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Breast carcinoma is the most common female cancer with considerable metastatic potential. Discovery of new therapeutic approaches for treatment of metastatic breast cancer is still needed. Here, we reported our finding with niclosamide, an FDA approved anthelmintic drug. The potency of niclosamide on breast cancer was assessed in vitro and in vivo. In this investigation, we found that niclosamide showed a dramatic growth inhibition against breast cancer cell lines and induced apoptosis of 4T1 cells in a dose-dependent manner. Further, Western blot analysis demonstrated the occurrence of its apoptosis was associated with activation of Cleaved caspases-3, down-regulation of Bcl-2, Mcl-1 and Survivin. Moreover, niclosamide blocked breast cancer cells migration and invasion, and the reduction of phosphorylated STAT3Tyr705, phosphorylated FAKTyr925 and phosphorylated SrcTyr416 were also observed. Furthermore, in our animal experiments, intraperitoneal administration of 20 mg/kg/d niclosamide suppressed 4T1 tumor growth without detectable toxicity. Histological and immunohistochemical analyses revealed a decrease in Ki67-positive cells, VEGF-positive cells and microvessel density (MVD) and an increase in Cleaved caspase-3-positive cells upon niclosamide. Notably, niclosamide reduced the number of myeloid-derived suppressor cells (MDSCs) in tumor tissues and blocked formation of pulmonary metastases. Taken together, these results demonstrated that niclosamide may be a promising candidate for breast cancer.

Acute liver failure (ALF) is a life-threatening illness. The extracorporeal cell-based bioartificial liver (BAL) system could bridge liver transplantation and facilitate liver regeneration for ALF patients by providing metabolic detoxification and synthetic functions. Previous BAL systems, based on hepatoma cells and non-human hepatocytes, achieved limited clinical advances, largely due to poor hepatic functions, cumbersome preparation or safety concerns of these cells. We previously generated human functional hepatocytes by lineage conversion (hiHeps). Here, by improving functional maturity of hiHeps and producing hiHeps at clinical scales (3 billion cells), we developed a hiHep-based BAL system (hiHep-BAL). In a porcine ALF model, hiHep-BAL treatment restored liver functions, corrected blood levels of ammonia and bilirubin, and prolonged survival. Importantly, human albumin and α-1-antitrypsin were detectable in hiHep-BAL-treated ALF pigs. Moreover, hiHep-BAL treatment led to attenuated liver damage, resolved inflammation and enhanced liver regeneration. Our findings indicate a promising clinical application of the hiHep-BAL system.

The influence of the chiral mean field on the $K^+$ transverse flow in heavy ion collisions at SIS energy is investigated within covariant kaon dynamics. For the kaon mesons inside the nuclear medium a quasi-particle picture including scalar and vector fields is adopted and compared to the standard treatment with a static potential. It is confirmed that a Lorentz force from spatial component of the vector field provides an important contribution to the in-medium kaon dynamics and strongly counterbalances the influence of the vector potential on the $K^+$ in-plane flow. The FOPI data can be reasonably described using in-medium kaon potentials based on effective chiral models. The information on the in-medium $K^+$ potential extracted from kaon flow is consistent with the knowledge from other sources.Comment: 24 pages, 6 figure

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Abstract. The electromagnetic properties of baryon octet are studied in the perturbative chiral quark model (PCQM). The relativistic quark wave function is extracted by fitting the theoretical results of the proton charge form factor to experimental data and the predetermined quark wave function is applied to study the electromagnetic form factors of other octet baryons as well as magnetic moments, charge and magnetic radii. The PCQM results are found, based on the predetermined quark wave function, in good agreement with experimental data.

Abstract.We apply the perturbative chiral quark model (PCQM) at one loop to analyze the axial form factor of the nucleon. This chiral quark model is based on an effective Lagrangian, where baryons are described by relativistic valence quarks and a perturbative cloud of Goldstone bosons as dictated by chiral symmetry. We apply the formalism to obtain analytical expressions for the axial form factor of the nucleon, which is given in terms of fundamental parameters of low-energy pion-nucleon physics (weak pion decay constant, strong pion-nucleon form factor) and of only one model parameter (radius of the nucleonic three-quark core).

Lineage conversion by expression of lineage-specific transcription factors is a process of epigenetic remodeling that has low efficiency. The mechanism by which a cell resists lineage conversion is largely unknown. Using hepatic-specific transcription factors Foxa3, Hnf1α and Gata4 (3TF) to induce hepatic conversion in mouse fibroblasts, we showed that 3TF induced strong activation of the ATM-p53 pathway, which led to proliferation arrest and cell death, and it further prevented hepatic conversion. Notably, ATM activation, independent of DNA damage, responded to chromatin opening during hepatic conversion. By characterizing the early molecular events during hepatic conversion, we found that Baf60b, a member of the SWI/SNF chromatin remodeling complex, links chromatin opening to ATM activation by facilitating ATM recruitment to the open chromatin regions of a panel of hepatic gene loci. These findings shed light on cellular responses to lineage conversion by revealing a function of the ATM-p53 pathway in sensing chromatin opening.