Expression of osteoprotegrin is enhanced in lung cancer tissues and promotes aggressive cellular traits in H3122 lung cancer cells

Background: Osteoprotegrin (OPG), a secreted protein and a member of the tumor necrosis factor receptor superfamily has been well-characterized and is an important regulator of bone remodeling by blocking osteoclast maturation thus preventing osteolysis. In recent years, OPG has been reported to have an association with the malignant capacity of various cancer types and cancer-associated bone metastasis, although the mechanisms of this are not clearly understood. Materials and Methods: In this study, OPG expression was analyzed in human lung cancer tissue and normal tissue based on the dataset of The Cancer Genome Atlas and Oncomine. The in vitro effect of OPG on H3122 lung cancer cells was also assessed by characterizing cell function following knock-down and forced overexpression in this cell line. Results: The expression of OPG was significantly increased in lung cancer tissues compared to the normal control group and OPG promoted the malignant phenotypes of H3122 cells in in vitro models. Conclusion: OPG may be a potential driver of lung cancer cells and therefore might have potential in therapy and diagnostics

Spin polarized proton beam generation from gas-jet targets by intense laser pulses

A method of generating spin polarized proton beams from a gas jet by using a multi-petawatt laser is put forward. With currently available techniques of producing pre-polarized monatomic gases from photodissociated hydrogen halide molecules and petawatt lasers, proton beams with energy ~ 50 MeV and ~ 80 % polarization are proved to be obtained. Two-stage acceleration and spin dynamics of protons are investigated theoretically and by means of fully self-consistent three dimensional particle-in-cell simulations. Our results predict the dependence of the beam polarization on the intensity of the driving laser pulse. Generation of bright energetic polarized proton beams would open a domain of polarization studies with laser driven accelerators, and have potential application to enable effective detection in explorations of quantum chromodynamics

Effectiveness of a multimodal standard nursing program on health-related quality of life in Chinese mainland female patients with breast cancer: protocol for a single-blind cluster randomized controlled trial.

BACKGROUND Breast cancer and its treatment-related adverse effects are harmful to physical, psychological, and social functioning, leading to health-related quality of life (HRQoL) impairment in patients. Many programs have been used with this population for HRQoL improvement; however, few studies have considered the physical, psychological, and social health domains comprehensively, and few have constructed multimodal standard nursing interventions based on specific theories. The purpose of this trial is to examine the effect of a health belief model (HBM)-based multimodal standard nursing program (MSNP) on HRQoL in female patients with breast cancer. METHODS This is a two-arm single-blind cluster randomized controlled trial (cRCT) in clinical settings. Twelve tertiary hospitals will be randomly selected from the 24 tertiary hospitals in Xi'an, China, and allocated to the intervention arm and control arm using a computer-generated random numbers table. Inpatient female patients with breast cancer from each hospital will receive either MSNP plus routine nursing care immediately after recruitment (intervention arm), or only routine nursing care (control arm). The intervention will be conducted by trained nurses for 12 months. All recruited female patients with breast cancer, participating clinical staff, and trained data collectors from the 12 hospitals will be blind with respect to group allocation. Patients of the control arm will not be offered any information about the MSNP during the study period to prevent bias. The primary outcome is HRQoL measured through the Functional Assessment of Cancer Therapy-Breast version 4.0 at 12 months. Secondary outcomes include pain, fatigue, sleep, breast cancer-related lymphedema, and upper limb function, which are evaluated by a visual analogue scale, the circumference method, and the Constant-Murley Score. DISCUSSION This trial will provide important evidence on the effectiveness of multimodal nursing interventions delivered by nurses in clinical settings. Study findings will inform strategies for scaling up comprehensive standard intervention programs on health management in the population of female patients with breast cancer. TRIAL REGISTRATION Chictr.org.cn ChiCTR-IOR-16008253 (April 9, 2016)

Biological influence of brain-derived neurotrophic factor (BDNF) on colon cancer cells

Brain-derived neurotrophic factor (BDNF) has been observed to be elevated in solid tumors including colorectal cancer. The present study aimed to investigate the effect of modulation of BDNF at the transcription level on the cellular function of colorectal cells and to increase our understanding of its biological role in human colon cancer. An investigation of a cohort of human colorectal tissues (tumor n=66; normal n=88) using quantitative PCR and immunohistochemistry demonstrated that BDNF is aberrantly expressed in human colon cancer and a significantly raised level of BDNF is associated with its stage at diagnosis. The expression profile of BDNF in human colon cancer cell lines was evaluated using RT‑PCR. A set of anti-BDNF ribozymes were used to transfect colon cancer cells in order to generate BDNF knockdown cells to evaluate the effect on growth and apoptosis. BDNF gene transcripts were successfully detected in the colon cancer cell lines, Caco‑2 and HRT18. BDNF knockdown in Caco‑2 and HRT18 cell lines resulted in decreased rates of growth and proliferation. Analysis of apoptosis showed that cell apoptosis was increased. It is concluded that BDNF, a neurotrophic growth factor aberrantly expressed in cancers such as colon cancer, has a profound impact on the cellular behavior of colon cancer cells and that BDNF is associated with a reduction in the apoptosis of colon cancer. BDNF is therefore a potential therapeutic target in colon cancer and its effect in human colon cancer requires further investigation

Biological influence of brain-derived neurotrophic factor on breast cancer cells

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin superfamily which has been indicated in the pathophysiology of the nervous system and is important in a number of neurological and psychological conditions. Recently, BDNF was also shown to play a role in the development and progression of solid tumour myeloma. It has been reported that BDNF is aberrantly expressed in human breast cancer and that a raised level of BDNF is associated with poor clinical outcome and reduced survival. The present study investigated the role of BDNF in human breast cancer. A panel of human breast cancer cells was used and the expression profile of BDNF was evaluated using RT-PCR. We constructed a set of anti-BDNF transgenes which were used to transfect breast cancer cells in order to generate BDNF knocked down cells. The impact of BDNF knockdown on growth and apoptosis was evaluated. Statistical analysis was performed using SPSS. P<0.05 was considered statistically significant. BDNF gene transcripts were successfully detected in the breast cancer cell lines MCF-7, MDA-MB-231 and ZR75-1 MDA-MB-231 and MCF-7 wild-type cells were subject to transfection of anti-BDNF transgenes, followed by the establishment of BDNF knocked down sublines. Knockdown of BDNF in MDA-MB-231 and MCF-7 cell lines resulted in decreased rates of growth and proliferation. Analysis of apoptosis showed that cell apoptosis was increased in cells stably transfected with ribozymes for BDNF compared with the vector control. It is concluded that BDNF, a neurotrophic growth factor aberrantly expressed in cancers such as breast cancer, has a profound impact on the cellular behaviour of breast cancer cells and that BDNF is associated with a reduction of the apoptosis of breast cancer. BDNF is, therefore, a potential therapeutic target in breast cancer and its effect in human breast cancer requires further investigation

Identification of the para-nitrophenol catabolic pathway, and characterization of three enzymes involved in the hydroquinone pathway, in pseudomonas sp. 1-7

<p>Abstract</p> <p>Background</p> <p><it>para</it>-Nitrophenol (PNP), a priority environmental pollutant, is hazardous to humans and animals. However, the information relating to the PNP degradation pathways and their enzymes remain limited.</p> <p>Results</p> <p><it>Pseudomonas </it>sp.1-7 was isolated from methyl parathion (MP)-polluted activated sludge and was shown to degrade PNP. Two different intermediates, hydroquinone (HQ) and 4-nitrocatechol (4-NC) were detected in the catabolism of PNP. This indicated that <it>Pseudomonas </it>sp.1-7 degraded PNP by two different pathways, namely the HQ pathway, and the hydroxyquinol (BT) pathway (also referred to as the 4-NC pathway). A gene cluster (<it>pdcEDGFCBA</it>) was identified in a 10.6 kb DNA fragment of a fosmid library, which cluster encoded the following enzymes involved in PNP degradation: PNP 4-monooxygenase (PdcA), <it>p</it>-benzoquinone (BQ) reductase (PdcB), hydroxyquinol (BT) 1,2-dioxygenase (PdcC), maleylacetate (MA) reductase (PdcF), 4-hydroxymuconic semialdehyde (4-HS) dehydrogenase (PdcG), and hydroquinone (HQ) 1,2-dioxygenase (PdcDE). Four genes (<it>pdcDEFG</it>) were expressed in <it>E. coli </it>and the purified <it>pdcDE</it>, <it>pdcG </it>and <it>pdcF </it>gene products were shown to convert HQ to 4-HS, 4-HS to MA and MA to β-ketoadipate respectively by <it>in vitro </it>activity assays.</p> <p>Conclusions</p> <p>The cloning, sequencing, and characterization of these genes along with the functional PNP degradation studies identified 4-NC, HQ, 4-HS, and MA as intermediates in the degradation pathway of PNP by <it>Pseudomonas </it>sp.1-7. This is the first conclusive report for both 4-NC and HQ- mediated degradation of PNP by one microorganism.</p

Optic disc shape in patients with long-lasting unilateral esotropia and exotropia

Background: Horizontal eye movements have been proposed to induce biomechanical stress and strain on optic nerve head. Since strabismus may lead to sustained adduction or abduction, we investigate the effects of long lasting unilateral horizontal strabismus on the morphology of optic disc. Methods: The observational cross-sectional study included patients with unilateral constant horizontal strabismus lasting for more than two years. The patients underwent an ophthalmological examination including refraction and morphometry of the optic nerve head. A prism cover test using right angle glass prism was performed to measure the magnitude of the ocular deviation. Results: The study included 70 patients with a unilateral constant strabismus (35 esotropic patients, 35 exotropic patients) with a mean age of 26 ± 19 years, mean refractive error of − 0.72 ± 3.3 diopters, mean axial length of 23.8 ± 1.7 mm, and a mean angle of deviation of 87 ± 36 prism diopters (Chinese right-angle glass method) in the esotropic group and − 97 ± 29 prism diopters in the exotropic group. In the whole study population and taken separately in the esotropic group and exotropic group, the disc ovality index (defined as ratio of minimal-to-maximal optic disc diameter) did not differ significantly between the deviating eyes and the contralateral fixating eyes (all P &gt; 0.05). As a corollary, the disc ovality index and the prevalence of parapapillary beta/gamma zone did not differ significantly between the esotropic group and the exotropic group (all P &gt; 0.05). Conclusions: Optic disc ovality did not differ markedly among long-lasting esotropic eyes, exotropic eyes, and non-strabismic eyes. It suggests that optic disc shape may not be markedly influenced in non-highly myopic eyes by a potential backward pull of the optic nerve on the optic disc structures in adduction or abduction

Mild Moxibustion Decreases the Expression of Prokineticin 2 and Prokineticin Receptor 2 in the Colon and Spinal Cord of Rats with Irritable Bowel Syndrome

It has been proven that prokineticin 2 (PK2) and its receptor PKR2 play an important role in hyperalgesia, while mild moxibustion can relieve visceral hypersensitivity in a rat model of irritable bowel syndrome (IBS). The goal of the present study was to determine the effects of mild moxibustion on the expression of PK2 and PKR2 in colon and spinal cord in IBS rat model, which was induced by colorectal distension using inflatable balloons. After mild moxibustion treatment, abdominal withdrawal reflex (AWR) scores were assessed by colorectal distension; protein and mRNA expression of PK2 and PKR2 in rat colon and spinal cord was determined by immunohistochemistry and fluorescence quantitative PCR. Compared with normal rats, the AWR scores of rats and the expressions of PK2/PKR2 proteins and mRNAs in colon and spinal cord tissue were significantly increased in the model group; compared with the model group, the AWR scores of rats and the expressions of PK2/PKR2 proteins and mRNAs in colon and spinal cord tissue were significantly decreased in the mild moxibustion group. These findings suggest that the analgesia effect of mild moxibustion may be associated with the reduction of the abnormally increased expression of the PK2/PKR2 proteins and mRNAs in the colon and spinal cord

Time Course of Gene Expression Profiling in the Liver of Experimental Mice Infected with Echinococcus multilocularis

BACKGROUND: Alveolar echinococcosis (AE) is a severe chronic parasitic disease which behaves like a slow-growing liver cancer. Clinical observations suggest that the parasite, Echinococcus multilocularis (E. multilocularis) influences liver homeostasis and hepatic cell metabolism. However, this has never been analyzed during the time course of infection in the common model of secondary echinococcosis in experimental mice. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profiles were assessed using DNA microarray analysis, 1, 2, 3 and 6 months after injection of E. multilocularis metacestode in the liver of susceptible mice. Data were collected at different time points to monitor the dynamic behavior of gene expression. 557 differentially expressed genes were identified at one or more time points, including 351 up-regulated and 228 down-regulated genes. Time-course analysis indicated, at the initial stage of E. multilocularis infection (month 1-2), that most of up-regulated pathways were related to immune processes and cell trafficking such as chemokine-, mitogen-activated protein kinase (MAPK) signaling, and down-regulated pathways were related to xenobiotic metabolism; at the middle stage (month 3), MAPK signaling pathway was maintained and peroxisome proliferator-activated receptor (PPAR) signaling pathway emerged; at the late stage (month 6), most of up-regulated pathways were related to PPAR signaling pathway, complement and coagulation cascades, while down-regulated pathways were related to metabolism of xenobiotics by cytochrome P450. Quantitative RT-PCR analysis of a random selection of 19 genes confirmed the reliability of the microarray data. Immunohistochemistry analysis showed that proliferating cell nuclear antigen (PCNA) was increased in the liver of E. multilocularis infected mice from 2 months to 6 months. CONCLUSIONS: E. multilocularis metacestode definitely exerts a deep influence on liver homeostasis, by modifying a number of gene expression and metabolic pathways. It especially promotes hepatic cell proliferation, as evidenced by the increased PCNA constantly found in all the experimental time-points we studied and by an increased gene expression of key metabolic pathways