p38 Mapk signal pathway involved in anti-inflammatory effect of chaihu-shugan-san and shen-ling-bai-zhu-san on hepatocyte in non-alcoholic steatohepatitis rats

Background: Traditional Chinese Medicine (TCM), has over thousands-of-years history of use. Chaihu-Shugan-San (CSS), and Shen-ling-bai-zhu-San (SLBZS), are famous traditional Chinese herbal medicine formulas, which have been used in China, for the treatment of many chronic diseases.Materials and Methods:This study investigated the anti-inflammatory effects of CSS and SLBZS on signaling molecules involved in p38 mitogen-activated protein kinase (p38 MAPK), pathway on hepatocytes of non-alcoholic steatohepatitis (NASH), rats induced by high fat diet. SD male rats were randomly divided into 8 groups: negative control group, model control group, high (9.6g/kg/day)/low (3.2g/kg/day)-dose CSS group, high (30g/kg/day)/low (10g/kg/day)-dose SLBZS group, high (39.6g/kg/day)/low (13.2g/kg/day)-dose integrated group. The rats of NASH model were induced by feeding a high-fat diet. After 16, wks, Hepatocytes were isolated from 6, rats in each group by collagenase perfusion. The liver histopathological changes and serum inflammatory cytokines TNF-α, IL-6 were determined. The proteins of TLR4,  phosphor-p38 MAPK and p38 MAPK involved in p38 MAPK signal pathway were assayed.Results: The statistical data indicated the NASH model rats reproduced typical histopathological features of NASH in human. CSS and SLBZS ameliorated lipid metabolic disturbance, attenuated NASH progression, decreased the levels of TNF-α and IL-6 in serum, as well as inhibited TLR4 protein expression, p38 MAPK phosphorylation, and activation of p38 MAPK. In conclusion, CSS and SLBZS might work as a significant anti-inflammatory effect on hepatocyte of NASH by inhibiting the activation of TLR4, p-p38 MAPK and p38 MAPK involved in p38 MAPK signal pathway.Conclusion: To some extent, CSS and SLBZS may be a potential alternative and complementary medicine to protect against liver injury, alleviate the inflammation reaction, moderate NASH progression.Key words: p38 mitogen-activated protein kinase; Toll like receptor 4; Hepatocytes; Non-alcoholic Steatohepatitis; Traditional Chinese medicine

In situ loading and delivery of short single- And double-stranded dna by supramolecular organic frameworks

Short DNA represents an important class of biomacromolecules that are widely applied in gene therapy, editing, and modulation. However, the development of simple and reliable methods for their intracellular delivery remains a challenge. Herein, we describe that seven water-soluble, homogeneous supramolecular organic frameworks (SOFs) with a well-defined pore size and high stability in water that can accomplish in situ inclusion of single-stranded (ss) and double-stranded (ds) DNA (21, 23, and 58 nt) and effective intracellular delivery (including two noncancerous and six cancerous cell lines). Fluorescence quenching experiments for single and double endlabeled ss- and ds-DNA support that the DNA sequences can be completely enveloped by the SOFs. Confocal laser scanning microscopy and flow cytometry reveal that five of the SOFs exhibit excellent delivery efficiencies that, in most of the studied cases, outperform the commercial standard Lipo2000, even at low SOF-nucleic acid ratios. In addition to high delivery efficiencies, the watersoluble, self-assembled SOF carriers have a variety of advantages, including convenient preparation, high stability, and in situ DNA inclusion, which are all critical for practical applications in nucleic acid delivery

Hydrodynamics, erosion and accretion of intertidal mudflats in extremely shallow waters

© 2019 Elsevier B.V. Intertidal flats are shallow-water environments that undergo cyclical variations in water depth, leading to a frequent occurrence of extremely shallow water stages (ESWS; water depths 0.2 m), and the rate of change was an order of magnitude faster than during RDWS. This larger and faster bed-level change occurred even though the ESWS duration only accounted for 10% of the entire tidal cycle. This result occurred because the bed shear stress due to combined current–wave action during ESWS, was, on average, two times higher than during RDWS at the flood stage causing more extensive erosion. Whereas during the ebb stage, this shear stress during ESWS was only half of that during RDWS resulting in greater accretion. The main implications of these results are that, because ESWS occur frequently (twice every tide) and are associated with large bed shear stress and bed-level changes, these conditions are likely to play an important role in morphological changes of intertidal flats. Our study shows that ESWS have a key influence on intertidal flat hydrodynamics and sediment dynamics. Thus our results are the basis for an improved understanding of the coastal morphodynamic processes on intertidal flats

Effect of soil-pile-structure interaction on seismic behaviour of nuclear power station via shaking table tests

To better understand the characteristics of the seismic response of nuclear power stations with fixed-base and pile-raft foundations, a series of shaking table tests were performed. The shaking table tests included three cases: free-field soil, fixed-base structure without soil, and superstructure with a pile-raft foundation embedded in the soil. One white noise excitation and three earthquake motions with different earthquake intensity were selected as the ground motion to identify the seismic response of the structure, raft, piles, and soils. The effects of earthquake intensity, earthquake frequency, soil-pile-structure interaction, and soil nonlinearity on the system dynamic responses were analysed. The test results show that the natural frequency and the damping ratio of the superstructure for the pile-raft foundation and the fixed-base structure are different, owing to the soil-pile-structure interaction effect. The acceleration amplification ratio of the fixed-base superstructure shows a significantly higher value than that of the superstructure with a pile-raft foundation. The average peak acceleration ratio of the raft for the pile-raft foundation (raft/soil surface) is 1.2. Under the long period wave excitations, the bending moment of the pile is greater than that of short-period wave excitations, and the peak bending moment occurs at the pile head. The vertical and horizontal displacement and residual displacement increases with the earthquake intensity. These observations suggested that the design of nuclear power station with a pile-raft foundation embedded in clay cannot be simplified as a fixed-base structure. Moreover, adopting pile-raft foundation for nuclear power station will extend the choice of finding suitable construction sites for the nuclear power stations, and the test results could provide references for engineers

Proteome profiling of cadmium-induced apoptosis by antibody array analyses in human bronchial epithelial cells

Protein array technology is a powerful platform for the simultaneous determination of the expression levels of a number of proteins as well as post-translational modifications such as phosphorylation. Here, we screen and report for the first time, the dominant signaling cascades and apoptotic mediators during the course of cadmium (Cd)-induced cytotoxicity in human bronchial epithelial cells (BEAS-2B) by antibody array analyses. Proteins from control and Cd-treated cells were captured on Proteome Profiler™ Arrays for the parallel determination of the relative levels of protein phosphorylation and proteins associated with apoptosis. Our results indicated that the p38 MAPK- and JNK-related signal transduction pathways were dramatically activated by Cd treatment. Cd potently stimulates the phosphorylations of p38α (MAPK14), JNK1/2 (MAPK8/9), and JUN; while the phosphorylations of Akt1, ERK1/2 (MAPK3/1), GSK3β, and mTOR were suppressed. Moreover, there was an induction of proapoptotic protein BAX, release of cytochrome c (CYCS) from mitochondria, activation of caspase-3/9 (CASP3/9); as well as decreased expression of cell cycle checkpoint proteins (TP53, p21, and p27) and several inhibitors of apoptosis proteins (IAPs) [including cIAP-1/2 (BIRC2/3), XIAP (BIRC4), and survivin (BIRC5)]. Pretreatment of cells with the thiol antioxidant glutathione or p38 MAPK/JNK inhibitors before Cd treatment effectively abrogated ROS activation of p38 MAPK/JNK pathways and apoptosis-related proteins. Taken together, our results demonstrate that Cd causes oxidative stress-induced apoptosis; and the p38 MAPK/JNK and mitochondrial pathways are more importantly participated for signal transduction and the induction of apoptosis in Cd-exposed human lung cells.published_or_final_versio

Improved cascaded h‐bridge multilevel inverters with voltage‐boosting capability

This paper proposes two improved cascaded H‐bridge (ICHB) multilevel inverters that feature voltage‐boosting capability. The conventional H‐bridge with a front‐end dc–dc boost converter was restructured for single‐stage operation. The developed three‐level topology not only saves one power switch but also exhibits lower voltage stress across its capacitor. Extension to five-level generation was also introduced by merely adding two power switches and one capacitor. The final five‐level topology outperforms the classical cascaded H‐bridge (CHB) multilevel inverter with a significant reduction in the power switch count, with a 42% and 50% reduction in both the isolated dc source and inductor counts. The power efficiency was also improved without compromising the modularity feature of the classical CHB multilevel inverter. The operation and theoretical analysis of the proposed topologies were validated via simulations and experimental tests

Use of moxibustion to treat primary dysmenorrhea at two interventional times: study protocol for a randomized controlled trial

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Ultrasound volume projection image quality selection by ranking from convolutional RankNet.

Periodic inspection and assessment are important for scoliosis patients. 3D ultrasound imaging has become an important means of scoliosis assessment as it is a real-time, cost-effective and radiation-free imaging technique. With the generation of a 3D ultrasound volume projection spine image using our Scolioscan system, a series of 2D coronal ultrasound images are produced at different depths with different qualities. Selecting a high quality image from these 2D images is the crucial task for further scoliosis measurement. However, adjacent images are similar and difficult to distinguish. To learn the nuances between these images, we propose selecting the best image automatically, based on their quality rankings. Here, the ranking algorithm we use is a pairwise learning-to-ranking network, RankNet. Then, to extract more efficient features of input images and to improve the discriminative ability of the model, we adopt the convolutional neural network as the backbone due to its high power of image exploration. Finally, by inputting the images in pairs into the proposed convolutional RankNet, we can select the best images from each case based on the output ranking orders. The experimental result shows that convolutional RankNet achieves better than 95.5% top-3 accuracy, and we prove that this performance is beyond the experience of a human expert

The disposition and pharmacokinetics of Dioscorea nipponica Makino extract in rats

This study was aimed to investigate the disposition and pharmacokinetics of the total saponins of dioscorea (TSD) in rats. Male Sprague-Dawley rats were orally administrated with 3H labeled TSD at a single dose ratio of 80 mg TSD per 1 kg rat. Blood samples and feces were collected at different time points to measure the level of TSD activity. At the final time point, determination of the disposition of TSD in lung, kidney, heart, liver, adrenal, and small intestine were performed. From the blood samples' emission of radioactivity, pharmacokinetic parameters were derived as T1/2 = 33.33 ± 4.48 h, T max = 6.5 ± 0.71 h, AUC = 119400 ± 421097.67, and C max = 2643.33 ± 192.26 dpm/ml. There was 51.609% of 3H labeled substance excreted in 24 h. These results suggested that blood concentration of 3H-TSD was extremely low and the majority of TSD was excreted in the feces. The TSD was extensively distributed to multitissues. The radioactivity level was measured to be the highest in the liver, adrenal gland, and wall of the gastrointestinal tract. The radioactivity of TSD was still being detected in blood after 96 h. This showed TSD was excreted in vivo very slowly. © 2008 Academic Journals.published_or_final_versio

Protective effect of wild Corni fructus methanolic extract against acute alcoholic liver injury in mice

Background: In Chinese folk medicine, Corni fructus (C. fructus) has traditionally been used to improve liver function, although the mechanism underlying its activity remains unclear. The aim of the present study was to evaluate the protective effects of wild C. fructus methanolic extract against acute alcoholic liver injury.Methods: Alcohol was administered to mice for three consecutive days, either alone or in combination with C. fructus methanolic extract (50, 100, or 200mg/kg body weight/d). Serum and liver tissue were collected from the animals and subjected to biochemical and histopathological analyses.Results:C. fructus significantly alleviated alcohol-induced liver injury by reducing serum alanine aminotransferase, aspartate aminotransferase, and thiobarbituric acid reactive species, inhibiting hydroxyl radicals (center dot OH), and increasing total superoxide dismutase, glutathione peroxidase, and glutathione in the liver (P<0.05). In addition, the C. fructus treatment inhibited the expression and activity of cytochrome P450 2E1 (P<0.05)Conclusions:C. fructus could be a promising natural substance for ameliorating acute alcohol-induced oxidative stress and hepatic injury.- This work was supported by the Construction Project of Shaanxi Collaborative Innovation Center (2015, Shaanxi Sci-tech University); High-End Foreign Experts Recruitment Program [Grant GDW20146100228]; and Key Construction Program of International Cooperation Base in S&T Shaanxi Province, China [Grant 2015SD0018].info:eu-repo/semantics/publishedVersio