Erchen decoction alleviates the progression of NAFLD by inhibiting lipid accumulation and iron overload through Caveolin-1 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: A combination of 6 different Chinese herbs known as Erchen decoction (ECD) has been traditionally used to treat digestive tract diseases and found to have a protective effect against nonalcoholic fatty liver disease (NAFLD). Despite its efficacy in treating NAFLD, the precise molecular mechanism by which Erchen Decoction regulated iron ion metabolism to prevent disease progression remained poorly understood. AIM OF STUDY: Our study attempted to confirm the specific mechanism of ECD in reducing lipid and iron in NAFLD from the perspective of regulating the expression of Caveolin-1 (Cav-1). STUDY DESIGN: In our study, the protective effect of ECD was investigated in Palmitic Acid + Oleic Acid-induced hepatocyte NAFLD model and high-fat diet-induced mice NAFLD model. To investigate the impact of Erchen Decoction (ECD) on lipid metabolism and iron metabolism via mediating Cav-1 in vitro, Cav-1 knockdown cell lines were established using lentivirus-mediated transfection techniques. MATERIALS AND METHODS: We constructed NAFLD model by feeding with high-fat diet for 12 weeks in vivo and Palmitic Acid + Oleic Acid treatment for 24 h in vitro. The regulation of Lipid and iron metabolism results by ECD were detected by serological diagnosis, immunofluorescent and immunohistochemical staining, and western blotting. The binding ability of 6 small molecules of ECD to Cav-1 was analyzed by molecular docking. RESULTS: We demonstrated that ECD alleviated the progression of NAFLD by inhibiting lipid accumulation, nitrogen oxygen stress, and iron accumulation in vivo and in vitro experiments. Furthermore, ECD inhibited lipid and iron accumulation in liver by up-regulating the expression of Cav-1, which indicated that Cav-1 was an important target for ECD to exert its curative effect. CONCLUSIONS: In summary, our study demonstrated that ECD alleviated the accumulation of lipid and iron in NAFLD through promoting the expression of Cav-1, and ECD might serve as a novel Cav-1 agonist to treat NAFLD.

Apatinib Inhibits Angiogenesis in Intrahepatic Cholangiocarcinoma by Regulating the Vascular Endothelial Growth Factor Receptor-2/Signal Transducer and Activator of Transcription Factor 3/Hypoxia Inducible Factor 1 Subunit Alpha Signaling Axis.

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC), which is difficult to diagnose and is usually fatal due to its late clinical presentation and a lack of effective treatment, has risen over the past decades but without much improvement in prognosis. OBJECTIVE: The study aimed to investigate the role of apatinib that targets vascular endothelial growth factor receptor-2 (VEGFR2) in ICC. METHODS: MTT assays, cell scratch assays, and tube formation assays were used to assess the effect of apatinib on human ICC cell line (HuCCT-1) and RBE cells proliferation, migration, and angiogenic capacity, respectively. Expression of vascular endothelial growth factor (VEGF), VEGFR2, signal transducer and activator of transcription factor 3 (STAT3), pSTAT3, and hypoxia inducible factor 1 subunit alpha (HIF-1α) pathway proteins was assessed using Western blotting and mRNA expression analysis in HuCCT-1 was performed using RT-qPCR assays. The pcDNA 3.1(-)-VEGFR2 and pcDNA 3.1(-)-HIF-1α were transfected into HuCCT-1 and RBE cells using Lipofectamine 2,000 to obtain overexpressed HuCCT-1 and RBE cells. RESULTS: We found that apatinib-inhibited proliferation, migration, and angiogenesis of HuCCT-1 and RBE cells in vitro in a dose-dependent manner. We also proved that apatinib effectively inhibits angiogenesis in tumor cells by blocking the expression of VEGF and VEGFR2 in these cells. In addition, we demonstrated that apatinib regulates the expression of STAT3 phosphorylation by inhibiting VEGFR2. Finally, we showed that apatinib regulates ICC angiogenesis and HIF-1α/VEGF expression via STAT3. CONCLUSIONS: Based on the above findings, we conclude that apatinib inhibits HuCCT-1 and RBE cell proliferation, migration, and tumor angiogenesis by inhibiting the VEGFR2/STAT3/HIF-1α axis signaling pathway. Apatinib can be a promising drug for ICC-targeted molecular therapy.

Cancer-Associated Fibroblasts Promote Angiogenesis of Hepatocellular Carcinoma by VEGF-Mediated EZH2/VASH1 Pathway.

BACKGROUND: Hepatocellular carcinoma is a highly vascularized tumor, so it is critical to study its angiogenesis. Cancer-associated fibroblasts and enhancer of zeste homolog 2 play an important role in tumor angiogenesis and became significant hallmarks of cancer. But the relationship between enhancer of zeste homolog-2 and cancer-associated fibroblasts in response to angiogenesis and its precise mechanism remains unclear. METHODS: The separation of cancer-associated fibroblasts was identified by immunofluorescence. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis was used to reveal the proliferation of human umbilical vein endothelial cells. Vascular endothelial growth factor level was quantified by enzyme-linked immunosorbent assay. The wound healing, transwell, and vascular tube formation assays were used to identify the capability of migration, invasion, and tube formation of human umbilical vein endothelial cells in vitro. The detection of tumor angiogenesis was also performed in vivo. Finally, the level of enhancer of zeste homolog-2 and vasohibin 1 were determined by quantitative real-time polymerase chain reaction and Western blotting. RESULTS: In comparison to control and condition medium noncancerous fibroblasts groups, the condition medium cancer-associated fibroblasts could significantly promote the proliferation, migration, invasion, and angiogenesis of human umbilical vein endothelial cells. We found that cancer-associated fibroblasts promoted angiogenesis of human umbilical vein endothelial cells via vascular endothelial growth factor secretion in vitro and in vivo. The upregulation of enhancer of zeste homolog 2 by vascular endothelial growth factor inhibited the expression of vasohibin 1, thus promoting the proliferation and angiogenesis of human umbilical vein endothelial cells. Taken together, the cancer-associated fibroblasts of hepatocellular carcinoma regulate the enhancer of zeste homolog-2/vasohibin 1 pathway via vascular endothelial growth factor secretion, thereby promoting the proliferation and angiogenesis of human umbilical vein endothelial cells. CONCLUSION: Our study identified the relationship between cancer-associated fibroblasts and enhancer of zeste homolog-2 and confirmed the pivotal role of cancer-associated fibroblasts in angiogenesis of hepatocellular carcinoma. Cancer-associated fibroblasts promote angiogenesis of hepatocellular carcinoma by vascular endothelial growth factor-mediated enhancer of zeste homolog-2/vasohibin 1 pathway and may be a potentially useful therapeutic target for hepatocellular carcinoma.

Exciplex Organic Light-Emitting Diodes with Nearly 20% External Quantum Efficiency: Effect of Intermolecular Steric Hindrance between the Donor and Acceptor Pair.

Exciplex emitters have emerged as an important class of thermally activated delayed fluorescence (TADF) materials for highly efficient OLEDs. A TADF exciplex emitter requires an intermolecular donor/acceptor pair. We have synthesized a bipolar donor-type material, DPSTPA, which was used to pair with known acceptor materials (2CzPN, 4CzIPN, or CzDBA). The OLEDs based on the exciplex emitters, DPSTPA/X, where X = 2CzPN and CzDBA, give green and orange-red colors with record-high external quantum efficiencies (EQEs) of 19.0 ± 0.6 and 14.6 ± 0.4%, respectively. In contrast, the exciplex pair DPSTPA/4CzIPN gave a very low photoluminescence quantum yield (PLQY) and a very low EQE value of the device. The DFT calculations indicate that the intermolecular distance between the donor and the acceptor plays a key factor for the PLQY and EQE. The observed low PLQY and the poor device performance for the DPSTPA/4CzIPN pair are probably because of the relatively long distance between the DPSTPA and 4CzIPN in the thin film caused by the four congested carbazole (Cz) groups of 4CzIPN, which effectively block the interaction of the nitrile acceptor with the triphenylamino donor of DPSTPA.

Apatinib affect VEGF-mediated cell proliferation, migration, invasion via blocking VEGFR2/RAF/MEK/ERK and PI3K/AKT pathways in cholangiocarcinoma cell.

BACKGROUND: Cholangiocarcinoma (CCA) is a form of cancer that easily aggress to contiguous structures. Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) are increased in majority species of cancers and suppress tumor progression by blocking VEGF/VEGFR2. Apatinib is a highly selective VEGFR2 antagonist which has inhibitive effect on antiapoptotic and cell growth in CCA. While, the effect of apatinib cell migration and invasion in CCA is still unknown. METHODS: CCA cell lines QBC939 and TFK-1 were transfected with siKDR to establish the KDR function loss cell model, and recombined human VEGF (rhVEGF) protein was added into the culture medium to enhance the VEGF expression. RT-qPCR and western bloting were used to detect the mRNA and protein expression levels of VEGFR2 to investigate whether it was effectively repressed or activated with rhVEGF or apatinib treatment. Then, MTT, wound healing assay, and transwell matrix assay were applied to measure the effect of apatinib and rhVEGF on cell viability, migration and invasion, respectively. RESULTS: The mRNA and protein expressions of VEGFR2 were significantly reduced with KDR RNAi in both QBC939 and TFK-1 cells, and rhVEGF treatment increased these expression levels (p < 0.05). Apatinib dramatically suppressed VEGF-mediated cell migration and invasion at the concentration of 100 nM treatment and significantly decreased the expression of metastasis-associated protein such as Slug, snail and MMP9. Moreover, all of these inhibiting effects of apatinib depended on the VEGFR2 existence. In addition, VEGFR2/RAF/MEK/ERK and PI3K/AKT signal pathways were enhanced by the introduction of rhVEGF, but were dramatically suppressed after the apatinib treatment. CONCLUSION: Apatinib inhibit VEGF-mediated cell migration and invasion in CCA cell lines via inhibiting the VEGFR2/RAF/MEK/ERK and PI3K/AKT pathways. It will be a potentially effective targeted drug for CCA.

MiR-137 suppresses migration and invasion by targeting EZH2-STAT3 signaling in human hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies and many cell-intrinsic identities and extrinsic epigenetic factors influence the metastatic potential of HCC cells. MicroRNA-137 is often found to be acting as tumor suppressors, however, how miR-137 involved in the metastasis progression in human HCC remains unclear. METHOD: QPCR was performed to detect the miR-137 mRNA levels in HCC cell linesand normal liver cell line HL7702.Then transwell assay and wound-healing assay were determined to investigate the motility of HCC cells introduced into lentivirus to ectopically upregulate endogenous miR-137 and EAH2 expressions. Targeting of enhancer of zeste homolog 2 (EZH2) gene by miR-137 in HCC was assessed by dual-luciferase activity assay and qPCR. Western blot was applied to explore the mechanism. In vivo, lung metastasis were evaluated using a mice tail vein injection model. RESULTS: In this study, we found that miR-137 is decreased in HCC cell lines and had an inhibitory effect on HCC migration and invasion in vitro. EZH2 was a direct downstream target gene of miR-137 in HCC and miR-137 suppressed invasion and migration by targeting EZH2-STAT3 signaling in HCC cells. Furthermore, EZH2 overexpression reversed the miR-137 mimics-induced inhibitory effects on migration and invasion of HCC cells. In addition, miR-137 inhibited lung metastasis of HCC in vivo by targeting EZH2-STAT3 signaling. CONCLUSION: MiR-137 suppressed migration and invasion by targeting EZH2-STAT3 signaling pathway in HCC cells in vitro and in vivo, suggesting miR-137-EZH2-STAT3 may be a potential therapeutic target for treatment of human hepatocellular carcinoma.

[Ultrasound-guided microwave ablation with artificial pleural effusion for liver tumor adjacent to diaphragmatic dome].

OBJECTIVE: To explore the value of ultrasound-guided microwave ablation with artificial pleural effusion for liver tumor adjacent to diaphragmatic dome.
 Methods: A total of 34 patients with liver tumors located at diaphragmatic dome in Hunan Provincial Tumor Hospital were recruited from January 2014 to October 2015. The number of lesions ≤3 or lesion diameter ≤5 cm was in line with the microwave ablation indications. B ultrasound-guided microwave ablation for the liver tumors was undertaken after the artificial pleural effusion being established. 3-4 weeks later after the microwave ablation, all patients were imaged with enhance CT or MRI. The effect of ablation and the complications were evaluated.
 Results: There were 49 lesions in 34 patients, including 30 cases (88.2%) of complete ablation (CA), 3 cases (8.8%) of partial ablation (PA) and one case with new lesions after ablation (2.9%). Thirty-four patients had (1 580±230.7) mL of pleural effusion volume, while one case had bloody pleural effusion. One case had a diaphragmatic thermal injury, and one case had a biliary tumor infection. All of them showed remission after symptomatic treatment. 
 Conclusion: Combination of ultrasound-guided microwave ablation with artificial pleural effusion is a safe and effective therapy for liver tumor adjacent to diaphragmatic dome.

Primary Sjögren syndrome that initially presented with repeated hypergammaglobulinemic purpura after prolonged sitting: A case report.

RATIONALE: Purpura is a common dermatologic manifestation in Sjögren syndrome (SS). When a patient presents with sicca symptoms, the diagnosis of SS is not difficult. PATIENT CONCERNS: Here, we reported a case of a 52-year-old Chinese woman who initially presented with nonpalpable purpura on both lower extremities, and these lesions had developed soon after prolonged sitting. In the past 2 years, she had repeated cutaneous nonpalpable purpura 4 times. She had no sicca symptoms, dry eyes, or dry mouth. DIAGNOSES: Combining the laboratory findings, Schirmer test, and labial gland biopsy, primary SS was confirmed. INTERVENTIONS: The patient was placed on a trial of hydroxychloroquine (200 mg once daily). OUTCOMES: The purpura on both lower extremities had faded at the sixth day after onset and at the third day after hydroxychloroquine treatment. LESSONS: These case was not easy to diagnosis primary SS because she had no sicca symptoms. A patient with primary SS who initially presented with recurrent purpura associated with prolonged sitting. Prolonged sitting had been a possible aggravating factor for the cutaneous purpura of this patient with primary SS.

A versatile ferrocene-containing material as a p-type charge generation layer for high-performance full color tandem OLEDs.

A novel p-type charge generation material, DPAF, composed of a ferrocene core and a bis(biphenyl)amino group is designed and synthesized for application to tandem OLED devices. This molecular design not only enhances the thermal properties of ferrocene and the hole mobility, but also maintains its electrochemical stability. The red, green, and blue tandem OLEDs all give excellent device performance with low efficiency roll-off by using n-type C60 and p-type DPAFs as charge generation layers.

Effect of Transcatheter Arterial Chemoembolization Combined with Argon-Helium Cryosurgery System on the Changes of NK Cells and T Cell Subsets in Peripheral Blood of Hepatocellular Carcinoma Patients.

Hepatocellular carcinoma (HCC) is one of the most aggressive tumors in humans. T lymphocytes and natural killer (NK) cells are the body's first line of defense to prevent tumor cell growth. Previous studies have demonstrated that transcatheter arterial chemoembolization (TACE) combined with argon-helium cryosurgery system (AHCS) can effectively treat liver cancer. However, the mechanism of the treatment is unclear yet. In the current study, we investigated the effects of TACE combined with AHCS on the changes of T cell subsets and NK cells in peripheral blood of HCC. Our data show that alpha-fetoprotein (AFP) levels in peripheral blood were significantly up-regulated in HCC patients before treatment when compared with healthy people and reduced after TACE combined with AHCS treatment (P < 0.01). In addition, we found that CD4+ cells and NK cells decreased (P < 0.05) and CD8+ cells increased (P < 0.05) in HCC patients when compared with healthy people. After treatment, the CD4+ cells, CD4+/CD8+ ratio, and NK cells were dramatically increased in HCC patients (P < 0.05). In contrast, CD8+ cells were significantly decreased (P < 0.05). TACE combined with AHCS treatment significantly prolonged 1-year survival rate of HCC patients and did not show significant side effects. Taken together, our data indicate that TACE combined with AHCS treatment improves patients' immune system. It is a feasible and effective therapeutic method for HCC patients.

MEK/ERK pathway is positively involved in hypoxia-induced vasculogenic mimicry formation in hepatocellular carcinoma which is regulated negatively by protein kinase A.

The aim of present investigation is to explore the molecular mechanisms of vasculogenic mimicry (VM) induced by hypoxia. Hepatocellular carcinoma cell lines were treated with CoCl2, and the VM-related parameters were assayed by real-time qPCR, Western blotting and immunofluorescence. Matrigel tube structure was also detected. We demonstrated that the expression of pMEK, MEK, pERK1/2 and ERK1/2 had a positive correlation with VM induced by hypoxia in MHCC97H while HepG2 signified VM under normoxia condition. PD98059 was negatively while epidermal growth factor positively participated in the increased tubes and area of VM. At the meaning time, the increased VM-related genes VE-cadherin, MMP2, MMP9, EphA2 and LAMC2 in hypoxia group were down-regulated by PD98059 in a dose-dependent manner. Furthermore, we elucidated that PKA, but not PKC, mediated the MEK/ERK pathway in a negative manner in VM. In conclusion, MEK/ERK pathway is positively involved in VM in hepatocellular carcinoma cell line, which was mediated by PKA negatively.

[BOLD-fMRI in sensory area and motor hand functional area with brain tumor in the central area].

OBJECTIVE: To explore the geomorphological performance, the characteristics of volume, and the largest signal intension of blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) in brain tumors located in or closed to the central area. METHODS: We recruited 13 normal volunteers and 31(13 benign tumors and 18 malignant tumors) patients with brain tumor located in or closed to the central area, to examine both side hand motor and tactile function by BOLD-fMRI and obtained the activation map and its superposition image with T1 imaging, the volume, and the largest signal intension of the functional area by SPM software which manipulated the raw data in the off-line work station. The volume and the largest signal intension data of the functional area were statistically analyzed by SPSS 13.0. RESULTS: The volume and the largest signal intension of the activation map in the normal functional area had hemisphere advantage. There was difference in the activated signal pixel number and the largest signal intension of the functional area between the benign brain tumors, malignant brain tumors, and the normal volunteers (P < 0.05). The shape, anatomic location, the volume, and the largest signal intension of the functional area were changed in the patients with brain tumors. CONCLUSION: BOLD-fMRI is a valid method to assess the pre-surgical risk of patients with brain tumors, which can get the volume, the largest signal intension, the basic shape,and the anatomic location of the functional area.

[Expression of Ang2 and Tie2 and their relation with the angiogenesis of hepatocellular carcinoma in rats].

OBJECTIVE: To investigate the relationship between the expression of Ang2, Tie2 and the angiogenesis of hepatocellular carcinoma in rats. METHODS: Thirty-eight healthy male rats were randomly divided into 3 groups: 5 rats in the control group; 25 rats in the experimental group were equally divided into 5-day, 10-day, 15-day, 20-day, and 25-day groups; the other 8 rats were used as the supplement of the experimental group. An allogenic transplanted rat model of CBRH-7919 hepatocellular carcinoma in situ was established by immunosuppression. The expressions of Ang2 and Tie2 were detected by immunohistochemical staining in cancerous tissues of different developmental stages and liver tissues of the control group. At the same time, microvessel density was determined by anti-CD31 immunohistochemical staining. RESULTS: CBRH-7919 hepatocellular carcinoma models were successfully set up in 24 rats. The expression level of Ang2 and Tie2 in cancerous tissues was much higher than that of liver tissues of the control group (P <0.05). The overexpression of Ang2 was pristine and continuous in different developmental stages. The expressions of Ang2 and Tie2 positively correlated with microvessal density in hepatocellular carcinoma (P<0.05). CONCLUSION: The up-regulation of Ang2 and Tie2 may play important roles in the angiogenesis of hepatocellular carcinoma. Ang2 may participate in the start of angiogenesis of hepatocellular carcinoma.