The role of regulatory B cells on hepatocellular carcinoma progression

Poster PresentationCongress Theme: Translating Discoveries into Prevention and CuresPURPOSE: Regulatory B cells (Bregs) play important roles in autoimmune diseases, but their function in hepatocellular carcinoma (HCC) progression remains unclear. This study attempted to unveil the role of Bregs on HCC progression. EXPERIMENTAL DESIGN: This study examined the distribution of intrahepatic B cells and circulating Bregs population at the level of phenotypes as well as functionality in HCC patients. The mechanisms of Bregs regulating liver tumor cells were further explored in a series of in vitro and in vivo functional studies. RESULTS: The percentage of B cells at tumor margin region was significantly higher than that in tumor or non-tumor region. Increased intrahepatic B cells at tumor margin were positively associated with tumor invasive features and more tumor recurrence. Besides, HCC patients had a significant higher percentage of circulating Bregs than healthy people. Increased circulating Bregs were positively correlated with advanced tumor staging, tumor multiplicity and venous infiltration. Next, our in vivo study firstly revealed that human Bregs promoted HCC tumor growth independent of Tregs in SCID mice. The migration of Bregs into tumor in mice was further confirmed by in vivo imaging and histology. Finally, the molecular mechanism of Bregs promoted proliferation and migration of HCC cells was proved by direct cell-cell interaction via CD40/CD154 signaling in vitro. Coculture of Bregs and HCC cells induced CD40/CD154-dependent cytokines secretion. CONCLUSION: Human Bregs promoted HCC growth and invasiveness by interacting with HCC tumor cells through CD40/CD154 signaling pathway. Bregs might be both a prognostic marker and a therapeutic target for HCC.published_or_final_versio

Interferon-gamma Inducible Protein 10 up-regulated by acute-phase graft injury induced late-phase cisplatin resistance after liver transplantation

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Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice - including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA

The clinical significance and potential therapeutic role of GPx3 in tumor recurrence after liver transplantation

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Clinical significance and therapeutic value of glutathione peroxidase 3 (GPx3) in hepatocellular carcinoma

AIMS: We aimed to investigate the clinical significance of GPx3 in hepatocellular carcinoma (HCC) and to characterize its tumor suppressive role. METHODS: HCC patients (113) who underwent hepatectomy were recruited to examine the clinical relevance of GPx3. The tumor suppressive role of GPx3 was studied by administration of recombinant GPx3 (rGPx3) or over-expression of GPx3 in HCC cells in vitro and in vivo. The therapeutic value of GPx3 for HCC was further investigated using human induced pluripotent stem cell derived mesenchymal stem cells (hiPSC-MSCs) as its delivery vehicle. RESULTS: Down-regulation of GPx3 significantly correlated with advanced tumor stage (P = 0.024), venous infiltration (P = 0.043) and poor overall survival (P = 0.007) after hepatectomy. Lower plasma GPx3 in HCC patients was significantly associated with larger tumor size (P = 0.011), more tumor nodules (P = 0.032) and higher recurrence (P = 0.016). Over-expression of GPx3 or administration of rGPx3 significantly inhibited proliferation and invasiveness of HCC cells in vitro and in vivo. Tumor suppressive activity of GPx3 was mediated through Erk-NFκB-SIP1 pathway. GPx3 could be delivered by hiPSC-MSCs into the tumor and exhibited tumor suppressive activity in vivo. CONCLUSIONS: GPx3 is a tumor suppressor gene in HCC and may possess prognostic and therapeutic value for HCC patients.published_or_final_versio

Tracking Target Signal Strengths on a Grid using Sparsity

Multi-target tracking is mainly challenged by the nonlinearity present in the measurement equation, and the difficulty in fast and accurate data association. To overcome these challenges, the present paper introduces a grid-based model in which the state captures target signal strengths on a known spatial grid (TSSG). This model leads to \emph{linear} state and measurement equations, which bypass data association and can afford state estimation via sparsity-aware Kalman filtering (KF). Leveraging the grid-induced sparsity of the novel model, two types of sparsity-cognizant TSSG-KF trackers are developed: one effects sparsity through $\ell_1$-norm regularization, and the other invokes sparsity as an extra measurement. Iterative extended KF and Gauss-Newton algorithms are developed for reduced-complexity tracking, along with accurate error covariance updates for assessing performance of the resultant sparsity-aware state estimators. Based on TSSG state estimates, more informative target position and track estimates can be obtained in a follow-up step, ensuring that track association and position estimation errors do not propagate back into TSSG state estimates. The novel TSSG trackers do not require knowing the number of targets or their signal strengths, and exhibit considerably lower complexity than the benchmark hidden Markov model filter, especially for a large number of targets. Numerical simulations demonstrate that sparsity-cognizant trackers enjoy improved root mean-square error performance at reduced complexity when compared to their sparsity-agnostic counterparts.Comment: Submitted to IEEE Trans. on Signal Processin

A novel oxygen carrier 'YQ23' suppresses the liver tumor metastasis by decreasing circulating endothelial progenitor cells and regulatory T cells

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Spawning rings of exceptional points out of Dirac cones

The Dirac cone underlies many unique electronic properties of graphene and topological insulators, and its band structure--two conical bands touching at a single point--has also been realized for photons in waveguide arrays, atoms in optical lattices, and through accidental degeneracy. Deformations of the Dirac cone often reveal intriguing properties; an example is the quantum Hall effect, where a constant magnetic field breaks the Dirac cone into isolated Landau levels. A seemingly unrelated phenomenon is the exceptional point, also known as the parity-time symmetry breaking point, where two resonances coincide in both their positions and widths. Exceptional points lead to counter-intuitive phenomena such as loss-induced transparency, unidirectional transmission or reflection, and lasers with reversed pump dependence or single-mode operation. These two fields of research are in fact connected: here we discover the ability of a Dirac cone to evolve into a ring of exceptional points, which we call an "exceptional ring." We experimentally demonstrate this concept in a photonic crystal slab. Angle-resolved reflection measurements of the photonic crystal slab reveal that the peaks of reflectivity follow the conical band structure of a Dirac cone from accidental degeneracy, whereas the complex eigenvalues of the system are deformed into a two-dimensional flat band enclosed by an exceptional ring. This deformation arises from the dissimilar radiation rates of dipole and quadrupole resonances, which play a role analogous to the loss and gain in parity-time symmetric systems. Our results indicate that the radiation that exists in any open system can fundamentally alter its physical properties in ways previously expected only in the presence of material loss and gain

CXCL10/CXCR3 signaling mobilized-regulatory T cells promote liver tumor recurrence after transplantation

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