Loss of CYLD promotes cell invasion via ALK5 stabilization in oral squamous cell carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) has a very poor prognosis because of its highly invasive nature, and the 5-year survival rate has not changed appreciably for the past 30 years. Although cylindromatosis (CYLD), a deubiquitinating enzyme, is thought to be a potent tumour suppressor, its biological and clinical significance in OSCC is largely unknown. This study aimed to clarify the roles of CYLD in OSCC progression. Our immunohistochemical analyses revealed significantly reduced CYLD expression in invasive areas in OSCC tissues, whereas CYLD expression was conserved in normal epithelium and carcinoma in situ. Furthermore, downregulation of CYLD by siRNA led to acquisition of mesenchymal features and increased migratory and invasive properties in OSCC cells and HaCaT keratinocytes. It is interesting that CYLD knockdown promoted transforming growth factor-β (TGF-β) signalling by inducing stabilization of TGF-β receptor I (ALK5) in a cell autonomous fashion. In addition, the response to exogenous TGF-β stimulation was enhanced by CYLD downregulation. The invasive phenotypes induced by CYLD knockdown were completely blocked by an ALK5 inhibitor. In addition, lower expression of CYLD was significantly associated with the clinical features of deep invasion and poor overall survival, and also with increased phosphorylation of Smad3, which is an indicator of activation of TGF-β signalling in invasive OSCC. These findings suggest that downregulation of CYLD promotes invasion with mesenchymal transition via ALK5 stabilization in OSCC cells.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2j19ATp

EMS Artwork: Treating an inmate in cardiac arrest

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from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2Cb2kMX

Dexmedetomidine to Help Nerve Regeneration in a Rat Sciatic Nerve Injury Model

Background. Several studies have shown that dexmedetomidine (DXM), a selective α2-adrenoceptor agonist, also has neuroprotective effects. However, its effect on impaired peripheral nerve regeneration has not been studied. Materials and Methods. Forty-five Sprague-Dawley rats were randomly assigned to three groups: group 1 (control SHAM), group 2 (sciatic nerve injury + normal saline), and group 3 (sciatic nerve injury + DXM). The rats of group 3 were subdivided into the following three groups: DXM 0.5, 6, and 20 μg·kg−1 (groups 3A, 3B, and 3C, resp.). The sciatic nerve injury was assessed for nerve regeneration at 2 and 6 weeks. Results. There were no differences between groups 2 and 3 in their sciatic functional index (SFI) values or histological findings at 2 weeks postinjury. However, SFI differences were statistically significant at 6 weeks postinjury in group 3. The gross findings with H&E staining showed that the number of axons was higher in group 3 than in group 2. There was no histological difference according to the DXM concentration. Conclusion. The coincidental functional and histological assessment results of this study suggest that DXM for 6 weeks positively affects damaged peripheral nerves.

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Orthogonal Gyroexpansion in Möbius Gyrovector Spaces

We investigate the Möbius gyrovector spaces which are open balls centered at the origin in a real Hilbert space with the Möbius addition, the Möbius scalar multiplication, and the Poincaré metric introduced by Ungar. In particular, for an arbitrary point, we can easily obtain the unique closest point in any closed gyrovector subspace, by using the ordinary orthogonal decomposition. Further, we show that each element has the orthogonal gyroexpansion with respect to any orthogonal basis in a Möbius gyrovector space, which is similar to each element in a Hilbert space having the orthogonal expansion with respect to any orthonormal basis. Moreover, we present a concrete procedure to calculate the gyrocoefficients of the orthogonal gyroexpansion.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2iYEDPB

A Novel Surrogate Safety Indicator Based on Constant Initial Acceleration and Reaction Time Assumption

The development of surrogate safety measures has drawn significant research interest in the field of traffic safety analysis. Innovative data sources such as video-based traffic surveillance systems have made it possible to collect large amounts of microscopic traffic data. By deriving traffic safety indicators such as the Deceleration Rate to Avoid a Crash (DRAC) statements concerning traffic safety over a determined road section can be made. This work presents the derivation of a novel surrogate safety indicator based on a Constant Initial Acceleration and reaction time assumption which considers the interaction between vehicles and describes the traffic safety of a road section. The evaluation is based on a video-based microscopic traffic data collection. To examine the efficiency, the new developed indicator is compared to the original Deceleration Rate to Avoid a Crash (DRAC) and the modified indicator (MDRAC) which includes the reaction time. The results showed that the new indicator is more sensitive in detecting critical situations than the other indicators and in addition describes the conflict situations more realistically.

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A 4-Week Repeated-Dose Oral Toxicity Study of Bojungikgi-Tang in Crl:CD Sprague Dawley Rats

Traditional herbal medicines have been used for centuries in Asian countries. However, recent studies have led to increasing concerns about the safety and toxicity of herbal prescriptions. Bojungikgi-tang (BJIGT), a herbal decoction, has been used in Korea to improve physical strength. To establish the safety information, BJIGT water extract was evaluated in a 4-week repeated-dose oral toxicity test in Crl:CD Sprague Dawley rats. BJIGT was orally administered in daily doses of 0, 500, 1000, and 2000 mg/kg/day for 4 weeks via oral gavage in male and female rats. We examined the mortality, clinical signs, body weight change, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters. No significant changes were observed in mortality, clinical sings, body weight, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters between the control group and the BJIGT-treated groups in the rats of both sexes. The results indicate that BJIGT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. Thus, this concentration is considered the nonobservable effect dose in rats and is appropriate for a 13-week subchronic toxicity study.

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Effect of Gonadotropin Types and Indications on Homologous Intrauterine Insemination Success: A Study from 1251 Cycles and a Review of the Literature

Objective. To evaluate the IUI success factors relative to controlled ovarian stimulation (COS) and infertility type, this retrospective cohort study included 1251 couples undergoing homologous IUI. Results. We achieved 13% clinical pregnancies and 11% live births. COS and infertility type do not have significant effect on IUI clinical outcomes with unstable intervention of various couples' parameters, including the female age, the IUI attempt rank, and the sperm quality. Conclusion. Further, the COS used seemed a weak predictor for IUI success; therefore, the indications need more discussion, especially in unexplained infertility cases involving various factors. Indeed, the fourth IUI attempt, the female age over 40 years, and the total motile sperm count

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2iZV3qZ