Open AccessEditorial
Acknowledgement to Reviewers of Diseases in 2016
Diseases 2017, 5(1), 2; doi:10.3390/diseases5010002 -
Open AccessFeature PaperReview
Mitochondrial Dynamics in Mitochondrial Diseases
Diseases 2017, 5(1), 1; doi:10.3390/diseases5010001 -
Abstract
Mitochondria are very versatile organelles in continuous fusion and fission processes in response to various cellular signals. Mitochondrial dynamics, including mitochondrial fission/fusion, movements and turnover, are essential for the mitochondrial network quality control. Alterations in mitochondrial dynamics can cause neuropathies such as Charcot-Marie-Tooth
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Mitochondria are very versatile organelles in continuous fusion and fission processes in response to various cellular signals. Mitochondrial dynamics, including mitochondrial fission/fusion, movements and turnover, are essential for the mitochondrial network quality control. Alterations in mitochondrial dynamics can cause neuropathies such as Charcot-Marie-Tooth disease in which mitochondrial fusion and transport are impaired, or dominant optic atrophy which is caused by a reduced mitochondrial fusion. On the other hand, mitochondrial dysfunction in primary mitochondrial diseases promotes reactive oxygen species production that impairs its own function and dynamics, causing a continuous vicious cycle that aggravates the pathological phenotype. Mitochondrial dynamics provides a new way to understand the pathophysiology of mitochondrial disorders and other diseases related to mitochondria dysfunction such as diabetes, heart failure, or Hungtinton’s disease. The knowledge about mitochondrial dynamics also offers new therapeutics targets in mitochondrial diseases. Full article
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Open AccessReview
Biomarkers in Lysosomal Storage Diseases
Diseases 2016, 4(4), 40; doi:10.3390/diseases4040040 -
Abstract
A biomarker is generally an analyte that indicates the presence and/or extent of a biological process, which is in itself usually directly linked to the clinical manifestations and outcome of a particular disease. The biomarkers in the field of lysosomal storage diseases (LSDs)
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A biomarker is generally an analyte that indicates the presence and/or extent of a biological process, which is in itself usually directly linked to the clinical manifestations and outcome of a particular disease. The biomarkers in the field of lysosomal storage diseases (LSDs) have particular relevance where spectacular therapeutic initiatives have been achieved, most notably with the introduction of enzyme replacement therapy (ERT). There are two main types of biomarkers. The first group is comprised of those molecules whose accumulation is directly enhanced as a result of defective lysosomal function. These molecules represent the storage of the principal macro-molecular substrate(s) of a specific enzyme or protein, whose function is deficient in the given disease. In the second group of biomarkers, the relationship between the lysosomal defect and the biomarker is indirect. In this group, the biomarker reflects the effects of the primary lysosomal defect on cell, tissue, or organ functions. There is no “gold standard” among biomarkers used to diagnosis and/or monitor LSDs, but there are a number that exist that can be used to reasonably assess and monitor the state of certain organs or functions. A number of biomarkers have been proposed for the analysis of the most important LSDs. In this review, we will summarize the most promising biomarkers in major LSDs and discuss why these are the most promising candidates for screening systems. Full article
Open AccessReview
The Cardiovascular Effects of Cocoa Polyphenols—An Overview
Diseases 2016, 4(4), 39; doi:10.3390/diseases4040039 -
Abstract
Cocoa is a rich source of high-quality antioxidant polyphenols. They comprise mainly catechins (29%–38% of total polyphenols), anthocyanins (4% of total polyphenols) and proanthocyanidins (58%–65% of total polyphenols). A growing body of experimental and epidemiological evidence highlights that the intake of cocoa polyphenols
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Cocoa is a rich source of high-quality antioxidant polyphenols. They comprise mainly catechins (29%–38% of total polyphenols), anthocyanins (4% of total polyphenols) and proanthocyanidins (58%–65% of total polyphenols). A growing body of experimental and epidemiological evidence highlights that the intake of cocoa polyphenols may reduce the risk of cardiovascular events. Beyond antioxidant properties, cocoa polyphenols exert blood pressure lowering activity, antiplatelet, anti-inflammatory, metabolic and anti-atherosclerotic effects, and also improve endothelial function. This paper reviews the role of cocoa polyphenols in cardiovascular protection, with a special focus on mechanisms of action, clinical relevance and correlation between antioxidant activity and cardiovascular health. Full article
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Open AccessArticle
Serum Wisteria Floribunda Agglutinin-Positive Mac-2 Binding Protein Could Not Always Predict Early Cirrhosis in Non-Viral Liver Diseases
Diseases 2016, 4(4), 38; doi:10.3390/diseases4040038 -
Abstract
Background: Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA(+)-M2BP) is a novel non-invasive marker of liver fibrosis. The goal of the study was to investigate whether the novel serum biomarker WFA(+)-M2BP or other non-invasive markers are useful for the prediction of liver fibrosis in
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Background: Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA(+)-M2BP) is a novel non-invasive marker of liver fibrosis. The goal of the study was to investigate whether the novel serum biomarker WFA(+)-M2BP or other non-invasive markers are useful for the prediction of liver fibrosis in patients with nonalcoholic steatohepatitis (NASH), autoimmune hepatitis (AIH), and primary biliary cholangitis (PBC). Methods: We examined a significant correlation between serum WFA(+)-M2BP levels and histological staging of fibrosis in several chronic liver diseases, such as NASH, AIH, and PBC. Results: WFA(+)-M2BP could not predict hepatic fibrosis in these patients. We also showed that the level of platelet counts is a useful predictor of hepatic fibrosis progression in patients with NASH, AIH, and PBC. There was a significant correlation between staging of fibrosis and grading of activity in the liver in all groups except for AIH patients. Conclusion: Platelet counts can predict hepatic fibrosis in patients with NASH, AIH, or PBC. Clinicians should pay attention to the grading of liver activity in the use of WFA(+)-M2BP. Full article
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Open AccessConcept Paper
Developing a Research Instrument to Document Awareness, Knowledge, and Attitudes Regarding Breast Cancer and Early Detection Techniques for Pakistani Women: The Breast Cancer Inventory (BCI)
Diseases 2016, 4(4), 37; doi:10.3390/diseases4040037 -
Abstract
There is a general hesitation in participation among Pakistani women when it comes to giving their responses in surveys related to breast cancer which may be due to the associated stigma and conservatism in society. We felt that no research instrument was able
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There is a general hesitation in participation among Pakistani women when it comes to giving their responses in surveys related to breast cancer which may be due to the associated stigma and conservatism in society. We felt that no research instrument was able to extract information from the respondents to the extent it was needed for the successful execution of our study. The need to develop a research instrument tailored for Pakistani women was based upon the fact that most Pakistani women come from a conservative background and sometimes view this topic as provocative and believe discussing publicly about it as inappropriate. Existing research instruments exhibited a number of weaknesses during literature review. Therefore, using them may not be able to extract information concretely. A research instrument was, thus, developed exclusively. It was coined as, “breast cancer inventory (BCI)” by a panel of experts for executing a study aimed at documenting awareness, knowledge, and attitudes of Pakistani women regarding breast cancer and early detection techniques. The study is still in the data collection phase. The statistical analysis involved the Kaiser-Meyer-Olkin (KMO) measure and Bartlett’s test for sampling adequacy. In addition, reliability analysis and exploratory factor analysis (EFA) were, also employed. This concept paper focuses on the development, piloting and validation of the BCI. It is the first research instrument which has high acceptability among Pakistani women and is able to extract adequate information from the respondents without causing embarrassment or unease. Full article
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Open AccessArticle
Association between Low Serum Bicarbonate Concentrations and Cardiovascular Disease in Patients in the End-Stage of Renal Disease
Diseases 2016, 4(4), 36; doi:10.3390/diseases4040036 -
Abstract
Background: Metabolic acidosis, a common condition particularly in the end-stage of renal disease patients, results in malnutrition, inflammation and oxidative stress. In this study, we focused on the association between low serum bicarbonate and cardiovascular disease in patients on intermittent dialysis. Methods: We
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Background: Metabolic acidosis, a common condition particularly in the end-stage of renal disease patients, results in malnutrition, inflammation and oxidative stress. In this study, we focused on the association between low serum bicarbonate and cardiovascular disease in patients on intermittent dialysis. Methods: We studied 52 on-line-pre-dilution hemodiafiltration (on-l HDF) patients, 32 males and 20 females, with a mean age of 58.01 ± 15.4 years old. Metabolic acidosis was determined by serum bicarbonate concentrations less than 22 mmol/L. Residual renal function (RRF) was defined by interdialytic urine volume. Kaplan–Meier curves and Cox regression models were performed to predict coronary artery disease (CAD), defined by ejection fraction <50%, or diastolic dysfunction congestive heart failure (CHF) and peripheral vascular disease (PVD). Results: Kaplan–Meier analyses showed that a lower or higher than 22 mmol/L serum bicarbonate metabolic acidosis status was significantly associated with both PVD and diastolic dysfunction (log-rank = 5.07, p = 0.02 and log-rank = 5.84, p = 0.01, respectively). A similar prevalence of serum bicarbonate on CAD or CHF by low ejection fraction was not shown. The RRF was associated with PVD event and serum bicarbonate less than 22 mmol/L (log-rank = 5.49, p = 0.01 and log-rank = 3.9, p = 0.04, respectively). Cox regression analysis revealed that serum bicarbonate and RRF were significant risk factors for PVD after adjustment for confounders. Furthermore, RRF adjusted for covariates was shown to be a significant risk factor for diastolic dysfunction. Conclusion: Low serum bicarbonate was associated with peripheral vascular disease and diastolic dysfunction in intermittent dialysis. The residual renal function may impact patients’ outcomes through its relationship with metabolic acidosis status, particularly for peripheral vascular disease manifestation. Full article
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Open AccessArticle
Integrative Systems Biology Investigation of Fabry Disease
Diseases 2016, 4(4), 35; doi:10.3390/diseases4040035 -
Abstract
Fabry disease (FD) is a rare X-linked recessive genetic disorder caused by a deficient activity of the lysosomal enzyme alpha-galactosidase A (GLA) and is characterised by intra-lysosomal accumulation of globotriaosylceramide (Gb3). We performed a meta-analysis of peer-reviewed publications including high-throughput omics technologies including
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Fabry disease (FD) is a rare X-linked recessive genetic disorder caused by a deficient activity of the lysosomal enzyme alpha-galactosidase A (GLA) and is characterised by intra-lysosomal accumulation of globotriaosylceramide (Gb3). We performed a meta-analysis of peer-reviewed publications including high-throughput omics technologies including naïve patients and those undergoing enzyme replacement therapy (ERT). This study describes FD on a systems level using a systems biology approach, in which molecular data sourced from multi-omics studies is extracted from the literature and integrated as a whole in order to reveal the biochemical processes and molecular pathways potentially affected by the dysregulation of differentially expressed molecules. In this way new insights are provided that describe the pathophysiology of this rare disease. Using gene ontology and pathway term clustering, FD displays the involvement of major biological processes such as the acute inflammatory response, regulation of wound healing, extracellular matrix (ECM) remodelling, regulation of peptidase activity, and cellular response to reactive oxygen species (ROS). Differential expression of acute-phase response proteins in the groups of naïve (up-regulation of ORM1, ORM2, ITIH4, SERPINA3 and FGA) and ERT (down-regulation of FGA, ORM1 and ORM2) patients could be potential hallmarks for distinction of these two patient groups. Full article
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Open AccessReview
The Role of the Nrf2/ARE Antioxidant System in Preventing Cardiovascular Diseases
Diseases 2016, 4(4), 34; doi:10.3390/diseases4040034 -
Abstract
It is widely believed that consuming foods and beverages that have high concentrations of antioxidants can prevent cardiovascular diseases and many types of cancer. As a result, many articles have been published that give the total antioxidant capacities of foods in vitro. However,
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It is widely believed that consuming foods and beverages that have high concentrations of antioxidants can prevent cardiovascular diseases and many types of cancer. As a result, many articles have been published that give the total antioxidant capacities of foods in vitro. However, many antioxidants behave quite differently in vivo. Some of them, such as resveratrol (in red wine) and epigallocatechin gallate or EGCG (in green tea) can activate the nuclear erythroid-2 like factor-2 (Nrf2) transcription factor. It is a master regulator of endogenous cellular defense mechanisms. Nrf2 controls the expression of many antioxidant and detoxification genes, by binding to antioxidant response elements (AREs) that are commonly found in the promoter region of antioxidant (and other) genes, and that control expression of those genes. The mechanisms by which Nrf2 relieves oxidative stress and limits cardiac injury as well as the progression to heart failure are described. Also, the ability of statins to induce Nrf2 in the heart, brain, lung, and liver is mentioned. However, there is a negative side of Nrf2. When over-activated, it can cause (not prevent) cardiovascular diseases and multi-drug resistance cancer. Full article
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Open AccessReview
Genetic Substrate Reduction Therapy: A Promising Approach for Lysosomal Storage Disorders
Diseases 2016, 4(4), 33; doi:10.3390/diseases4040033 -
Abstract
Lysosomal storage diseases are a group of rare genetic disorders characterized by the accumulation of storage molecules in late endosomes/lysosomes. Most of them result from mutations in genes encoding for the catabolic enzymes that ensure intralysosomal digestion. Conventional therapeutic options include enzyme replacement
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Lysosomal storage diseases are a group of rare genetic disorders characterized by the accumulation of storage molecules in late endosomes/lysosomes. Most of them result from mutations in genes encoding for the catabolic enzymes that ensure intralysosomal digestion. Conventional therapeutic options include enzyme replacement therapy, an approach targeting the functional loss of the enzyme by injection of a recombinant one. Even though this is successful for some diseases, it is mostly effective for peripheral manifestations and has no impact on neuropathology. The development of alternative therapeutic approaches is, therefore, mandatory, and striking innovations including the clinical development of pharmacological chaperones and gene therapy are currently under evaluation. Most of them, however, have the same underlying rationale: an attempt to provide or enhance the activity of the missing enzyme to re-establish substrate metabolism to a level that is consistent with a lack of progression and/or return to health. Here, we will focus on the one approach which has a different underlying principle: substrate reduction therapy (SRT), whose uniqueness relies on the fact that it acts upstream of the enzymatic defect, decreasing storage by downregulating its biosynthetic pathway. Special attention will be given to the most recent advances in the field, introducing the concept of genetic SRT (gSRT), which is based on the use of RNA-degrading technologies (RNA interference and single stranded antisense oligonucleotides) to promote efficient substrate reduction by decreasing its synthesis rate. Full article
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Open AccessReview
Nonsense Suppression as an Approach to Treat Lysosomal Storage Diseases
Diseases 2016, 4(4), 32; doi:10.3390/diseases4040032 -
Abstract
In-frame premature termination codons (PTCs) (also referred to as nonsense mutations) comprise ~10% of all disease-associated gene lesions. PTCs reduce gene expression in two ways. First, PTCs prematurely terminate translation of an mRNA, leading to the production of a truncated polypeptide that often
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In-frame premature termination codons (PTCs) (also referred to as nonsense mutations) comprise ~10% of all disease-associated gene lesions. PTCs reduce gene expression in two ways. First, PTCs prematurely terminate translation of an mRNA, leading to the production of a truncated polypeptide that often lacks normal function and/or is unstable. Second, PTCs trigger degradation of an mRNA by activating nonsense-mediated mRNA decay (NMD), a cellular pathway that recognizes and degrades mRNAs containing a PTC. Thus, translation termination and NMD are putative therapeutic targets for the development of treatments for genetic diseases caused by PTCs. Over the past decade, significant progress has been made in the identification of compounds with the ability to suppress translation termination of PTCs (also referred to as readthrough). More recently, NMD inhibitors have also been explored as a way to enhance the efficiency of PTC suppression. Due to their relatively low threshold for correction, lysosomal storage diseases are a particularly relevant group of diseases to investigate the feasibility of nonsense suppression as a therapeutic approach. In this review, the current status of PTC suppression and NMD inhibition as potential treatments for lysosomal storage diseases will be discussed. Full article
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Open AccessReview
Mitochondrial Dysfunction in Lysosomal Storage Disorders
Diseases 2016, 4(4), 31; doi:10.3390/diseases4040031 -
Abstract
Lysosomal storage diseases (LSDs) describe a heterogeneous group of rare inherited metabolic disorders that result from the absence or loss of function of lysosomal hydrolases or transporters, resulting in the progressive accumulation of undigested material in lysosomes. The accumulation of substances affects the
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Lysosomal storage diseases (LSDs) describe a heterogeneous group of rare inherited metabolic disorders that result from the absence or loss of function of lysosomal hydrolases or transporters, resulting in the progressive accumulation of undigested material in lysosomes. The accumulation of substances affects the function of lysosomes and other organelles, resulting in secondary alterations such as impairment of autophagy, mitochondrial dysfunction, inflammation and apoptosis. LSDs frequently involve the central nervous system (CNS), where neuronal dysfunction or loss results in progressive neurodegeneration and premature death. Many LSDs exhibit signs of mitochondrial dysfunction, which include mitochondrial morphological changes, decreased mitochondrial membrane potential (ΔΨm), diminished ATP production and increased generation of reactive oxygen species (ROS). Furthermore, reduced autophagic flux may lead to the persistence of dysfunctional mitochondria. Gaucher disease (GD), the LSD with the highest prevalence, is caused by mutations in the GBA1 gene that results in defective and insufficient activity of the enzyme β-glucocerebrosidase (GCase). Decreased catalytic activity and/or instability of GCase leads to accumulation of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph) in the lysosomes of macrophage cells and visceral organs. Mitochondrial dysfunction has been reported to occur in numerous cellular and mouse models of GD. The aim of this manuscript is to review the current knowledge and implications of mitochondrial dysfunction in LSDs. Full article
Open AccessReview
Honey and Cancer: Current Status and Future Directions
Diseases 2016, 4(4), 30; doi:10.3390/diseases4040030 -
Abstract
Cancer is a leading cause of death worldwide and poses a challenge to treatment. With overwhelming evidence of the role played by diet and lifestyle in cancer risk and prevention, there is a growing interest into the search for chemopreventative or chemotherapeutic agents
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Cancer is a leading cause of death worldwide and poses a challenge to treatment. With overwhelming evidence of the role played by diet and lifestyle in cancer risk and prevention, there is a growing interest into the search for chemopreventative or chemotherapeutic agents derived from natural products. Honey is an important source of bioactive compounds derived from plants and recent years have seen an increased interest in its anticancer properties. This review examines the role of honey in targeting key hallmarks of carcinogenesis, including uncontrolled proliferation, apoptosis evasion, angiogenesis, growth factor signalling, invasion, and inflammation. The evidence for honey as an adjunct to conventional cancer therapy is also presented. The review also highlights gaps in the current understanding and concludes that, before translation of evidence from cell culture and animal studies into the clinical setting, further studies are warranted to examine the effects of honey at a molecular level, as well as on cells in the tumour environment. Full article
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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 diffusion
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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 Olive
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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 be
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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 research
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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 was
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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 an
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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, hypotonia,
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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