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 deli...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.展开更多
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 genet...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.展开更多
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 popula...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 < 0.0001) increased 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.展开更多
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 im...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.展开更多
By the time a gastroenterology patient is moved to parenteral nutrition, he or she is usually in poor health. All parenteral nutrition formulae contain essen-tial nutrients, avoiding components that could cause an adv...By the time a gastroenterology patient is moved to parenteral nutrition, he or she is usually in poor health. All parenteral nutrition formulae contain essen-tial nutrients, avoiding components that could cause an adverse reaction. The lipid component is often provided by a soy extract, containing all the fatty acids considered to be essential in the diet. Several trials have considered parenteral nutrition formulas with added fish oils, high in the long chain omega-3 polyunsaturated fatty acids, eicosapentaenoic acid(EPA) and docosahexaenoic acid(DHA). Given the range of biological functions associated with such compounds, especially in reducing inflammatory symptoms, this move would appear rational. However, while data from such trials are often positive, there has been variability among results. Some of this variability could be caused by environmental contaminants in the fish, and/or oxidation of the lipids because of poor storage. The situation is complicated by a recent report that fish oils may counter the effects of platinum chemotherapy. However, this effect associated with a minor component, hexadeca-4,7,10,13-tetraenoic acid. It is suggested that pure DHA and EPA would be beneficial additions to parenteral nutrition, reducing the probability of carcinogenesis and enhancing rational disease management. However, the jury is still out on fish oils more generally.展开更多
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 ...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 disease.展开更多
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...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.展开更多
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...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。展开更多
文摘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.
基金Supported by The Ministry of Business,Innovation and EmploymentDutch Digestive Foundation
文摘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.
基金Foundation for Research, Science and Technology, C02X0403: Gene-specific Foods
文摘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 < 0.0001) increased 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.
文摘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.
基金Supported by Auckland Division,Cancer Society of New Zealand
文摘By the time a gastroenterology patient is moved to parenteral nutrition, he or she is usually in poor health. All parenteral nutrition formulae contain essen-tial nutrients, avoiding components that could cause an adverse reaction. The lipid component is often provided by a soy extract, containing all the fatty acids considered to be essential in the diet. Several trials have considered parenteral nutrition formulas with added fish oils, high in the long chain omega-3 polyunsaturated fatty acids, eicosapentaenoic acid(EPA) and docosahexaenoic acid(DHA). Given the range of biological functions associated with such compounds, especially in reducing inflammatory symptoms, this move would appear rational. However, while data from such trials are often positive, there has been variability among results. Some of this variability could be caused by environmental contaminants in the fish, and/or oxidation of the lipids because of poor storage. The situation is complicated by a recent report that fish oils may counter the effects of platinum chemotherapy. However, this effect associated with a minor component, hexadeca-4,7,10,13-tetraenoic acid. It is suggested that pure DHA and EPA would be beneficial additions to parenteral nutrition, reducing the probability of carcinogenesis and enhancing rational disease management. However, the jury is still out on fish oils more generally.
基金the Auckland Medical Research Foundation, New Zealand and Goodfellow Trust, Urology Department, Auckland Hospital, New Zealand for funding the patient recruitment related to this communication.
文摘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 disease.
基金Supported by Foundation for Research,Science and Technology,C02X0403:Gene-specific Foods
文摘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.
