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  • 1
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    Inhibition of Metastatic Potential in Breast Carcinoma In Vivo and In Vitro through Targeting VEGFRs and FGFRs
    Hindawi Limited ; 2013
    In:  Evidence-Based Complementary and Alternative Medicine Vol. 2013 ( 2013), p. 1-13
    Details
    In: Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 2013 ( 2013), p. 1-13
    Abstract: Angiogenesis and lymphangiogenesis are considered to play key roles in tumor metastasis. Targeting receptor tyrosine kinases essentially involved in the angiogenesis and lymphangiogenesis would theoretically prevent cancer metastasis. However, the optimal multikinase inhibitor for metastasis suppression has yet to be developed. In this study, we evaluated the effect of NSTPBP 0100194-A (194-A), a multikinase inhibitor of vascular endothelial growth factor receptors (VEGFRs)/fibroblast growth factor receptors (FGFRs), on lymphangiogenesis and angiogenesis in a mammary fat pad xenograft model of the highly invasive breast cancer cell line 4T1-Luc + . We investigated the biologic effect of 194-A on various invasive breast cancer cell lines as well as endothelial and lymphatic endothelial cells. Intriguingly, we found that 194-A drastically reduced the formation of lung, liver, and lymph node metastasis of 4T1-Luc + and decreased primary tumor growth. This was associated with significant reductions in intratumoral lymphatic vessel length (LVL) and microvessel density (MVD). 194-A blocked VEGFRs mediated signaling on both endothelial and lymphatic endothelial cells. Moreover, 194-A significantly inhibited the invasive capacity induced by VEGF-C or FGF-2 in vitro in both 4T1 and MDA-MB231 cells. In conclusion, these experimental results demonstrate that simultaneous inhibition of VEGFRs/FGFRs kinases may be a promising strategy to prevent breast cancer metastasis.
    Type of Medium: Online Resource
    ISSN: 1741-427X , 1741-4288
    URL: Article
    DOI: 10.1155/2013/718380
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2013
    detail.hit.zdb_id: 2148302-4
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  • 2
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    Ratio of Early Mitral Inflow Velocity to the Global Diastolic Strain Rate and Global Left Ventricular Longitudinal Systolic Strain Predict Overall Mortality and Major Adverse Cardiovascular Events in Hemodialysis Patients
    Hindawi Limited ; 2019
    In:  Disease Markers Vol. 2019 ( 2019-09-05), p. 1-12
    Details
    In: Disease Markers, Hindawi Limited, Vol. 2019 ( 2019-09-05), p. 1-12
    Abstract: Background . The ratio of early mitral inflow velocity to the global diastolic strain rate (E/E’sr) and global longitudinal systolic strain (GLS) of the left ventricle (LV) are emerging indices of diastolic and systolic functions, respectively, for the LV. Their prognostic significance in the prediction of mortality and cardiovascular (CV) outcomes remains underexplored in hemodialysis (HD) patients. Methods . This prospective study included 190 maintenance HD patients. The E/E’sr ratio and GLS were assessed using two-dimensional speckle tracking echocardiography. The clinical outcomes included overall mortality, CV mortality, and major adverse cardiovascular events (MACE). The associations between the E/E’sr ratio, GLS, and clinical outcomes were evaluated using multivariate Cox regression analysis. The incremental values of the E/E’sr ratio and GLS in outcome prediction were assessed by χ 2 changes in Cox models. Results . Over a median follow-up period of 3.7 years, there were 35 overall deaths, 16 CV deaths, and 45 MACE. Impaired diastolic function with a higher E/E’sr ratio was associated with overall mortality (HR, 1.484; 95% CI, 1.201−1.834; p 〈 0.001 ), CV mortality (HR, 1.584; 95% CI, 1.058–2.371; p = 0.025 ), and MACE (HR, 1.205; 95% CI, 1.040−1.397; p = 0.013 ) in multivariate adjusted Cox analysis. Worsening GLS was associated with overall mortality (HR, 1.276; 95% CI, 1.101−1.480; p = 0.001 ), CV mortality (HR, 1.513; 95% CI, 1.088−2.104; p = 0.014 ), and MACE (HR, 1.214; 95% CI, 1.103−1.337; p 〈 0.001 ). The E/E’sr ratio and GLS had better outcome prediction than the E to early diastolic mitral annular velocity (E/E’) ratio and left ventricular ejection fraction (LVEF). Moreover, adding the E/E’sr ratio and GLS to Cox models containing relevant clinical and conventional echocardiographic parameters improved the prediction of overall mortality ( p 〈 0.001 ), CV mortality ( p 〈 0.001 ), and MACE ( p 〈 0.001 ). Conclusion . The E/E’sr ratio and GLS, as emerging indices of LV diastolic and systolic functions, significantly predict mortality and CV outcomes and outperform conventional echocardiographic parameters in outcome prediction in HD patients.
    Type of Medium: Online Resource
    ISSN: 0278-0240 , 1875-8630
    URL: Article
    DOI: 10.1155/2019/7512805
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2019
    detail.hit.zdb_id: 2033253-1
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  • 3
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    Significance of Hepatitis B Recurrence in Liver Transplantation Recipients
    Hindawi Limited ; 2020
    In:  BioMed Research International Vol. 2020 ( 2020-08-31), p. 1-5
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2020 ( 2020-08-31), p. 1-5
    Abstract: Background . A combination of antihepatitis B immunoglobulin and antiviral agents is the most common regimen for prophylaxis of hepatitis B recurrence after liver transplantation. However, hepatitis B recurrence still happens. The significance of hepatitis B recurrence is less mentioned. Materials . Forty-eight of the 313 hepatitis B liver transplant recipients having hepatitis B recurrence were included in this study. The patients were divided into group A, the patients transplanted for hepatitis B-related liver failure, and group B, the patients transplanted for hepatitis B-related cirrhosis and HCC. The clinical manifestations after hepatitis B recurrence were recorded. Results . Among the 48 patients with hepatitis B recurrence, 23 patients were in group A and 25 patients in group B. The age was 51.6 ± 9.4 years in group A and 52.8 ± 6.4 in group B ( p = 0.869 ). The MELD score prior to transplantation was 23.1 ± 9.9 in group A patients and 12.9 ± 5.6 in group B patients ( p 〈 0.001 ). The median (interquartile) interval from transplantation to hepatitis B recurrence was 10 (2-19) months for group A patients and 13 (8.5-35) months for group B patients ( p = 0.051 ). After hepatitis B recurrence, the liver function was almost normal in both groups. In group B patients, 10 patients had HCC recurrence with 7 of 10 patients having hepatitis B recurrence earlier than HCC recurrence. The interval between hepatitis B and HCC recurrence was 1 to 15 months. The 1-, 3-, and 5-year survival rates were 82.6%, 73.9%, and 69.0%, respectively, for group A patients and 96%, 76%, and 68%, respectively, for group B patients ( p = 0.713 ). Conclusion . The patients have uneventful liver function under antiviral agent while hepatitis B recurred. For the patients having HCC prior to transplantation, close monitoring of HCC recurrence is necessary if hepatitis B recurs.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2020/2489526
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2020
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  • 4
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    Renal Function Improvement by Telbivudine in Liver Transplant Recipients with Chronic Kidney Disease
    Hindawi Limited ; 2017
    In:  BioMed Research International Vol. 2017 ( 2017), p. 1-8
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2017 ( 2017), p. 1-8
    Abstract: Chronic renal failure is a frequent complication in liver transplantation. Telbivudine, anti-hepatitis B virus (HBV) nucleoside, can improve renal function. It is interesting if using telbivudine for prophylaxis of HBV recurrence has additional value on renal function improvement. 120 liver transplant recipients with lamivudine prophylaxis for HBV recurrence were 1 : 1 randomized into lamivudine-continuous ( n = 60 ) and telbivudine-replacement ( n = 60 ) groups. Fifty-eight patients in lamivudine-continuous group and 54 in telbivudine-replacement group completed the study. In telbivudine-replacement group, the estimated glomerular filtration rate (eGRF) was improved from 63.0 ± 16.3 ml/min to 72.8 ± 21.1 ml/min at 12 months after telbivudine administration ( p = 0.003). Stratifying the patients according to renal function staging, the eGRF was improved from 74.7 ± 6.9 ml/min to 84.2 ± 16.6 ml/min ( p = 0.002) in 32 stage II patients and from 48.2 ± 7.3 ml/min to 59.7 ± 11.8 ml/min in 20 stage III patients after 12 months of telbivudine administration ( p 〈 0.001 ). Eleven (18.3%) patients with telbivudine developed polyneuritis during the trial and post hoc following-up. In conclusion, renal function was improved by telbivudine in liver transplant recipients with long-term chronic kidney disease. However, the high incidence of polyneuritis induced by telbivudine has to be closely monitored. This trial is registered with ClinicalTrials NCT02447705 .
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2017/9324310
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2017
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  • 5
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    Xanthohumol, a Prenylated Flavonoid from Hops ( Humulus lupulus ), Prevents Platelet Activation in Human Platelets
    Hindawi Limited ; 2012
    In:  Evidence-Based Complementary and Alternative Medicine Vol. 2012 ( 2012), p. 1-10
    Details
    In: Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 2012 ( 2012), p. 1-10
    Abstract: Xanthohumol is the principal prenylated flavonoid in the hop plant ( Humulus lupulus L.). Xanthohumol was found to be a very potent cancer chemopreventive agent through regulation of diverse mechanisms. However, no data are available concerning the effects of xanthohumol on platelet activation. The aim of this paper was to examine the antiplatelet effect of xanthohumol in washed human platelets. In the present paper, xanthohumol exhibited more-potent activity in inhibiting platelet aggregation stimulated by collagen. Xanthohumol inhibited platelet activation accompanied by relative [Ca 2+ ] i mobilization, thromboxane A 2 formation, hydroxyl radical (OH ● ) formation, and phospholipase C (PLC) γ 2, protein kinase C (PKC), mitogen-activated protein kinase (MAPK), and Akt phosphorylation. Neither SQ22536, an inhibitor of adenylate cyclase, nor ODQ, an inhibitor of guanylate cyclase, reversed the xanthohumol-mediated inhibitory effect on platelet aggregation. Furthermore, xanthohumol did not significantly increase nitrate formation in platelets. This study demonstrates for the first time that xanthohumol possesses potent antiplatelet activity which may initially inhibit the PI3-kinase/Akt, p38 MAPK, and PLC γ 2-PKC cascades, followed by inhibition of the thromboxane A 2 formation, thereby leading to inhibition of [Ca 2+ ] i and finally inhibition of platelet aggregation. Therefore, this novel role of xanthohumol may represent a high therapeutic potential for treatment or prevention of cardiovascular diseases.
    Type of Medium: Online Resource
    ISSN: 1741-427X , 1741-4288
    URL: Article
    DOI: 10.1155/2012/852362
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2012
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  • 6
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    Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma
    Hindawi Limited ; 2015
    In:  BioMed Research International Vol. 2015 ( 2015), p. 1-26
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2015 ( 2015), p. 1-26
    Abstract: We would like to highlight the application of natural products to hepatocellular carcinoma (HCC). We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, and herbal medicines that exert their different anticancer effects via different intracellular signaling pathways and serve as antioxidants. In this review, we will discuss seven common flavonoids that exert different biological effects against HCC via different pathways.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2015/840542
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2015
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  • 7
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    Effect of Prophylactic Antifungal Protocols on the Prognosis of Liver Transplantation: A Propensity Score Matching and Multistate Model Approach
    Hindawi Limited ; 2016
    In:  BioMed Research International Vol. 2016 ( 2016), p. 1-7
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2016 ( 2016), p. 1-7
    Abstract: Background . Whether routine antifungal prophylaxis decreases posttransplantation fungal infections in patients receiving orthotopic liver transplantation (OLT) remains unclear. This study aimed to determine the effectiveness of antifungal prophylaxis for patients receiving OLT. Patients and Methods . This is a retrospective analysis of a database at Chang Gung Memorial Hospital. We have been administering routine antibiotic and prophylactic antifungal regimens to recipients with high model for end-stage liver disease scores ( 〉 20) since 2009. After propensity score matching, 402 patients were enrolled. We conducted a multistate model to analyze the cumulative hazards, probability of fungal infections, and risk factors. Results . The cumulative hazards and transition probability of “transplantation to fungal infection” were lower in the prophylaxis group. The incidence rate of fungal infection after OLT decreased from 18.9% to 11.4% ( p = 0.052 ); overall mortality improved from 40.8% to 23.4% ( p 〈 0.001 ). In the “transplantation to fungal infection” transition, prophylaxis was significantly associated with reduced hazards for fungal infection (hazard ratio: 0.57, 95% confidence interval: 0.34–0.96, p = 0.033 ). Massive ascites, cadaver transplantation, and older age were significantly associated with higher risks for mortality. Conclusion . Prophylactic antifungal regimens in high-risk recipients might decrease the incidence of posttransplant fungal infections.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2016/6212503
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2016
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  • 8
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    Effects of Converting Tacrolimus Formulation from Twice-Daily to Once-Daily in Liver Transplantation Recipients
    Hindawi Limited ; 2014
    In:  BioMed Research International Vol. 2014 ( 2014), p. 1-7
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2014 ( 2014), p. 1-7
    Abstract: Typically, tacrolimus is administrated twice daily. Prolonged-release tacrolimus is the once-daily formulation and may be more convenient for patients. Experience with the administration of the once-daily formulation is still limited. This study enrolled 210 liver transplant recipients who had stable liver function and converted tacrolimus from a twice-daily to once-daily formulation on a 1 mg to 1 mg basis. Among 210 patients, seven patients (3.3%) were withdrawn from the once-daily formulation due to allergy and fatigue. For the other patients, the trough concentration after converting to the once-daily formulation was lower than that of the twice-daily formulation. Liver enzymes were mildly elevated in 3 months after formulation conversion and serum creatinine and uric acid were mildly decreased. Seven patients (3.4%) had clinical suspicion of acute rejection after the formulation conversion and three of them were caused by nonadherence. 155 patients (76.4%) experienced a more convenient life with an increase of social activity. Forty-seven patients (23.2%) experienced the convenience of once-daily formulation during overseas trips. In conclusion, tacrolimus can be safely converted from the twice-daily to the once-daily formulation for most stable liver recipients. Acute rejection may occur in a minority of patients during formulation conversion and should be carefully monitored.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2014/265658
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2014
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  • 9
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    Formulated Chinese Medicine Shaoyao Gancao Tang Reduces Tau Aggregation and Exerts Neuroprotection through Anti-Oxidation and Anti-Inflammation
    Hindawi Limited ; 2018
    In:  Oxidative Medicine and Cellular Longevity Vol. 2018 ( 2018-10-28), p. 1-16
    Details
    In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2018 ( 2018-10-28), p. 1-16
    Abstract: Misfolded tau proteins induce accumulation of free radicals and promote neuroinflammation by activating microglia-releasing proinflammatory cytokines, leading to neuronal cell death. Traditional Chinese herbal medicines (CHMs) have been widely used in clinical practice to treat neurodegenerative diseases associated with oxidative stress and neuroinflammation. This study examined the neuroprotection effects of formulated CHMs Bai-Shao (made of Paeonia lactiflora ), Gan-Cao (made of Glycyrrhiza uralensis ), and Shaoyao Gancao Tang (SG-Tang, made of P. lactiflora and G. uralensis at 1 : 1 ratio) in cell model of tauopathy. Our results showed that SG-Tang displayed a greater antioxidative and antiaggregation effect than Bai-Shao and Gan-Cao and a stronger anti-inflammatory activity than Bai-Shao but similar to Gan-Cao. In inducible 293/SH-SY5Y cells expressing proaggregant human tau repeat domain ( Δ K280 tau RD ), SG-Tang reduced tau misfolding and reactive oxygen species (ROS) level in ΔK280 tau RD 293 cells and promoted neurite outgrowth in ΔK280 tau RD SH-SY5Y cells. Furthermore, SG-Tang displayed anti-inflammatory effects by reducing nitric oxide (NO) production in mouse BV-2 microglia and increased cell viability of ΔK280 tau RD -expressing SH-SY5Y cells inflamed by BV-2 conditioned medium. To uncover the neuroprotective mechanisms of SG-Tang, apoptosis protein array analysis of inflamed tau expressing SH-SY5Y cells was conducted and the suppression of proapoptotic proteins was confirmed. In conclusion, SG-Tang displays neuroprotection by exerting antioxidative and anti-inflammatory activities to suppress neuronal apoptosis in human tau cell models. The study results lay the base for future applications of SG-Tang on tau animal models to validate its effect of reducing tau misfolding and potential disease modification.
    Type of Medium: Online Resource
    ISSN: 1942-0900 , 1942-0994
    URL: Article
    DOI: 10.1155/2018/9595741
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2018
    detail.hit.zdb_id: 2455981-7
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  • 10
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    De Novo Endotoxin-Induced Production of Antibodies against the Bile Salt Export Pump Associated with Bacterial Infection following Major Hepatectomy
    Hindawi Limited ; 2018
    In:  BioMed Research International Vol. 2018 ( 2018), p. 1-9
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2018 ( 2018), p. 1-9
    Abstract: Background . Clinically severe infection-related inflammation after major liver resection may cause hyperbilirubinemia. This study aims to clarify the impact of bacterial infection and endotoxins on the hepatobiliary transporter system and to explore possible mechanisms of endotoxin-related postoperative hyperbilirubinemia. Method . Mice that underwent major hepatectomy with removal of at least 70% of liver volume were exposed to lipopolysaccharide (LPS) at different dosages. Subsequently, hepatobiliary transporter compounds related to bile salt excretion were further investigated. Results . The expression of genes related to hepatobiliary transporter compounds was not significantly different in the liver tissue of mice after major hepatectomy and LPS exposure. However, bile salt export pump (BSEP) protein expression within the liver tissue of mice treated with LPS after major hepatectomy was relatively weaker and was even further reduced in the high-dose LPS group. The formation of antibodies against the BSEP in response to endotoxin exposure was also detected. Conclusion . This study illustrates a possible mechanism whereby the dysfunction of hepatobiliary transporter systems caused by endotoxin-induced autoantibodies may be involved in the development of postoperative jaundice associated with bacterial infection after major hepatectomy.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2018/6197152
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2018
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