Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells

<p>Abstract</p> <p>Background</p> <p>β-catenin mutations that constitutively activate the canonical Wnt signaling have been observed in a subset of hepatocellular carcinomas (HCCs). These mutations are associated with chromosomal stability, low histological grade, low tumor invasion and better patient survival. We hypothesized that canonical Wnt signaling is selectively activated in well-differentiated, but repressed in poorly differentiated HCCs. To this aim, we characterized differentiation status of HCC cell lines and compared their expression status of Wnt pathway genes, and explored their activity of canonical Wnt signaling.</p> <p>Results</p> <p>We classified human HCC cell lines into "well-differentiated" and "poorly differentiated" subtypes, based on the expression of hepatocyte lineage, epithelial and mesenchymal markers. Poorly differentiated cell lines lost epithelial and hepatocyte lineage markers, and overexpressed mesenchymal markers. Also, they were highly motile and invasive. We compared the expression of 45 Wnt pathway genes between two subtypes. TCF1 and TCF4 factors, and LRP5 and LRP6 co-receptors were ubiquitously expressed. Likewise, six Frizzled receptors, and canonical Wnt3 ligand were expressed in both subtypes. In contrast, canonical ligand Wnt8b and noncanonical ligands Wnt4, Wnt5a, Wnt5b and Wnt7b were expressed selectively in well- and poorly differentiated cell lines, respectively. Canonical Wnt signaling activity, as tested by a TCF reporter assay was detected in 80% of well-differentiated, contrary to 14% of poorly differentiated cell lines. TCF activity generated by ectopic mutant β-catenin was weak in poorly differentiated SNU449 cell line, suggesting a repressive mechanism. We tested Wnt5a as a candidate antagonist. It strongly inhibited canonical Wnt signaling that is activated by mutant β-catenin in HCC cell lines.</p> <p>Conclusion</p> <p>Differential expression of Wnt ligands in HCC cells is associated with selective activation of canonical Wnt signaling in well-differentiated, and its repression in poorly differentiated cell lines. One potential mechanism of repression involved Wnt5a, acting as an antagonist of canonical Wnt signaling. Our observations support the hypothesis that Wnt pathway is selectively activated or repressed depending on differentiation status of HCC cells. We propose that canonical and noncanonical Wnt pathways have complementary roles in HCC, where the canonical signaling contributes to tumor initiation, and noncanonical signaling to tumor progression.</p

Vitiligo in a Patient Treated with Interferon Alpha-2a for Behçet’s Disease

Behçet’s disease (BD) and vitiligo are diseases of unknown etiology. Interferon (IFN) alpha therapy is commonly used in Behçet uveitis. Interferon treatment in various diseases have also been observed causing certain autoimmune diseases such as vitiligo because of its immunomodulatory activity. The association between IFN therapy and vitiligo has been reported in the literature. We report a 21-year-old man with BD in whom vitiligo occurred during IFN treatment. To the best of our knowledge, this is the first reported case of such an association

Untreated depression in the first trimester of pregnancy leads to postpartum depression: high rates from a natural follow-up study

Conclusion: Untreated depression during pregnancy is an important predictor of postpartum depression. This natural follow-up study is important because it presents very striking rates of postpartum depression. Referral of patients with depression during pregnancy to psychiatric treatment should be provided and is strongly encouraged

The depression in women in pregnancy and postpartum period: A follow-up study

Conclusion: Depression rates are high in Eastern Turkey. Exposure to violence during pregnancy and the existence of a previous mental disorder were risk factors for perinatal depression in this study. Performing screening tests can identify women at risk of pregnancy-related depression. Prevention programs should be established in areas where the prevalence of depression is high

Clinical characteristics of intermediate uveitis in adult Turkish patients

<b>AIM:</b>To describe the clinical characteristics of Turkish patients with intermediate uveitis (IU) and to investigate the effect of clinical findings and complications on final visual acuity (VA).<b>METHODS:</b>We retrospectively analyzed the medical records of patients with IU who had at least 6mo of follow-up and were older than 16y<i>.</i><b>RESULTS:</b>A total of 78 eyes of 45 patients were included in the study and the mean follow-up period was 19.4mo. The mean age at the time of presentation was 42.9s. Systemic disease associations were found in 17.7% of cases; sarcoidosis (8.8%) and multiple sclerosis (6.6%) were the most common diseases. Recurrence rate (odds ratio=45.53; 95%CI:2.181-950.58), vitritis equals to or more than 3+ cells (odds ratio =57.456; 95%CI:4.154-794.79) and presenting with VA less than 20/40 (odds ratio =43.81; 95%CI:2.184-878.71) were also found as high risk factors for poor final VA. At the last follow-up examination, 67.9% of eyes had VA of 20/40 or better.<b>CONCLUSION:</b> IU is frequently seen at the beginning of the fourth decade of life. The disease is most commonly idiopathic in adult Turkish patients. Patients with severe vitritis at presentation and patients with frequent recurrences are at high risk for poor visual outcome

The COVID-19 from Neurological Overview

Elmali, Ayse Deniz/0000-0001-6380-9550; Afsar, Nazire/0000-0001-8123-8560; Sahin, Sevki/0000-0003-2016-9965;WOS: 000556540500002[No abstract available

Intravitreal bevacizumab for treatment of central serous chorioretinopathy

Purpose: To compare the outcomes of treatment with intravitreal bevacizumab (IVB) versus observation in central serous chorioretinopathy (CSCR). Methods: In a retrospective comparative study, records of 45 patients with CSCR were reviewed. Twenty-two patients received IVB (1.25 mg/0.05 ml) while 23 subjects were observed. All subjects underwent measurement of best corrected visual acuity (BCVA) and intraocular pressure (IOP), dilated fundus examination and optical coherence tomography (OCT) imaging at baseline and follow up visits. Outcome measures included central macular thickness (CMT) and BCVA in logarithm of minimum angle of resolution (logMAR) notations. Results: Mean age was 44.1 ± 9.3 (range: 24 to 64) years and mean follow-up period was 10.4 ± 11.2 (range: 3 to 43; median: 6) months. All patients demonstrated resolution of neurosensory detachment and improvement in visual acuity. At final visit, there was no significant difference in mean CMT between the IVB and observation groups (275 vs 284 μm, P> 0.05). Mean baseline logMAR visual acuity was 0.38 ± 0.24 in the IVB group which improved to 0.24 ± 0.31 at final follow-up (P = 0.011); mean baseline logMAR visual acuity was 0.42 ± 0.28 in the observation group and improved to 0.12 ± 0.18 (P = 0.001). Visual improvement was more marked in the observation group (0.30 vs 0.14 logMAR, P< 0.05) and mean final visual acuity was also significantly better (P = 0.05). Conclusion: There was no significant difference between IVB injection and observation in terms of anatomical outcomes of treatment for CSCR. In terms of visual outcomes, observation was superior to IVB injection