The Expression and Localization of N-Myc Downstream-Regulated Gene 1 in Human Trophoblasts

The protein N-Myc downstream-regulated gene 1 (NDRG1) is implicated in the regulation of cell proliferation, differentiation, and cellular stress response. NDRG1 is expressed in primary human trophoblasts, where it promotes cell viability and resistance to hypoxic injury. The mechanism of action of NDRG1 remains unknown. To gain further insight into the intracellular action of NDRG1, we analyzed the expression pattern and cellular localization of endogenous NDRG1 and transfected Myc-tagged NDRG1 in human trophoblasts exposed to diverse injuries. In standard conditions, NDRG1 was diffusely expressed in the cytoplasm at a low level. Hypoxia or the hypoxia mimetic cobalt chloride, but not serum deprivation, ultraviolet (UV) light, or ionizing radiation, induced the expression of NDRG1 in human trophoblasts and the redistribution of NDRG1 into the nucleus and cytoplasmic membranes associated with the endoplasmic reticulum (ER) and microtubules. Mutation of the phosphopantetheine attachment site (PPAS) within NDRG1 abrogated this pattern of redistribution. Our results shed new light on the impact of cell injury on NDRG1 expression patterns, and suggest that the PPAS domain plays a key role in NDRG1's subcellular distribution. © 2013 Shi et al

c-MET Protects Breast Cancer Cells from Apoptosis Induced by Sodium Butyrate

Sodium Butyrate (NaBu) is regarded as a potential reagent for cancer therapy. In this study, a specific breast cancer cell population that is resistant NaBu treatment was identified. These cells possess cancer stem cell characters, such as the capability of sphere formation in vitro and high tumor incident rate (85%) in mouse model. Forty percent of the NaBu resistant cells express the cancer stem cells marker, the CD133, whereas only 10% intact cells present the CD133 antigen. Furthermore, the endogenous expressing c-MET contributes to the survival of cancer stem cell population from the treatment of NaBu. The CD133+ group also presents a higher level of c-MET. A combination treatment of MET siRNA and NaBu efficiently prohibited the breast cancer progression, and the incident rate of the tumor decrease to 18%. This study may help to develop a new and alternative strategy for breast cancer therapy

Effect of combined treatment with alendronate and calcitriol on femoral neck strength in osteopenic rats

<p>Abstract</p> <p>Background</p> <p>Hip fracture is associated with pronounced morbidity and excess mortality in elderly women with postmenopausal osteoporosis. Many drugs have been developed to treat osteoporosis and to reduce the risk of osteoporotic fractures. We investigated the effects of combined alendronate and vitamin D₃treatment on bone mass and fracture load at the femoral neck in ovariectomized (OVX) rats, and evaluated the relationship between bone mass parameters and femoral neck strength.</p> <p>Methods</p> <p>Thirty 12-week-old female rats underwent either a sham-operation (n = 6) or OVX (n = 24). Twenty weeks later, OVX rats were further divided into four groups and received daily doses of either saline alone, 0.1 mg/kg alendronate, 0.1 μg/kg calcitriol, or a combination of both two drugs by continuous infusion via Alzet mini-osmotic pumps. The sham-control group received saline alone. After 12 weeks of treatment, femoral necks were examined using peripheral quantitative computed tomography (pQCT) densitometry and mechanical testing.</p> <p>Results</p> <p>Saline-treated OVX rats showed significant decreases in total bone mineral content (BMC) (by 28.1%), total bone mineral density (BMD) (by 9.5%), cortical BMC (by 26.3%), cancellous BMC (by 66.3%), cancellous BMD (by 29.0%) and total cross-sectional bone area (by 30.4%) compared with the sham-control group. The combined alendronate and calcitriol treatments improved bone loss owing to estrogen deficiency. On mechanical testing, although OVX significantly reduced bone strength of the femoral neck (by 29.3%) compared with the sham-control group, only the combined treatment significantly improved the fracture load at the femoral neck in OVX rats to the level of the sham-controls. The correlation of total BMC to fracture load was significant, but that of total BMD was not.</p> <p>Conclusion</p> <p>Our results showed that the combined treatment with alendronate and calcitriol significantly improved bone fragility of the femoral neck in OVX osteopenic rats.</p

Recapitulation of tumor heterogeneity and molecular signatures in a 3D brain cancer model with decreased sensitivity to histone deacetylase inhibition

INTRODUCTION Physiologically relevant pre-clinical ex vivo models recapitulating CNS tumor micro-environmental complexity will aid development of biologically-targeted agents. We present comprehensive characterization of tumor aggregates generated using the 3D Rotary Cell Culture System (RCCS). METHODS CNS cancer cell lines were grown in conventional 2D cultures and the RCCS and comparison with a cohort of 53 pediatric high grade gliomas conducted by genome wide gene expression and microRNA arrays, coupled with immunohistochemistry, ex vivo magnetic resonance spectroscopy and drug sensitivity evaluation using the histone deacetylase inhibitor, Vorinostat. RESULTS Macroscopic RCCS aggregates recapitulated the heterogeneous morphology of brain tumors with a distinct proliferating rim, necrotic core and oxygen tension gradient. Gene expression and microRNA analyses revealed significant differences with 3D expression intermediate to 2D cultures and primary brain tumors. Metabolic profiling revealed differential profiles, with an increase in tumor specific metabolites in 3D. To evaluate the potential of the RCCS as a drug testing tool, we determined the efficacy of Vorinostat against aggregates of U87 and KNS42 glioblastoma cells. Both lines demonstrated markedly reduced sensitivity when assaying in 3D culture conditions compared to classical 2D drug screen approaches. CONCLUSIONS Our comprehensive characterization demonstrates that 3D RCCS culture of high grade brain tumor cells has profound effects on the genetic, epigenetic and metabolic profiles of cultured cells, with these cells residing as an intermediate phenotype between that of 2D cultures and primary tumors. There is a discrepancy between 2D culture and tumor molecular profiles, and RCCS partially re-capitulates tissue specific features, allowing drug testing in a more relevant ex vivo system

Prediction of Elevated Temperature Fatigue Crack Growth Rates in TI-6AL-4V Alloy – Neural Network Approach

The results obtained from two experimental test programs (TP-1 and TP-2) were used to train neural networks to predict elevated temperature, fatigue crack growth rates in Ti-6Al-4V alloy. Two programs, TP-1 and TP-2, were conducted at room and elevated temperatures under high humidity and laboratory air environments, respectively. While elevated temperature effects were investigated in TP-2, stress ratio effects were studied in TP-1 using several stress ratios. Networks were trained using the elevated temperature data to predict the crack growth rates at a given stress intensity under different temperatures. The experimental and predicted fatigue crack growth rates showed a least squared error of 0.03. Thus, this approach was found to predict fatigue crack growth rates in Ti-6Al-4V alloy at elevated temperatures

Prediction of Elevated Temperature Fatigue Crack Growth Rates in TI-6AL-4V Alloy – Neural Network Approach

The results obtained from two experimental test programs (TP-1 and TP-2) were used to train neural networks to predict elevated temperature, fatigue crack growth rates in Ti-6Al-4V alloy. Two programs, TP-1 and TP-2, were conducted at room and elevated temperatures under high humidity and laboratory air environments, respectively. While elevated temperature effects were investigated in TP-2, stress ratio effects were studied in TP-1 using several stress ratios. Networks were trained using the elevated temperature data to predict the crack growth rates at a given stress intensity under different temperatures. The experimental and predicted fatigue crack growth rates showed a least squared error of 0.03. Thus, this approach was found to predict fatigue crack growth rates in Ti-6Al-4V alloy at elevated temperatures

Current situation and future prospects ofEchinococcus granulosusvaccine candidates: A systematic review

Cystic echinococcosis is a worldwide zoonotic disease, represents a threat for livestock and humans, manifests as a quiescent, subclinical and chronic hydatid cyst infection. The disease imposes high expenditures and economic losses in medical and veterinary. Prophylactic vaccination would be one of the effective preventive health care against echinococcosis. During the last decades, many studies have characterized the protective antigens ofEchinococcus granulosusand their role in immunization of various animal host species. Herein, we aimed to systematically evaluate and represent the best antigens as possible vaccine candidates for cystic echinococcosis. Data were systematically searched from five databases including ProQuest, PubMed, Scopus, ScienceDirect and Web of Science, up to 1 February 2020. Two reviewers independently screened and assessed data extraction and quality assessment. A total of 47 articles were eligible for inclusion criteria in the current study. The most common antigens used for vaccination againstE. granulosuswere EG95 and antigen B. Freund's adjuvant and Quil A have been predominantly utilized. In addition, regarding the antigen delivery, animal models, measurement of immune responses and reduction in hydatid cyst have been discussed in the text. The data demonstrated that DNA vaccines with antigen B and recombinant protein vaccines based on EG95 antigen have the best results and elicited protective immune responses