Nuclear factor I-C regulates E-cadherin via control of KLF4 in breast cancer

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Progression to metastasis is the leading cause of most cancer-related mortality; however, much remains to be understood about what facilitates the spread of tumor cells. In the present study, we describe a novel pathway in breast cancer that regulates epithelial-to-mesenchymal transition (EMT), motility, and invasiveness. Methods We examined nuclear factor I-C (NFI-C) expression in MCF10A human breast epithelial cells, MCF7 non-invasive breast cancer cells, and MDA-MB231 invasive breast cancer cells by real-time PCR and western blotting. To investigate the loss- and gain-function of NFI-C, we determined whether NFI-C regulated KLF4 expression by real-time PCR, western blotting, and promoter assay. To understand the biological functions of NFI-C, we observed cell invasion, migration, adhesion in human tumor cells by transwell assay, wound healing assay, quantitative RT-PCR, cell adhesion assay, western blotting, and immunohistochemistry. Results We identified the downstream factors of NFI-C, such as KLF4 and E-cadherin, which play roles in EMT. NFI-C is expressed in normal mammary gland or noninvasive breast cancer cells with epithelial characteristics. NFI-C overexpression induced expression of KLF4 and E-cadherin, but not Slug, in breast cancer cells. NFI-C bound directly to the KLF4 promoter and stimulated KLF4 transcriptional activity, thereby regulating E-cadherin expression during tumorigenesis. Cells overexpressing NFI-C maintained their epithelial differentiation status, which could drive mesenchymal-epithelial transition (MET) via the NFI-C-KLF4-E-cadherin axis in breast cancer cells. Consequently, NFI-C suppressed EMT, migration, and invasion in breast cancer cells. Conclusions Our study reveals a novel signaling pathway that is important during breast cancer tumorigenesis: the NFI-C-KLF4-E-cadherin pathway. The results indicate the important role of NFI-C in regulating KLF4 during tumorigenesis

Usefulness of fecal immunochemical test and fecal calprotectin for detection of active ulcerative colitis

Background/Aims Ulcerative colitis undergoes periods of exacerbation and remission. Fecal calprotectin levels increase with gut inflammation and correlate with endoscopic disease activity in ulcerative colitis. Intestinal blood loss and fecal immunochemical test levels also correlate with endoscopic disease activity. This study statistically evaluated the usefulness of fecal calprotectin, fecal immunochemical test, and C-reactive protein (CRP) as markers of disease activity. Methods A total 106 ulcerative colitis patients who underwent endoscopy and fecal calprotectin, fecal immunochemical test, and CRP testing, from March 2015 to August 2016, were retrospectively reviewed. Disease activity was assessed using a partial Mayo score and Mayo endoscopic score. The ability of fecal and serologic tests to reflect endoscopic disease severity was statistically evaluated. Results Among 106 patients, 68 underwent endoscopy and stool study within 2 weeks. In patients with mild to severe activity, fecal immunochemical test and fecal calprotectin were superior to CRP at Mayo endoscopic score detection rate. The area under the curves of fecal immunochemical test and fecal calprotectin for the detection of Mayo endoscopic score ≥1 were 0.956 and 0.942, respectively, and were superior to that of CRP (0.756). At Mayo endoscopic score, the effects of combination of fecal immunochemical test and CRP or fecal calprotectin and CRP were found to be higher than those of the independent fecal immunochemical test or fecal calprotectin. Conclusions Fecal immunochemical test and fecal calprotectin can effectively detect active ulcerative colitis better than remission. As these markers reflect the status of mucosal inflammation, they may reduce the requirement for invasive endoscopic examination

The Antidiabetic Drug Lobeglitazone Protects Mice From Lipogenesis-Induced Liver Injury via Mechanistic Target of Rapamycin Complex 1 Inhibition

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder closely linked with type II diabetes (T2D). The progression of NAFLD is associated with the induction of lipogenesis through hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. An increase in lipogenesis induces endoplasmic reticulum (ER) stress and accelerates oxidative liver injury in the pathogenesis of NAFLD. Lobeglitazone, one of thiazolidinediones (TZDs), is used as an antidiabetic drug to lower serum glucose level through an increase in insulin sensitivity. It is known to improve pathological symptoms in animals and humans with NAFLD. However, the underlying molecular mechanism of the protective effects of lobeglitazone against NAFLD has not been elucidated. Here, we show that under the physiological condition of acute lipogenesis, lobeglitazone inhibits hepatic lipid synthesis, the subsequent ER stress, and ω-oxidation of fatty acids by inhibiting the mTORC1 pathway. As a result, lobeglitazone protected mice from lipogenesis-induced oxidative liver injury. Taken together, lobeglitazone might be a suitable drug for the treatment of patients with diabetes and NAFLD

High-Intensity Focused Ultrasound Therapy Versus Coblation for the Treatment of Inferior Turbinate Hypertrophy: A Clinical Trial

Objectives To compare the efficacy and safety of high-intensity focused ultrasound (HIFU) therapy with coblation for the treatment of inferior turbinate hypertrophy (ITH). Methods In this randomized controlled clinical trial, 20 patients underwent inferior turbinate surgery, which consisted of either HIFU or coblation therapy. Efficacy, safety, and tolerability were evaluated by subjective symptom scores, acoustic rhinometry, and nasal endoscopy. Results The modified nasal obstruction symptom evaluation (NOSE) score and nasal obstruction visual analog scale (NO-VAS) significantly decreased in both groups 12 weeks postoperatively. The between-group differences in the evaluation scores were not statistically significant. On nasal endoscopy, the HIFU patients showed improvements in mucosal swelling sooner than the patients undergoing coblation therapy. Nasal crusting significantly increased in the patients undergoing coblation compared to the patients undergoing HIFU therapy until postoperative week 4. Mucosal preservation was superior in the HIFU patients. Although HIFU was less painful than coblation therapy during the procedure, the difference was not significant (4.9 vs. 6.3, P=0.143). The difference in global satisfaction between the two groups was not statistically significant, although satisfaction was slightly higher among the HIFU patients than among the coblation patients (4.6 vs. 4.1, P=0.393). Conclusion HIFU provided results similar to those of coblation therapy for patients with nasal obstruction due to ITH, but HIFU therapy caused less discomfort during the procedure. HIFU therapy appears to be a good noninvasive alternative to the current surgical modalities for ITH

The effecet of UNCL inactivation on the expression of mechanical stress related genes in cultured human PDL fibroblasts

A mutation of UNCL, an inner nuclear membrane RNAbinding protein, has been found to eliminate mechanotransduction in Drosophila. UNCL is expressed in human periodontal tissue including in periodontal ligament (PDL) fibroblasts. However, it is unclear how a mechanical stimulus is translated into cellular responses in PDL fibroblasts. The aim of this study was to evaluate the effect of UNCl on mechanical stress related genes in PDL fibroblasts in response to mechanical stress. The mRNA of TGF-β, COX-2, and MMP-2 was up-regulated after UNCL inactivation in PDL fibroblasts under the compression force. Under the tensile force, inactivation of UNCL decreased the expression of Biglycan, RANKL, MMP-2, and TIMP-2 mRNAs while it increased the expression of TIMP-1. p38-MAPK was expressed in PDL fibroblasts under compression forces whereas phospho-ERK1/2, p65- NFkB, and c-fos were expressed under tension forces. The expression and phosphorylation of the mechanical stress related genes, kinases, and transcription factors were changed according to the types of stress. Furthermore, most of them were regulated by the inactivation of UNCL. This suggests that UNCL is involved in the regulation of mechanical stress related genes through the signaling pathway in PDL fibroblasts

A Case of Infected Left Atrial Myxoma With Concomitant Mitral Valve Endocarditis

Myxoma is the most common primary tumor in the heart. Cardiac myxomas can present in various manners including embolization and fever, sometimes simulating endocarditis. However, they are rarely infected. We report here a case of an infected left atrial myxoma that seeded a normal mitral valve and atypically presented with multiple embolic events in the lower extremities along with multiple splenic and a cerebellar infarction

Successful Percutaneous Coronary Intervention for Acute Coronary Syndrome in a Patient With Severe Hemophilia A

Patients with hemophilia generally have a reduced frequency of coronary artery disease compared to the general population. As advances in the management of hemophilia have increased their life expectancy, the prevalence of coronary artery disease also has increased. However, there are no standard treatment guidelines for coronary artery disease in patients with hemophilia, especially in the field of coronary intervention. We report the case of a patient with severe hemophilia A who presented with acute coronary syndrome and was successfully treated with percutaneous coronary intervention

Multiple Sequential Complications After Sirolimus-Eluting Stent Implantation: Very Late Stent Thrombosis, Stent Fracture, In-Stent Restenosis, and Peri-Stent Aneurysm

A 55-year-old male patient presented with an acute myocardial infarction. A sirolimus-eluting stent (SES) was implanted in the proximal left anterior descending artery (LAD). Eight months later, there was a newly developed distal LAD lesion. An additional SES was implanted. Twenty-eight months after the index procedure of primary coronary intervention, the electrocardiogram showed ST elevation in the precordial leads and an emergency coronary angiogram showed diffuse stent thrombosis (ST) in the proximal LAD. Thirty-four months after the index procedure, coronary angiography showed a large peri-stent coronary aneurysm in the proximal LAD and focal in-stent restenosis (ISR) at the proximal edge of the distal LAD stent. On fluoroscopy, a fracture was noted in the middle part of the distal SES. A zotarolimus- eluting stent (ZES) was deployed and overlapped the restenosis and fracture sites. Forty months after the index procedure, there were no changes in the size of the aneurysm or in the other stent complications including the fracture and restenosis. At present, the patient has remained asymptomatic for eight months

Two-year Clinical Outcomes of Patients with Long Segments Drug-Eluting Stents: Comparison of Sirolimus-Eluting Stent with Paclitaxel-Eluting Stent

Limited data are available on the long-term clinical efficacy of drug-eluting stent (DES) in diffuse long lesions. From May 2006 to May 2007, a total of 335 consecutive patients (374 lesions) were underwent percutaneous coronary intervention with implantation of long DES (≥ 30 mm) in real world practice. Eight-month angiographic outcomes and 2-yr clinical outcomes were compared between SES (n = 218) and PES (n = 117). Study endpoints were major adverse cardiac events including cardiac death, myocardial infarction, target-lesion revascularization, target-vessel revascularization and stent thrombosis. Baseline characteristics were similar in the two groups as were mean stent length (44.9 ± 15.2 mm in SES and 47.4 ± 15.9 in PES, P = 0.121). Late loss at 8 months follow-up was significantly lower in SES than in PES group (0.4 ± 0.6 mm in SES vs 0.7 ± 0.8 mm in PES, P = 0.007). Mean follow-up duration was 849 ± 256 days, and 2-yr cumulative major adverse cardiac events were significantly lower in the SES than in the PES group (5.5% in SES vs 15.4% in PES, P = 0.003). In conclusion, long-term DES use in diffuse long coronary lesions is associated with favorable results, with SES being more effective and safer than PES in this real-world clinical experience