Identification of human fetal liver miRNAs by a novel method

AbstractMicroRNAs (miRNAs) are short 20–25 nucleotides RNA molecules that have been shown to regulate gene expressions in a variety of eukaryotic systems. miRNAs are widespread in eukaryotes and several hundred of miRNAs have been identified, but still a lot of miRNAs have not been detected in various eukaryotic organisms. However, it is not an easy work to clone miRNAs by traditional methods. Here, we describe the identification of 27 miRNAs from a human fetal liver cDNA library by a novel cloning method. Low molecular weight RNA fraction (⩽200nt) from fetal liver tissue was extracted, and polyadenylated by poly(A) polymerase. A 5′ RNA adaptor was ligated to poly(A)-tailed RNA using T4 RNA ligase. After reverse transcription, the cDNA was amplified by PCR with two adaptor primers. The PCR product with a size about 109bp was recovered and cloned into T vector. After sequencing, database searching, and expression profiling, 5 novel miRNAs were discovered among other 22 known miRNAs in human fetal liver. These finding indicate that a large diverse population of miRNAs may function to regulate gene expression in hepatocyte

Socio-demographic determinants of diet quality in Australian adults using the validated Healthy Eating Index for Australian adults (HEIFA-2013)

Diet quality indices have been shown to predict cardiovascular disease, cancer, Type 2 Diabetes, obesity and all-cause mortality. This study aimed to determine the socio-demographics of Australian adults with poor diet quality. Diet quality was assessed for participants of the 2011–2012 National Nutrition and Physical Activity Survey aged 18 years or above (n = 9435), with the validated 11-component Healthy Eating Index for Australians (HEIFA-2013), based on the 2013 Australian Dietary Guidelines. Differences in scores by demographics (ANOVA) and regression models for associations between the HEIFA-2013 score and demographic characteristics were conducted. The mean (SD) HEIFA-2013 score was 45.5 (14.7) out of 100 due to poor intakes of vegetables, fruit, grains, dairy and fat and high intakes of added sugar, sodium and discretionary foods. Lower mean HEIFA-2013 scores (SD) were found for males 43.3 (14.7), young-adults 41.6 (14.2) obese 44.1 (14.3), smokers 40.0 (14.2), low socio-economic status 43.7 (14.9) and Australian country-of-birth 44.2 (14.6) (p < 0.05). The overall diet quality of the Australian population is poor and targeted interventions for young-adults, males, obese and those with lower socio-economic status are recommended

Altered Regional and Circuit Resting-State Activity Associated with Unilateral Hearing Loss

The deprivation of sensory input after hearing damage results in functional reorganization of the brain including cross-modal plasticity in the sensory cortex and changes in cognitive processing. However, it remains unclear whether partial deprivation from unilateral auditory loss (UHL) would similarly affect the neural circuitry of cognitive processes in addition to the functional organization of sensory cortex. Here, we used resting-state functional magnetic resonance imaging to investigate intrinsic activity in 34 participants with UHL from acoustic neuroma in comparison with 22 matched normal controls. In sensory regions, we found decreased regional homogeneity (ReHo) in the bilateral calcarine cortices in UHL. However, there was an increase of ReHo in the right anterior insular cortex (rAI), the key node of cognitive control network (CCN) and multimodal sensory integration, as well as in the left parahippocampal cortex (lPHC), a key node in the default mode network (DMN). Moreover, seed-based resting–state functional connectivity analysis showed an enhanced relationship between rAI and several key regions of the DMN. Meanwhile, lPHC showed more negative relationship with components in the CCN and greater positive relationship in the DMN. Such reorganizations of functional connectivity within the DMN and between the DMN and CCN were confirmed by a graph theory analysis. These results suggest that unilateral sensory input damage not only alters the activity of the sensory areas but also reshapes the regional and circuit functional organization of the cognitive control network

Hydrothermally treated coral scaffold promotes proliferation of mesenchymal stem cells and enhances segmental bone defect healing

Introduction: Synthetic hydroxyapatite (HAp) scaffolds have shown promising therapeutic outcomes in both animals and patients. In this study, we aim to evaluate the chemical and physical phenotype, biocompatibility, and bone repair effects of hydrothermally treated coral with natural coral and synthetic HAp.Methods: The phase composition, surface pattern, 3D structures, and porosity of the scaffolds were characterized, and cell viability, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs) after seeding onto the scaffold were determined. The scaffolds were implanted into rats to assess their bone repair effects using micro-CT analysis, mechanical testing, and histological staining.Results: The results showed that the phase composition, porous structure, and porosity of hydrothermally treated coral were comparable to pure HAp scaffold. While only the natural coral happens to be dominantly calcium carbonate. Higher cell proliferation and osteogenic differentiation potential were observed in the hydrothermally treated coral scaffold compared to natural coral and pure HAp. Histological results also showed increased new bone formation in the hydrothermally treated coral group.Discussion: Overall, our study suggests that hydrothermal modification enhances the cytocompatibility and therapeutic capacity of coral without altering its physical properties, showing superior effectiveness in bone repair to synthetic HAp

Cardioprotective effect of Shenxiong glucose injection on acute myocardial infarction in rats via reduction in myocardial intracellular calcium ion overload

Purpose: To explore the cardioprotective effects and potential mechanisms of Shenxiong Glucose Injection (SGI) in rat acute myocardial infarction (AMI).Methods: AMI model was created by ligating left anterior descending coronary artery. After 7 days’ consecutive intravenous administration of SGI, serum samples were used to conduct biochemical analysis while hearts were excised and processed for infraction size, enzyme activity, histopathology and qPCR studies. Intracellular Ca2+ {(Ca2+)i} overload in H9c2 cells was measured by laser scanning confocal microscope (LSCM).Results: In AMI rats, pretreatment with SGI significantly ameliorated myocardial histopathologic damage. It exerted cardioprotective effect by decreasing myocardial infarct size, electrocardiogram (ECG) ST segment elevation, and CK, cTnI, BNP levels in serum. In addition, SGI significantly decreased calmodulin (CaM) and calmodulin-dependent protein kinase II (CaMK II) mRNA expression, but increased Ca2+-Mg2+-ATPase and Na+-K+-ATPase activities in myocardium. In doxorubicin (DOX)- induced H9c2 cells injury model, SGI reversed (Ca2+)i overload to protect cells.Conclusion: The results demonstrate SGI exerts cardioprotective effect by decreasing myocardial infarct size, restoring ST segment and reversing (Ca2+)i overload. It suggests that SGI may be a new clinical candidate to treat myocardial infarction.Keywords: Shenxiong glucose injection, Tanshinol, Ligustrazine, Myocardial infarction, Intracellular Ca2+ overload, Calmodulin, Calmodulin-dependent protein kinase I

Heat shock protein 90 promotes RNA helicase DDX5 accumulation and exacerbates hepatocellular carcinoma by inhibiting autophagy

Objective: Hepatocellular carcinoma (HCC), the main type of liver cancer, has a high morbidity and mortality, and a poor prognosis. RNA helicase DDX5, which acts as a transcriptional co-regulator, is overexpressed in most malignant tumors and promotes cancer cell growth. Heat shock protein 90 (HSP90) is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival. Methods: DDX5 mRNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot, respectively. The interaction of DDX5-HSP90 was determined by molecular docking, immunoprecipitation, and laser scanning confocal microscopy. The autophagy signal was detected by Western blot. The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines. Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor. Results: HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway. The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating the β-catenin signaling pathway. The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model. High levels of HSP90 and DDX5 protein were associated with poor prognoses. Conclusions: HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation. DDX5 and HSP90 are therefore potential therapeutic targets for HCC

Numerical investigation on blast-induced rock fragmentation with different stemming structures

Abstract Stemming is one of the main concerns in blast of rock engineering due to its impact on explosion energy consumption and rock excavation performance. In this study, blast-induced rock fragmentation under different stemming conditions is numerically studied using combined numerical modelling and image processing. After careful determination the parameters of constitutive material models, the developed numerical model in LS-DYNA is verified based on the blast testing results including rock fracturing and fragment size distribution (FSD). The calibrated constitutive models are then used to model the pressure variation and rock disintegration produced by blasting with different stemming structures. The size data of simulated rock fragmentation are obtained by image-processing the cut surfaces of the numerical model with the program ImageJ, and the blast-created rock FSD is characterized using a three-parameter generalized extreme value function. The effects of the combination of explosive, air/sand deck and stemming on blast-induced rock fragmentation are quantitatively analysed, considering various stemming modes, stemming lengths and air/sand deck lengths. The results show that the blast-created fragment size decreases with an increase in stemming length, a decreasing in air/sand deck length, replacement of top stemming (stemming at borehole collar with air deck) with bottom stemming (stemming directly contact explosive) and alteration of air deck to sand deck, while the FSD range exhibits the opposite tendency. Bottom stemming is recommended for practical blasting due to its efficiency in rock fragmentation and robustness with respect to stemming length

Evaluation of Excavation-Damaged Zone around Underground Tunnels by Theoretical Calculation and Field Test Methods

Excavation-damaged zones (EDZs) induced in underground mining and civil engineering potentially threaten tunnel safety and stability, and increase construction and support costs. In this paper, an investigation of the excavation damaged zone (EDZ) around roadways in Fankou lead-zinc mine in Guangzhou, China is performed by applying a seismic velocity method accompanied by SET-PLT-01 nonmetallic ultrasonic detector. Meanwhile, the in situ stress in the mining area was measured based on the stress relief method with the Swedish high-precision LUT system. The results indicate that the stress field is dominated by the maximum horizontal tectonic stress, and the extents of the EDZ on the roof-floor region are greater than that on the sidewall. In addition, both of the in situ stresses and EDZs show an increasing trend with an increase of depth. Analytical solutions of EDZ around circular openings in the brittle rock mass subjected to non-hydrostatic stress fields are presented in terms of the Mohr−Coulomb and generalized Hoek−Brown criteria, and validated by several cases mentioned above. The extents of EDZ solved by closed-form solutions were found to be in a great agreement with those obtained in the field. Finally, a series of parametric studies are conducted to investigate the effects of cohesion (c), friction angle (φ), geological strength index (GSI), mi, uniaxial compressive strength (σc), and disturbance factor (D) on EDZ. It is shown that the effects of c, φ, GSI, and σc are significant; however, more attention should be paid to consider the dynamic disturbances induced by mechanical drilling, blasting, and seismic waves in tunnel excavations or operations