Open AccessArticle
Role of Diffusion Tensor Imaging in Prognostication and Treatment Monitoring in Niemann-Pick Disease Type C1
Diseases 2016, 4(3), 29; doi:10.3390/diseases4030029 -
Abstract
Niemann-Pick Disease, type C1 (NPC1) is a rapidly progressive neurodegenerative disorder characterized by cholesterol sequestration within late endosomes and lysosomes, for which no reliable imaging marker exists for prognostication and management. Cerebellar volume deficits are found to correlate with disease severity and [...] Read more.
Niemann-Pick Disease, type C1 (NPC1) is a rapidly progressive neurodegenerative disorder characterized by cholesterol sequestration within late endosomes and lysosomes, for which no reliable imaging marker exists for prognostication and management. Cerebellar volume deficits are found to correlate with disease severity and diffusion tensor imaging (DTI) of the corpus callosum and brainstem, which has shown that microstructural disorganization is associated with NPC1 severity. This study investigates the utility of cerebellar DTI in clinical severity assessment. We hypothesize that cerebellar volume, fractional anisotropy (FA) and mean diffusivity (MD) negatively correlate with NIH NPC neurological severity score (NNSS) and motor severity subscores. Magnetic resonance imaging (MRI) was obtained for thirty-nine NPC1 subjects, ages 1–21.9 years (mean = 11.1, SD = 6.1). Using an atlas-based automated approach, the cerebellum of each patient was measured for FA, MD and volume. Additionally, each patient was given an NNSS. Decreased cerebellar FA and volume, and elevated MD correlate with higher NNSS. The cognition subscore and motor subscores for eye movement, ambulation, speech, swallowing, and fine motor skills were also statistically significant. Microstructural disorganization negatively correlated with motor severity in subjects. Additionally, Miglustat therapy correlated with lower severity scores across ranges of FA, MD and volume in all regions except the inferior peduncle, where a paradoxical effect was observed at high FA values. These findings suggest that DTI is a promising prognostication tool. Full article
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Open AccessReview
Food Antioxidants and Their Anti-Inflammatory Properties: A Potential Role in Cardiovascular Diseases and Cancer Prevention
Diseases 2016, 4(3), 28; doi:10.3390/diseases4030028 -
Abstract
Mediterranean-style diets caused a significant decline in cardiovascular diseases (CVDs) in early landmark studies. The effect of a traditional Mediterranean diet on lipoprotein oxidation showed that there was a significant reduction in oxidative stress in the intervention group (Mediterranean diet + Virgin [...] Read more.
Mediterranean-style diets caused a significant decline in cardiovascular diseases (CVDs) in early landmark studies. The effect of a traditional Mediterranean diet on lipoprotein oxidation showed that there was a significant reduction in oxidative stress in the intervention group (Mediterranean diet + Virgin Olive Oil) compared to the low-fat diet group. Conversely, the increase in oxidative stress causing inflammation is a unifying hypothesis for predisposing people to atherosclerosis, carcinogenesis, and osteoporosis. The impact of antioxidants and anti-inflammatory agents on cancer and cardiovascular disease, and the interventive mechanisms for the inhibition of proliferation, inflammation, invasion, metastasis, and activation of apoptosis were explored. Following the Great Oxygen Event some 2.3 billion years ago, organisms have needed antioxidants to survive. Natural products in food preservatives are preferable to synthetic compounds due to their lower volatility and stability and generally higher antioxidant potential. Free radicals, reactive oxygen species, antioxidants, pro-oxidants and inflammation are described with examples of free radical damage based on the hydroxyl, nitric oxide and superoxide radicals. Flavonoid antioxidants with 2- or 3-phenylchroman structures such as quercetin, kaempferol, myricetin, apigenin, and luteolin, constituents of fruits, vegetables, tea, and wine, which may reduce coronary disease and cancer, are described. The protective effect of flavonoids on the DNA damage caused by hydroxyl radicals through chelation is an important mechanism, though the converse may be possible, e.g., quercetin. The antioxidant properties of carotenoids, which are dietary natural pigments, have been studied in relation to breast cancer risk and an inverse association was found with plasma concentrations: higher levels mean lower risk. The manipulation of primary and secondary human metabolomes derived especially from existing or transformed gut microbiota was explored as a possible alternative to single-agent dietary interventions for cancer and cardiovascular disease. Sustained oxidative stress leading to inflammation and thence to possibly to cancer and cardiovascular disease is described for spices and herbs, using curcumin as an example of an intervention, based on activation of transcription factors which suggest that oxidative stress, chronic inflammation, and cancer are closely linked. Full article
Open AccessReview
Distribution and Evolutionary History of the Mobile Genetic Element s2m in Coronaviruses
Diseases 2016, 4(3), 27; doi:10.3390/diseases4030027 -
Abstract
The mobile genetic element s2m has been described in several families of single-stranded RNA viruses. The function remains elusive, but an increasing number of s2m-containing sequences are being deposited in publicly available databases. Currently, more than 700 coronavirus sequences containing s2m can [...] Read more.
The mobile genetic element s2m has been described in several families of single-stranded RNA viruses. The function remains elusive, but an increasing number of s2m-containing sequences are being deposited in publicly available databases. Currently, more than 700 coronavirus sequences containing s2m can be found in GenBank, including the severe acute respiratory syndrome (SARS) coronavirus genome. This is an updated review of the pattern of s2m in coronaviruses, the possible functional implications and the evolutionary history. Full article
Open AccessFeature PaperReview
Human Coronaviruses: A Review of Virus–Host Interactions
Diseases 2016, 4(3), 26; doi:10.3390/diseases4030026 -
Abstract
Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory outcomes. In the past 14 years, the onset of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the [...] Read more.
Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory outcomes. In the past 14 years, the onset of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans. The study of HCoV-host interactions has contributed extensively to our understanding of HCoV pathogenesis. In this review, we discuss some of the recent findings of host cell factors that might be exploited by HCoVs to facilitate their own replication cycle. We also discuss various cellular processes, such as apoptosis, innate immunity, ER stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-κB) pathway that may be modulated by HCoVs. Full article
Open AccessArticle
Influence of Vitamins on Secondary Reactive Oxygen Species Production in Sera of Patients with Resectable NSCLC
Diseases 2016, 4(3), 25; doi:10.3390/diseases4030025 -
Abstract
Background: Singlet oxygen (1O2) oxidizes targets through the production of secondary reactive oxygen species (SOS). Cancers induce oxidative stress changing with progression, the resulting antioxidant status differing from one patient to the other. The aim of this study [...] Read more.
Background: Singlet oxygen (1O2) oxidizes targets through the production of secondary reactive oxygen species (SOS). Cancers induce oxidative stress changing with progression, the resulting antioxidant status differing from one patient to the other. The aim of this study was to determine the oxidative status of patients with resectable Non-Small cell lung cancers (NSCLC) and the potential influence of antioxidants, compared to sera from healthy donors. Materials and Methods: Serum samples from 10 women and 28 men, 19 adenocarcinomas (ADK), 15 patients N1 or M1 were submitted to a photoreaction producing 1O2. Then, samples were supplemented with vitamins (Vit C, Vit E), or glutathione (GSH). Results: Squamous cell carcinomas (SCC) and metastatic SCCs induced a lower SOS rate. While Vit C increased SOS in controls as in patients with metastases, Vit E or the combination of Vit E and C strongly reduced SOS. GSH alone lightly decreased SOS in controls but had no effect in patients either alone or combined with Vit C. Conclusion: In “early” lung cancers, SOS are comparable or lower than for healthy persons. The role of Vitamins varies with gender, cancer type, and metastases. This suggests that an eventual supplementation should be performed on a per-patient basis to evidence any effect. Full article
Open AccessReview
The Protective Effect of Antioxidants Consumption on Diabetes and Vascular Complications
Diseases 2016, 4(3), 24; doi:10.3390/diseases4030024 -
Abstract
Obesity and diabetes is generally accompanied by a chronic state of oxidative stress, disequilibrium in the redox balance, implicated in the development and progression of complications such as micro- and macro-angiopathies. Disorders in the inner layer of blood vessels, the endothelium, play [...] Read more.
Obesity and diabetes is generally accompanied by a chronic state of oxidative stress, disequilibrium in the redox balance, implicated in the development and progression of complications such as micro- and macro-angiopathies. Disorders in the inner layer of blood vessels, the endothelium, play an early and critical role in the development of these complications. Blunted endothelium-dependent relaxation and/or contractions are quietly associated to oxidative stress. Thus, preserving endothelial function and oxidative stress seems to be an optimization strategy in the prevention of vascular complications associated with diabetes. Diet is a major lifestyle factor that can greatly influence the incidence and the progression of type 2 diabetes and cardiovascular complications. The notion that foods not only provide basic nutrition but can also prevent diseases and ensure good health and longevity is now attained greater prominence. Some dietary and lifestyle modifications associated to antioxidative supply could be an effective prophylactic means to fight against oxidative stress in diabesity and complications. A significant benefit of phytochemicals (polyphenols in wine, grape, teas), vitamins (ascorbate, tocopherol), minerals (selenium, magnesium), and fruits and vegetables in foods is thought to be capable of scavenging free radicals, lowering the incidence of chronic diseases. In this review, we discuss the role of oxidative stress in diabetes and complications, highlight the endothelial dysfunction, and examine the impact of antioxidant foods, plants, fruits, and vegetables, currently used medication with antioxidant properties, in relation to the development and progression of diabetes and cardiovascular complications. Full article
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Open AccessReview
Disorders of Sleep and Ventilatory Control in Prader-Willi Syndrome
Diseases 2016, 4(3), 23; doi:10.3390/diseases4030023 -
Abstract
Prader-Willi syndrome (PWS) is an imprinted genetic disorder conferred by loss of paternal gene expression from chromosome 15q11.2-q13. Individuals with PWS have impairments in ventilatory control and are predisposed toward sleep disordered breathing due to a combination of characteristic craniofacial features, obesity, [...] Read more.
Prader-Willi syndrome (PWS) is an imprinted genetic disorder conferred by loss of paternal gene expression from chromosome 15q11.2-q13. Individuals with PWS have impairments in ventilatory control and are predisposed toward sleep disordered breathing due to a combination of characteristic craniofacial features, obesity, hypotonia, and hypothalamic dysfunction. Children with PWS progress from failure to thrive during infancy to hyperphagia and morbid obesity during later childhood and onward. Similarly, the phenotype of sleep disordered breathing in PWS patients also evolves over time from predominantly central sleep apnea in infants to obstructive sleep apnea (OSA) in older children. Behavioral difficulties are common and may make establishing effective therapy with continuous positive airway pressure (CPAP) more challenging when OSA persists after adenotonsillectomy. Excessive daytime sleepiness (EDS) is also common in patients with PWS and may continue after OSA is effectively treated. We describe here the characteristic ventilatory control deficits, sleep disordered breathing, and excessive daytime sleepiness seen in individuals with PWS. We review respiratory issues that may contribute to sudden death events in PWS patients during sleep and wakefulness. We also discuss therapeutic options for treating sleep disordered breathing including adenotonsillectomy, weight loss, and CPAP. Lastly, we discuss the benefits and safety considerations related to growth hormone therapy. Full article
Open AccessReview
The Role of Glucosinolate Hydrolysis Products from Brassica Vegetable Consumption in Inducing Antioxidant Activity and Reducing Cancer Incidence
Diseases 2016, 4(2), 22; doi:10.3390/diseases4020022 -
Abstract
The bioactivity of glucosinolates (GSs), and more specifically their hydrolysis products (GSHPs), has been well documented. These secondary metabolites evolved in the order Brassicales as plant defense compounds with proven ability to deter or impede the growth of several biotic challenges including [...] Read more.
The bioactivity of glucosinolates (GSs), and more specifically their hydrolysis products (GSHPs), has been well documented. These secondary metabolites evolved in the order Brassicales as plant defense compounds with proven ability to deter or impede the growth of several biotic challenges including insect infestation, fungal and bacterial infection, and competition from other plants. However, the bioactivity of GSHPs is not limited to activity that inhibits these kingdoms of life. Many of these compounds have been shown to have bioactivity in mammalian systems as well, with epidemiological links to cancer chemoprevention in humans supported by in vitro, in vivo, and small clinical studies. Although other chemopreventive mechanisms have been identified, the primary mechanism believed to be responsible for the observed chemoprevention from GSHPs is the induction of antioxidant enzymes, such as NAD(P)H quinone reductase (NQO1), heme oxygenase 1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and glutathione S transferases (GSTs), through the Keap1-Nrf2-ARE signaling pathway. Induction of this pathway is generally associated with aliphatic isothiocyanate GSHPs, although some indole-derived GSHPs have also been associated with induction of one or more of these enzymes. Full article
Open AccessReview
Targeting MicroRNA in Cancer Using Plant-Based Proanthocyanidins
Diseases 2016, 4(2), 21; doi:10.3390/diseases4020021 -
Abstract
Proanthocyanidins are oligomeric flavonoids found in plant sources, most notably in apples, cinnamon, grape skin and cocoa beans. They have been also found in substantial amounts in cranberry, black currant, green tea, black tea and peanut skins. These compounds have been recently [...] Read more.
Proanthocyanidins are oligomeric flavonoids found in plant sources, most notably in apples, cinnamon, grape skin and cocoa beans. They have been also found in substantial amounts in cranberry, black currant, green tea, black tea and peanut skins. These compounds have been recently investigated for their health benefits. Proanthocyanidins have been demonstrated to have positive effects on various metabolic disorders such as inflammation, obesity, diabetes and insulin resistance. Another upcoming area of research that has gained widespread interest is microRNA (miRNA)-based anticancer therapies. MicroRNAs are short non-coding RNA segments, which plays a crucial role in RNA silencing and post-transcriptional regulation of gene expression. Currently, miRNA based anticancer therapies are being investigated either alone or in combination with current treatment methods. In this review, we summarize the current knowledge and investigate the potential of naturally occurring proanthocyanidins in modulating miRNA expression. We will also assess the strategies and challenges of using this approach as potential cancer therapeutics. Full article
Open AccessArticle
Trimester-Specific Reference Intervals of Thyroid Function Testing in Pregnant Women from Basrah, Iraq Using Electrochemiluminescent Immunoassay
Diseases 2016, 4(2), 20; doi:10.3390/diseases4020020 -
Abstract
Background: Thyroid function test results of healthy pregnant women differ from those of healthy non-pregnant women. This study aimed to determine trimester-specific reference ranges for total tetraiodothyronin (T4), free T4, total triiodothyronin (T3) and thyroid stimulation hormone (TSH) using electrochemiluminescence techniques from [...] Read more.
Background: Thyroid function test results of healthy pregnant women differ from those of healthy non-pregnant women. This study aimed to determine trimester-specific reference ranges for total tetraiodothyronin (T4), free T4, total triiodothyronin (T3) and thyroid stimulation hormone (TSH) using electrochemiluminescence techniques from apparently healthy pregnant women in Basrah. Material and Methods: A cross sectional study was conducted between January 2014 and June 2015. The total enrolled pregnant women were 893. Clinical examination, estimation of free T4, total T4, total T3, TSH, and anti-thyroid peroxidase (anti-TPO) using electrochemiluminescence technique done for each. Results: Trimester specific normal range of TSH in μIU/mL was 0.04–3.77, 0.30–3.21 and 0.60–4.50 μIU/mL respectively, for each trimester. For FreeT4, the trimester specific reference range was 0.8–1.53, 0.7–1.20 and 0.7–1.20 ng/dL for each trimester, respectively. The reference range for total T4 for the first, second and third trimester was 7.31–15.00, 8.92–17.38, and 7.98–17.70 μg/dL, respectively. Furthermore, last trimester specific reference range for total T3 was 0.90–2.51, 1.99–2.87 and 1.20–2.70 ng/mL, respectively. Conclusion: Using this thyroid function study, we established for first time trimester-specific reference ranges for each thyroid function test and thyroid antibody status for the first time in Iraq. The reference ranges are different from all previous studies outside Iraq and the reference kit range from the method we used. Full article
Open AccessReview
Specialized Diagnostic Investigations to Assess Ocular Status in Hypertensive Diseases of Pregnancy
Diseases 2016, 4(2), 19; doi:10.3390/diseases4020019 -
Abstract
This review describes specialized diagnostic investigations to assess ocular status in hypertensive diseases of pregnancy. Ocular assessment can aid in early detection for prompt multidisciplinary treatment, obstetric intervention and follow-up. The investigations accurately predict the possible causes of blindness in hypertensive diseases [...] Read more.
This review describes specialized diagnostic investigations to assess ocular status in hypertensive diseases of pregnancy. Ocular assessment can aid in early detection for prompt multidisciplinary treatment, obstetric intervention and follow-up. The investigations accurately predict the possible causes of blindness in hypertensive diseases of pregnancy. The investigations include fluorescein angiography, ophthalmodynamometry, fluorophotometry, imaging modalities, OCT, ultrasonography, doppler velocimetry and blood chemistry analysis. The review includes a summary of imaging techniques and related recent developments to assess the neuro-ophthalmic aspects of the disease. The imaging modalities have been instrumental in understanding the complex neuropathophysiological mechanisms of eclamptic seizures. The importance of blood chemistry analysis in hypertensive diseases of pregnancy has been emphasized. The investigations have made a significant contribution in improving the standards of antenatal care and reducing maternal and fetal morbidity and mortality. Full article
Open AccessArticle
Positive Response to Thermobalancing Therapy Enabled by Therapeutic Device in Men with Non-Malignant Prostate Diseases: BPH and Chronic Prostatitis
Diseases 2016, 4(2), 18; doi:10.3390/diseases4020018 -
Abstract
Background: The most common types of non-malignant prostate diseases are benign prostatic hyperplasia (BPH) and chronic prostatitis (CP). The aim of this study was to find out whether thermobalancing therapy with a physiotherapeutic device is effective for BPH and CP. Methods: During [...] Read more.
Background: The most common types of non-malignant prostate diseases are benign prostatic hyperplasia (BPH) and chronic prostatitis (CP). The aim of this study was to find out whether thermobalancing therapy with a physiotherapeutic device is effective for BPH and CP. Methods: During a 2.5-year period, 124 men with BPH over the age of 55 were investigated. Clinical parameters were tested twice: via the International Prostate Symptom Score (IPSS) and via ultrasound measurement of prostate volume (PV) and uroflowmetry maximum flow rate (Qmax), before and after six months of therapy. In 45 men with CP under the age of 55, the dynamics of the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) were studied. Results: The results of the investigated index tests in men with BPH confirmed a decrease in IPSS (p < 0.001), a reduction in PV (p < 0.001), an increase in Qmax (p < 0.001), and an improvement of quality of life (QoL) (p < 0.001). NIH-CPSI scores in men with CP indicated positive dynamics. Conclusions: The observed positive changes in IPSS, PV, and Qmax in men with BPH and the improvement in NIH-CPSI-QoL in patients with CP after using a physiotherapeutic device for six months as mono-therapy, support the view that thermobalancing therapy with the device can be recommended for these patients. Furthermore, the therapeutic device is free of side effects. Full article
Open AccessArticle
Women’s Views on Handling and Managing Their Breast Cancer in Pakistan: A Qualitative Study
Diseases 2016, 4(2), 17; doi:10.3390/diseases4020017 -
Abstract
In this study, we examine and analyze the experiences of women and their perceptions on handling and managing their breast cancer. Seven women from Peshawar, Pakistan who had breast cancer and have been cured, were interviewed. Qualitative content analysis of their life [...] Read more.
In this study, we examine and analyze the experiences of women and their perceptions on handling and managing their breast cancer. Seven women from Peshawar, Pakistan who had breast cancer and have been cured, were interviewed. Qualitative content analysis of their life stories was performed using a computerized software Atlas.ti. In the coding process, 128 codes were initially developed. These codes were then grouped into 12 categories, which were then further refined into 8 theoretically grounded categories: awareness and education about breast cancer, cultural barriers, early detection, quality of care and treatment, support, side effects, courage and learned to face challenges. The early views of participant’s feelings about breast cancer are mostly similar to the general population in Pakistan. Before starting treatment, all participant were unaware of the treatment process and had fear in their mind. They were hesitant in starting their treatment and were worried. However, when they were cured, their attitudes toward breast cancer and even to their whole lives were changed. Comprehensive awareness programs in a culturally acceptable language and facilities for routine breast examinations should be easily accessible to all women in Pakistan in order to promote early detection. In order to eradicate cultural barriers, female staff who are trained to perform routine breast examinations, should be available in all facilities and treatment centers. Full article
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Open AccessArticle
Early Detection for Dengue Using Local Indicator of Spatial Association (LISA) Analysis
Diseases 2016, 4(2), 16; doi:10.3390/diseases4020016 -
Abstract
Dengue is a viral disease caused by a flavivirus that is transmitted by mosquitoes of the genus Aedes. There is currently no specific treatment or commercial vaccine for its control and prevention; therefore, mosquito population control is the only alternative for [...] Read more.
Dengue is a viral disease caused by a flavivirus that is transmitted by mosquitoes of the genus Aedes. There is currently no specific treatment or commercial vaccine for its control and prevention; therefore, mosquito population control is the only alternative for preventing the occurrence of dengue. For this reason, entomological surveillance is recommended by World Health Organization (WHO) to measure dengue risk in endemic areas; however, several works have shown that the current methodology (aedic indices) is not sufficient for predicting dengue. In this work, we modified indices proposed for epidemic periods. The raw value of the epidemiological wave could be useful for detecting risk in epidemic periods; however, risk can only be detected if analyses incorporate the maximum epidemiological wave. Risk classification was performed according to Local Indicators of Spatial Association (LISA) methodology. The modified indices were analyzed using several hypothetical scenarios to evaluate their sensitivity. We found that modified indices could detect spatial and differential risks in epidemic and endemic years, which makes them a useful tool for the early detection of a dengue outbreak. In conclusion, the modified indices could predict risk at the spatio-temporal level in endemic years and could be incorporated in surveillance activities in endemic places. Full article
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Open AccessReview
Prader-Willi Syndrome: The Disease that Opened up Epigenomic-Based Preemptive Medicine
Diseases 2016, 4(1), 15; doi:10.3390/diseases4010015 -
Abstract
Prader-Willi syndrome (PWS) is a congenital neurodevelopmental disorder caused by loss of function of paternally expressed genes on chromosome 15 due to paternal deletion of 15q11–q13, maternal uniparental disomy for chromosome 15, or an imprinting mutation. We previously developed a DNA methylation-based [...] Read more.
Prader-Willi syndrome (PWS) is a congenital neurodevelopmental disorder caused by loss of function of paternally expressed genes on chromosome 15 due to paternal deletion of 15q11–q13, maternal uniparental disomy for chromosome 15, or an imprinting mutation. We previously developed a DNA methylation-based PCR assay to identify each of these three genetic causes of PWS. The assay enables straightforward and rapid diagnosis during infancy and therefore allows early intervention such as nutritional management, physical therapy, or growth hormone treatment to prevent PWS patients from complications such as obesity and type 2 diabetes. It is known that various environmental factors induce epigenomic changes during the perinatal period, which increase the risk of adult diseases such as type 2 diabetes and intellectual disabilities. Therefore, a similar preemptive approach as used in PWS would also be applicable to acquired disorders and would make use of environmentally-introduced “epigenomic signatures” to aid development of early intervention strategies that take advantage of “epigenomic reversibility”. Full article
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Open AccessReview
Effect of Dietary Bioactive Compounds on Mitochondrial and Metabolic Flexibility
Diseases 2016, 4(1), 14; doi:10.3390/diseases4010014 -
Abstract
Metabolic flexibility is the capacity of an organism to adequately respond to changes in the environment, such as nutritional input, energetic demand, etc. An important player in the capacity of adaptation through different stages of metabolic demands is the mitochondrion. In this [...] Read more.
Metabolic flexibility is the capacity of an organism to adequately respond to changes in the environment, such as nutritional input, energetic demand, etc. An important player in the capacity of adaptation through different stages of metabolic demands is the mitochondrion. In this context, mitochondrial dysfunction has been attributed to be the onset and center of many chronic diseases, which are denoted by an inability to adapt fuel preferences and induce mitochondrial morphological changes to respond to metabolic demands, such as mitochondrial number, structure and function. Several nutritional interventions have shown the capacity to induce changes in mitochondrial biogenesis/degradation, oxidative phosphorylation efficiency, mitochondrial membrane composition, electron transfer chain capacity, etc., in metabolic inflexibility states that may open new target options and mechanisms of action of bioactive compounds for the treatment of metabolic diseases. This review is focused in three well-recognized food bioactive compounds that modulate insulin sensitivity, polyphenols, ω-3 fatty acids and dietary fiber, by several mechanism of action, like caloric restriction properties and inflammatory environment modulation, both closely related to mitochondrial function and dynamics. Full article
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Open AccessReview
Zebrafish Models of Prader-Willi Syndrome: Fast Track to Pharmacotherapeutics
Diseases 2016, 4(1), 13; doi:10.3390/diseases4010013 -
Abstract
Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder characterized by an insatiable appetite, leading to chronic overeating and obesity. Additional features include short stature, intellectual disability, behavioral problems and incomplete sexual development. Although significant progress has been made in understanding the [...] Read more.
Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder characterized by an insatiable appetite, leading to chronic overeating and obesity. Additional features include short stature, intellectual disability, behavioral problems and incomplete sexual development. Although significant progress has been made in understanding the genetic basis of PWS, the mechanisms underlying the pathogenesis of the disorder remain poorly understood. Treatment for PWS consists mainly of palliative therapies; curative therapies are sorely needed. Zebrafish, Danio rerio, represent a promising way forward for elucidating physiological problems such as obesity and identifying new pharmacotherapeutic options for PWS. Over the last decade, an increased appreciation for the highly conserved biology among vertebrates and the ability to perform high-throughput drug screening has seen an explosion in the use of zebrafish for disease modeling and drug discovery. Here, we review recent advances in developing zebrafish models of human disease. Aspects of zebrafish genetics and physiology that are relevant to PWS will be discussed, and the advantages and disadvantages of zebrafish models will be contrasted with current animal models for this syndrome. Finally, we will present a paradigm for drug screening in zebrafish that is potentially the fastest route for identifying and delivering curative pharmacotherapies to PWS patients. Full article
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Open AccessReview
Uric Acid for Cardiovascular Risk: Dr. Jekyll or Mr. Hide?
Diseases 2016, 4(1), 12; doi:10.3390/diseases4010012 -
Abstract
Uric acid (UA) is a potent endogenous antioxidant. However, high concentrations of this molecule have been associated with cardiovascular disease (CVD) and renal dysfunction, involving mechanisms that include oxidative stress, inflammatory processes, and endothelial injury. Experimental and in vitro results suggest that [...] Read more.
Uric acid (UA) is a potent endogenous antioxidant. However, high concentrations of this molecule have been associated with cardiovascular disease (CVD) and renal dysfunction, involving mechanisms that include oxidative stress, inflammatory processes, and endothelial injury. Experimental and in vitro results suggest that this biomarker behaves like other antioxidants, which can shift from the physiological antioxidant action to a pro-oxidizing effect according to their level and to microenvironment conditions. However, data on patients (general population or CAD cohorts) are controversial, so the debate on the role of hyperuricemia as a causative factor for CVD is still ongoing. Increasing evidence indicates UA as more meaningful to assess CVD in women, even though this aspect needs deeper investigation. It will be important to identify thresholds responsible for UA “biological shift” from protective to harmful effects in different pathological conditions, and according to possible gender-related differences. In any case, UA is a low-tech and inexpensive biomarker, generally performed at patient’s hospitalization and, therefore, easily accessible information for clinicians. For these reasons, UA might represent a useful additive tool as much as a CV risk marker. Thus, in view of available evidence, progressive UA elevation with levels higher than 6 mg/dL could be considered an “alarm” for increased CV risk. Full article
Open AccessFeature PaperReview
Antioxidants and Cardiovascular Risk Factors
Diseases 2016, 4(1), 11; doi:10.3390/diseases4010011 -
Abstract
Cardiovascular disease (CVD), the world’s primary cause of death and disability, represents a global health problem and involves a great public financial commitment in terms of both inability to work and pharmaceutical costs. CVD is characterized by a cluster of disorders, associated [...] Read more.
Cardiovascular disease (CVD), the world’s primary cause of death and disability, represents a global health problem and involves a great public financial commitment in terms of both inability to work and pharmaceutical costs. CVD is characterized by a cluster of disorders, associated with complex interactions between multiple risk factors. The early identification of high cardiovascular risk subjects is one of the main targets of primary prevention in order to reduce the adverse impact of modifiable factors, from lifestyle changes to pharmacological treatments. The cardioprotective effect of food antioxidants is well known. Indeed, a diet rich in fruits and vegetables results in an increase in serum antioxidant capacity and a decrease in oxidative stress. In contrast, studies on antioxidant supplementation, even those that are numerically significant, have revealed no clear benefit in prevention and therapy of CVD. Both short- and long-term clinical trials have failed to consistently support cardioprotective effects of supplemental antioxidant intake. The aim of this review is to evaluate the antioxidant effects on the main cardiovascular risk factors including hypertension, dyslipidemia, diabetes. Full article
Open AccessReview
Targeted Therapy of Hepatitis B Virus-Related Hepatocellular Carcinoma: Present and Future
Diseases 2016, 4(1), 10; doi:10.3390/diseases4010010 -
Abstract
Cancer immunotherapy using a patient’s own T cells redirected to recognize and kill tumor cells has achieved promising results in metastatic melanoma and leukemia. This technique involves harnessing a patient’s T cells and then delivering a gene that encodes a new T [...] Read more.
Cancer immunotherapy using a patient’s own T cells redirected to recognize and kill tumor cells has achieved promising results in metastatic melanoma and leukemia. This technique involves harnessing a patient’s T cells and then delivering a gene that encodes a new T cell receptor (TCR) or a chimeric antigen receptor (CAR) that allow the cells to recognize specific cancer antigens. The prospect of using engineered T cell therapy for persistent viral infections like hepatitis B virus (HBV) and their associated malignancies is promising. We recently tested in a first-in-man clinical trial, the ability of HBV-specific TCR-redirected T cells to target HBsAg-productive hepatocellular carcinoma (HCC) and demonstrated that these redirected T cells recognized HCC cells with HBV–DNA integration [1] We discuss here the possibility to use HBV-specific TCR-redirected T cells targeting hepatitis B viral antigens as a tumor specific antigen in patients with HBV-related HCC, and the potential challenges facing the development of this new immunotherapeutic strategy. Full article