.01) blood glucose lowering response in both the models. <strong>Conclusion:</strong> Swertiamarin was effective in the achieving stricter glycemic control in carbohydrate challenged mice through the inhibition of carbohydrate metabolizing enzymes.

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