The Evaluation of Right Ventricular Synchrony by Two-Dimensional Speckle Tracking Echocardiography in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.

Objectives: Numerous studies have demonstrated impaired right ventricular (RV) synchronicity in pulmonary arterial hypertension (PAH). However, few studies have focused on connective tissue disease (CTD)-associated PAH. This study evaluates RV dyssynchrony and its prognostic value in CTD-associated PAH.

CD24LCN2 liver progenitor cells in ductular reaction contributed to macrophage inflammatory responses in chronic liver injury.

Background: CD24CK19/CD24SOX9 resident liver cells are activated and expanded after chronic liver injury in a ductular reaction. However, the sources and functions of these cells in liver damage remain disputed.

Results: The current study combined genetic lineage tracing with in vitro small-molecule-based reprogramming to define liver progenitor cells (LPCs) derived from hepatic parenchymal and non-parenchymal tissues.

Establishment of Functional Liver Spheroids From Human Hepatocyte-Derived Liver Progenitor-Like Cells for Cell Therapy.

Globally, about two million people die from liver diseases every year. Liver transplantation is the only reliable therapy for severe end-stage liver disease, however, the shortage of organ donors is a huge limitation. Human hepatocytes derived liver progenitor-like cells (HepLPCs) have been reported as a novel source of liver cells for development of models, cell therapies, and tissue-engineering applications, but their functionality as transplantation donors is unclear.

The combined induction of liver progenitor cells and the suppression of stellate cells by small molecules reverts chronic hepatic dysfunction.

We developed a cocktail of soluble molecules mimicking the milieu supporting liver regeneration that could convert mature hepatocytes to expandable liver progenitor-like cells . This study aimed to induce endogenous liver progenitor cells by the administration of the soluble molecules to provide an alternative approach for the resolution of liver fibrosis. cultured hepatocyte-derived liver progenitor-like cells (HepLPCs) were transplanted into CCL4-treated mice to investigate the therapeutic effect against liver fibrosis.

Evaluation of Left Ventricular Diastolic Function by 2-D Speckle Tracking Echocardiography in Patients with Connective Tissue Disease-Associated Pulmonary Artery Hypertension.

The purpose of this study was to evaluate the role of 2-D speckle tracking imaging in assessing left ventricular diastolic function in patients with connective tissue disease (CTD). A total of 98 CTD patients and 32 healthy controls were prospectively recruited. Early (E) and late (A) diastolic velocities of the transmitral flow were measured by pulsed Doppler echocardiography.

An extracorporeal bioartificial liver embedded with 3D-layered human liver progenitor-like cells relieves acute liver failure in pigs.

Clinical advancement of the bioartificial liver is hampered by the lack of expandable human hepatocytes and appropriate bioreactors and carriers to encourage hepatic cells to function during extracorporeal circulation. We have recently developed an efficient approach for derivation of expandable liver progenitor-like cells from human primary hepatocytes (HepLPCs). Here, we generated immortalized and functionally enhanced HepLPCs by introducing , a hepatocyte nuclear factor that enables potentially complete hepatic function.

[Metabolic Characteristics of WBC-deplted RBC suspension during Different Storage Stage in MAP Based on UPLC-MS/MS].

Objective: To explore the metabolic characteristics and metabolic markers of WBC-depleted RBCs in MAP preservation solution and to analyzed the metabolic profile of RBC in MAP preservation solution by using metabolomics.

Methods: The changes of metabolitcs in 10 U WBC-depleted RBC suspension at 3-different storage period (D 0, D 14 and D 35) were detected by using the UPLC-MS/MS, the charaeteristic ions and metabolic markers of RBC stored in preservation sblution for 0 d, 14 d and 35 days were analyzed by using the principal component analysis(PCA).

Results: The number of characteristic ions in RBC and supernatant extracts detected during the initial, middle and final storage could be clearly distinguiseed.

Expansion and differentiation of human hepatocyte-derived liver progenitor-like cells and their use for the study of hepatotropic pathogens.

The study of pathophysiological mechanisms in human liver disease has been constrained by the inability to expand primary hepatocytes in vitro while maintaining proliferative capacity and metabolic function. We and others have previously shown that mouse mature hepatocytes can be converted to liver progenitor-like cells in vitro with defined chemical factors. Here we describe a protocol achieving efficient conversion of human primary hepatocytes into liver progenitor-like cells (HepLPCs) through delivery of developmentally relevant cues, including NAD -dependent deacetylase SIRT1 signaling.

Synergistic antitumoral efficacy of a novel replicative adenovirus SG611-PDCD5 and daunorubicin in human leukemic cells.

Background: Daunorubicin is a traditional chemotherapeutic agent that plays a pivotal role in leukemia therapy. However, the dose-related toxicity remains a considerable challenge. The apoptosis-regulating gene, , is downregulated in various tumors, including leukemias, and may provide a potential target for the diagnosis and treatment of leukemia.

Synergistic antitumor activity of triple-regulated oncolytic adenovirus with VSTM1 and daunorubicin in leukemic cells.

V-set and transmembrane domain-containing 1 (VSTM1), which is downregulated in bone marrow cells from leukemia patients, may provide a diagnostic and treatment target. Here, a triple-regulated oncolytic adenovirus was constructed to carry a VSTM1 gene expression cassette, SG611-VSTM1, and contained the E1a gene with a 24-nucleotide deletion within the CR2 region under control of the human telomerase reverse transcriptase promoter, E1b gene directed by the hypoxia response element, and VSTM1 gene controlled by the cytomegalovirus promoter. Real-time quantitative PCR and Western blot analyses showed that SG611-VSTM1 expressed VSTM1 highly efficiently in the human leukemic cell line K562 compared with SG611.

p53 promotes inflammation-associated hepatocarcinogenesis by inducing HMGB1 release.

Background & Aims: Hepatocellular carcinoma (HCC) develops in response to chronic hepatic injury. Although induced cell death is regarded as the major component of p53 tumor-suppressive activity, we recently found that sustained p53 activation subsequent to DNA damage promotes inflammation-associated hepatocarcinogenesis. Here we aim at exploring the mechanism linking p53 activation and hepatic inflammation during hepatocarcinogenesis.

Rats deficient for p53 are susceptible to spontaneous and carcinogen-induced tumorigenesis.

The p53 tumor suppressor gene is highly mutated in human cancers. Individuals who inherit one p53 mutant allele are susceptible to a wide range of tumor types, including breast cancer and sarcoma. We recently generated p53 knockout rats through gene targeting in embryonic stem cells.

[In vitro construction and confirmation of adenovirus containing a mifepristone (RU486)-inducible regulation system for NRF2 gene].

Objective: To construct an adenovirus containing a mifepristone (RU486)-inducible regulation system for NRF2 gene, express the product in H460 cell and verify whether the mentioned system can control the gene expression and assess its efficiency.

Methods: A RU486-inducible regulation system for Nrf2 gene was introduced into an adenovirus. The confirmation was performed through the LUC and Dsred genes.

[Synergistic killing effect of the conditionally replicating adenoviruses carrying programmed cell death 5 gene and etoposide on K562 cells].

The expression levels of programmed cell death 5 (PDCD5) are down-regulated in many malignancies. SG611-pdcd5, a recombinant conditionally replicative adenovirus carrying pdcd5 gene expression cassette, can evidently kill the leukemic cells and protect selectively the normal cells. The purpose of this study was to investigate the synergistic killing effect of SG611-pdcd5 and low-dose etoposide (VP-16) on K562 cells.

Endotoxin accumulation prevents carcinogen-induced apoptosis and promotes liver tumorigenesis in rodents.

Unlabelled: Increasing evidence suggests that the presence of endotoxemia is of substantial clinical relevance to patients with cirrhosis, but it is unclear whether and how gut-derived LPS amplifies the tumorigenic response of the liver. We found that the circulating levels of LPS were elevated in animal models of carcinogen-induced hepatocarcinogenesis. Reduction of LPS using antibiotics regimen in rats or genetic ablation of its receptor Toll-like receptor 4 (TLR4) in mice prevented excessive tumor growth and multiplicity.

[Establishment and characterization of a human gallbladder carcinoma cell line EH-GB1 originated from a metastatic tumor].

Objective: To establish a human gallbladder carcinoma cell line derived from a metastatic gallbladder carcinoma and identify its biological characteristics.

Methods: Tissue samples were separated from the surgical specimen obtained from a patient with metastatic carcinoma and single-cell suspension was prepared. Then the cells were cultured in DMEM medium supplemented with 15% fetal bovine serum.

[Measurement of the cross section in Li(2P)+H2-->LiH+H reaction].

At a Li density of approximately 10(13) cm(-3), the lithium vapor was irradiated in a five-arm stainless steel heat pipe oven containing Li and H2 with pulses of radiation from a N2-laser-pumped dye laser, populating Li(2P) state by the Li(2S-->2P) resonance transition at 670.8 nm. Typical operating pressure of H2 was 60-300 Pa.

[Collisional energy transfer between excited Rb atoms].

Energy pooling (EP) was observed in Rb vapor following pulsed optical excitation to the 5P1/2 state. The 5P3/2 state was populated by the energy transfer process: Rb(5P1/2)+Rb(5S1/2) --> Rb(5P3/2)+Rb(5Sl/2). The resulting densities of Rb atoms at the 5P1/2 level were obtained from the absorption of narrow spectral line from a Rb hollow cathode lamp, connecting the 5P1/2 state to 7S state.

Abrogation of local cancer recurrence after radiofrequency ablation by dendritic cell-based hyperthermic tumor vaccine.

Local recurrence is a therapeutic challenge for radiofrequency ablation (RFA) in treatment of small solid focal malignancies. Here we show that RFA induced heat shock proteins (HSPs) expression and high mobility group box-1 (HMGB1) translocation in xenografted melanoma, which might create a proinflammatory microenvironment that favors tumor antigen presentation and activation of the effector T cells. On this basis, we investigate whether a prime-boost strategy combining a prime with heat-shocked tumor cell lysate-pulsed dendritic cell (HT-DC) followed by an in situ boost with radiofrequency thermal ablation can prevent local tumor recurrence.

[Construction and verification of a novel triple-regulated oncolytic adenovirus carrying gene Pdcd5].

The purpose of this study was to construct a recombinant conditionally replicating adenovirus (CRAd) expressing programmed cell death 5 (pdcd5). Pdcd5 gene was inserted in the E3 region of SG600-a CRAd in which the key genes for virus replication E1a and E1b were controlled under the human telomerase reverse transcriptase promoter (hTERTp) and the hypoxia response element (HRE) respectively, and with a deletion of 24 nucleotides within CR2 region of E1a. The insertion and orientation of all recombined plasmids were confirmed by restriction enzyme digestion and polymerase chain reaction (PCR).

A gutless adenoviral vector expressing full-length anti-Her2 antibody.

1. Therapeutic monoclonal antibodies are increasingly being used in clinical cancer treatment, but their complex technology and high cost limit their use. Helper-dependent (HD) adenoviruses are among the most efficient and safe gene therapy vectors capable of mediating long-term expression.