Regulation of Skp2 Expression and Activity and Its Role in Cancer Progression

The regulation of cell cycle entry is critical for cell proliferation and tumorigenesis. One of the key players regulating cell cycle progression is the F-box protein Skp2. Skp2 forms a SCF complex with Skp1, Cul-1, and Rbx1 to constitute E3 ligase through its F-box domain. Skp2 protein levels are regulated during the cell cycle, and recent studies reveal that Skp2 stability, subcellular localization, and activity are regulated by its phosphorylation. Overexpression of Skp2 is associated with a variety of human cancers, indicating that Skp2 may contribute to the development of human cancers. The notion is supported by various genetic mouse models that demonstrate an oncogenic activity of Skp2 and its requirement in cancer progression, suggesting that Skp2 may be a novel and attractive therapeutic target for cancers

Altered neuronatin expression in the rat dorsal root ganglion after sciatic nerve transection

<p>Abstract</p> <p>Background</p> <p>Several molecular changes occur following axotomy, such as gene up-regulation and down-regulation. In our previous study using Affymetrix arrays, it was found that after the axotomy of sciatic nerve, there were many novel genes with significant expression changes. Among them, neuronatin (Nnat) was the one which expression was significantly up-regulated. Nnat was identified as a gene selectively expressed in neonatal brains and markedly reduced in adult brains. The present study investigated whether the expression of Nnat correlates with symptoms of neuropathic pain in adult rats with transected sciatic nerve.</p> <p>Methods</p> <p>Western blotting, immunohistochemistry, and the Randall and Selitto test were used to study the protein content, and subcellular localization of Nnat in correlation with pain-related animal behavior.</p> <p>Results</p> <p>It was found that after nerve injury, the expression of Nnat was increased in total protein extracts. Unmyelinated C-fiber and thinly myelinated A-δ fiber in adult dorsal root ganglions (DRGs) were the principal sub-population of primary afferent neurons with distributed Nnat. The increased expression of Nnat and its subcellular localization were related to mechanical hyperalgesia.</p> <p>Conclusions</p> <p>The results indicated that there was significant correlation between mechanical hyperalgesia in axotomy of sciatic nerve and the increased expression of Nnat in C-fiber and A-δ fiber of adult DRG neurons.</p

Pregnancy-induced hypertension is an independent risk factor for meconium aspiration syndrome: A retrospective population based cohort study

Objective: Meconium aspiration syndrome (MAS), possibly resulting from fetal hypoxia, is a respiratory distress disorder in the infant. Pregnancy-induced hypertension (PIH) can cause placental dysfunction and lead to fetal hypoxia, which may induce the development of MAS. Therefore, the aim of this study was to determine the association between PIH and MAS and to identify the predictive risk factors. Materials and methods: This was a retrospective cohort study. We selected patients with newly diagnosed PIH and a matched cohort group from the Taiwan National Health Insurance Research Database (NHIRD), from January 1, 2000 till December 31, 2013. For each patient in the PIH cohort, 4 subjects without PIH, matched for age and year of delivery, were randomly selected as the comparison cohort. The incidence of meconium aspiration syndrome was assessed in both groups. Results: Among the 23.3 million individuals registered in the NHIRD, 29,013 patients with PIH and 116,052 matched controls were identified. Patients who experienced PIH had a higher incidence of MAS than did those without PIH. According to a multivariate analysis, PIH (odds ratio [OR] = 1.70, 95% confidence interval [CI] = 1.49–1.93, p < 0.0001) was independently associated with increased risk of MAS. Additionally, age ≥30 years (OR = 1.26, 95% CI = 1.12–1.42, p = 0.0001), nulliparity (OR = 1.13, 95% CI = 1.01–1.27, p = 0.0367) and patients with diabetes mellitus (OR = 3.09, 95% CI = 1.35–7.09, p = 0.0078) were also independent risk factors of MAS. Conclusion: Patients with PIH obtained higher subsequent risk for the development of MAS than those without PIH. Besides, age ≥30 years, nulliparity and patients with diabetes mellitus are the independent risk factors of developing MAS. Keywords: Pregnancy-induced hypertension, Hypertension in pregnancy, Gestational hypertension, Preeclampsia, Meconium aspiration syndrom

Crops For the Future (CFF): an overview of research efforts in the adoption of underutilised species

Main conclusion Crops For the Future (CFF), as an entity, has established a broad range of research activities to promote the improvement and adoption of currently underutilised crops. Abstract This paper summarises selected research activities at Crops For the Future (CFF) in pursuit of its mission 'to develop solutions for diversifying future agriculture using underutilised crops'. CFF is a research company focussed on the improvement of underutilised crops, so that they might be grown and consumed more widely with benefits to human food and nutritional security; its founding guarantors were the Government of Malaysia and the University of Nottingham. From its base in Malaysia, it engages in research around the world with a focus on species and system diversification. CFF has adopted a food system approach that adds value by delivering prototype food, feed and knowledge products. Bambara groundnut (Vigna subterranea) was adopted as an exemplar crop around which to develop CFF's food system approach with emphasis on the short-day photoperiod requirement for pod-filling and the hard-to-cook trait. Selective breeding has allowed the development of lines that are less susceptible to photoperiod but also provided a range of tools and approaches that are now being exploited in other crops such as winged bean (Psophocarpus tetragonolobus), amaranth (Amaranthus spp.), mor-inga (Moringa oleifera) and proso (Panicum miliaceum) and foxtail (Setaria italica) millets. CFF has developed and tested new food products and demonstrated that several crops can be used as feed for black soldier fly which can, in turn, be used to feed fish thereby reducing the need for fishmeal. Information about underutilised crops is widely dispersed; so, a major effort has been made to develop a knowledge base that can be interrogated and used to answer practical questions about potential exploitation of plant and nutritional characteristics. Future research will build on the success with Bambara groundnut and include topics such as urban agriculture, rural development and diversification, and the development of novel foods. CFF's remit and research objective

Sonoporation-mediated gene transfer into adult rat dorsal root ganglion cells

<p>Abstract</p> <p>Background</p> <p>Gene transfer into many cell types has been successfully used to develop alternative and adjunct approaches to conventional medical treatment. However, effective transfection of postmitotic neurons remains a challenge. The aim of this study was to develop a method for gene transfer into rat primary dorsal root ganglion neurons using sonoporation.</p> <p>Methods</p> <p>Dissociated cells from adult rat dorsal root ganglion (DRG) cells were sonicated for 1-8 s at 2.5-10 W to determine the optimal ultrasound duration and power for gene transfection and cell survival. Transfection efficiency was compared between sonoporation, liposome and lentiviral vector gene transfer techniques.</p> <p>Results</p> <p>The optimum ultrasound intensity was 5 W for 2 s and yielded an efficiency of gene transfection of 31% and a survival rate of 35%.</p> <p>Conclusions</p> <p>Sonoporation can be optimized to minimize cell death and yield a high percentage of transfected neurons and that this technique can be easily applied to primary cultures of rat dorsal root ganglion neurons.</p

Cytochrome P450-mediated co-metabolism of fluoroquinolones by Haematococcus lacustris for simultaneously promoting astaxanthin and lipid accumulation

Microalgae-based antibiotic removal treatment has attracted attention because of its low carbon and sustainable advantages. The microalgal co-metabolism system with a suitable carbon source leads to enhanced performance of pollutant removal. However, currently, limited knowledge is available for the removal of fluoroquinolone using a microalgae-mediated co-metabolism system. In this study, we first investigated that the biotic processes by alga Haematococcus lacustris in the co-metabolism system by adding glycerol would be the main contributors responsible for the removal of 10 mg/L ofloxacin (OFL) with the efficiency of 79.73% and the removal of 10 mg/ L enrofloxacin (ENR) with the efficiency of 54.10%, respectively. Furthermore, we found that pyruvate from glycerol was converted into substrates and precursors, thereby resulting in the significant accumulations of microalgal astaxanthin and lipid. The astaxanthin content of H. lacustris was achieved at 4.81% and 4.69% treated with OFL and ENR in the presence of glycerol, with 16.04% and 14.55% of lipid content, respectively. The proposed metabolites and pathways were identified to plausibly explain the biodegradation of fluoroquinolone by H. lacustris. The molecular analyses demonstrated that cytochrome P450 (CYP450) enzymes are responsible for the biodegradation of fluoroquinolone, and it was further verified that fluoroquinolones might insert into CYP450 to finally form an efficient and tight binding conformation by molecular dynamic simulation. These findings provide a microalgae-based route for feasible and sustainable biodegradation of antibiotics using a co-metabolism strategy comprising glycerol as a carbon source, with the synergistic accumulation of valuable products.peer-reviewe

Correlation of Interleukin-17-Producing Effector Memory T Cells and CD4 +

Background and Objectives. Hyperparathyroidism and hyperphosphatemia contribute to the inflammatory effects in chronic hemodialysis (HD) patients. Interleukin-17-producing CD4+ effector memory T (Th17) cells and CD4+CD25+Foxp3 regulatory T (Treg) cells both play critical roles in immune activation and inflammation. We investigated the relationship between the Treg and Th17 cells and the phosphate level in chronic HD patients. Methods. 105 patients aged ≥35 years on chronic HD over 3 months were enrolled. The peripheral blood mononuclear cells were collected, cultured, and stimulated by phytohemagglutinin-L, phorbol myristate acetate, and ionomycin at different time points for T cell differentiation. Results. The T cell differentiation was as follows: Th17 cells (mean ± standard deviation (SD): 25.61% ± 10.2%) and Treg cells (8.45% ± 4.3%). The Th17 cell differentiation was positively correlated with the phosphate and albumin levels and negatively correlated with age. The Treg cell differentiation was negatively correlated with albumin level and age. In the nondiabetes group (n=53), the Th17 cell differentiation was predominantly correlated with the phosphate and iPTH (intact parathyroid hormone) levels as well as the dialysis vintage. Conclusion. Higher phosphate and iPTH levels and longer dialysis duration may increase Th17 cell differentiation, especially in the nondiabetic chronic HD patients