Bioscience Horizons最新文献

{"title":"Cell replacement therapy in Parkinson's disease","authors":"T. R. Barrow","doi":"10.1093/BIOHORIZONS/HZV002","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZV002","url":null,"abstract":"With an ageing population, the incidence of Parkinson’s disease is increasing. The disease has an overwhelming impact on those it affects and has a limited repertoire of drug therapies available, each with problematic side effects. Stem cell therapy is an exciting prospect in the treatment of several neurodegenerative conditions. This article takes an in depth look at the great potential of cell replacement therapy for Parkinson’s disease, providing supporting evidence for investment in this potential treatment. After considering the basis for cell replacement therapy, the article looks at stem cells of different origins, summing up the strengths and limitations of each in relation to Parkinson’s disease. In addition to highlighting the cell replacement therapies available, the article also provides a chronology of research into this emerging field over the last 30 years.","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZV002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60765384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRIMA-1 as a cancer therapy restoring mutant p53: a review","authors":"E. Lewis","doi":"10.1093/BIOHORIZONS/HZV006","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZV006","url":null,"abstract":"With a continuing increase in the prevalence of cancer, there is an increasing pressure to produce novel cancer therapies. The production of targeted cancer therapies could lead to the replacement of conventional cancer chemotherapy and, consequently, the minimization of the associated distressing side effects. This review addresses the process of restoring a mutant tumour suppressor protein, p53, in the apoptosis pathway as a potential therapeutic target for cancer therapy. Current literature highlights the small molecule PRIMA-1 as a particularly promising novel cancer therapy; however, there are currently many potential therapies being investigated; CP-31398 is another small molecule with potential anti-cancer effects. PRIMA-1 acts to restore the mutant p53 by modifying thiol groups in the core domains of the protein. Its success is well documented, with many studies in different cancer models proving its effectiveness. This, however, is not unanimous, with some questions being raised about its efficacy and other aspects such as possible resistance mechanisms as well as potentially harmful degra dation products. This said, PRIMA-1 has entered Stage II clinical trials and with more data collected on in vivo models and potential complications of the drug, it could ultimately provide an alternative to conventional cancer chemotherapy. This could therefore help to prevent cancer patients suffering the displeasing side effects with which it is associated.","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZV006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60765743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia signalling and regulation in chemosensory behaviour of Caenorhabditis elegans","authors":"G. Macnee, M. Hejmadi","doi":"10.1093/BIOHORIZONS/HZV003","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZV003","url":null,"abstract":"Adaptation to hypoxia is essential to survival in most organisms; disruption of oxygen homeostasis is linked to the pathology of multiple diseases including neurodegeneration, ischaemic stroke and cancer. Hypoxia-inducible factor 1 (HIF-1) is a key transcription factor in the detection of oxygen depletion and in mediating the response to hypoxia to maintain cellular oxygen homeostasis. This study investigated hypoxia signalling in vivo using a Caenorhabditis elegans HIF-1 mutant model. The chemosensory behaviour of C. elegans was analysed through the use of chemosensory assays with a chemoattractant and a chemorepellent; the response was quantified by calculating the chemotaxis index of species. Chemosensory assays were used to analyse behavioural changes of C. elegans under oxic and hypoxic conditions and to analyse the effects of mood stabilizing drugs lithium chloride (LiCl) and valproic acid (VA). HIF-1 mutant C. elegans showed an impaired chemosensory response to a 48 h hypoxia exposure. Treatment with LiCl significantly rescued the chemosensory response of HIF-1 mutants under hypoxia, suggesting a protective effect. Treatment with VA decreased the chemosensory response of HIF-1 mutants with hypoxia expo sure. Interestingly, VA also decreased the chemosensory response of wild-type species under oxic conditions, suggesting a mechanism of action independent of hypoxia.","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZV003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60765400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Weighing up the evidence: a meta-analysis and therapeutic audit of the treatments for obesity","authors":"Josh Lawley","doi":"10.1093/BIOHORIZONS/HZU003","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZU003","url":null,"abstract":"There is an urgent need to find the most cost-effective treatment to help manage the ‘epidemic of obesity’. This study examined the long-term efficacy of lifestyle, pharmaceutical and surgical interventions of reducing weight in obese patients by carrying out a meta-analysis of published studies. English language randomized controlled trials were identified from Pubmed and the Cochrane Library in March 2013 that examined interventions for a minimum of 1 year in adults aged 18–70 years. Trials were selected on the basis of a Jadad score of > 2 for pharmaceutical interventions and > 1 for surgical interventions. Exercise and diet-combined therapy was more effective in producing weight loss than diet alone (mean of 5.18 ± 3.37 kg vs. 3.54 ± 3.67 kg), with a mean difference of 1.26 kg with 95% confidence interval (CI): 0.35–2.17 kg). Bariatric surgery resulted in a mean of 16.82% more body weight lost compared with a control group (95% CI: 14.60–19.03%). With respect to drug therapies, patients treated with lorcaserin lost a mean of 3.23 kg (95% CI: 2.70 to 3.75 kg) more than placebo (or 3.00% at 95% CI: 3.41–2.59). In contrast, patients treated with orlistat only lost a mean of 2.85 kg more than placebo (95% CI: 2.49–3.20 kg), equivalent to 2.88% (95% CI: 2.43–3.33%). These results indicate that bariatric surgery is the most effective intervention at causing clinically significant long-term weight loss, for patients with a body mass index of > 35 kg/m 2 . However, it is also associated with considerable risks. Further research is also needed to identify whether lorcaserin or orlistat have a greater effect in particular patient sub-groups and examine the long-term efficacy of other drugs currently used off label for weight loss.","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZU003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60765580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensitivity, specificity and responsiveness of magnetic resonance imaging and ultrasound in rheumatoid arthritis diagnosis","authors":"D. Wain","doi":"10.1093/BIOHORIZONS/HZU005","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZU005","url":null,"abstract":"Rheumatoid arthritis is associated with numerous fiscal and morbidity considerations, which has been shown to be alleviated with earlier diagnosis. The aim of this report is to develop recommendations, backed by an evidence-based search, on the use of specific imaging modalities in the clinical environment of rheumatoid arthritis diagnosis. Three key questions were gener ated, looking specifically at whether the sensitivity, specificity and responsiveness of magnet resonance imaging (MRI) and ultrasound (US) showed any advantage over clinical examination and conventional radiography in the early detection and response to treatment of rheumatoid arthritis. A systematic PubMed search was performed in October 2013 identifying 5986 results, with exclusion and keyword criteria applied; a total of 65 papers were considered for this review, upon which 5 recommendations have been made. These recommendations encompass an evaluation of the MRI outcome measures in rheumatology (OMERACT) methodology with specific attention applied to the joints assessed and the time constraints. A further assessment of the automated MRI volume of the enhanced inflammatory tissue methodology, paying particular attention to specificity of the automated method, and in power-Doppler US a clarification of the non-pathological reading of joint vascularization. Also identified in this report is the need to further assess the capabilities in both staffing and training levels of staff and its cost-effectiveness in both the MRI and US clinical setting.","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZU005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60765609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The roles of Hedgehog signalling and NF-κB activity in pancreatic cancer and opportunities for treatment","authors":"J. Ranson","doi":"10.1093/BIOHORIZONS/HZU004","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZU004","url":null,"abstract":"Pancreatic cancer is the seventh most common form of cancer-related death in the world, affecting hundreds of thousands of people worldwide every year. Treatment for this type of cancer is largely ineffective and future treatments are likely to involve targeting signalling pathways involved in the proliferation of pluripotent stem cells. There are a variety of signalling pathways involved in the pathogenesis of the disease, including Hedgehog (Hh) and nuclear factor-kappaB (NF- κ B). Overexpression of Hh ligands or alterations in other areas of the Hh signalling pathway may lead to tumour formation. Inhibition of Hh ligands, Smoothened or Gli proteins, or up-regulation of Patched expression, could form the basis of new treatments. NF- κ B is often active in pancreatic cancer cells and down-regulation of NF- κ B activating molecules can inhibit tumour progression in cell culture studies. Clinical trials show some promising results in novel drugs. There is growing evidence to suggest the interaction between these two signalling pathways. NF- κ B appears to play a role upstream of the Hh pathway. This article looks at the roles these pathways play in pancreatic cancer and explores current research into targeting them for treatment.","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZU004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60765594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate: valuable for physical performance and maintenance of brain function during exercise","authors":"J. Todd","doi":"10.1093/BIOHORIZONS/HZU001","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZU001","url":null,"abstract":"Lactate accumulation has long been associated with impaired sports performance, with many supporting the lactate acidosis hypothesis. However, due to advances in experimental design and research, numerous beneficial roles of lactate have been established that may impact upon sports performance. Recent studies highlight lactate as a biomarker of fatigue rather than as a direct cause. The lactate-shuttle mechanism facilitates the utilization of lactate as an energy substrate in both type I and type II skeletal muscle fibres, promoting energy sufficiency during exercise. Recent literature also supports a role for lactate in enhancing human oxidative capacity by up-regulating skeletal muscle mitochondrial biogenesis. In addition, lactate-neuron and lactate-astrocyte shuttles enable lactate to supply energy to support cognitive function, during periods of low blood glucose such as prolonged aerobic exercise. This review aims to clarify the role of lactate in modulating aerobic performance and critically investigates the mechanisms responsible.","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZU001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60765521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An effective treatment for Alzheimer's disease must consider both amyloid and tau","authors":"C. Lansdall","doi":"10.1093/BIOHORIZONS/HZU002","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZU002","url":null,"abstract":"Alzheimer’s disease (AD) is a devastating neurodegenerative disorder resulting in cognitive impairment, loss of executive functions and progressive dementia. AD is the most common cause of dementia and incidence is increasing, probably due to a rapidly ageing population. Despite research efforts and a substantial unmet medical need, no effective cure has been identi fied and treatment remains symptomatic. In this review, I assess the current status of AD research and examine future approaches for the development of a potential disease-modifying treatment. Research has focused primarily on amyloid pathology, after a correlation was discovered between mutations in several genes associated with amyloid processing and AD. The Amyloid Cascade Hypothesis suggests that increased amyloid beta (Aβ) aggregation is the major cause of AD, triggering the toxic events that lead to progressive neurodegeneration. However, no drug candidate targeting the cascade has yet produced a successful treatment. It is now speculated that treatment requires early targeting of Aβ, when pathology remains reversible, and clinical trials are focusing on assessing Aβ compounds in pro-dromal AD. Lack of an effective A β-focused treatment has resulted in the consideration of hyperphosphorylated neurofibrillary tangles of tau (NFT), another major pathologi cal hallmark of AD. Studies have repeatedly demonstrated a strong correlation between NFT build up and cognitive decline, and recent studies have identified a number of tau genetic markers associated with AD. Compounds preventing the hyper phosphorylation of tau may therefore halt disease progression; however, the failure of previous tauopathy trials in progressive supranuclear palsy (PSP) has highlighted potential set-backs. The importance of tau as an independent cause of AD, and therefore a target for treatment, may be clarified by ongoing tau-focused clinical studies. Although A β and tau are both highly relevant, their relationship in causing AD remains unknown. Amyloid- and tau-targeting treatments may individually prove effective, however the convergent progression of A β and tau pathology suggests combination therapy may eventually be required, particularly in late stages of disease when both are abundant. While ongoing work focuses on single target therapies, a dual Aβ and tau targeting approach may be more likely to produce a breakthrough.","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZU002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60765539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A critical review of the treatment options available for obstructive sleep apnoea: an overview of the current literature available on treatment methods for obstructive sleep apnoea and future research directions","authors":"A. Booth, Yasmina Djavadkhani, N. Marshall","doi":"10.1093/BIOHORIZONS/HZU011","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZU011","url":null,"abstract":"© The Author 2014. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 1 A critical review of the treatment options available for obstructive sleep apnoea: an overview of the current literature available on treatment methods for obstructive sleep apnoea and future research directions","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZU011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60765769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"‘Neonates do not feel pain’: a critical review of the evidence","authors":"A. Marchant","doi":"10.1093/BIOHORIZONS/HZU006","DOIUrl":"https://doi.org/10.1093/BIOHORIZONS/HZU006","url":null,"abstract":"Up until 1985, the nervous system of the neonate was widely considered to be underdeveloped for pain sensation. Analgesia to alleviate distress from ‘painful’ procedures in which neonates were, and still are, subject to was often considered trivial. Pain in the neonate and (in some cases) the disabled neonate is especially hard to investigate, as they are unable to verbally communicate. There is also no known direct biological marker of pain, only behavioural and stress-related physiological correlates. This critical review gives evidence for and against the hypothesis ‘Neonates do not feel Pain’. Evidence of both the neonatal response to analgesics and long-term effects of neonatal pain are also investigated, with the aim of further supporting or falsifying the hypothesis. Convergence of the observations covered in this review show that most, if not all, studies are in favour of pain-related behaviour and physiology in the neonate, both of which having a similar phenotype to that seen in the older infant and adult. The evidence investigated in this review also supports the hypothesis that cortical development appears to accommodate the subjectivity of pain, but it is not vital for pain experience. Further data and theory have the potential to bring more invaluable evidence to the table regarding whether or not the neonate is able to feel pain.","PeriodicalId":52095,"journal":{"name":"Bioscience Horizons","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/BIOHORIZONS/HZU006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60765645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}