Multifunctional Bagasse Foam with Improved Thermal Insulation and Flame Retardancy by a Borax-Induced Self-Assembly and Ambient Pressure Drying Technique.

Cellulose foams are considered an effective alternative to plastic foam, because of their advantages of low density, high porosity, low thermal conductivity, and renewable nature. However, they still suffer from complex processing, poor mechanical properties, and flammability. As an agricultural waste, bagasse is rich in cellulose, which has attracted much attention. Inspired by the fact that borate ions can effectively enhance the strength of plant tissue by their cross-linking with polysaccharides, the present work designs and fabricates a series of multifunctional bagasse foams with robust strength and improved thermal insulation and flame retardancy via a unique borax-induced self-assembly and atmospheric pressure drying route using bagasse as a raw material, borate as a cross-linking agent, and chitosan as an additive. As a result, the optimized foam exhibits a high porosity (93.5%), a high hydrophobic water contact angle (150.4°), a low thermal conductivity (63.4 mW/(m·K) at 25 °C), and an outstanding flame retardancy. The present study provides a novel and inspiring idea for large-scale production of cellulose foams through an environmentally friendly and cost-effective approach.

Infiltrating regulatory T cells promote invasiveness of liver cancer cells via inducing epithelial-mesenchymal transition.

BACKGROUND: Regulatory T (Treg) cells are a major component of the microenvironment of hepatocellular carcinoma (HCC) contributing to immunosuppression. The present study aimed to evaluate the effects of Treg cells on the invasion potential of HCC. METHODS: Infiltrating Treg cells were isolated from fresh HCC tissues by immunomagnetic bead separation and detected by flow cytometry. Circulating tumor cells (CTCs) were detected using the CellSearch platform. The cell migration and invasion potentials were evaluated by Transwell assays. The cell viability was tested by the cell counting kit-8 (CCK8) approach, and the apoptosis rates were determined by flow cytometry. The concentrations of active transforming growth factor-ß1 (TGFß1) were measured by enzyme-linked immunosorbent assay. RESULTS: Infiltrating Treg cells significantly correlated with the number of CTCs and vascular invasion (both P<0.05). Moreover, these cells could greatly promote HCC migration, invasion, and proliferation, and inhibit HCC apoptosis. Polymerase chain reaction and Western blot assays revealed that Treg cells significantly decreased the expression levels of epithelium-related molecules and increased the expression levels of mesenchyme-related molecules. Treg cells could activate Smad2/3 via secreting TGFß1, and these effects could be impaired by knocking down the expression of TGFß1 in Treg cells. CONCLUSIONS: The involvement of infiltrating Treg cells in triggering the TGFß1 signaling pathway and promoting the epithelial-mesenchymal transition (EMT) of cancer cells during tumor hematogenous dissemination is presumably responsible for increasing the invasiveness potential of HCC cells. Targeting Treg cells in microenvironments can be a promising therapeutic strategy to improve the prognosis for patients with HCC undergoing resection.

The effects of SAHA on radiosensitivity in pancreatic cancer cells by inducing apoptosis and targeting RAD51.

Suberoyl anilide hydroxamic acid (SAHA) is one of the most promising Histone deacetylases(HDAC) inhibitors which has shown significant anti-tumor activity for many malignancies. We explored the potential mechanism of the radiosensitivity effect of SAHA in Panc-1 cells and attempted to develop SAHA as a systemic treatment strategy for pancreatic cancer. Growth inhibition was detected by CCK-8 assay. Radiosensitizing enhancement ratio was determined by clonogenic assay. The cell cycle and apoptosis assay was detected using flow cytometry and annexin-V/PI. The level of Bax, Bcl-2, Ku70, Ku86, RAD51, RAD54 protein expression were detected using Western blot analysis. Gene silencing was processed by lentiviral vector and qRT-PCR was performed to detect mRNA expression. The results revealed that SAHA inhibited the proliferation of Panc-1 cells. SAHA enhanced the radiosensitivity with a sensitization enhancement ratio(SER) of 1.10 of the Panc-1 cells. SAHA induced G2-M phase arrest and apoptosis of Panc-1 cells with radiation. SAHA upregulated Bax and downregulated Bcl-2, Ku70, Ku86, RAD51, RAD54 protein expression of irradiated Panc-1 cells. SAHA enhanced the radiosensitivity of Panc-1 cells by modulating RAD51 expression. SAHA enhanced radiosensitivity to pancreatic carcinoma Panc-1 cells. It was associated with the G2-M phase arrest and apoptosis via modulation of Bax and Bcl-2 expression. Downregulation of Ku70, Ku86, RAD51 and RAD54 expression caused suppression of HR-mediated DNA repair. SAHA is a good radiosensitizer for pancreatic cancer treatment.

A mouse radiation-induced liver disease model for stereotactic body radiation therapy validated in patients with hepatocellular carcinoma.

PURPOSE: Lower radiation tolerance of the whole liver hinders dose escalations of stereotactic body radiation therapy (SBRT) in hepatocellular carcinoma (HCC) treatment. This study was conducted to define the exact doses that result in radiation-induced liver disease (RILD) as well as to determine dose constraints for the critical organs at risk (OARs) in mice; these parameters are still undefined in HCC SBRT. METHODS: This study consisted of two phases. In the primary phase, mice treated with helical tomotherapy-based SBRT were stratified according to escalating radiation doses to the livers. The pathological differences, signs [such as mouse performance status (MPS)], and serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/albumin levels were observed. Radiation-induced disease severities of the OARs were scored using systematic evaluation standards. In the validation phase in humans, 13 patients with HCC who had undergone radiotherapy before hepatectomy were enrolled to validate RILD pathological changes in a mouse study. RESULTS: The evaluation criteria of the mouse liver radiotherapy-related signs were as follows: MPS ≥ 2.0 ± 0.52, AST/ALT ≥ 589.2 ± 118.5/137.4 ± 15.3 U/L, serum albumin ≤ 16.8 ± 2.29 g/L. The preliminary dose constraints of the OARs were also obtained, such as those for the liver (average dose ≤ 26.36 ± 1.71 Gy) and gastrointestinal tract (maximum dose ≤ 22.63 Gy). Mouse RILD models were able to be developed when the livers were irradiated with average doses of ≥31.76 ± 1.94 Gy (single fraction). RILD pathological changes in mice have also been validated in HCC patients. CONCLUSIONS: Mouse RILD models could be developed with SBRT based on the dose constraints for the OARs and evaluation criteria of mouse liver radiotherapy-related signs, and the authors' results favor the study of further approaches to treat HCC with SBRT.

A polymeric nanoparticle formulation of curcumin in combination with sorafenib synergistically inhibits tumor growth and metastasis in an orthotopic model of human hepatocellular carcinoma.

Curcumin, a yellow polyphenol extracted from the rhizome of turmeric root (Curcuma longa) has potent anti-cancer properties in many types of tumors with ability to reverse multidrug resistance of cancer cells. However, widespread clinical application of this agent in cancer and other diseases has been limited due to its poor aqueous solubility. The recent findings of polymeric nanoparticle formulation of curcumin (NFC) have shown the potential for circumventing the problem of poor solubility, however evidences for NFC's anti-cancer and reverse multidrug resistance properties are lacking. Here we provide models of human hepatocellular carcinoma (HCC), the most common form of primary liver cancer, in vitro and in vivo to evaluate the efficacy of NFC alone and in combination with sorafenib, a kinase inhibitor approved for treatment of HCC. Results showed that NFC not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. Moreover, in combination with sorafenib, NFC induced HCC cell apoptosis and cell cycle arrest. Mechanistically, NFC and sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway. Furthermore, the combination therapy significantly decreased the population of CD133-positive HCC cells, which have been reported as cancer initiating cells in HCC. Taken together, NanoCurcumin provides an opportunity to expand the clinical repertoire of this agent. Additional studies utilizing a combination of NanoCurcumin and sorafenib in HCC are needed for further clinical development.

Grain Boundary Structures and Electronic Properties of Hexagonal Boron Nitride on Cu(111).

Grain boundaries (GBs) of hexagonal boron nitride (h-BN) grown on Cu(111) were investigated by scanning tunneling microscopy/spectroscopy (STM/STS). The first experimental evidence of the GBs composed of square-octagon pairs (4|8 GBs) was given, together with those containing pentagon-heptagon pairs (5|7 GBs). Two types of GBs were found to exhibit significantly different electronic properties, where the band gap of the 5|7 GB was dramatically decreased as compared with that of the 4|8 GB, consistent with our obtained result from density functional theory (DFT) calculations. Moreover, the present work may provide a possibility of tuning the inert electronic property of h-BN via grain boundary engineering.

Quasi-freestanding monolayer heterostructure of graphene and hexagonal boron nitride on Ir(111) with a zigzag boundary.

In-plane heterostructure of hexagonal boron nitride and graphene (h-BN-G) has become a focus of graphene research owing to its tunable bandgap and intriguing properties. We report herein the synthesis of a quasi-freestanding h-BN-G monolayer heterostructure on a weakly coupled Ir(111) substrate, where graphene and h-BN possess distinctly different heights and surface corrugations. An atomically sharp zigzag type boundary has been found to dominate the patching interface between graphene and h-BN, as evidenced by high-resolution Scanning tunneling microscopy investigation as well as density functional theory calculation. Scanning tunneling spectroscopy studies indicate that the graphene and h-BN tend to exhibit their own intrinsic electronic features near the patching boundary. The present work offers a deep insight into the h-BN-graphene boundary structures both geometrically and electronically together with the effect of adlayer-substrate coupling.

TLR4-dependant immune response, but not hepatitis B virus reactivation, is important in radiation-induced liver disease of liver cancer radiotherapy.

Toll-like receptor 4 (TLR4) is an important trigger of the immune response against hepatitis B virus (HBV) infection and liver injuries. The roles of HBV reactivation versus TLR4-dependant immune response may be critical factors in preventing radiation-induced liver diseases (RILDs) after liver cancer radiotherapy. This study consists of three phases. In the primary phase, livers of mutant TLR4 (TLR4(-)) mice were irradiated with 30 Gy in either the absence or presence of HBV infection. The latter was done by introduction of plasmid pAAV/HBV 1.2. In the advanced phase, RILDs were compared in normal TLR4 (TLR4(+)) versus TLR4(-) mice. In the validation phase, 28 liver cancer patients who had undergone radiotherapy before hepatectomy were enrolled. Liver biopsies near tumors, irradiated with 35-48 Gy, were used to construct tissue microarrays. HBV reactivation, TLR4 expression, and severity of RILDs were studied in both mouse and human. More HBV reactivation, without significant RILD, was observed in irradiated versus unirradiated TLR4(-) mice. RILD scores of TLR4(+) mice were higher than TLR4(-) mice. In humans, serious RILDs tended to develop in patients with high TLR4 expression, but not in patients with low TLR4 or high HBV surface antigen expression. High TLR4 expression was seen in only 2 of 12 HBV-reactive patients, but in HBV-nonreactive patients, it was seen in 6 of 9 (P < 0.03). In summary, RILDs correlated with high TLR4 expression, but not with HBV reactivation, which is inhibited in liver with high TLR4 expression after liver cancer radiotherapy.

18F-FDG PET/CT imaging in primary cardiac angiosarcoma: diagnosis and follow-up.

A 40-year-old woman presented with recurrent chest tightness and shortness of breath for 10 days. The echocardiogram and MRI revealed a mass in the right atrium. FDG PET/CT was performed for further evaluation. The images demonstrated abnormally increased activity in the right atrial mass. The result of pathological examination after the surgical removal of the mass was consistent with angiosarcoma. Despite of receiving aggressive therapy including radiation, the patient had recurrent and metastatic malignancy 8 months later.

Toward single-layer uniform hexagonal boron nitride-graphene patchworks with zigzag linking edges.

The atomic layer of hybridized hexagonal boron nitride (h-BN) and graphene has attracted a great deal of attention after the pioneering work of P. M. Ajayan et al. on Cu foils because of their unusual electronic properties (Ci, L. J.; et al. Nat. Mater. 2010, 9, 430-435). However, many fundamental issues are still not clear, including the in-plane atomic continuity as well as the edge type at the boundary of hybridized h-BN and graphene domains. To clarify these issues, we have successfully grown a perfect single-layer h-BN-graphene (BNC) patchwork on a selected Rh(111) substrate, via a two-step patching growth approach. With the ideal sample, we convinced that at the in-plane linking interface, graphene and h-BN can be linked perfectly at an atomic scale. More importantly, we found that zigzag linking edges were preferably formed, as demonstrated by atomic-scale scanning tunneling microscopy images, which was also theoretically verified using density functional theory calculations. We believe the experimental and theoretical works are of particular importance to obtain a fundamental understanding of the BNC hybrid and to establish a deliberate structural control targeting high-performance electronic and spintronic devices.

Single and polycrystalline graphene on Rh(111) following different growth mechanisms.

Graphene grown on the same substrate but under different growth conditions may evolve diverse characteristics and disparate growth mechanisms. To explore this issue, graphene is prepared on Rh(111) by both ultrahigh vacuum and ambient-pressure chemical vapor deposition methods and the different growth behaviors, the atomic-scale structures, and the stacking geometry are analysed, mainly by virtue of scanning tunneling microscope. Interestingly, with ultrahigh vacuum chemical vapor deposition growth at 600 °C, a template growth of graphene by the Rh(111) lattice is obtained, reflected with the formation of a uniform graphene moiré. In comparison, with the ambient-pressure chemical vapor deposition at 1000 °C by different quenching processes, monolayer and randomly stacked few-layer polycrystalline graphene is achieved, probably directed by combined surface catalysis and segregation mechanisms. In this case, strong and weak interactions between graphene and Rh substrates are suggested, with the samples prepared under vacuum and ambient-pressure conditions, respectively. This work is expected to contribute greatly to the exploration of interactions between graphene and a substrate, as well as the segregation mechanism of graphene growth on polycrystalline transitional metal substrates.

Enhanced production of CTGF and IL-11 from highly metastatic hepatoma cells under hypoxic conditions: an implication of hepatocellular carcinoma metastasis to bone.

PURPOSE: The biology underlying bone-specific metastasis (BM) of hepatocellular carcinoma (HCC) is poorly understood. The goal of the present study is to further elucidate the molecular and cellular mechanisms underlying HCC with BM. METHODS: The expression of connective tissue growth factor (CTGF) and interleukin-11 (IL-11) in RNA extracted from 127 formalin-fixed, paraffin-embedded HCC specimens was examined by quantitative real-time polymerase chain reaction. A cellular hypoxic model was established in vitro to investigate CTGF and osteoprotegerin (OPG) expression and roles in hypoxia-induced tumor aggressiveness. RESULTS: The mean CTGF expression in BM versus non-metastatic samples was 3.63-times higher, and IL-11 expression was detected in 62.5 % (10/16) of BM samples versus only in 18.9 % (21/111) of the non-metastatic ones. Highly metastatic HCC cell lines tended to show strong expression of CTGF and IL-11, but low expression of OPG. Hypoxic stimulation of HCC 97L cells increased the level of CTGF mRNA by 2.80-fold within 1.5 h, and hypoxia-inducible factor-1α mRNA levels in these cells could be increased by stimulation with recombinant CTGF protein. Furthermore, OPG and matrix metalloproteinase-2 and -9 levels were also induced under hypoxic conditions. CONCLUSIONS: Expression levels of intratumoral CTGF or IL-11 were independent prognostic factors for the development of BM in HCC patients. Tumor hypoxia enhanced the expression of CTGF, which initiates the invasive angiogenesis cascade and enhances expression of many hypoxia-associated genes. Cellular release of OPG may play a role in tumor cell survival. The hypoxia-induced cascade in HCC cells may contribute to invasion and metastasis in vivo.

Thinning segregated graphene layers on high carbon solubility substrates of rhodium foils by tuning the quenching process.

We report the synthesis of large-scale uniform graphene films on high carbon solubility substrates of Rh foils for the first time using an ambient-pressure chemical vapor deposition method. We find that, by increasing the cooling rate in the growth process, the thickness of graphene can be tuned from multilayer to monolayer, resulting from the different segregation amount of carbon atoms from bulk to surface. The growth feature was characterized with scanning electron microscopy, Raman spectra, transmission electron microscopy, and scanning tunneling microscopy. We also find that bilayer or few-layer graphene prefers to stack deviating from the Bernal stacking geometry, with the formation of versatile moiré patterns. On the basis of these results, we put forward a segregation growth mechanism for graphene growth on Rh foils. Of particular importance, we propose that this randomly stacked few-layer graphene can be a model system for exploring some fantastic physical properties such as van Hove singularities.

Atomic-scale morphology and electronic structure of manganese atomic layers underneath epitaxial graphene on SiC(0001).

We report the fabrication of a novel epitaxial graphene(EG)/Mn/SiC(0001) sandwiched structure through the intercalation of as-deposited Mn atoms on graphene surfaces, with the aid of scanning tunneling microscope, low energy electron diffraction, and X-ray photoelectron spectroscopy. We found that Mn can intercalate below both sp(3)-hybridized carbon-rich interface layer and monolayer graphene, along with the formation of various embedded Mn islands showing different surface morphologies. The unique trait of the sandwiched system is that the strong interaction between the carbon-rich interface layer and SiC(0001) can be decoupled to some degrees, and contemporaneous, an n-doping effect is observed by mapping the energy band of the system using angle-resolved photoemission spectroscopy. Moreover, what deserves our special attention is that the intercalated islands can only evolve below monolayer graphene when a bilayer coexists, accounting for an intriguing graphene thickness-dependent intercalation effect. In the long run, we believe that the construction of graphene/Mn/SiC(0001) systems offers ideal candidates for exploring some intriguing physical properties such as the magnetic property of two-dimensional transition metal systems.

Tunable spin-orbit interaction in trilayer graphene exemplified in electric-double-layer transistors.

Taking advantage of ultrahigh electric field generated in electric-double-layer transistors (EDLTs), we investigated spin-orbit interaction (SOI) and its modulation in epitaxial trilayer graphene. It was found in magnetotransport that the dephasing length L(φ) and spin relaxation length L(so) of carriers can be effectively modulated with gate bias. As a direct result, SOI-induced weak antilocalization (WAL), together with a crossover from WAL to weak localization (WL), was observed at near-zero magnetic field. Interestingly, among existing localization models, only the Iordanskii-Lyanda-Geller-Pikus theory can successfully reproduce the obtained magnetoconductance well, serving as evidence for gate tuning of the weak but distinct SOI in graphene. Realization of SOI and its large tunability in the trilayer graphene EDLTs provides us with a possibility to electrically manipulate spin precession in graphene systems without ferromagnetics.

Stimulation of hepatoma cell invasiveness and metastatic potential by proteins secreted from irradiated nonparenchymal cells.

PURPOSE: To determine whether factors secreted by irradiated liver nonparenchymal cells (NPCs) may influence invasiveness and/or metastatic potential of hepatocellular carcinoma (HCC) cells and to elucidate a possible mechanism for such effect. METHODS AND MATERIALS: Primary rat NPCs were cultured and divided into irradiated (10-Gy X-ray) and nonirradiated groups. Forty-eight hours after irradiation, conditioned medium from irradiated (SR) or nonirradiated (SnonR) cultures were collected and added to sublethally irradiated cultures of the hepatoma McA-RH7777 cell line. Then, hepatoma cells were continuously passaged for eight generations (RH10Gy-SR and RH10Gy-SnonR). The invasiveness and metastatic potential of McA-RH7777, RH10Gy-SnonR, and RH10Gy-SR cells were evaluated using an in vitro gelatinous protein (Matrigel) invasion and an in vivo metastasis assay. In addition, SR and SnonR were tested using rat cytokine antibody arrays and enzyme-linked immunosorbent assay (ELISA). RESULTS: In vitro gelatinous protein invasion assay indicated that the numbers of invading cells was significantly higher in RH10Gy-SR (40 ± 4.74) than in RH10Gy-SnonR (30.6 ± 3.85) cells, and lowest in McA-RH7777 (11.4 ± 3.56) cells. The same pattern was observed in vivo in a lung metastasis assay, as evaluated by number of metastatic lung nodules seen with RH10Gy-SR (28.83 ± 5.38), RH10Gy-SnonR (22.17 ± 4.26), and McA-RH7777 (8.3 ± 3.8) cells. Rat cytokine antibody arrays and ELISA demonstrated that metastasis-promoting cytokines (tumor necrosis factor-α and interleukin-6), circulating growth factors (vascular endothelial growth factor and epidermal growth factor), and metalloproteinases (MMP-2 and MMP-9) were upregulated in SR compared with SnonR. CONCLUSIONS: Radiation can increase invasiveness and metastatic potential of sublethally irradiated hepatoma cells, and soluble mediators released from irradiated NPCs promote this potential. Increased secretion of metastasis-related cytokines and factors from NPCs after irradiation may be a possible mechanism for the radiation-induced invasiveness and metastatic potential of HCC.

Expression of deleted in malignant brain tumours 1 (DMBT1) relates to the proliferation and malignant transformation of hepatic progenitor cells in hepatitis B virus-related liver diseases.

AIMS: The molecular mechanisms underlying proliferation and malignant transformation of hepatic progenitor cells (HPCs) remain largely unknown. The purpose of this study was to evaluate the correlation between the expression of deleted in malignant brain tumours 1 (DMBT1) and the biological behaviour of HPCs in different hepatitis B virus (HBV)-related human liver diseases. METHODS AND RESULTS: Expression of DMBT1 in HPCs was investigated by double immunofluorescence labelling in control-group and HBV-related liver diseases, including hepatitis, hepatocellular carcinoma (HCC), non-tumoral liver tissue away from HCC, non-tumoral cirrhotic tissue adjacent to HCC, and non-HCC cirrhosis. DMBT1-positive HPCs were isolated by laser capture microdissection and subjected to duplex polymerase chain reaction in order to detect homozygous deletion of DMBT1. The number of DMBT1-positive HPCs increased in direct proportion to inflammation severity. Loss of heterozygosity for DMBT1 was more frequent in HCC tumour area and non-tumoral cirrhotic tissue adjacent to HCC, compared with other HBV-related liver diseases (P < 0.05). CONCLUSIONS: DMBT1 may play an important role in the proliferation of HPCs in HBV-related liver diseases. Moreover, down-expression of DMBT1 might enhance the risk of malignant transformation of HPCs.

Growth and atomic-scale characterizations of graphene on multifaceted textured Pt foils prepared by chemical vapor deposition.

The synthesis of centimeter-scale uniform graphene on Pt foils was accomplished via a traditional ambient pressure chemical vapor deposition (CVD) method. Using scanning electron microscopy (SEM) and Raman spectroscopy, we reveal the macroscopic continuity, the thickness, as well as the defect state of as-grown graphene. Of particular importance is that the Pt foils after CVD growth have multifaceted texture, which allows us to explore the substrate crystallography effect on the growth rate and the continuity of graphene. By virtue of atomically resolved scanning tunneling microscopy (STM), we conclude that graphene grows mainly in registry with the symmetries of Pt(111), Pt(110), and Pt(100) facets, leading to hexagonal lattices and striped superstructures. Nevertheless, the carbon lattices on interweaving facets with different identities are connected seamlessly, which ensure the graphene growth from nanometer to micrometer levels. With these results, another prototype for clarifying the preliminary growth mechanism of the CVD process is demonstrated as an analogue of graphene on Cu foils.

Defect-like structures of graphene on copper foils for strain relief investigated by high-resolution scanning tunneling microscopy.

Understanding of the continuity and the microscopic structure of as-grown graphene on Cu foils through the chemical vapor deposition (CVD) method is of fundamental significance for optimizing the growth parameters toward high-quality graphene. Because of the corrugated nature of the Cu foil surface, few experimental efforts on this issue have been made so far. We present here a high-resolution scanning tunneling microscopy (STM) study of CVD graphene directly on Cu foils. Our work indicates that graphene can be grown with a perfect continuity extending over both crystalline and noncrystalline regions, highly suggestive of weak graphene-substrate interactions. Due to thermal expansion mismatch, defect-like wrinkles and ripples tend to evolve either along the boundaries of crystalline terraces or on noncrystalline areas for strain relief. Furthermore, the strain effect arising from the conforming of perfect two-dimensional graphene to the highly corrugated surface of Cu foils is found to induce local bonding configuration change of carbon from sp(2) to sp(3), evidenced by the formation of "three-for-six" lattices.

Hepatic progenitor cell represents a transitioning cell population between liver epithelium and stroma.

Following an acute injury, the liver may maintain its structure and function through mitotic division of mature hepatocytes (i.e. hepatic regeneration). However, the regeneration ability of hepatocytes can be impaired in chronic liver diseases including chronic viral infection and alcohol abuse. Hepatic progenitor cells/oval cells (HPCs/OCs), capable of differentiation into both hepatocytes and cholangiocytes, occur and proliferate during chronic injury. Unfortunately, a use of HPCs for clinical therapy is blocked by the difficulty of exact identity of HPCs in liver. Focusing on the links between phenotype of HPCs and real stem cells originating from fetal liver or bone marrow (BM), the recent studies of HPCs neglect functional analysis and the close relationship between activation of HPCs and extracellular matrix (ECM) remodeling. It is currently widely accepted that mesenchymal-epithelial transition (EMT) and epithelial-mesenchymal transition (MET) play important roles not only in liver development but also in healing of chronic injured adult liver. Co-expression of epithelial/mesenchymal and HPCs markers has been demonstrated in cells undergoing EMT/MET. These cells led to hepatic regeneration after transplanted into rats with chronic liver injury. Notably, there is an increased expression of mesenchymal markers in HPCs after exposure to transforming growth factor-beta1 (TGF-ß1). Based on these evidences, we hypothesize that HPCs represent a transitioning cell population undergoing EMT/MET, both parenchymal and mesenchymal cells of liver may be the direct sources of HPCs.