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

Effects of Acupuncture, Electroacupuncture, and Electrostimulation Treatments on Plantaris by Casting Model

It is essential to seek the therapeutic strategy for attenuating muscle atrophy because muscle atrophy diminishes the quality of life. Acupuncture and electrostimulation have been used as a therapeutic intervention to control pain under pathological conditions. However, little is known about the effects of acupuncture and electrostimulation on skeletal muscle mass and function. PURPOSE: To test whether acupuncture, electroacupuncture, and electrostimulation affect muscle mass and contractile properties METHODS: Forty female Sprague Dawley rats were randomly divided into 5 groups: 1) Control (CON), 2) Cast (CT), 3) CT+ Acupuncture (AC), 4) CT+ Electroacupuncture (EA), and 5) CT+ Electrostimulation (ES) (n=8 each). The plaster casting material was wrapped from the trunk to the middle of one hind paw. Acupuncture and Electro-Acupuncture treatment (2-15 Hz, 2-4 Voltage) was applied by needling ST36 and GB34 (acupoints). Electrostimulation (2-15 Hz, 2-4 Voltage) was conducted by needling in the lateral and medial Gastrocnemius. All treatments were conducted 15 minutes with 3 times/wk for 14 days. Two major atrophy markers, muscle-specific E3 ubiquitin ligases, MAFbx/atrogin1 and muscle ring Finger -1 (MuRF1), were measured using the Western blot method. Data were analyzed using one-way ANOVA with the Least Significant Difference post hoc test. RESULTS: After 2 weeks of casting, plantaris showed significant atrophy in CT compared to the CON group (143.94±13.08 vs. 223.9±20.93 mg; p\u3c0.05). MAFbx/atrogin1 and MuRF1 were significantly increased with CT, while decreased with treatments (AC, EA, and ES). The peak twitch tension was significantly decreased in CT, while increased in AC and ES. However, AC, EA, ES did not alleviate muscle atrophy associated with casting. CONCLUSION: Acupuncture and electrostimulation can be used as effective therapeutic interventions for decreased muscle strength that is associated with casting-induced muscle atrophy

Probiotic properties and adsorption of Enterococcus faecalis PSCT3-7 to vermiculite

The probiotic properties of Enterococcus (E.) faecalis PSCT3-7, a new strain isolated from the intestines of pigs fed dietary fiber containing 50% sawdust, were investigated. E. faecalis PSCT3-7 tolerated a pH range of 3 to 8 and 0.3% bile salts, and it inhibited the growth of Salmonella Typhimurium in a concentration-dependent manner. In addition, E. faecalis showed resistance to several antibacterial agents. Vermiculite, a nutrient and microbial carrier, increased the bile tolerance of the strain. Scanning electron microscope images revealed good adsorption of E. faecalis PSCT3-7 onto vermiculite. E. faecalis PSCT3-7 represents a potential probiotic candidate to administer with vermiculite to swine

A Novel Selective Sphingosine Kinase 2 Inhibitor, HWG-35D, Ameliorates the Severity of Imiquimod-Induced Psoriasis Model by Blocking Th17 Differentiation of Naïve CD4 T Lymphocytes

Sphingosine kinases (SK) catalyze the phosphorylation of sphingosine to generate sphingosine-1-phosphate. Two isoforms of SK (SK1 and SK2) exist in mammals. Previously, we showed the beneficial effects of SK2 inhibition, using ABC294640, in a psoriasis mouse model. However, ABC294640 also induces the degradation of SK1 and dihydroceramide desaturase 1 (DES1). Considering these additional effects of ABC294640, we re-examined the efficacy of SK2 inhibition in an IMQ-induced psoriasis mouse model using a novel SK2 inhibitor, HWG-35D, which exhibits nM potency and 100-fold selectivity for SK2 over SK1. Topical application of HWG-35D ameliorated IMQ-induced skin lesions and normalized the serum interleukin-17A levels elevated by IMQ. Application of HWG-35D also decreased skin mRNA levels of interleukin-17A, K6 and K16 genes induced by IMQ. Consistent with the previous data using ABC294640, HWG-35D also blocked T helper type 17 differentiation of naive CD4+ T cells with concomitant reduction of SOCS1. Importantly, HWG-35D did not affect SK1 or DES1 expression levels. These results reaffirm an important role of SK2 in the T helper type 17 response and suggest that highly selective and potent SK2 inhibitors such as HWG-35D might be of therapeutic use for the treatment of psoriasis

Effects of Continuous Positive Airway Pressure on White Matter Microstructure in Patients With Obstructive Sleep Apnea

Background and Objective Obstructive sleep apnea (OSA) has significant effects on quality of life and may lead to cognitive impairments. Continuous positive airway pressure (CPAP) is the standard treatment for OSA and has been shown to improve sleep disturbances and daytime dysfunction. In this study, we aimed to assess the effects of CPAP on white matter (WM) integrity using longitudinal diffusion tensor imaging (DTI) tests. Methods Twenty-two male patients with moderate to severe OSA were recruited, and thepatients underwent DTI scanning before and 6–44 months after CPAP treatment. Sixteen male patients with untreated OSA who were not compliant with CPAP were included as a reference group. We compared the functional anisotropy (FA) values between baseline and follow-up magnetic resonance imaging in both the CPAP and untreated groups using tract-specific statistical analysis (TSSA) method. Results The TSSA analysis showed that FA values in the middle part of the right corticospinal tract were increased after treatment in the CPAP group. In the untreated group, no significant change in FA value was observed between baseline and follow-up. In the CPAP group, the post-treatment FA value in the anterior part of the right anterior thalamic radiation was significantly correlated with the duration of CPAP therapy, after controlling for age, body mass index, and baseline FA value. Conclusions Our study suggests that long-term CPAP treatment could gradually reverse OSA-induced injury to the WM microstructure, particularly WM associated with the motor and limbic systems. The study findings provide new insights into the mechanisms of cognitive improvement after CPAP treatment in patients with OSA

Enhancement of angiogenic and vasculogenic potential of endothelial progenitor cells by haptoglobin

AbstractEndothelial progenitor cells (EPCs) were transfected with the haptoglobin (Hp) gene to investigate the effect of Hp on cell function. Hp potentiated the gene expression of various pro-angiogenic factors in the EPCs. The Hp-modified EPCs also increased in vitro tube formation on Matrigel compared with control cells. In hindlimb ischaemia models, Hp–EPCs showed a greater ability for improving blood perfusion and recovery from ischaemic injury. These results indicate that Hp improves EPC function in neovasculogenesis, which suggests that ex vivo modification of EPCs with the Hp gene can be applied to the treatment of vascular damage