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LOX upregulates FAK phosphorylation to promote metastasis in osteosarcoma

Genes & Diseases 2023年第1期10卷 254-266页

作者： Xiang Chen Margaret Clement mjohn hicks Poonam Sarkar MWaleed Gaber Tsz-Kwong Man Department of Pediatrics Baylor College of MedicineOne Baylor PlazaHoustonTX 77030USA Department of Pathology Baylor College of MedicineOne Baylor PlazaHoustonTX 77030USA Dan L.Duncan Comprehensive Cancer Center 7200 Cambridge StreetHoustonTX 77054USA Texas Children's Cancer and Hematology Centers 1102 Bates StHoustonTX 77030USA

Osteosarcoma is a malignant bone tumor that commonly occurs in the pediatric *** the use of chemotherapy and surgery,metastasis remains to be the leading cause of death in patients with *** have previously reported that cytoplasmic mislocalization of p27 is associated with a poor outcome in *** this study,we further show that lysyl oxidase(LOx)expression was associated with p27 *** is an enigmatic molecule that acts as a tumor suppressor or a metastatic promoter;however,its role in osteosarcoma is still ***,we performed both in vitro and in vivo analyses to dissect the role of Lox in *** result of our survival analysis indicated that Lox expression significantly correlated with a poor outcome in osteosarcoma with or without controlling for the initial metastasis status(P<0.05).Functionally,we found that higher LoX expression promoted osteosarcoma cell proliferation,migration,and invasiveness in vitro and produced a higher number of mice with pulmonary metastases in an orthotopic xenograft mouse ***,phospho-FAK was increased in osteosarcoma cells with high LOX *** results further showed that FAK inhibition significantly reduced tumor cell proliferation and migration in vitro as well as LoX-mediated metastasis in ***,our findings suggest that there is a novel link between p27 mislocalization and LOX *** plays a pivotal role in osteosarcoma metastasis by upregulating FAK *** inhibition may constitute a promising therapeutic strategy to reduce the development of metastasis in osteosarcoma with Lox overexpression.

关键词： Focal adhesion kinase Lysyl oxidase Metastasis Osteosarcoma

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Challenges facing sustainable protein production:Opportunities for cereals

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Plant Communications 2023年第6期4卷 55-69页

作者： Luqman B.Safdar mjohn Foulkes Friedrich H.Kleiner Iain R.Searle Rahul A.Bhosale Ian D.Fisk Scott A.Boden School of Agriculture Food and WineWaite Research InstituteUniversity of AdelaideGlen OsmondSA 5064Australia School of Biosciences University of NottinghamSutton Bonington CampusLoughborough LE125RDUK Faculty of Applied Science Kavli Institute of NanoscienceDelft University of Technology van der Maasweg 92629 HZ Delftthe Netherlands 4School of Biological SciencesUniversity of AdelaideAdelaideSA 5005Australia

Rising demands for protein worldwide are likely to drive increases in livestock production,asmeat provides-40%of dietary *** will come at a significant environmental cost,and a shift toward plant-based protein sources would therefore provide major *** legumes provide substantial amounts of plant-based protein,cereals are the major constituents of global foods,with wheat alone accounting for 15–20%of the required dietary protein *** of protein content in wheat is limited by phenotyping challenges,lack of genetic potential of modern germplasms,negative yield trade-offs,and environmental costs of nitrogen *** wheat as a case study,we discuss how increasing protein content in cereals through a revised breeding strategy combined with robust phenotyping could ensure a sustainable protein supply while minimizing the environmental impact of nitrogen fertilizer.

关键词： sustainability protein nutrition grain protein content innovative breeding

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Distinct profiles of systemic biomarkers of oxidative stress in chronic human pathologies:Cardiovascular,psychiatric,neurodegenerative,rheumatic,infectious,neoplasmic and endocrinological diseases

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Advances in Bioscience and Biotechnology 2013年第3期4卷 331-339页

作者： Michel Brack Olivier Brack Yves Menezo Dominique Bonnefont Rousselot Gerard Dreyfus mjohn Chapman Anatol Kontush Ge Sante et Retraite ParisFrance Consultant en Statistiques EschesFrance Procrelys Maison Medicale Ambroise PareLyonFrance Laboratoire Clement ParisFrance London Fertlity Associates LondonUK Department of Metabolic Biochemistry La Pitie Salpetriere-Charles Foix(AP-HP)ParisFrance Department of Biochemistry Faculty of PharmacyParis Descartes UniversityParisFrance Ecole Superieure de Physique et de Chimie Industrielles ESPCIParisFrance (CNRS UMR 7084) Laboratoire d’electroniqueParisFrance Universite Pierre et Marie Curie-Paris 6 ParisFrance UMR 939“Dyslipoproteinemia Inflammation and Atherosclerosis”INSERMParisFrance AP-HP Groupe hospitalier Pitie-SalpetriereParisFrance

Oxidative stress is involved in chronic and acute pathologies: cardiovascular, neurodegenerative, neoplastic, inflammatory and infectious diseases. Clinical trials focused on prevention of cardiovascular and neoplastic diseases involving antioxidant supplementation have however provided predominantly negative obserations in large-scale studies. Screening of patient cohorts to assess baseline oxidative stress on the basis of a biomarker profile is decisive but lacking. For the first time, we evaluated the level of oxidative stress, testing more than 10 established biomarkers, in a comprehensive initial survey of 617 patients displaying chronic human pathologies. Multiple diseasespecific abnormalities were identified in plasma, whole blood and/or urine. This is the case for vitamins and oligo elements, vitamin C, vitamin E, β-carotene, selenium, zinc and copper;endogenous antioxidants such as reduced and oxidised glutathione, thiols, urate, and glutathione peroxidase activity, and a biomarker of oxidative DNA damage (8-hydroxy-2’-deoxy guanosine). The distinct biomarker profiles suggest the involvment of multiple forms of oxidative insults which arein some way partially specific to each pathological condition. This finding is in favor of the determination of an integrated score to combine contributions of distinct biomarkers, in order to screen patients presenting elevated levels of oxidative stress.

关键词： Vitamin C Vitamin E β-Carotene Glutathione Thiols Urate 8-Hydroxy-2’-Deoxyguanosine

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