Salvianolic Acid B Prevents Arsenic Trioxide-Induced Cardiotoxicity In Vivo and Enhances Its Anticancer Activity In Vitro

Clinical attempts to reduce the cardiotoxicity of arsenic trioxide (ATO) without compromising its anticancer activities remain to be an unresolved issue. In this study, we determined whether Sal B can protect against ATO-induced cardiac toxicity in vivo and increase the toxicity of ATO toward cancer cells. Combination treatment of Sal B and ATO was investigated using BALB/c mice and human hepatoma (HepG2) cells and human cervical cancer (HeLa) cells. The results showed that the combination treatment significantly improved the ATO-induced loss of cardiac function, attenuated damage of cardiomyocytic structure, and suppressed the ATO-induced release of cardiac enzymes into serum in BALB/c mouse models. The expression levels of Bcl-2 and p-Akt in the mice treated with ATO alone were reduced, whereas those in the mice given the combination treatment were similar to those in the control mice. Moreover, the combination treatment significantly enhanced the ATO-induced cytotoxicity and apoptosis of HepG2 cells and HeLa cells. Increases in apoptotic marker cleaved poly (ADP-ribose) polymerase and decreases in procaspase-3 expressions were observed through western blot. Taken together, these observations indicate that the combination treatment of Sal B and ATO is potentially applicable for treating cancer with reduced cardiotoxic side effects

Tetraethyl 2,2′-(2,3,5,6-tetrafluoro-p-phenylenedimethylene)dipropanoate1

In the mol­ecule of the title compound, C22H26F4O8, a crystallographic inversion centre is located at the centroid of the benzene ring. C—H⋯F and C—H⋯O intra­molecular hydrogen bonds are observed as well as an inter­molecular C—H⋯O inter­action

Evolution from quantum anomalous Hall insulator to heavy-fermion semimetal in magic-angle twisted bilayer graphene

The ground states of twisted bilayer graphene (TBG) at chiral and flat-band limit with integer fillings are known from exact solutions, while their dynamical and thermodynamical properties are revealed by unbiased quantum Monte Carlo (QMC) simulations. However, to elucidate experimental observations of correlated metallic, insulating and superconducting states and their transitions, investigations on realistic, or non-chiral cases are vital. Here we employ momentum-space QMC method to investigate the evolution of correlated states in magic-angle TBG away from chiral limit at charge neutrality with polarized spin/valley, which approximates to an experimental case with filling factor $\nu=-3$. We find that the ground state evolves from quatum anomalous Hall insulator into an intriguing correlated semi-metallic state as AA hopping strength reaches experimental values. Such a state resembles the recently proposed heavy-fermion representations with localized electrons residing at AA stacking regions and delocalized electrons itinerating via AB/BA stacking regions. The spectral signatures of the localized and itinerant electrons in the heavy-fermion semimetal phase are revealed, with the connection to experimental results being discussed.Comment: 6 pages, 4 figures with supplementary material (6 pages, 11 figures

1,2-Diphenyl­ethane-1,2-diyl diiso­nico­tinate monohydrate1

In the novel title compound, C26H20N2O4·H2O, the two phenyl rings make a dihedral angle of 45.3 (1)° with each other, and the dihedral angle between the two pyridyl planes is 69.8 (1)°

Effects of Chitosan Oligosaccharides on Human Blood Components

Chitosan oligosaccharide (COS) is known for its unique biological activities such as anti-tumor, anti-inflammatory, anti-oxidant, anti-bacterial activity, biological recognition, and immune enhancing effects, and thus continuous attracting many research interests in drug, food, cosmetics, biomaterials and tissue engineering fields. In comparison to its corresponding polymer, COS has much higher absorption profiles at the intestinal level, which results in permitting its quick access to the blood flow and potential contacting with blood components. However, the effects of COS on blood components remain unclear to date. Herein, two COS with different molecular weight (MW) were characterized by FTIR and 1H NMR, and then their effects on human blood components, including red blood cells (RBCs) (hemolysis, deformability, and aggregation), coagulation system [activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and the concentration of fibrinogen (Fib)], complement (C3a and C5a activation), and platelet (activation and aggregation), were comprehensively studied. In the case of RBCs, COS exhibited a low risk of hemolysis in a dose and molecular weight dependent manner and the irreversible aggregation was observed in their high concentration. For coagulation system, COS has a mild anticoagulation activity through blocking the intrinsic coagulation pathway. In addition, COS showed no effect on complement activation in C3a and C5a and on platelet activation while inhibition of platelet aggregation was evident. Finally, the mechanism that effects of COS on blood components was discussed and proposed

DNA vaccination with a gene encoding Toxoplasma gondii GRA6 induces partial protection against toxoplasmosis in BALB/c mice

<p>Abstract</p> <p>Background</p> <p>Infection with the protozoan <it>Toxoplasma gondii </it>causes serious public health problems and is of great economic importance worldwide. Protection from acute toxoplasmosis is known to be mediated by CD8+ T cells, but the <it>T. gondii </it>antigens and host genes required for eliciting protective immunity have been poorly defined. The <it>T. gondii </it>dense granule protein 6 (GRA6), recently proved to be highly immunogenic and produces fully immune protection in <it>T. gondii </it>infected BALB/c mice with an H-2L^dgene. The CD8+ T cell response of H-2L^dmice infected by the <it>T. gondii </it>strain seemed to target entirely to a single GRA6 peptide HF10-H-2L^dcomplex.</p> <p>Results</p> <p>To determine whether a GRA6-based DNA vaccine can elicit protective immune responses to <it>T. gondii </it>in BALB/c mice, we constructed a eukaryotic expression vector pcDNA3.1-HisGRA6 and tested its immunogenicity in a mouse model. BALB/c mice were vaccinated intramuscularly with three doses of GRA6 DNA and then challenged with a lethal dose of <it>T. gondii </it>RH strain tachyzoites. All immunized mice developed high levels of serum anti-GRA6 IgG antibodies, and <it>in vitro </it>splenocyte proliferation was strongly enhanced in mice adjuvanted with levamisole (LMS). Immunization with pcDNA3.1-HisGRA6 with LMS resulted in 53.3% survival of challenged BALB/c mice as compared to 40% survival of BALB/c without LMS. Additionally, immunized Kunming mice without an allele of H-2L^dfailed to survive.</p> <p>Conclusions</p> <p>Our result supports the concept that the acquired immune response is MHC restricted. This study has a major implication for vaccine designs using a single antigen in a population with diverse MHC class I alleles.</p

Comparative genomic analysis of the IDD genes in five Rosaceae species and expression analysis in Chinese white pear (Pyrus bretschneideri)

The INDETERMINATE DOMAIN (IDD) gene family encodes hybrid transcription factors with distinct zinc finger motifs and appears to be found in all higher plant genomes. IDD genes have been identified throughout the genomes of the model plants Arabidopsis thaliana and Oryza sativa, and the functions of many members of this gene family have been studied. However, few studies have investigated the IDD gene family in Rosaceae species (among these species, a genome-wide identification of the IDD gene family has only been completed in Malus domestica). This study focuses on a comparative genomic analysis of the IDD gene family in five Rosaceae species (Pyrus bretschneideri, Fragaria vesca, Prunus mume, Rubus occidentalis and Prunus avium). We identified a total of 68 IDD genes: 16 genes in Chinese white pear, 14 genes in F. vesca, 13 genes in Prunus mume, 14 genes in R. occidentalis and 11 genes in Prunus avium. The evolution of the IDD genes in these five Rosaceae species was revealed by constructing a phylogenetic tree, tracking gene duplication events, and performing a sliding window analysis and a conserved microsynteny analysis. The expression analysis of different organs showed that most of the pear IDD genes are found at a very high transcription level in fruits, flowers and buds. Based on our results with those obtained in previous research, we speculated that PbIDD2 and PbIDD8 might participate in flowering induction in pear. A temporal expression analysis showed that the expression patterns of PbIDD3 and PbIDD5 were completely opposite to the accumulation pattern of fruit lignin and the stone cell content. The results of the composite phylogenetic tree and expression pattern analysis indicated that PbIDD3 and PbIDD5 might be involved in the metabolism of lignin and secondary cell wall (SCW) formation. In summary, we provide basic information about the IDD genes in five Rosaceae species and thereby provide a theoretical basis for studying the function of these IDD genes

Banna Virus, China, 1987–2007

Banna viruses (BAVs) have been isolated from pigs, cattle, ticks, mosquitoes, and human encephalitis patients. We isolated and analyzed 20 BAVs newly isolated in China; this finding extends the distribution of BAVs from tropical zone to north temperate climates and demonstrate regional variations in BAV phylogeny and mosquito species possibly involved in BAV transmission

Nutlin-3 overcomes arsenic trioxide resistance and tumor metastasis mediated by mutant p53 in Hepatocellular Carcinoma

Background: Arsenic trioxide has been demonstrated as an effective anti-cancer drug against leukemia and solid tumors both in vitro and in vivo. However, recent phase II trials demonstrated that single agent arsenic trioxide was poorly effective against hepatocellular carcinoma (HCC), which might be due to drug resistance. Methods: Mutation detection of p53 gene in arsenic trioxide resistant HCC cell lines was performed. The therapeutic effects of arsenic trioxide and Nutlin-3 on HCC were evaluated both in vitro and in vivo. A series of experiments including MTT, apoptosis assays, co-Immunoprecipitation, siRNA transfection, lentiviral infection, cell migration, invasion, and epithelial-mesenchy-mal transition (EMT) assays were performed to investigate the underlying mechanisms. Results: The acquisition of p53 mutation contributed to arsenic trioxide resistance and enhanced metastatic potential of HCC cells. Mutant p53 (Mutp53) silence could re-sensitize HCC resistant cells to arsenic trioxide and inhibit the metastatic activities, while mutp53 overexpression showed the opposite effects. Neither arsenic trioxide nor Nutlin-3 could exhibit obvious effects against arsenic trioxide resistant HCC cells, while combination of them showed significant effects. Nutlin-3 can not only increase the intracellular arsenicals through inhibition of p-gp but also promote the p73 activation and mutp53 degradation mediated by arsenic trioxide. In vivo experiments indicated that Nutlin-3 can potentiate the antitumor activities of arsenic trioxide in an orthotopic hepatic tumor model and inhibit the metastasis to lung. Conclusions: Acquisitions of p53 mutations contributed to the resistance of HCC to arsenic trioxide. Nutlin-3 could overcome arsenic trioxide resistance and inhibit tumor metastasis through p73 activation and promoting mutant p53 degradation mediated by arsenic trioxide

Giant magnetic quantum oscillations in the thermal conductivity of TaAs: Indications of chiral zero sound

Charge transport of topological semimetals has been in the focus of intensive investigations because of their non-trivial band topology. Heat transport of these materials, on the other hand, is largely unexplored and remains elusive. Here we report on an observation of unprecedented, giant magnetic quantum oscillations of thermal conductivity in the prototypical Weyl semimetal TaAs. The oscillations are antiphase with the quantum oscillating electronic density of states of a Weyl pocket, and their amplitudes amount to two orders of magnitude of the estimation based on the Wiedemann-Franz law. Our analyses show that all the conventional heat-transport mechanisms through diffusions of propagating electrons, phonons and electron-hole bipolar excitations, are far inadequate to account for these phenomena. Taking further experimental facts that the parallel field configuration favors much higher magneto-thermal conductivity, we propose that the newly proposed chiral zero sound provides a reasonable explanation to these exotic phenomena. More work focusing on other topological semimetals along the same line is badly called for.Comment: 15 pages, 5 figure