The significance of acute-phase small-for-size liver graft injury in mobilization of circulating EPCs/MDSCs/Tregs after LDLT for HCC patients

Oral Presentation - Session O40 HCC and Living Donor Transplantation: O40.06INTRODUCTION AND OBJECTIVE: Higher incidence of tumor recurrence is a major obstacle of living donor liver transplanatation (LDLT) for the patients with hepatocellular carcinoma (HCC). We have already demonstrated that acute phase small-for-size liver graft injury plays important role on late phase tumor recurrence and metastases in a serial animal studies. Understanding the molecular mechanism of acute phase small-for-size liver graft injury is essential for development of therapeutic strategy to reduce the likelihood of tumor recurrence after LDLT. In the current clinical study, we aim to investigate the impact of acute-phase small-for-size graft injury on mobilization of circulating endothelial progenitor cells (EPCs), myeloid-derived suppressive cells (MDSCs) and regulatory T cells (Tregs) in HCC patients after liver transplantation and to explore the molecular mechanism therein. METHODS: From May 2000 to November 2009, 115 adult HCC recipients were included in the current study. The intragraft microRNA profiles of the grafts greater (Group 1) and less than 60% (Group 2) of standard liver weight (SLW) were characterized by Low Density Array (LDA) analysis. Post-operative circulating EPCs (CD34+CD133+CD45-), MDSCs (CD34+CD13+CD33+) and Tregs (CD4+CD25+FOXP3+) were compared by FACS analysis. Intragraft hepatic stellate cell activation, macrophage infiltration and gene expression of Rac, Pyk2, Egr-1 and VEGF at the early phase after reperfusion were also detected by immunostaining and real-time RT-PCR, respectively. Clinical-pathological data including the incidence of tumor recurrence and metastasis were compared between the two groups. RESULTS: The patients were grouped into Group 1 (>= 60% SLW, n=37) and Group 2 (<60% SLW, n=78). The numbers of patients beyond Milan criteria [15/37(40.5%) vs 29/49(59.2%), p=0.838] or UCSF criteria [9/37(24.3%) vs 19/60(31.7%), p=1] were similar between the two groups. Much more patients in Group 2 developed tumor recurrence and lung metastasis [19/78(24.4%) vs 3/37(8%), p=0.04]. Level of circulating EPCs was significantly higher in Group 2 (Day 3: 0.09% vs 0.002%, p=0.019; Week 4: 0.12% vs 0.033%, p=0.037; Week 8: 0.0585% vs 0.025%, p=0.018; Week 12: 0.055% vs 0.028%, p=0.025). A tendency of larger populations of circulating MDSCs and Tregs was also found in Group 2. Most of the patients with tumor recurrence had hepatic sinusoidal injury at early phase after liver transplantation. Significant activation of hepatic stellate cells was found in Group 2 together with stronger intragraft protein expression of FAK and CAK compared to Group 1. Intragraft mRNA levels of Egr-1, RhoA, FAK and VEGF were also significantly higher in Group 2. microRNA LDA analysis demonstrated that mir-233, mir-141, mir-1308, mir-548 and mir-576 were differentially expressed between the two groups. These mirRNAs were predicted to regulate targeting genes linked to graft injury (MAPK, CCL4 and Egr-1), tumor invasiveness (STAT5, CDC2 and EGFR), angiogenesis (VEGF, FLT4 and ANGPTL5), and macrophage infiltration (MIP2). CONCLUSION: A significantly higher population of postoperative circulating EPCs, which are mobilized by small-for-size graft injury, may lead to a higher incidence of tumor recurrence and metastasis after LDLT. The distinct intragraft miRNA expression profile linked to acute-phase injury and angiogenesis may play a role in the mobilization of circulating EPCs, MDSCs, and Tregs.postprintThe 23rd International Congress of The Transplantation Society (TTS 2010), Vancouver, Canada, 15-19 August 2010. In Transplantation, 2010, v. 90 no. 2S, p. 268, abstract no. 51

Using a Mixed-Methods Approach to Explore Changes in Adolescent Well-Being across Several European Countries

The promotion of positive mental health is a becoming priority worldwide. Despite all the efforts invested in preventive and curative work, it is estimated that one in four persons will experience a mental health condition at some point in their lives. Even more worrying is the fact that up to a half of all mental health problems have their onset before the age of 14. Recent statistics (national and international surveys, meta-analyses, international reports) point out to the fact that child and adolescent mental health problems are on the rise. The present study will try to corroborate these results and further explore their meaning, by employing a sequential mixed methods research design (quantitative–qualitative). The quantitative part will analyze time trends using Health Behaviors in School-aged Children data (four survey cycles: 2002, 2006, 2010, 2014) on mental well-being from four European countries (the Czechia, Germany, Italy, and United Kingdom). The qualitative part will rely on focus groups to explore the perspectives of 13- and 15-year- old boys and girls on gender differences and on the changes in adolescent mental well-being over time, as well as measures through which these issues could be addressed. Thematic analysis will be employed to analyze qualitative data. The results of this study could make a major contribution to our understanding of the current trends in adolescent mental well-being, as well as the ways in which existing data could be linked to international and national health policies

Entanglement of photons in their dual wave-particle nature

Wave-particle duality is the most fundamental description of the nature of a quantum object, which behaves like a classical particle or wave depending on the measurement apparatus. On the other hand, entanglement represents nonclassical correlations of composite quantum systems, being also a key resource in quantum information. Despite the very recent observations of wave-particle superposition and entanglement, whether these two fundamental traits of quantum mechanics can emerge simultaneously remains an open issue. Here we introduce and experimentally realize a scheme that deterministically generates entanglement between the wave and particle states of two photons. The elementary tool allowing this achievement is a scalable single-photon setup which can be in principle extended to generate multiphoton wave-particle entanglement. Our study reveals that photons can be entangled in their dual wave-particle behavior and opens the way to potential applications in quantum information protocols exploiting the wave-particle degrees of freedom to encode qubits

‘Talkin’ ‘bout my generation’: using a mixed-methods approach to explore changes in adolescent well-being across several European countries

The promotion of positive mental health is a becoming priority worldwide. Despite all the efforts invested in preventive and curative work, it is estimated that one in four persons will experience a mental health condition at some point in their lives. Even more worrying is the fact that up to a half of all mental health problems have their onset before the age of 14. Recent statistics(national & international surveys, meta-analyses, international reports) point out to the fact that child and adolescent mental health problems are on the rise. The present study will try to corroborate these results and further explore their meaning, by employing a sequential mixed methods research design (quantitative-qualitative). The quantitative part will analyse time trends using Health Behaviours in School-aged Children (HBSC) data (four survey cycles: 2002, 2006, 2010, 2014) on mental well-being from four European countries (the Czech Republic, Germany, Italy, and the United Kingdom). The qualitative part will rely on focus groups to explore the perspectives of 13- and 15-year-old boys and girls on gender differences and on the changes in adolescent mental well-being over time, as well as measures through which these issues could be addressed. Thematic analysis will be employed to analyse qualitative data. The results of this study could make a major contribution to our understanding of the current trends in adolescent mental well-being, as well as the ways in which existing data could be linked to international and national health policies.Publisher PDFPeer reviewe

Circulating fibroblast growth factor 21 Is a sensitive biomarker for severe ischemia/reperfusion injury in patients with liver transplantation

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The role of regulatory B cells on hepatocellular carcinoma progression

Poster PresentationCongress Theme: Translating Discoveries into Prevention and CuresPURPOSE: Regulatory B cells (Bregs) play important roles in autoimmune diseases, but their function in hepatocellular carcinoma (HCC) progression remains unclear. This study attempted to unveil the role of Bregs on HCC progression. EXPERIMENTAL DESIGN: This study examined the distribution of intrahepatic B cells and circulating Bregs population at the level of phenotypes as well as functionality in HCC patients. The mechanisms of Bregs regulating liver tumor cells were further explored in a series of in vitro and in vivo functional studies. RESULTS: The percentage of B cells at tumor margin region was significantly higher than that in tumor or non-tumor region. Increased intrahepatic B cells at tumor margin were positively associated with tumor invasive features and more tumor recurrence. Besides, HCC patients had a significant higher percentage of circulating Bregs than healthy people. Increased circulating Bregs were positively correlated with advanced tumor staging, tumor multiplicity and venous infiltration. Next, our in vivo study firstly revealed that human Bregs promoted HCC tumor growth independent of Tregs in SCID mice. The migration of Bregs into tumor in mice was further confirmed by in vivo imaging and histology. Finally, the molecular mechanism of Bregs promoted proliferation and migration of HCC cells was proved by direct cell-cell interaction via CD40/CD154 signaling in vitro. Coculture of Bregs and HCC cells induced CD40/CD154-dependent cytokines secretion. CONCLUSION: Human Bregs promoted HCC growth and invasiveness by interacting with HCC tumor cells through CD40/CD154 signaling pathway. Bregs might be both a prognostic marker and a therapeutic target for HCC.published_or_final_versio

Interferon-gamma Inducible Protein 10 up-regulated by acute-phase graft injury induced late-phase cisplatin resistance after liver transplantation

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Lycium barbarum Extracts Protect the Brain from Blood-Brain Barrier Disruption and Cerebral Edema in Experimental Stroke

BACKGROUND AND PURPOSE: Ischemic stroke is a destructive cerebrovascular disease and a leading cause of death. Yet, no ideal neuroprotective agents are available, leaving prevention an attractive alternative. The extracts from the fruits of Lycium barbarum (LBP), a Chinese anti-aging medicine and food supplement, showed neuroprotective function in the retina when given prophylactically. We aim to evaluate the protective effects of LBP pre-treatment in an experimental stroke model. METHODS: C57BL/6N male mice were first fed with either vehicle (PBS) or LBP (1 or 10 mg/kg) daily for 7 days. Mice were then subjected to 2-hour transient middle cerebral artery occlusion (MCAO) by the intraluminal method followed by 22-hour reperfusion upon filament removal. Mice were evaluated for neurological deficits just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, immunohistochemical analysis, and Western blot experiments. Evans blue (EB) extravasation was determined to assess blood-brain barrier (BBB) disruption after MCAO. RESULTS: LBP pre-treatment significantly improved neurological deficits as well as decreased infarct size, hemispheric swelling, and water content. Fewer apoptotic cells were identified in LBP-treated brains by TUNEL assay. Reduced EB extravasation, fewer IgG-leaky vessels, and up-regulation of occludin expression were also observed in LBP-treated brains. Moreover, immunoreactivity for aquaporin-4 and glial fibrillary acidic protein were significantly decreased in LBP-treated brains. CONCLUSIONS: Seven-day oral LBP pre-treatment effectively improved neurological deficits, decreased infarct size and cerebral edema as well as protected the brain from BBB disruption, aquaporin-4 up-regulation, and glial activation. The present study suggests that LBP may be used as a prophylactic neuroprotectant in patients at high risk for ischemic stroke.published_or_final_versio

Sustainable Development Goal 3

Sustainable Development Goals (SDGs) aim to develop a better and sustainable future for the world and the goals are part of an action plan to address poverty, hunger, health, gender equity and various pressing world issues. One of these goals looks at health and wellness. Ageing populations have become a crucial issue worldwide and this short monograph explores ageing and how the consequences of an ageing population may affect our health care system through the case study on Hong Kong's population. The book looks at several critical health issues related to ageing. The elderly, particularly those with low socioeconomic status, rely more on the acute-centric care rather than primary care. The book suggests that secondary care service may only be effective to limited extent as a healthcare measure and an optimum health care system should be one that focuses on primary care. The authors put forth a compelling argument for disease prevention and screening schemes and explain how they are more cost-effective and beneficial to the society and the system. This thoughtful book will provide beneficial insights into the relationship of ageing and sustainable development goals in the context of health and wellness for policy makers and healthcare professionals

The clinical significance and potential therapeutic role of GPx3 in tumor recurrence after liver transplantation

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