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recent advances in understanding of interactions between genes and diet in the etiology of colorectal cancer

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World Journal of Gastrointestinal Oncology 2010年第3期2卷 125-129页

作者： lynnette r ferguson Discipline of Nutrition University of Auckland

At an international level, colorectal cancer (CrC) is a major cause of morbidity and mortality. Diet plays a major etiologic role, and a range of putative dietary carcinogens have been identified. The probability with which these lead to mutations, and thereby cause cancer, is strongly impacted by variants in genes coding for xenobiotic metabolizing or DNA repair enzymes. Nutrient def iciencies also play a role, which will be exacerbated by variants in metabolic genes. However, many of the causal genes in sporadic CrC have hitherto proved elusive. The power of large international collabor ations, coupled with genome-wide association studies, has implicated a major functional role of the tumour growth factor-β pathway in CrC susceptibility. Nutrient regulation of gene expression may be especially important here. Future large collaborative studies must consider gene-gene and gene-diet interactions, coupled with high throughput genomic technologies, in order to uncover the relative roles of genetic variants, mutagenic xenobiotics, nutrient imbalance and gene expression in the etiology of CrC.

关键词： Transforming growth factor β Colorectal cancer Single nucleotide polymorphisms Genome wide association studies Gene expression

Micro rNA biomarkers predicting risk,initiation and progression of colorectal cancer

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World Journal of Gastroenterology 2016年第33期22卷 7389-7401页

作者： Kyungjin Lee lynnette r ferguson Medical Programme and Discipline of Nutrition and Dietetics and Auckland Cancer Society research Centre Faculty of Medical and Health ScienceThe University of Auckland Discipline of Nutrition and Dietetics and Auckland Cancer Society research Centre Faculty of Medical and Health ScienceThe University of Auckland

Colorectal cancer is a major global cause of morbidity and mortality. Current strategies employed to increase detection of early,curable stages of this disease are contributing to a reduction of the negative health impact from it. While there is a genetic component to the risk of disease,diet and environment are known to have major effects on the risk of an individual for developing the disease. However,there is the potential to reduce the impact of this disease further b y preventing disease develop ment. Biomarkers which can either predict the risk for or early stages of colorectal cancer could allow intervention at a time when prospects could be modified by environmental factors,including lifestyle and diet choices. Thus,such biomarkers could be used to identify high risk individuals who would benefit from lifestyle and dietary interventions to prevent this disease. This review will give an overview on one type of biomarker in the form of micro rNAs,which have the potential to predict an individual's risk for colorectal cancer,as well as providing a highly sensitive and non-invasive warning of disease presence and/or progression. Micro rNA biomarkers which have been studied and whose levels look promising for this purpose include Mi r-18 a,Mi r-21,Mi r-92 a,Mi r-135 b,Mi r-760,Mi r-601. Not only have several individual micro rNAs appeared promising as biomarkers,but panels of these may be even more useful. Furthermore,understanding dietary sources and ways of dietary modulation of these micro rNAs might be fruitful in reducing the incidence and slowing the progression of colorectal cancer.

关键词： Biomarkers Epigenetics risk Colorectal cancer Predisposition MicrorNA

Why interleukin-10 supplementation does not work in Crohn's disease patients

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World Journal of Gastroenterology 2013年第25期19卷 3931-3941页

作者： Gareth J Marlow Dominique van Gent lynnette r ferguson Discipline of Nutrition Faculty of Medical and Health Sciences The University of Auckland Auckland 1142 New Zealand Gareth J Marlow Lynnette R Ferguson Nutrigenomics New Zealand The University of Auckland

Inflammatory bowel diseases (IBD) such as Crohn's disease (CD) or ulcerative colitis are chronic intestina disorders, which are on the increase in "Westernised" countries. IBD can be caused by both genetic and environmental factors. Interleukin-10 (IL-10) is an immunoregulatory cytokine that has been identified as being involved in several diseases including IBD. Studies have shown that polymorphisms in the promoter region reduce serum levels of IL-10 and this reduction has been associated with some forms of IBD. Mouse models have shown promising results with IL-10 supplementation, as such IL-10 supplementation has been touted as being a possible alternative treatment for CD in humans. Clinical trials have shown that recombinant human IL-10 is safe and well tolerated up to a dose o 8 μg/kg. However, to date, the results of the clinica trials have been disappointing. Although CD activity was reduced as measured by the CD activity index IL-10 supplementation did not result in significantly reduced remission rates or clinical improvements when compared to placebo. This review discusses why IL-10supplementation is not effective in CD patients currently and what can be addressed to potentially make IL-10 supplementation a more viable treatment option in the future. Based on the current research we conclude that IL-10 supplementation is not a one size fits all treatment and if the correct population of patients is chosen then IL-10 supplementation could be of benefit.

关键词： Inflammatory bowel disease Crohn’s disease Interleukin-10 recombinant human interleukin-10

Potential prospects of nanomedicine for targeted therapeutics in inflammatory bowel diseases

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World Journal of Gastroenterology 2012年第23期18卷 2895-2901页

作者： Madharasi VA Pichai lynnette r ferguson Discipline of Nutrition Faculty of Medical and Health Sciences University of Auckland

Inflammatory bowel diseases (IBDs) such as Crohn's disease are highly debilitating. There are inconsistencies in response to and side effects in the current conventional medications, failures in adequate drug delivery, and the lack of therapeutics to offer complete remission in the presently available treatments of IBD. This suggests the need to explore beyond the horizons of conventional approaches in IBD therapeutics. This review examines the arena of the evolving IBD nanomedicine, studied so far in animal and in vitro models, before comprehensive clinical testing in humans. The investigations carried out so far in IBD models have provided substantial evidence of the nanotherapeutic approach as having the potential to overcome some of the current drawbacks to conventional IBD therapy. We analyze the pros and cons of nanotechnology in IBD therapies studied in different models, aimed at different targets and mechanisms of IBD pathogenesis, in an attempt to predict its possible impact in humans.

关键词： Inflammatory bowel disease Crohn's disease Ulcerative colitis Tumor necrosis factor-m Nanomedicine

Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel diseases risk

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World Journal of Gastroenterology 2008年第29期14卷 4652-4661页

作者： lynnette r ferguson Claudia Huebner Ivonne Petermann richard B Gearry Murray L Barclay Pieter Demmers Alan McCulloch Dug Yeo Han Discipline of Nutrition the University of AucklandPrivate Bag 92019 Auckland 1142 New Zealand Department of Gastroenterology Christchurch HospitalChristchurch 8140 New Zealand Crop and Food research Mosgiel 9053 New Zealand Agresearch Limited Mosgiel 9053 New Zealand

AIM: To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-α) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand population, in the context of international studies. METHODS: DNA samples from 388 patients with Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis (IC) and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common polymorphisms in the TNF-α receptor: -238 G→A, -308 G→A and -857C→T, using a Taqmanr assay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies. rESULTS: Individuals carrying the -308 G/A allele had a significantly (Or = 1.91, χ2 = 17.36, P reased risk of pancolitis, and a 1.57-fold increased risk (Or = 1.57, χ2 = 4.34, P = 0.037) of requiring a bowel resection in UC. Carrying the -857 C/T variant decreased the risk of ileocolonic CD (Or = 0.56, χ2 =4.32, P = 0.037), and the need for a bowel resection (Or = 0.59, χ2 = 4.85, P = 0.028). The risk of UC was reduced in individuals who were smokers at diagnosis, (Or = 0.48, χ2 = 4.86, P = 0.028). CONCLUSION: TNF-α is a key cytokine known to play a role in inflammatory response, and the locus for the gene is found in the IBD3 region on chromosome 6p21, known to be associated with an increased risk for IBD. The -308 G/A SNP in the TNF-α promoter is functional, and may account in part for the increased UC risk associated with the IBD3 genomic region. The -857 C/T SNP may decrease IBD risk in certain groups. Pharmaco- or nutrigenomic approaches may be desir- able for individuals with such affected genotypes.

关键词： Tumour necrosis factor alpha Singlenucleotide polymorphisms Inflammatory boweldiseases Crohn's disease Ulcerative colitis

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个体化营养与健康

英国医学杂志中文版 2021年第3期24卷 165-170页

作者： Jose M Ordovas lynnette r ferguson E Shyong Tai John C Mathers 袁亦芳(译) 武阳丰(校) JM-USDA-HNrCA at Tufts University BostonMAUSA Centro Nacional Investigaciones Cardiovasculares MadridSpain IMDEA Food Institute CEI UAM+CSICMadridSpain Faculty of Medical and Health Sciences The University of AucklandAucklandNew Zealand National University of Singapore Singapore Human Nutrition research Centre Institute of Cellular MedicineNewcastle UniversityNewcastle Upon TyneUnited Kingdom 北京大学临床研究所

Jose Ordovas及其同事认为,根据个体特征和行为进行个体化营养干预具有前景,但在实施之前还需要做更多的工作。膳食因素公认是导致心脏病、卒中、2型糖尿病、癌症等常见疾病的主要因素之一1-3。尽管已知疾病与膳食模式相关联.试图改变... 详细信息

Jose Ordovas及其同事认为,根据个体特征和行为进行个体化营养干预具有前景,但在实施之前还需要做更多的工作。膳食因素公认是导致心脏病、卒中、2型糖尿病、癌症等常见疾病的主要因素之一1-3。尽管已知疾病与膳食模式相关联.试图改变膳食习惯进而影响公众健康和福祉的干预措施仍收效甚微。对于能够影响健康结果的行为,将干预措施个体化可能更凑效4-5,在本文中我们考量了个体化营养的相关证据。

关键词：膳食因素干预措施个体化营养膳食习惯 2型糖尿病公众健康膳食模式营养与健康

role of β-microseminoprotein from prostate cancer initiationto recurrence: A mini-review

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World Journal of Clinical Urology 2014年第1期3卷 20-30页

作者： Nishi Karunasinghe Karen Bishop Pamela Murray Yuanye Xu Megan Goudie Lance Ng Shuotun Zhu Dug Yeo Han lynnette r ferguson Jonathan Masters Benji Benjamin Michael Holmes Auckland Cancer Society research Centre Faculty of Medical and Health Sciences The University of Auckland Discipline of Nutrition Faculty of Medical and Health Sciences The University of Auckland Urology Department Auckland Hospital radiology Department Auckland Hospital Urology Department Waikato Hospital

Medline/Pubmed articles relevant to this topic were considered using the search terms ?-microseminoprotein, MSMB, prostate secretory protein of 94 amino acids and PSP94. Full articles were retrieved when the abstract was considered relevant. In addition, other data related to this topic including our own are discussed. Summary of fi ndings-?-microseminoprotein(MSMB) is increasingly being considered as a marker for prostatecancer, as reduced levels have been associated with the disease. Here we review various aspects of this protein including its biological and physiological variants, binding proteins and immune modulation; its importance as a marker for biochemical recurrence of prostate cancer; prostate cancer related splice variants and its therapeutic utility. Two of the most important properties of MSMB are related to anticancer functions and immune modulation. Predominant expression of two(short and full-length) splice variants of MSMB has been observed from normal prostate and several other tissues. In benign prostate hyperplasia the short isoform is dominant, constituting 98% of this isoform, whereas in prostate cancer 96% constitute the fulllength isoform. The MSMB promoter single nucleotide polymorphism rs10993994 with the C allele functions as an activated cyclic adenosine monophosphate response element binding protein binding site. This C variant of rs10993994 could be responsible for the production of splice variants under variable conditions. MSMB has binding motifs to a few known proteins including immunoglobulin G and several Cysteine-rich secretory proteins family proteins. MSMB bound to these proteins is considered as immune modulating. Use of MSMB as a urinary marker for detecting aggressive prostate cancers that could resist radiation and surgical treatments, seems possible, but needs further investigation. The ratio of MSMB splice variants could also be a possible approach in understanding prostate cancers, with higher ratios indicating severe di

关键词： β-microseminoprotein Anticancer properties Immune modulation Splice variants Promoter single nucleotide polymorphism rs10993994 Biochemical recurrence

MET receptor tyrosine kinase promotes the generation of functional synapses in adult cortical circuits

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Neural regeneration research 2025年第5期20卷 1431-1444页

作者： Yuehua Cui Xiaokuang Ma Jing Wei Chang Chen Neha Shakir Hitesch Guirram Zhiyu Dai Trent Anderson Deveroux ferguson Shenfeng Qiu Basic Medical Sciences University of Arizona College of Medicine-PhoenixPhoenixAZUSA Department of Medicine University of Arizona College of Medicine-PhoenixPhoenixAZUSA

Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse *** have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine *** investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing *** found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection *** findings are further corroborated by increased synaptic activity and transient generation of immature silent *** MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and *** data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult *** findings may have implications for regenerative therapy in aging and neurodegeneration conditions.

关键词： aging circuit connectivity cortical circuits molecular mechanisms neural regeneration neurodegeneration synapses

Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural regeneration research 2025年第6期20卷 1789-1800页

作者： Carina Hromada Patrick Heimel Markus Kerbl LászlóGál Sylvia Nürnberger Barbara Schaedl James ferguson Nicole Swiadek Xavier Monforte Johannes C.Heinzel Antal Nógrádi Andreas H.Teuschl-Woller David Hercher Department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue regeneration ViennaAustria Ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria Department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria Department of Hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization