A Robust Gene Expression Prognostic Signature for Overall Survival in High-Grade Serous Ovarian Cancer.

The objective of this research was to develop a robust gene expression-based prognostic signature and scoring system for predicting overall survival (OS) of patients with high-grade serous ovarian cancer (HGSOC). Transcriptomic data of HGSOC patients were obtained from six independent studies in the NCBI GEO database. Genes significantly deregulated and associated with OS in HGSOCs were selected using GEO2R and Kaplan-Meier analysis with log-rank testing, respectively. Enrichment analysis for biological processes and pathways was performed using Gene Ontology analysis. A resampling/cross-validation method with Cox regression analysis was used to identify a novel gene expression-based signature associated with OS, and a prognostic scoring system was developed and further validated in nine independent HGSOC datasets. We first identified 488 significantly deregulated genes in HGSOC patients, of which 232 were found to be significantly associated with their OS. These genes were significantly enriched for cell cycle division, epithelial cell differentiation, p53 signaling pathway, vasculature development, and other processes. A novel 11-gene prognostic signature was identified and a prognostic scoring system was developed, which robustly predicted OS in HGSOC patients in 100 sampling test sets. The scoring system was further validated successfully in nine additional HGSOC public datasets. In conclusion, our integrative bioinformatics study combining transcriptomic and clinical data established an 11-gene prognostic signature for robust and reproducible prediction of OS in HGSOC patients. This signature could be of clinical value for guiding therapeutic selection and individualized treatment

Association Between Aldehyde dehydrogenase-2 Polymorphisms and Risk of Alzheimer's Disease and Parkinson's Disease: A Meta-Analysis Based on 5,315 Individuals

Objective: A number of studies have reported that aldehyde dehydrogenase-2 (ALDH2) polymorphisms maybe associated with the risk of Alzheimer's disease (AD) and Parkinson's disease (PD). However, the results of such studies are inconsistent. We therefore conducted a meta-analysis to clarify the association between ALDH2 polymorphisms and the risk of AD and PD.Methods: Five online databases were searched and the relevant studies were reviewed from inception through May 10, 2018. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated in each genetic model of the general population and various subgroups. Furthermore, we simultaneously performed heterogeneity, cumulative, sensitivity, and publication bias analyses.Results: Overall, nine case-control studies involving 5,315 subjects were included in this meta-analysis. Potential associations were found between the ALDH2 rs671 G>A polymorphism and the risk of AD (A vs. G: OR = 1.46, 95%CI = 1.01–2.11, P = 0.05, I2 = 84.2%; AA vs. GG: OR = 2.22, 95%CI = 1.03–4.77, P = 0.04, I2 = 79.2%; AA vs. GG+GA: OR = 1.94, 95%CI = 1.03–3.64, P =0.04, I2 = 71.1%). In addition, some similar results were observed in other subgroups. Moreover, no significant association between ALDH2 polymorphisms and PD risk.Conclusions: In conclusion, our meta-analysis indicated that the ALDH2 rs671 G>A polymorphism plays an important role in AD development

HCCS1-armed, quadruple-regulated oncolytic adenovirus specific for liver cancer as a cancer targeting gene-viro-therapy strategy

<p>Abstract</p> <p>Background</p> <p>In previously published studies, oncolytic adenovirus-mediated gene therapy has produced good results in targeting cancer cells. However, safety and efficacy, the two most important aspects in cancer therapy, remain serious challenges. The specific expression or deletion of replication related genes in an adenovirus has been frequently utilized to regulate the cancer cell specificity of a virus. Accordingly, in this study, we deleted 24 bp in E1A (bp924-bp947) and the entirety of E1B, including those genes encoding E1B 55kDa and E1B19kDa. We used the survivin promoter (SP) to control E1A in order to construct a new adenovirus vector named Ad.SP.E1A(Δ24).ΔE1B (briefly Ad.SPDD). HCCS1 (hepatocellular carcinoma suppressor 1) is a novel tumor suppressor gene that is able to specifically induce apoptosis in cancer cells. The expression cassette AFP-HCCS1-WPRE-SV40 was inserted into Ad.SPDD to form Ad.SPDD-HCCS1, enabling us to improve the safety and efficacy of oncolytic-mediated gene therapy for liver cancer.</p> <p>Results</p> <p>Ad.SPDD showed a decreased viral yield and less toxicity in normal cells but enhanced toxicity in liver cancer cells, compared with the cancer-specific adenovirus ZD55 (E1B55K deletion). Ad.SPDD-HCCS1 exhibited a potent anti-liver-cancer ability and decreased toxicity in vitro. Ad.SPDD-HCCS1 also showed a measurable capacity to inhibit Huh-7 xenograft tumor growth on nude mice. The underlying mechanism of Ad.SPDD-HCCS1-induced liver cancer cell death was found to be via the mitochondrial apoptosis pathway.</p> <p>Conclusions</p> <p>These results demonstrate that Ad.SPDD-HCCS1 was able to elicit reduced toxicity and enhanced efficacy both in vitro and in vivo compared to a previously constructed oncolytic adenovirus. Ad.SPDD-HCCS1 could be a promising candidate for liver cancer therapy.</p

Stable Hydrazone-Linked Covalent Organic Frameworks Containing O,N,O'-Chelating Sites for Fe(III) Detection in Water.

Two stable crystalline hydrazone-linked covalent organic frameworks (COFs) (Bth-Dha and Bth-Dma) containing functional O,N,O'-chelating sites have been designed and successfully synthesized by the Schiff-base condensation reactions between benzene-1,3,5-tricarbohydrazide (Bth) and 2,5-dihydroxyterephthalaldehyde (Dha) or 2,5-dimethoxyterephthal-aldehyde (Dma), respectively. Bth-Dma exhibits strong fluorescence in the solid state and in an aqueous dispersion, while no fluorescence can be observed for Bth-Dha. Interestingly, the as-synthesized Bth-Dma can be used as a turn-off fluorescence sensor for the Fe(III) ion in aqueous solution with outstanding selectivity and sensitivity. The recognition process can be attributed to the coordination interaction between Fe(III) ion and the O,N,O'-chelating sites in the pore wall of Bth-Dma COF, as verified by X-ray photoelectron spectroscopy and 1H NMR spectroscopy. To the best of our knowledge, this is the first report on the rational design of luminescent COF with predesigned O,N,O'-chelating sites as a fluorescence sensor for highly selective and sensitive metal ion detection. This work may pave the way for designing luminescent COF sensors with functional binding sites for detecting specific metal ions

ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors

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Down-regulation of Toll-like receptor 4 gene expression by short interfering RNA attenuates bone cancer pain in a rat model

<p>Abstract</p> <p>Background</p> <p>This study demonstrates a critical role in CNS innate immunity of the microglial Toll-like receptor 4 (TLR4) in the induction and maintenance of behavioral hypersensitivity in a rat model of bone cancer pain with the technique of RNA interference (RNAi). We hypothesized that after intramedullary injection of Walker 256 cells (a breast cancer cell line) into the tibia, CNS neuroimmune activation and subsequent cytokine expression are triggered by the stimulation of microglial membrane-bound TLR4.</p> <p>Results</p> <p>We assessed tactile allodynia and spontaneous pain in female Sprague-Dawley (SD) rats after intramedullary injection of Walker 256 cells into the tibia. In a complementary study, TLR4 small interfering RNA(siRNA) was administered intrathecally to bone cancer pain rats to reduce the expression of spinal TLR4. The bone cancer pain rats treated with TLR4 siRNA displayed significantly attenuated behavioral hypersensitivity and decreased expression of spinal microglial markers and proinflammatory cytokines compared with controls. Only intrathecal injection of TRL4 siRNA at post-inoculation day 4 could prevent initial development of bone cancer pain; intrathecal injection of TRL4 siRNA at post-inoculation day 9 could attenuate, but not completely block, well-established bone cancer pain.</p> <p>Conclusions</p> <p>TLR4 might be the main mediator in the induction of bone cancer pain. Further study of this early, specific, and innate CNS/microglial response, and how it leads to sustained glial/neuronal hypersensitivity, might lead to new therapies for the prevention and treatment of bone cancer pain syndromes.</p

Fysisk prestation och matchkrav inom elitfotboll - Samband mellan smålagsspel och de mest intensiva perioder inom fotboll

De fysiska kraven hos elitfotbollsspelare är stora och såväl aerob som anaerob förmåga är viktiga för prestationen. Individuella skillnader i fysisk kapacitet spelare emellan är välkänt men individuell träningsplanering med lämplig belastning för att optimera spelares enskilda behov är inte lika väl studerat. Syftet med denna studie är att undersöka sambandet mellan spelares matchkrav i fotboll i form av högintensiva perioder (peakperioder) och träningsrespons på smålagsspel. Vi har studerat individuella spelares högintensiva perioder i match, olika typer av smålagsspel (4v4, 6v6 och 8v8) och andra fysiska tester. Studien har en kvantitativ experimentell design där GPS-data i fotboll är analyserad. 17 elitfotbollsspelare (Ålder 23.7 ± 4.8 år, vikt 76.4 ± 4.8 kg, längd 181.1 ± 5.2 cm) från allsvenskan och superettan i svensk herrfotboll deltog i studien. Resultaten visar att olika typer av smålagsspel belastar spelarna på olika sätt, där vissa fysiska variabler har ett medel (>0.30) till stark korrelation (>0.70), medan andra variabler visar en svag (>0.10) till ingen korrelation (<0.10). Sambandet mellan fysiska tester och matchkrav i form av peakperioder visar att endast Repeated Sprint Ability (RSA) kan ha en relevant användning för att förutse prestation i peakperioder. Information om vilken typ av smålagsspel som har vilken effekt och hur de belastar spelaren samt matchkrav på individ- och gruppnivå kan underlätta för tränaren vid utformning av träningsplanering. Slutligen krävs mer forskning inom området för att säkerhetsställa att tillämpningen av smålagsspel samt de fysiska testerna, gentemot matchkraven i form av peakperioder, blir så matchlik och optimal som möjligt