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

Kinetic temperature of massive star-forming molecular clumps measured with formaldehyde IV. The ALMA view of N113 and N159W in the LMC

We mapped the kinetic temperature structure of two massive star-forming regions, N113 and N159W, in the Large Magellanic Cloud (LMC). We have used ~1.′′6 (~0.4 pc) resolution measurements of the para-H2CO JKaKc = 303–202, 322–221, and 321–220 transitions near 218.5 GHz to constrain RADEX non local thermodynamic equilibrium models of the physical conditions. The gas kinetic temperatures derived from the para-H2CO line ratios 322–221/303–202 and 321–220/303–202 range from 28 to 105 K in N113 and 29 to 68 K in N159W. Distributions of the dense gas traced by para-H2CO agree with those of the 1.3 mm dust and Spitzer 8.0 μm emission, but they do not significantly correlate with the Hα emission. The high kinetic temperatures (Tkin ≳ 50 K) of the dense gas traced by para-H2CO appear to be correlated with the embedded infrared sources inside the clouds and/or young stellar objects in the N113 and N159W regions. The lower temperatures (Tkin < 50 K) were measured at the outskirts of the H2CO-bearing distributions of both N113 and N159W. It seems that the kinetic temperatures of the dense gas traced by para-H2CO are weakly affected by the external sources of the Hα emission. The non thermal velocity dispersions of para-H2CO are well correlated with the gas kinetic temperatures in the N113 region, implying that the higher kinetic temperature traced by para-H2CO is related to turbulence on a ~0.4 pc scale. The dense gas heating appears to be dominated by internal star formation activity, radiation, and/or turbulence. It seems that the mechanism heating the dense gas of the star-forming regions in the LMC is consistent with that in Galactic massive star-forming regions located in the Galactic plane

The Effect of Intra-Abdominal Hypertension Incorporating Severe Acute Pancreatitis in a Porcine Model

Introduction: Abdominal compartment syndrome (ACS) and intra abdominal hypertension(IAH) are common clinical findings in patients with severe acute pancreatitis(SAP). It is thought that an increased intra abdominal pressure(IAP) is associated with poor prognosis in SAP patients. But the detailed effect of IAH/ACS on different organ system is not clear. The aim of this study was to assess the effect of SAP combined with IAH on hemodynamics, systemic oxygenation, and organ damage in a 12 h lasting porcine model

Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

The decay channel $\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p})$ is studied using a sample of $1.06\times 10^8$ $\psi^\prime$ events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the $p\bar{p}$ invariant mass spectrum. The enhancement can be fit with an $S$-wave Breit-Wigner resonance function with a resulting peak mass of $M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2$ and a narrow width that is $\Gamma<38 {\rm MeV/}c^2$ at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

Multi-scale spatio-temporal analysis of human mobility

The recent availability of digital traces generated by phone calls and online logins has significantly increased the scientific understanding of human mobility. Until now, however, limited data resolution and coverage have hindered a coherent description of human displacements across different spatial and temporal scales. Here, we characterise mobility behaviour across several orders of magnitude by analysing ∼850 individuals' digital traces sampled every ∼16 seconds for 25 months with ∼10 meters spatial resolution. We show that the distributions of distances and waiting times between consecutive locations are best described by log-normal and gamma distributions, respectively, and that natural time-scales emerge from the regularity of human mobility. We point out that log-normal distributions also characterise the patterns of discovery of new places, implying that they are not a simple consequence of the routine of modern life

Search for Charged Higgs Bosons in e+e- Collisions at \sqrt{s} = 189 GeV

A search for pair-produced charged Higgs bosons is performed with the L3 detector at LEP using data collected at a centre-of-mass energy of 188.6 GeV, corresponding to an integrated luminosity of 176.4 pb^-1. Higgs decays into a charm and a strange quark or into a tau lepton and its associated neutrino are considered. The observed events are consistent with the expectations from Standard Model background processes. A lower limit of 65.5 GeV on the charged Higgs mass is derived at 95 % confidence level, independent of the decay branching ratio Br(H^{+/-} -> tau nu)

Fe3O4–Au and Fe2O3–Au Hybrid Nanorods: Layer-by-Layer Assembly Synthesis and Their Magnetic and Optical Properties

A layer-by-layer technique has been developed to synthesize FeOOH–Au hybrid nanorods that can be transformed into Fe2O3–Au and Fe3O4–Au hybrid nanorods via controllable annealing process. The homogenous deposition of Au nanoparticles onto the surface of FeOOH nanorods can be attributed to the strong electrostatic attraction between metal ions and polyelectrolyte-modified FeOOH nanorods. The annealing atmosphere controls the phase transformation from FeOOH–Au to Fe3O4–Au and α-Fe2O3–Au. Moreover, the magnetic and optical properties of as-synthesized Fe2O3–Au and Fe3O4–Au hybrid nanorods have been investigated

Cattle Mammary Bioreactor Generated by a Novel Procedure of Transgenic Cloning for Large-Scale Production of Functional Human Lactoferrin

Large-scale production of biopharmaceuticals by current bioreactor techniques is limited by low transgenic efficiency and low expression of foreign proteins. In general, a bacterial artificial chromosome (BAC) harboring most regulatory elements is capable of overcoming the limitations, but transferring BAC into donor cells is difficult. We describe here the use of cattle mammary bioreactor to produce functional recombinant human lactoferrin (rhLF) by a novel procedure of transgenic cloning, which employs microinjection to generate transgenic somatic cells as donor cells. Bovine fibroblast cells were co-microinjected for the first time with a 150-kb BAC carrying the human lactoferrin gene and a marker gene. The resulting transfection efficiency of up to 15.79×10−2 percent was notably higher than that of electroporation and lipofection. Following somatic cell nuclear transfer, we obtained two transgenic cows that secreted rhLF at high levels, 2.5 g/l and 3.4 g/l, respectively. The rhLF had a similar pattern of glycosylation and proteolytic susceptibility as the natural human counterpart. Biochemical analysis revealed that the iron-binding and releasing properties of rhLF were identical to that of native hLF. Importantly, an antibacterial experiment further demonstrated that rhLF was functional. Our results indicate that co-microinjection with a BAC and a marker gene into donor cells for somatic cell cloning indeed improves transgenic efficiency. Moreover, the cattle mammary bioreactors generated with this novel procedure produce functional rhLF on an industrial scale

Low Levels of Human HIP14 Are Sufficient to Rescue Neuropathological, Behavioural, and Enzymatic Defects Due to Loss of Murine HIP14 in Hip14−/− Mice

Huntingtin Interacting Protein 14 (HIP14) is a palmitoyl acyl transferase (PAT) that was first identified due to altered interaction with mutant huntingtin, the protein responsible for Huntington Disease (HD). HIP14 palmitoylates a specific set of neuronal substrates critical at the synapse, and downregulation of HIP14 by siRNA in vitro results in increased cell death in neurons. We previously reported that mice lacking murine Hip14 (Hip14−/−) share features of HD. In the current study, we have generated human HIP14 BAC transgenic mice and crossed them to the Hip14−/− model in order to confirm that the defects seen in Hip14−/− mice are in fact due to loss of Hip14. In addition, we sought to determine whether human HIP14 can provide functional compensation for loss of murine Hip14. We demonstrate that despite a relative low level of expression, as assessed via Western blot, BAC-derived human HIP14 compensates for deficits in neuropathology, behavior, and PAT enzyme function seen in the Hip14−/− model. Our findings yield important insights into HIP14 function in vivo