Heme activates TLR4-mediated inflammatory injury via MyD88/TRIF signaling pathway in intracerebral hemorrhage

<p>Abstract</p> <p>Background</p> <p>Inflammatory injury plays a critical role in intracerebral hemorrhage (ICH)-induced neurological deficits; however, the signaling pathways are not apparent by which the upstream cellular events trigger innate immune and inflammatory responses that contribute to neurological impairments. Toll-like receptor 4 (TLR4) plays a role in inflammatory damage caused by brain disorders.</p> <p>Methods</p> <p>In this study, we investigate the role of TLR4 signaling in ICH-induced inflammation. In the ICH model, a significant upregulation of TLR4 expression in reactive microglia has been demonstrated using real-time RT-PCR. Activation of microglia was detected by immunohistochemistry, cytokines were measured by ELISA, MyD88, TRIF and NF-κB were measured by Western blot and EMSA, animal behavior was evaluated by animal behavioristics.</p> <p>Results</p> <p>Compared to WT mice, TLR4^−/−mice had restrained ICH-induced brain damage showing in reduced cerebral edema and lower neurological deficit scores. Quantification of cytokines including IL-6, TNF-α and IL-1β and assessment of macrophage infiltration in perihematoma tissues from TLR4^−/−, MyD88^−/−and TRIF^−/−mice showed attenuated inflammatory damage after ICH. TLR4^−/−mice also exhibited reduced MyD88 and TRIF expression which was accompanied by decreased NF-κB activity. This suggests that after ICH both MyD88 and TRIF pathways might be involved in TLR4-mediated inflammatory injury possibly via NF-κB activation. Exogenous hemin administration significantly increased TLR4 expression and microglial activation in cultures and also exacerbated brain injury in WT mice but not in TLR4^−/−mice. Anti-TLR4 antibody administration suppressed hemin-induced microglial activation in cultures and in the mice model of ICH.</p> <p>Conclusions</p> <p>Our findings suggest that heme potentiates microglial activation <it>via </it>TLR4, in turn inducing NF-κB activation <it>via </it>the MyD88/TRIF signaling pathway, and ultimately increasing cytokine expression and inflammatory injury in ICH. Targeting TLR4 signaling may be a promising therapeutic strategy for ICH.</p

Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (mu_B > 500 MeV), effects of chiral symmetry, and the equation-of-state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2022, in the context of the worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal

Sequence variations in DNA repair gene XPC is associated with lung cancer risk in a Chinese population: a case-control study

<p>Abstract</p> <p>Background</p> <p>The nucleotide excision repair (NER) protein, xeroderma pigmentosum C (XPC), participates in recognizing DNA lesions and initiating DNA repair in response to DNA damage. Because mutations in <it>XPC </it>cause a high risk of cancer in XP patients, we hypothesized that inherited sequence variations in <it>XPC </it>may alter DNA repair and thus susceptibility to cancer.</p> <p>Methods</p> <p>In this hospital-based case-control study, we investigated five <it>XPC </it>tagging, common single nucleotide polymorphisms (tagging SNPs) in 1,010 patients with newly diagnosed lung cancer and 1,011 matched cancer free controls in a Chinese population.</p> <p>Results</p> <p>In individual tagging SNP analysis, we found that rs3731055<it>AG+AA </it>variant genotypes were associated with a significantly decreased risk of lung adenocarcinoma [adjusted odds ratio (OR), 0.71; 95% confidence interval (CI), 0.56–0.90] but an increased risk of small cell carcinomas [adjusted OR, 1.79; 95% CI, 1.05–3.07]. Furthermore, we found that haplotype <it>ACCCA </it>was associated with a decreased risk of lung adenocarcinoma [OR, 0.78; 95% CI, 0.62–0.97] but an increased risk of small cell carcinomas [OR, 1.68; 95% CI, 1.04–2.71], which reflected the presence of rs3731055<it>A </it>allele in this haplotype. Further stratified analysis revealed that the protective effect of rs3731055<it>AG+AA </it>on risk of lung adenocarcinoma was more evident among young subjects (age ≤ 60) and never smokers.</p> <p>Conclusion</p> <p>These results suggest that inherited sequence variations in <it>XPC </it>may modulate risk of lung cancer, especially lung adenocarcinoma, in Chinese populations. However, these findings need to be verified in larger confirmatory studies with more comprehensively selected tagging SNPs.</p

Synthesis, Magnetic Anisotropy and Optical Properties of Preferred Oriented Zinc Ferrite Nanowire Arrays

Preferred oriented ZnFe2O4 nanowire arrays with an average diameter of 16 nm were fabricated by post-annealing of ZnFe2 nanowires within anodic aluminum oxide templates in atmosphere. Selected area electron diffraction and X-ray diffraction exhibit that the nanowires are in cubic spinel-type structure with a [110] preferred crystallite orientation. Magnetic measurement indicates that the as-prepared ZnFe2O4 nanowire arrays reveal uniaxial magnetic anisotropy, and the easy magnetization direction is parallel to the axis of nanowire. The optical properties show the ZnFe2O4 nanowire arrays give out 370–520 nm blue-violet light, and their UV absorption edge is around 700 nm. The estimated values of direct and indirect band gaps for the nanowires are 2.23 and 1.73 eV, respectively

Interactive and Single Effects of Ectomycorrhiza Formation and Bacillus cereus on Metallothionein MT1 Expression and Phytoextraction of Cd and Zn by Willows

Single and joint ectomycorrhizal (+ Hebeloma mesophaeum) and bacterial (+ Bacillus cereus) inoculations of willows (Salix viminalis) were investigated for their potential and mode of action in the promotion of cadmium (Cd) and zinc (Zn) phytoextraction. Dual fungal and bacterial inoculations promoted the biomass production of willows in contaminated soil. Single inoculations either had no effect on the plant growth or inhibited it. All inoculated willows showed increased concentrations of nutritional elements (N, P, K and Zn) and decreased concentrations of Cd in the shoots. The lowest biomass production and concentration of Cd in the willows (+ B. cereus) were combined with the strongest expression of metallothioneins. It seems that biotic stress from bacterial invasion increased the synthesis of these stress proteins, which responded in decreased Cd concentrations. Contents of Cd and Zn in the stems of willows were combination-specific, but were always increased in dual inoculated plants. In conclusion, single inoculations with former mycorrhiza-associated B. cereus strains decreased the phytoextraction efficiency of willows by causing biotic stress. However, their joint inoculation with an ectomycorrhizal fungus is a very promising method for promoting the phytoextraction of Cd and Zn through combined physiological effects on the plant

Experimental and theoretical confirmation of an orthorhombic phase transition in niobium at high pressure and temperature

Compared to other body-centered cubic (bcc) transition metals, Nb has been the subject of fewer compression studies and there are still aspects of its phase diagram which are unclear. Here, we report a combined theoretical and experimental study of Nb under high pressure and temperature. We present the results of static laser-heated diamond anvil cell experiments up to 120 GPa using synchrotron-based fast x-ray diffraction combined with ab initio quantum molecular dynamics simulations. The melting curve of Nb is determined and evidence for a solid-solid phase transformation in Nb with increasing temperature is found. The high-temperature phase of Nb is orthorhombic Pnma. The bcc-Pnma transition is clearly seen in the experimental data on the Nb principal Hugoniot. The bcc-Pnma coexistence observed in our experiments is explained. Agreement between the measured and calculated melting curves is very good except at 40–60 GPa where three experimental points lie below the theoretical melting curve by 250 K (or 7%); a possible explanation is given