Diseases

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Open AccessFeature PaperReview

Milk’s Role as an Epigenetic Regulator in Health and Disease

by Bodo C. Melnik and Gerd Schmitz

Diseases 2017, 5(1), 12; https://doi.org/10.3390/diseases5010012 - 15 Mar 2017

Cited by 78 | Viewed by 20530

It is the intention of this review to characterize milk’s role as an epigenetic regulator in health and disease. Based on translational research, we identify milk as a major epigenetic modulator of gene expression of the milk recipient. Milk is presented as an [...] Read more.

It is the intention of this review to characterize milk’s role as an epigenetic regulator in health and disease. Based on translational research, we identify milk as a major epigenetic modulator of gene expression of the milk recipient. Milk is presented as an epigenetic “doping system” of mammalian development. Milk exosome-derived micro-ribonucleic acids (miRNAs) that target DNA methyltransferases are implicated to play the key role in the upregulation of developmental genes such as FTO, INS, and IGF1. In contrast to miRNA-deficient infant formula, breastfeeding via physiological miRNA transfer provides the appropriate signals for adequate epigenetic programming of the newborn infant. Whereas breastfeeding is restricted to the lactation period, continued consumption of cow’s milk results in persistent epigenetic upregulation of genes critically involved in the development of diseases of civilization such as diabesity, neurodegeneration, and cancer. We hypothesize that the same miRNAs that epigenetically increase lactation, upregulate gene expression of the milk recipient via milk-derived miRNAs. It is of critical concern that persistent consumption of pasteurized cow’s milk contaminates the human food chain with bovine miRNAs, that are identical to their human analogs. Commercial interest to enhance dairy lactation performance may further increase the epigenetic miRNA burden for the milk consumer. Full article

(This article belongs to the Special Issue Targeting Epigenetics in Human Health and Diseases: From Mechanisms to Therapeutics and Beyond)

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1107 KiB

Open AccessReview

Targeting H19, an Imprinted Long Non-Coding RNA, in Hepatic Functions and Liver Diseases

by Chad Pope, Shashank Mishra, Joshua Russell, Qingqing Zhou and Xiao-Bo Zhong

Diseases 2017, 5(1), 11; https://doi.org/10.3390/diseases5010011 - 8 Mar 2017

Cited by 40 | Viewed by 7919

Abstract

H19 is a long non-coding RNA regulated by genomic imprinting through methylation at the locus between H19 and IGF2. H19 is important in normal liver development, controlling proliferation and impacting genes involved in an important network controlling fetal development. H19 also plays a [...] Read more.

H19 is a long non-coding RNA regulated by genomic imprinting through methylation at the locus between H19 and IGF2. H19 is important in normal liver development, controlling proliferation and impacting genes involved in an important network controlling fetal development. H19 also plays a major role in disease progression, particularly in hepatocellular carcinoma. H19 participates in the epigenetic regulation of many processes impacting diseases, such as activating the miR-200 pathway by histone acetylation to inhibit the epithelial-mesenchymal transition to suppress tumor metastasis. Furthermore, H19’s normal regulation is disturbed in diseases, such as hepatocellular carcinoma. In this disease, aberrant epigenetic maintenance results in biallelic expression of IGF2, leading to uncontrolled cellular proliferation. This review aims to further research utilizing H19 for drug discovery and the treatment of liver diseases by focusing on both the epigenetic regulation of H19 and how H19 regulates normal liver functions and diseases, particularly by epigenetic mechanisms. Full article

(This article belongs to the Special Issue Targeting Epigenetics in Human Health and Diseases: From Mechanisms to Therapeutics and Beyond)

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Open AccessFeature PaperReview

The Spectrum of Neurological Manifestations Associated with Gaucher Disease

by Tamanna Roshan Lal and Ellen Sidransky

Diseases 2017, 5(1), 10; https://doi.org/10.3390/diseases5010010 - 2 Mar 2017

Cited by 55 | Viewed by 8917

Abstract

Gaucher disease, the most common lysosomal storage disorder, is due to a deficiency in the enzyme glucocerebrosidase. This leads to the accumulation of its normal substrate, glucocerebroside, in tissue macrophages, affecting the hematological, visceral, bone and neurologic systems. Gaucher disease is classified into [...] Read more.

Gaucher disease, the most common lysosomal storage disorder, is due to a deficiency in the enzyme glucocerebrosidase. This leads to the accumulation of its normal substrate, glucocerebroside, in tissue macrophages, affecting the hematological, visceral, bone and neurologic systems. Gaucher disease is classified into three broad phenotypes based upon the presence or absence of neurological involvement: type 1 (non-neuronopathic), type 2 (acute neuronopathic), and type 3 (subacute neuronopathic). Phenotypically, there is a wide spectrum of visceral and neurological manifestations. Enzyme replacement is effective in managing the visceral disease; however, treating the neurological manifestations has proved to be more challenging. This review discusses the various neurological manifestations encountered in Gaucher disease, and provides a brief overview regarding the treatment and ongoing research challenges. Full article

(This article belongs to the Collection Lysosomal Storage Diseases)

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Open AccessReview

Male Infertility: The Effect of Natural Antioxidants and Phytocompounds on Seminal Oxidative Stress

by Malik Adewoyin, Muhammad Ibrahim, Ramli Roszaman, Muhammad Lokman Md Isa, Nur Aizura Mat Alewi, Ainin Azwani Abdul Rafa and Mohd Nur Nasyriq Anuar

Diseases 2017, 5(1), 9; https://doi.org/10.3390/diseases5010009 - 1 Mar 2017

Cited by 112 | Viewed by 20054

Abstract

Defective sperm function has been identified as the most common cause of infertility. The objective of this study was to review recent findings on the effects of various antioxidants on male fertility. High amounts of poly unsaturated fatty acid are found in the [...] Read more.

Defective sperm function has been identified as the most common cause of infertility. The objective of this study was to review recent findings on the effects of various antioxidants on male fertility. High amounts of poly unsaturated fatty acid are found in the mammalian spermatozoa membranes, thereby making them susceptible to lipid peroxidation. Although, free radicals and reactive oxygen species (ROS) play major roles in reproduction, they are strongly associated with oxidative stress. Furthermore, factors such as obesity, inflammation, pollutants and cigarette smoking are negatively correlated with spermatogenesis. Endogenous antioxidants system exists to mediate these damages. In a normal physiological state, the seminal plasma contains antioxidant enzyme mechanism that is capable of quenching these ROS as well as protecting the spermatozoa against any likely damage. However, high level of ROS triggered by inflammatory cells and oxidation of fatty acid in obese subjects may down play antioxidant mechanism resulting in oxidative stress. Evaluation of such oxidative stress is the first step in the treatment of male infertility through administration of suitable antioxidant. Notably, antioxidant such as vitamin E and C, carotenoids and carnitine have been found beneficial in restoring a balance between ROS generation and scavenging activities. There are emerging evidences that herbal products can also boost male reproductive functions. Nonetheless, a good lifestyle, regular exercise, avoidance of stress and observing safety rules at work are habits that can reverse male infertility. Full article

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Open AccessReview

Lysosomal Storage Disorders and Malignancy

by Gregory M. Pastores and Derralynn A. Hughes

Diseases 2017, 5(1), 8; https://doi.org/10.3390/diseases5010008 - 27 Feb 2017

Cited by 11 | Viewed by 6107

Abstract

Lysosomal storage disorders (LSDs) are infrequent to rare conditions caused by mutations that lead to a disruption in the usual sequential degradation of macromolecules or their transit within the cell. Gaucher disease (GD), a lipidosis, is among the most common LSD, with an [...] Read more.

Lysosomal storage disorders (LSDs) are infrequent to rare conditions caused by mutations that lead to a disruption in the usual sequential degradation of macromolecules or their transit within the cell. Gaucher disease (GD), a lipidosis, is among the most common LSD, with an estimated incidence of 1 in 40,000 among the Caucasian, non-Jewish population. Studies have indicated an increased frequency of polyclonal and monoclonal gammopathy among patients with GD. It has been shown that two major sphingolipids that accumulate in GD, namely, β-glucosylceramide 22:0 (βGL1-22) and glucosylsphingosine (LGL1), can be recognized by a distinct subset of CD1d-restricted human and murine type II natural killer T (NKT) cells. Investigations undertaken in an affected mouse model revealed βGL1-22- and LGL1-specific NKT cells were present and constitutively promoted the expression of a T-follicular helper (TFH) phenotype; injection of these lipids led to downstream induction of germinal center B cells, hypergammaglobulinemia, and the production of antilipid antibodies. Subsequent studies have found clonal immunoglobulin in 33% of sporadic human monoclonal gammopathies is also specific for the lysolipids LGL1 and lysophosphatidylcholine (LPC). Furthermore, substrate reduction ameliorated GD-associated gammopathy in mice. It had been hypothesized that chronic antigenic stimulation by the abnormal lipid storage and associated immune dysregulation may be the underlying mechanism for the increased incidence of monoclonal and polyclonal gammopathies, as well as an increased incidence of multiple myeloma in patients with GD. Current observations support this proposition and illustrate the value of investigations into rare diseases, which as ‘experiments of nature’ may provide insights into conditions found in the general population that continue to remain incompletely understood. Full article

(This article belongs to the Collection Lysosomal Storage Diseases)

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Open AccessBrief Report

Detection of Alphacoronavirus vRNA in the Feces of Brazilian Free-Tailed Bats (Tadarida brasiliensis) from a Colony in Florida, USA

by Tania S. Bonny, John P. Driver, Taylor Paisie, Marco Salemi, John Glenn Morris, Lisa A. Shender, Lisa Smith, Carolyn Enloe, Kevin Oxenrider, Jeffery A. Gore, Julia C. Loeb, Chang-Yu Wu and John A. Lednicky

Diseases 2017, 5(1), 7; https://doi.org/10.3390/diseases5010007 - 27 Feb 2017

Cited by 3 | Viewed by 7135

Abstract

Bats are natural reservoirs of coronaviruses and other viruses with zoonotic potential. Florida has indigenous non-migratory populations of Brazilian free-tailed bats (Tadarida brasiliensis) that mostly roost in colonies in artificial structures. Unlike their counterparts in Brazil and Mexico, the viruses harbored [...] Read more.

Bats are natural reservoirs of coronaviruses and other viruses with zoonotic potential. Florida has indigenous non-migratory populations of Brazilian free-tailed bats (Tadarida brasiliensis) that mostly roost in colonies in artificial structures. Unlike their counterparts in Brazil and Mexico, the viruses harbored by the Florida bats have been underexplored. We report the detection of an alphacoronavirus RNA-dependent RNA polymerase (RdRp) gene sequence in the feces of two of 19 different T. brasiliensis that were capture/release bats that had been evaluated for overall health. The RdRp sequence is similar but not identical to previously detected sequences in the feces of two different species of bats (T. brasiliensis and Molossus molossus) in Brazil. In common with the experience of others doing similar work, attempts to isolate the virus in cell cultures were unsuccessful. We surmise that this and highly related alphacoronavirus are carried by Brazilian free-tailed bats living in a wide eco-spatial region. As various coronaviruses (CoVs) that affect humans emerged from bats, our study raises the question whether CoVs such as the one detected in our work are yet-to-be-detected pathogens of humans and animals other than bats. Full article

(This article belongs to the Special Issue Advances in Coronaviruses Research: Important Emerging Human Pathogens)

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Open AccessReview

A Prospective Treatment Option for Lysosomal Storage Diseases: CRISPR/Cas9 Gene Editing Technology for Mutation Correction in Induced Pluripotent Stem Cells

by Chloe L. Christensen and Francis Y. M. Choy

Diseases 2017, 5(1), 6; https://doi.org/10.3390/diseases5010006 - 24 Feb 2017

Cited by 7 | Viewed by 8542

Abstract

Ease of design, relatively low cost and a multitude of gene-altering capabilities have all led to the adoption of the sophisticated and yet simple gene editing system: clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9). The CRISPR/Cas9 system holds promise for the [...] Read more.

Ease of design, relatively low cost and a multitude of gene-altering capabilities have all led to the adoption of the sophisticated and yet simple gene editing system: clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9). The CRISPR/Cas9 system holds promise for the correction of deleterious mutations by taking advantage of the homology directed repair pathway and by supplying a correction template to the affected patient’s cells. Currently, this technique is being applied in vitro in human-induced pluripotent stem cells (iPSCs) to correct a variety of severe genetic diseases, but has not as of yet been used in iPSCs derived from patients affected with a lysosomal storage disease (LSD). If adopted into clinical practice, corrected iPSCs derived from cells that originate from the patient themselves could be used for therapeutic amelioration of LSD symptoms without the risks associated with allogeneic stem cell transplantation. CRISPR/Cas9 editing in a patient’s cells would overcome the costly, lifelong process associated with currently available treatment methods, including enzyme replacement and substrate reduction therapies. In this review, the overall utility of the CRISPR/Cas9 gene editing technique for treatment of genetic diseases, the potential for the treatment of LSDs and methods currently employed to increase the efficiency of this re-engineered biological system will be discussed. Full article

(This article belongs to the Collection Lysosomal Storage Diseases)

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Open AccessArticle

Substrate Deprivation Therapy to Reduce Glycosaminoglycan Synthesis Improves Aspects of Neurological and Skeletal Pathology in MPS I Mice

by Ainslie L. K. Derrick-Roberts, Matilda R. Jackson, Carmen E. Pyragius and Sharon Byers

Diseases 2017, 5(1), 5; https://doi.org/10.3390/diseases5010005 - 23 Feb 2017

Cited by 14 | Viewed by 5815

Abstract

Mucopolysaccharidosis type I (MPS I) is the most common form of the MPS group of genetic diseases. MPS I results from a deficiency in the lysosomal enzyme α-l-iduronidase, leading to accumulation of undegraded heparan and dermatan sulphate glycosaminoglycan (GAG) chains in [...] Read more.

Mucopolysaccharidosis type I (MPS I) is the most common form of the MPS group of genetic diseases. MPS I results from a deficiency in the lysosomal enzyme α-l-iduronidase, leading to accumulation of undegraded heparan and dermatan sulphate glycosaminoglycan (GAG) chains in patient cells. MPS children suffer from multiple organ failure and die in their teens to early twenties. In particular, MPS I children also suffer from profound mental retardation and skeletal disease that restricts growth and movement. Neither brain nor skeletal disease is adequately treated by current therapy approaches. To overcome these barriers to effective therapy we have developed and tested a treatment called substrate deprivation therapy (SDT). MPS I knockout mice were treated with weekly intravenous injections of 1 mg/kg rhodamine B for six months to assess the efficacy of SDT. Mice were assessed using biochemistry, micro-CT and a battery of behaviour tests to determine the outcome of treatment. A reduction in female bodyweight gain was observed with the treatment as well as a decrease in lung GAG. Behavioural studies showed slight improvements in inverted grid and significant improvements in learning ability for female MPS I mice treated with rhodamine B. Skeletal disease also improved with a reduction in bone mineral volume observed. Overall, rhodamine B is safe to administer to MPS I knockout mice where it had an effect on improving aspects of neurological and skeletal disease symptoms and may therefore provide a potential therapy or adjunct therapy for MPS I patients. Full article

(This article belongs to the Collection Lysosomal Storage Diseases)

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Open AccessArticle

Risk of Asymptomatic Bacteriuria among People with Sickle Cell Disease in Accra, Ghana

by Eric S. Donkor, Jonathan A. Osei, Isaac Anim-Baidoo and Samuel Darkwah

Diseases 2017, 5(1), 4; https://doi.org/10.3390/diseases5010004 - 15 Feb 2017

Cited by 7 | Viewed by 4455

Abstract

Asymptomatic bacteriuria (ASB) is benign except in certain medical conditions such as pregnancy and immunosuppression. In Ghana, there are hardly any studies on urinary infections among sickle cell disease (SCD) patients, and the few studies carried out in Africa focused on pediatric SCD [...] Read more.

Asymptomatic bacteriuria (ASB) is benign except in certain medical conditions such as pregnancy and immunosuppression. In Ghana, there are hardly any studies on urinary infections among sickle cell disease (SCD) patients, and the few studies carried out in Africa focused on pediatric SCD populations. The current study aimed to investigate the risk of ASB among SCD patients at a tertiary hospital in Ghana. This was a cross-sectional study involving 110 SCD patients and 110 age and sex matched healthy controls. Urine specimens were collected from all the study subjects and analyzed by standard microbiological methods. Demographic information were also collected from the study subjects. The overall ASB prevalence was significantly higher among SCD patients (17.2%) than among the control group (8.2%), and the relative risk was 2.11 (p = 0.0431; CI = 1.00–4.45). Being female was as a predictor of ASB among the SCD patients (OR = 14.76; CI = 11.23–18.29; p = 0.0103). The most common organism isolated from the study participants was coagulase negative Staphylococcus species (4.1%), followed by Escherichia coli (2.7%); etiology of ASB in the SCD patients was more diverse compared to healthy people. All the E. coli isolates were susceptible to amikacin, sparfloxacin and norfloxacin but resistant to ampicillin. Full article

(This article belongs to the Section Infectious Disease)

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Open AccessCommunication

The Association between Dietary Intake of Antioxidants and Ocular Disease

by Andrea Braakhuis, Ryan Raman and Ehsan Vaghefi

Diseases 2017, 5(1), 3; https://doi.org/10.3390/diseases5010003 - 30 Jan 2017

Cited by 28 | Viewed by 6604

Abstract

To assess the association between dietary antioxidant intake and the incidence of the three major oxidative stress-related eye diseases, cataracts, glaucoma, and age-related macular degeneration, 78 cases from the University of Auckland Optometry and Vision Science clinic and 149 controls were recruited. Participants [...] Read more.

To assess the association between dietary antioxidant intake and the incidence of the three major oxidative stress-related eye diseases, cataracts, glaucoma, and age-related macular degeneration, 78 cases from the University of Auckland Optometry and Vision Science clinic and 149 controls were recruited. Participants completed an antioxidant food-frequency questionnaire, analysed through multiple logistic regression. Protective associations were identified with higher consumption of fruit and vegetables (OR = 0.99; 95% CI: 0.98, 1.00; p = 0.004), vitamin C (OR = 0.63; 95% CI: 0.23, 1.03; p = 0.022), and β-carotene (OR = 0.56; 95% CI: 0.15, 0.98; p = 0.007). Meanwhile, harmful associations were observed with greater consumption of meat/nuts (OR = 1.03; 95% CI: 1.01, 1.05; p = 0.006) and cholesterol (OR = 1.09; 95% CI: 1.50, 2.46; p = 0.005). Diets rich in fruit and vegetables appear to be protective against cataracts, glaucoma, and age-related macular degeneration, while diets higher in meat and nuts may increase the risk of oxidative stress-related eye diseases. In addition, higher intakes of vitamin C and β-carotene from food, with reduction of dietary cholesterol intake, may be beneficial towards the outcome of oxidative stress-related eye diseases. Full article

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Open AccessEditorial

Acknowledgement to Reviewers of Diseases in 2016

by Diseases Editorial Office

Diseases 2017, 5(1), 2; https://doi.org/10.3390/diseases5010002 - 11 Jan 2017

Viewed by 3001

Abstract

The editors of Diseases would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2016.[...] Full article

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Open AccessFeature PaperReview

Mitochondrial Dynamics in Mitochondrial Diseases

by Juan M. Suárez-Rivero, Marina Villanueva-Paz, Patricia De la Cruz-Ojeda, Mario De la Mata, David Cotán, Manuel Oropesa-Ávila, Isabel De Lavera, Mónica Álvarez-Córdoba, Raquel Luzón-Hidalgo and José A. Sánchez-Alcázar

Diseases 2017, 5(1), 1; https://doi.org/10.3390/diseases5010001 - 23 Dec 2016

Cited by 123 | Viewed by 11694

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 [...] Read more.

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

(This article belongs to the Special Issue Mitochondria and Mitophagia in Rare Diseases)

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Diseases, Volume 5, Issue 1 (March 2017) – 12 articles

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