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Hepatoma research 2020年第3期6卷 1-14页

作者： Aparna Jayachandran ritu Shrestha Kim r.bridle Darrell H.G.Crawford The University of Queensland Faculty of MedicineBrisbaneQLD 4006Australia Gallipoli Medical research Institute Greenslopes Private HospitalBrisbaneQLD 4120Australia

Hepatocellular carcinoma(HCC)is a significant global health problem with high morbidity and *** incidence is increasing exponentially worldwide with a close overlap between annual incidence and death *** though significant advances have been made in HCC treatment,fewer than 20%of patients with HCC are suitable for potentially curative *** hemochromatosis(HH)is an important genetic risk factor for *** is an autosomal recessive disorder of iron metabolism,characterised by elevated iron deposition in most organs including the liver,leading to progressive organ *** is a complication of HH,nearly always occurring in patients with cirrhosis and contributes to increased mortality *** the susceptibility of development of HCC in HH patients has gained much *** review summarises the current knowledge with regard to the association of HH and HCC in order to encourage further *** this review,we focus particularly on HFE gene-related ***,we highlight and discuss emerging clinical research which addresses the prevalence of HCC in HH patients and the coincidence of HH with other risk factors for HCC *** also focus on the therapeutic tools in the management of HCC associated with HH.

关键词： Hepatocellular carcinoma hereditary hemochromatosis HFE gene C282Y mutation H63D mutation liver cirrhosis

Exosome-based liquid biopsy in the management of hepatocellular carcinoma

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Hepatoma research 2018年第8期4卷 48-59页

作者： Aparna Jayachandran Sasidhar Venkata Manda ritu Shrestha Kim r.bridle Prashanth Prithviraj Darrell H.G.Crawford School of Clinical Medicine The University of QueenslandBrisbaneQLD4072Australia Gallipoli Medical research Institute Greenslopes Private HospitalBrisbaneQLD4120Australia Apollo Hospitals Educational and research Foundation HyderabadTelangana500096India Fiona Elsey Cancer research Institute BallaratVIC3350Australia

Hepatocellular carcinoma (HCC) commonly presents at an advanced stage due to the lack of efficient early screening tools. Early, non-invasive biomarkers useful in the diagnosis and prognosis of HCC would be of significant benefit for HCC management. Development of exosome-based liquid biopsy as a non-invasive method for the management of HCC has gained much traction. Exosomes are small membranous vesicles secreted by most cell types including HCC cells. Exosomes serve as couriers for the intercellular transfer of important biomolecules, including, protein, nucleic acids and lipids to nearby and distant cells in the body. The molecular cargos carried by exosome have been described to play significant roles in cancer progression. Herein, we will dissect how HCC-derived exosomes confer aggressive traits such as tumour growth, invasion, immune remodelling and drug resistance to HCC cells. We review the current literature concerning exosomes as biomarkers in a diagnostic setting, evaluating their prognostic, predictive and monitoring capabilities. This review will highlight and discuss emerging research in the utility of exosome-based liquid biopsies therapeutic tools in HCC management. Here we will also focus on advances in exosome biology in preclinical studies.

关键词： Hepatocellular carcinoma liquid biopsy exosomes microrNA epithelial-to-mesenchymal transition cancer stem cell

Immune checkpoint blockade therapies for HCC: current status and future implications

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Hepatoma research 2019年第9期5卷 1-17页

作者： ritu Shrestha Kim r.bridle Darrell H.G.Crawford Aparna Jayachandran The University of Queensland Faculty of MedicineBrisbaneQueensland 4120Australia Gallipoli Medical research Institute Greenslopes Private HospitalBrisbaneQueensland 4120Australia

Hepatocellular carcinoma(HCC)is the most lethal and common type of liver cancer with limited treatment options at the advanced *** use of immune checkpoint inhibitor(ICI)based immunotherapy is exponentially increasing in the treatment of patients with advanced solid *** expression of immune checkpoints on tumor cells leading to lower activity of T-cells is one of the major mechanisms of immune *** blockade immunotherapies with antibodies against PD-1,PD-L1 or CTLA-4 are being investigated in clinical trials in HCC *** have improved survival in patients with inoperable advanced stage HCC where other curative treatments are not ***,the response rates remain low with only a small subset of patients responding to this *** is an unmet need to identify predictive markers to select those HCC patients who would benefit from ICI ***,epithelial-to-mesenchymal transition(EMT),a major process driving HCC invasion and metastasis by regulating the phenotypic cellular switching from epithelial to mesenchymal state,has been implicated as a resistance mechanism associated with ICI *** role of EMT as a regulator of immune checkpoint molecule in HCC is just ***,the consequence of EMT as a resistance mechanism in HCC patients undergoing ICI treatments remains *** this review,we summarize the recent clinical studies with ICIs in HCC and highlight the trials underway featuring novel monotherapies and combinatorial approaches based on immune and non-immune *** will discuss the ongoing efforts to discover new immune checkpoint molecules in HCC as potential drug *** also highlight the role of EMT in facilitating therapy resistance in HCC treated with ICIs and discuss potential strategies to circumvent resistance in ICI treated HCC patients.

关键词： Hepatocellular carcinoma immunotherapy immune checkpoint inhibitors epithelial-to-mesenchymal transition programmed cell death protein-1 programmed death-ligand 1 resistance

Whole-body in vivo enzyme activity of fatty acid metabolism in barramundi,Lates calcarifer

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Whole-body in vivo enzyme activity of fatty acid metabolism ...

Advances in Water Quality Monitoring of Inorganics: Current Trends

The 14th International Symposium on Fish Nutrition & Feeding

作者： ramez Alhazzaa andrew bridle Peter Nichols Chris Carter NCMCrS University of TasmaniaLocked Bag 1370LauncestonTAS 7250Australia TAFI University of TasmaniaPrivate Bag 49HobartTAS 7001Australia Food Futures Flagship CSIRO Marine & Atmospheric ResearchCastray EsplanadeHobartTAS 7000Australia

Fish oil(FO) supply is strongly dependent on the availability and sustainability of wild fisheries and is under pressure from increasing demand of the expanding agricultural and pharmaceutical *** plant oils are rich in polyunsaturated fatty acids(PUFA) and emerging as practical replacements for *** fish on different precursors ofω3 long chain (≥C) PUFA(LC-PUFA) to increase LC-PUFA content in flesh is of potential interest in *** test the preferential utilisation of dietary fatty acids and capacity of barramundi to synthesise LC-PUFA from shorter(C) precursors,three identical diets differing only in lipid source were fed to juvenile fish raised in freshwater and seawater for 8 *** from Echium plantagineum(EO),rich in SDA(18:4ω3),and from canola(CO),containing ALA(18:3ω3),were compared with a FO diet rich in EPA+DHA(20:5ω3 &(22:6ω3),.FA mass balance showed no significant effects for varied salinity on FA *** enzymes involved in FA biosynthesis varied in apparent in vivo activity depending on dietary ***-fed fish,containing SDA to bypass the rate-limiting△-6 FA desaturase(FAD6) step within PUFA synthesis pathway,did not show activity for this enzyme,while CO inclusion in diets increased FAD6 and to a less extent when feeding on *** activity was shown by the downstream△5 FA desaturase(FAD5) enzyme needed to synthesise de novoω-3 LC-PUFA products in EO-fed fish compared to FO and ***-fed fish accumulated oleic acid and showed significantly higher apparent activity for△9 FA desaturase(FAD9) compared with the EO and CO ***β-oxidation of total dietary and de novo fatty acids recorded the greatest rates in fish fed on FO compared with plant *** prefer to accumulate most of the dietary SFA,MUFA and utilise PUFA by elongation and desaturation to the more beneficial *** biosynthesis did not produce excess amounts of the final products and catabolised LC-PUFA preferentially from

关键词： Lates calcarifer lipid metabolism fatty acid mass balance

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Journal of Water resource and Protection 2013年第4期5卷 40-48页

作者： Florence Bullough Cecilia Fenech Helen bridle Department of Earth Science and Engineering Royal School of Mines Imperial College London London UK Institute for Biological Chemistry Biophysics and Bioengineering Heriot-Watt University Edinburgh UK School of Biotechnology Dublin City University Dublin UK

New methods of analysis for water quality monitoring to detect inorganic substances are required to meet the demands of determining concentration, particularly at low detection limits, analysing speciation and even identifying the pollution source. Such information is essential to inform public health decisions and to comply with more stringent legislation. This paper concentrates on two case studies, reviewing the development in monitoring methods, and predicting future trends. Arsenic and nitrates detection was selected as these pollutants are particularly problematic from a human health perspective. Additionally, the challenges faced in developing monitoring methods for these chemicals are relevant to a wide range of other inorganics. The current state of the art in detection approaches for these chemicals are discussed along with recommendations for future research to further improve the methods.

关键词： Water Quality Monitoring Detection Methods Arsenic Nitrates Speciation Source Tracking

Adaptation to Climate Change in the Pastoral and Agropastoral Systems of Borana, South Ethiopia: Options and Barriers

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American Journal of Climate Change 2019年第1期8卷 40-60页

作者： Nega Debela David McNeil Kerry bridle Caroline Mohammed Tasmanian Institute of Agriculture University of Tasmania Hobart Australia

The pastoral and agropastoral systems of the Borana in southern Ethiopia are highly vulnerable to climate change and its impacts. Assistance to enable these smallholders to successfully adapt to future climate change in locally relevant ways can be usefully informed by the analysis and better understanding of past and ongoing adaptation. We conducted farm household surveys, focus group discussions, expert consultations and secondary data collation in 2012 in the Borana. The study employed a combination of Pressure-State-response (PSr) framework to analyse how climate change put pressure on pastoral and agropastoral farming systems and livelihoods, and Pelling’s (2011) typological framework to analyse local adaptation responses. results showed that pastoral and agropastoral households, their communities and institutions adopted a wide range of adaptation options primarily through adjusting their farming practices and diversifying into non-pastoral livelihoods. The smallholders primarily pursued a resilience approach to adaptation with short term goals intended to avoid system disruptions instead of long-term transformational approaches that significantly address the root causes of vulnerability. A range of barriers constrained local adaptive capacity and shaped routes for adaptation. Adaptation pathways that address critical barriers to adapt, integrate indigenous institutions into adaptation and link adaptation with local development process are necessary to bring long-term and non-marginal, major changes that reduce vulnerability and ensure co-benefit of improving livelihoods.

关键词： Adaptation Options Barriers resilience Smallholder Agriculture Vulnerability

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新黑暗时代

Combination curcumin and vitamin E treatment attenuates diet-induced steatosis in Hfe-/-mice

作者： (英)詹姆斯·布莱德尔(James bridle)

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World Journal of Gastrointestinal Pathophysiology 2017年第2期8卷 67-76页

作者： Mandy Heritage Lesley Jaskowski Kim bridle Catherine Campbell David Briskey Laurence Britton Linda Fletcher Luis Vitetta V Nathan Subramaniam Darrell Crawford School of Medicine The University of Queensland Gallipoli Medical research Institute Greenslopes Private Hospital Envoi Specialist Pathologists School of Human Movement and Nutrition Sciences The University of Queensland Department of Gastroenterology and Hepatology Princess Alexandra Hospital The University of Sydney Sydney Medical School Medlab Clinical Ltd The QIMr Berghofer Medical research Institute Institute of Health and Biomedical Innovation Queensland University of Technology

AIM To investigate the synergistic hepato-protective properties of curcumin and vitamin E in an Hfe^(-/-)high calorie diet model of *** Hfe^(-/-)C57BL/6J mice were fed either a high calorie diet or a high calorie diet with 1 mg/g curcumin; 1.5 mg/g vitamin E; or combination of 1 mg/g curcumin + 1.5 mg/g vitamin E for 20 wk. Serum and liver tissue were collected at the completion of the experiment. Liver histology was graded by a pathologist for steatosis, inflammation and fibrosis. rNA and protein was extracted from liver tissue to examine gene and protein expression associated with fatty acid oxidation, mitochondrial biogenesis and oxidative stress *** Hfe^(-/-)mice fed the high calorie diet developed steatohepatitis and pericentral fibrosis. Combination treatment with curcumin and vitamin E resulted in a greater reduction of percent steatosis than either vitamin E or curcumin therapy alone. Serum alanine aminotransferase and non-alcoholic fatty liver disease(NAFLD) activity score were decreased following combination therapy with curcumin and vitamin E compared with high calorie diet alone. No changes were observed in inflammatory or fibrosis markers following treatment. Epididymal fat pad weights were significantly reduced following combination therapy, however total body weight and liver weight were unchanged. Combination therapy increased the m rNA expression of Adipo r2, Ppar-α, Cpt1 a, Nrf-1 and Tfb2 m suggesting enhanced fatty acid oxidation and mitochondrial biogenesis. In addition, combination treatment resulted in increased catalase activity in Hfe^(-/-)mice. CONCLUSION Combination curcumin and vitamin E treatment decreases liver injury in this steatohepatitis model, indicating that combination therapy may be of value in NAFLD.

关键词： Non-alcoholic fatty liver disease Hemochromatosis Iron overload Steatosis High calorie diet