Analysis of epithelial-mesenchymal transition markers in the histogenesis of hepatic progenitor cell in HBV-related liver diseases.

BACKGROUND: The origin and heterogeneity of hepatic progenitor cells (HPCs) remain unclear. This study aimed to investigate the involvement of epithelial-mesenchymal transition (EMT) in the histogenesis of HPCs. METHODS: Surgical liver specimens from patients with HBV-related hepatitis and cirrhosis were investigated with double immunofluorescence labeling to detect antigens associated with HPCs and EMT. Ductular reactions were subjected to quantitative reverse transcription PCR following isolation by laser capture microdissection. Electron microscopic examination was performed to find an ultrastructural evidence of EMT. RESULTS: The number of EpCAM-positive HPCs was proportional to the disease severity. The S100A4 expression of HPCs was firstly observed in mild hepatitis and increased significantly in moderate hepatitis, but decreased in severe hepatitis and cirrhosis. The levels of MMP-2, Twist, and Snail increased in direct proportion to the number of HPCs. Some hepatocytes adjacent to portal tracts in cirrhosis showed positivity for MMP-2. Although CK7 and E-cadherin levels decreased in mild and moderate hepatitis, HPCs re-expressed both of them in severe hepatitis and cirrhosis. However, HPCs expressed neither vimentin nor αSMA. The relative mRNA expression levels of EpCAM and EMT-associated markers supported immunohistochemical results. Electron microscopic examination demonstrated the existence of intercellular junctions among HPCs, cholangiocytes, and intermediate hepatocyte-like cells. CONCLUSION: We provided preliminary evidence for the involvement of EMT in the histogenesis of HPCs from cholangiocytes in HBV-related liver diseases. HPCs may re-transdifferentiate into hepatocytes, and the differentiation direction depends, at least in part, on interactions between HPCs and the surrounding microenvironment, especially the non-resolving inflammation caused by HBV infection.

Interaction between circulating cancer cells and platelets: clinical implication.

Metastasis is the main cause of cancer-associated mortality. During this complicated process, some cancer cells, also called circulating tumor cells (CTCs), detach from primary sites, enter bloodstream and extravasate at metastatic site. Thrombocytosis is frequently observed in patients with metastatic cancers suggesting the important role of platelets in metastasis. Therefore this review focuses on how platelets facilitate the generation of CTCs, protect them from various host attacks, such as immune assaults, apoptosis and shear stress, and regulate CTCs intravasation/extravasation. Platelet-derived cytokines and receptors are involved in this cascade. Identification the mechanisms underlie platelet-CTCs interactions could lead to the development of new platelet-targeted therapeutic strategy to reduce metastasis.

Aspirin inhibit platelet-induced epithelial-to-mesenchymal transition of circulating tumor cells (Review).

Metastasis, a cascade of events beginning with epithelial-to-mesenchymal transition (EMT), is the main cause of cancer-related mortality. EMT endows circulating cancer cells (CTCs) with invasive and anti-apoptotic properties. These transitioning cells leave the primary tumor site and travel through the circulation to populate remote organs, even prior to the onset of clinical symptoms. During this journey, CTCs activate platelets, which in turn secrete α-granules. These α-granules contain high levels of transforming growth factor-ß (TGF-ß) and platelet-derived growth factor (PDGF), both considered to be powerful activators of EMT. Recently, regular aspirin use was associated with a reduced risk of cancer metastasis. However, the molecular mechanism underlying the chemotherapeutic effects of aspirin on metastasis has not been fully elucidated. As platelets lack a nucleus, regular aspirin use may exert long-lasting effects on irreversible inhibition of cyclooxygenase (COX)-1 and, subsequently, the secretion of α-granules, which contributes to the maintenance of the EMT state of CTCs. Thus, we hypothesized that the inhibition of platelet-induced EMT of CTCs through the COX-1 signaling pathway may contribute to the intriguing antimetastatic potential of aspirin.

Phospholamban antisense RNA improves SR Ca2+-ATPase activity and left ventricular function in STZ-induced diabetic rats.

OBJECTIVE: To study the effect of phospholamban antisense RNA (asPLB) on sarcoplasmic reticulum Ca2+-ATPase activity and cardiac function in rats with diabetes mellitus (DM) mediated by recombinant adeno-associated virus (rAAV) vector. METHODS: Six weeks after the induction of DM by streptozotocin injected intraperitoneally, the rats were divided into three groups, namely: DM-rAAV-asPLB group, DM-saline group and DM group (control group). The rats in the DM-rAAV-asPLB group were intramyocardially injected with rAAV-asPLB, the rats in the DM-saline group were injected with saline, and those in the control group did not receive any treatment. Six weeks after gene transfer, the expressions of PLB protein and PLB phosphorylation were detected by Western-blot, while the activity of sarcoplasmic reticulum (SR) Ca2+-ATPase and left ventricular function were measured. RESULTS: The PLB protein expression level was significantly higher whereas the PLB phosphorylation, SR Ca2+-ATPase activity and left ventricular function were significantly lower in the DM-saline group than in the control group. No significant difference was found in PLB protein expression level, PLB phosphorylation or SR Ca2+-ATPase activity between the DM-rAAV-asPLB group and the control group. The left ventricular function in the DM-rAAV-asPLB group was poorer than in the control group and was better than in the DM-saline group. CONCLUSION: rAAV-asPLB can down-regulate PLB protein expression and up-regulate PLB phosphorylation and SR Ca2+-ATPase activity, thus contributing to the improvement of in vivo left ventricular function.

[Correlation between increased spinal cord signal intensity on T2-weighted MRI and clinical prognosis of compressive cervical myelopathy].

OBJECTIVE: To analyze the correlations between increased spinal cord signal intensity on magnetic resonance images (MRI) and the clinical prognosis of compressive cervical myelopathy. METHODS: Sixty-six patients with cervical spondylotic myelopathy underwent surgeries through the anterior approach. In all the patients, the diagnoses were established on the basis of both neurological examination and MRI findings that showed spinal cord compression. The patients were divided into two groups according to preoperative MRI, namely isointense MRI T1/T2 signal group and iso/hyperintense MRI T1/T2 group. The JOA scores of the patients were evaluated before and at 6 and 12 months after the operation. RESULTS: The patients were followed up for 12 to 38 months after the operation (mean 21 months), and no statistically significant difference were found in the pre- and postoperative JOA scores between the two groups (P>0.05). CONCLUSION: The peoperative hyperintense signals on T2 weighted MRI does not correlate to the prognosis of patients with compressive cervical myelopathy, who may also have favorable clinical outcomes after the operation.