Celecoxib is an effective adjuvant therapy in the treatment of manic episodes (without psychotic features) of bipolar mood disorder. The mood-stabilizing role of the drug might be mediated via its action on the inflammatory cascade.
BackgroundWnt5A, which is a member of the non-transforming Wnt protein family, is implicated in inflammatory processes. It is also highly expressed by ovarian cancer cells. ROR2, which is a member of the Ror-family of receptor tyrosine kinases, acts as a receptor or co-receptor for Wnt5A. The Wnt5A–ROR2 signaling pathway plays essential roles in the migration and invasion of several types of tumor cell and influences their cell polarity. We investigated the modulation of Wnt5A–ROR2 by inflammatory mediators and its involvement in the migration of the human ovarian cancer cell line SKOV-3.MethodsSKOV-3 cells were treated with LPS (lipopolysaccharide), LTA (lipoteichoic acid) and recombinant human IL-6 alone or in combination with STAT3 inhibitor (S1155S31-201) or NF-kB inhibitor (BAY11-7082) for 4, 8, 12, 24 and 48 h. The Wnt5A and ROR2 expression levels were determined at the gene and protein levels. Cells were transfected with specific siRNA against Wnt5A in the absence or presence of human anti-ROR2 antibody and cell migration was assessed using transwells.ResultsThere was a strong downregulation of Wnt5A expression in the presence of STAT3 or NF-kB inhibitors. Cell stimulation with LTA or IL-6 for 8 h led to significantly increased levels of Wnt5A (5- and 3-fold higher, respectively). LPS, LTA or IL-6 treatment significantly increased ROR2 expression (2-fold after 48 h). LPS- or LTA-induced Wnt5A or ROR2 expression was abrogated in the presence of STAT3 inhibitor (p < 0.001). IL-6-induced Wnt5A expression was abrogated by both STAT3 and NF-kB inhibitors (p < 0.001). Although not significant, IL-6-induced ROR2 expression showed a modest decrease when STAT3 inhibitor was used. Moreover, cell migration was decreased by 80 % in siRNA Wnt5A-transfected cells in the presence of anti-human ROR2 antibody (p < 0.001).ConclusionsThis study revealed for the first time that inflammatory mediators modulate Wnt5A and ROR2 through NF-kB and STAT3 transcription factors and this may play a role in ovarian cancer cell migration. The results described here provide new insight into the role of the Wnt5A–ROR2 complex in ovarian cancer progression in relation to inflammation.
BACKGROUND AND OBJECTIVES:The prediction of in vitro fertilization (IVF) outcomes by anti-Müllerian hormone (AMH) measurement is getting increasing attention from clinicians. This study compares the relationship between serum or intrafollicular AMH levels and IVF outcomes in women with and without polycystic ovary syndrome (PCOS).METHODS:This prospective study was carried out in two university-based fertility clinics. Serum samples were collected on cycle day 3 and follicular fluid (FF) was collected on the day of oocyte retrieval from 26 women with PCOS and 42 normo-ovulatory controls. AMH levels were measured in the samples using immunoenzymatic assay. The relationship between serum or FF AMH levels and IVF outcomes, including number of oocytes retrieved, oocyte maturation rate, fertilization rate, implantation rate, high quality grade embryo rate, and biochemical and clinical pregnancy rates were further assessed.RESULTS:Median serum basal AMH and FF AMH levels were significantly higher in the PCOS group as compared to controls, the values being 14.2 ng/mL vs. 3.2 ng/mL (P<.001) and 8.2 ng/g protein vs. 4.7 ng/g protein (P<.01), respectively. In both groups, serum basal AMH levels showed a positive correlation with number of oocytes retrieved (r=0.323; P=.037 in control vs. r=0.529; P=.005 in PCOS). In the control group, there was a positive relationship between serum basal AMH levels and percentage of matured oocytes (r = 0.331; P=.032) and implantation rate (r=0.305; P=.05).CONCLUSION:Serum basal, and not intrafollicular, AMH levels may be a good predictive factor for quantitative and qualitative IVF outcomes in normo-ovulatory, but not in PCOS patients.
The purpose of this study was three fold: (1) to reveal the implications of Wnt5A for cytokine and chemokine production by human ovarian cancer cell line SKOV-3 cells, (2) to determine the influence of Wnt5A on chemotactic SKOV-3 cell migration, and (3) to assess the effect of inflammatory mediators on Wnt5A expression levels and to describe its underlying molecular mechanisms. A cytokine array was performed using a conditioned medium harvested from SKOV-3 cells transfected with specific siRNAs against Wnt5A or with scrambled siRNA and a transfection reagent alone as negative controls for 48 h. Chemotactic cell migration was performed using transwells. Inflammation-induced Wnt5A expression was determined by treating cells with recombinant human (rh) IL-1β, IFNβ, or TNFα alone or in combination with STAT3 and NF-κB inhibitors for different time durations. The cytokine array showed the suppression of GCSF, GM-CSF, IL-1α, IL-2, IL-13, and MCP-3 production, whereas cell RANTES and IL-7 showed increased levels in Wnt5A knock-down cells compared with those in controls. Chemotactic migration decreased significantly when the conditioned medium from Wnt5A knock-down cells was applied to the upper chamber of the transwell. Compared with the control, there were 30-fold and five-fold increases in Wnt5A mRNA levels in cells treated, with rhIL-1β and rhIFNβ, respectively after 8 h (P < 0.001). Compared with the control, TNF-α had a 1.8-fold increased levels of Wnt5A mRNA after 4 h (P < 0.01). Both NF-κB and STAT3 inhibitors decreased inflammation-induced Wnt5A expression. This study revealed a previously unrecognized immunomodulatory role of endogenous Wnt5A in ovarian cancer cells, which could further influence chemotactic cell migration.
Epilepsy is one of the most serious neurological problems, characterized by frequent spontaneous seizures. It is always accompanied with a multitude of difficulties, such as behavioural, cognitive, and psychiatric disturbances. 1,2 Temporal lobe epilepsy (TLE) is one of the most recognized kinds of epilepsy in humans.Abnormal structural changes in the hippocampus referred to as hippocampal sclerosis and neurodegeneration are associated with TLE. 3 Unilateral intrahippocampal administration of kainic acid provides a well-specified model of TLE, leading to oxidative damage and mitochondrial malfunction in brain tissue, especially in the limbic system 4 with subsequent development of devastating visuospatial memory loss. 5 Cognitive deficit, particularly learning and memory deterioration, is a major controversial issue and the most frequent neuropsychological feature in TLE patients. 6 Brain inflammation enhances neuronal excitability, promotes the development of seizures and is presumably related to the synaptic and
Wnt5A and receptor tyrosine kinase-like orphan receptor 2 (ROR2) proteins both regulate developmental processes, cell movement, and cell polarity. The purpose of this study was to evaluate a possible regulatory role of Wnt5A on ROR2 expression in human ovarian cancer cell lines. Moreover, the expression of Wnt5A and ROR2 mRNA and protein levels were assessed in human epithelial serous ovarian cancer (HSOC) specimens. ROR2 was strongly decreased in cells treated with siRNA against Wnt5A compared with scramble-treated or lipofectamine-treated cells (P < 0.001). There was 34% decreased cell invasion (P < 0.01) in Wnt5A knock-down cells compared with lipofectamine-treated and scramble-treated cells; however, cell invasion remained unchanged upon addition of anti-ROR2 antibody to the culture media of these cells. In contrast, addition of anti-ROR2 antibody to the culture media for lipofectamine-treated and scramble-treated cells led to 32% decreased cell invasion (P < 0.01). Normal ovarian specimens were negative, and variable immunostaining was observed in HSOC for Wnt5A and ROR2 immunostaining. Furthermore, there was a positive correlation between Wnt5A and ROR2 expression in high-grade SOC samples at the mRNA level (P < 0.05; r = 0.38). This is the first report to show the regulatory role of Wnt5A on ROR2 expression in ovarian cancer.
Serum basal T, AMH as well as their ratio and intrafollicular P4/AMH ratio may be used as predictors for retrieved oocyte number and their nuclear maturation rate, respectively.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.