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Showing papers in "Frontiers in Bioscience in 2018"


Journal ArticleDOI
TL;DR: Recent progress in Mn absorption, distribution and elimination across different tissues, as well as the intracellular regulation of Mn homeostasis in cells are addressed.
Abstract: Manganese (Mn) is an essential nutrient for intracellular activities; it functions as a cofactor for a variety of enzymes, including arginase, glutamine synthetase (GS), pyruvate carboxylase and Mn superoxide dismutase (Mn-SOD). Through these metalloproteins, Mn plays critically important roles in development, digestion, reproduction, antioxidant defense, energy production, immune response and regulation of neuronal activities. Mn deficiency is rare. In contrast Mn poisoning may be encountered upon overexposure to this metal. Excessive Mn tends to accumulate in the liver, pancreas, bone, kidney and brain, with the latter being the major target of Mn intoxication. Hepatic cirrhosis, polycythemia, hypermanganesemia, dystonia and Parkinsonism-like symptoms have been reported in patients with Mn poisoning. In recent years, Mn has come to the forefront of environmental concerns due to its neurotoxicity. Molecular mechanisms of Mn toxicity include oxidative stress, mitochondrial dysfunction, protein misfolding, endoplasmic reticulum (ER) stress, autophagy dysregulation, apoptosis, and disruption of other metal homeostasis. The mechanisms of Mn homeostasis are not fully understood. Here, we will address recent progress in Mn absorption, distribution and elimination across different tissues, as well as the intracellular regulation of Mn homeostasis in cells. We will conclude with recommendations for future research areas on Mn metabolism.

268 citations


Journal ArticleDOI
TL;DR: Wang et al. as mentioned in this paper proposed a 3D-CNN model based on a convolutional autoencoder, which is pre-trained to capture anatomical shape variations in structural brain MRI scans for source domain.
Abstract: Early diagnosis is playing an important role in preventing progress of the Alzheimer's disease (AD). This paper proposes to improve the prediction of AD with a deep 3D Convolutional Neural Network (3D-CNN), which can show generic features capturing AD biomarkers extracted from brain images, adapt to different domain datasets, and accurately classify subjects with improved fine-tuning method. The 3D-CNN is built upon a convolutional autoencoder, which is pre-trained to capture anatomical shape variations in structural brain MRI scans for source domain. Fully connected upper layers of the 3D-CNN are then fine-tuned for each task-specific AD classification in target domain. In this paper, deep supervision algorithm is used to improve the performance of already proposed 3D Adaptive CNN. Experiments on the ADNI MRI dataset without skull-stripping preprocessing have shown that the proposed 3D Deeply Supervised Adaptable CNN outperforms several proposed approaches, including 3D-CNN model, other CNN-based methods and conventional classifiers by accuracy and robustness. Abilities of the proposed network to generalize the features learnt and adapt to other domains have been validated on the CADDementia dataset.

133 citations


Journal ArticleDOI
TL;DR: It is concluded that several promising EEG/ERP indices of synaptic neurotransmission are worth considering as potential biomarkers of Alzheimer's disease and some practical issues are highlighted and future challenges are highlighted.
Abstract: Here we critically review studies that used electroencephalography (EEG) or event-related potential (ERP) indices as a biomarker of Alzheimer's disease. In the first part we overview studies that relied on visual inspection of EEG traces and spectral characteristics of EEG. Second, we survey analysis methods motivated by dynamical systems theory (DST) as well as more recent network connectivity approaches. In the third part we review studies of sleep. Next, we compare the utility of early and late ERP components in dementia research. In the section on mismatch negativity (MMN) studies we summarize their results and limitations and outline the emerging field of computational neurology. In the following we overview the use of EEG in the differential diagnosis of the most common neurocognitive disorders. Finally, we provide a summary of the state of the field and conclude that several promising EEG/ERP indices of synaptic neurotransmission are worth considering as potential biomarkers. Furthermore, we highlight some practical issues and discuss future challenges as well.

127 citations


Journal ArticleDOI
TL;DR: A better understanding of its role in individual tumor types, careful selection of patients, and identification of suitable combinations with currently available anticancer treatments will be critical for a successful translation of preclinically tested approaches of FAP targeting into clinical setting.
Abstract: Fibroblast activation protein (FAP, seprase) is a serine protease with post-proline dipeptidyl peptidase and endopeptidase enzymatic activity. FAP is upregulated in several tumor types, while its expression in healthy adult tissues is scarce. FAP molecule itself and FAP+ stromal cells play an important although probably context-dependent and tumor type-specific pathogenetic role in tumor progression. We provide an overview of FAP expression under both physiological and pathological conditions with focus on human malignancies. We also review and critically analyze the results of studies which used various strategies for the therapeutic targeting of FAP including the use of low molecular weight inhibitors, FAP activated prodrugs, anti-FAP antibodies and their conjugates, FAP-CAR T cells, and FAP vaccines. A unique enzymatic activity and selective expression in tumor microenvironment make FAP a promising therapeutic target. A better understanding of its role in individual tumor types, careful selection of patients, and identification of suitable combinations with currently available anticancer treatments will be critical for a successful translation of preclinically tested approaches of FAP targeting into clinical setting.

117 citations


Journal ArticleDOI
TL;DR: This method provides an efficient way to enrich the exosomes from blood (plasma), which could be potentially employed for clinical diagnostic assessment and therapeutic intervention.
Abstract: Exosomes are a subset of extracellular vesicles (EVs) that have important roles in intercellular communication. They contain and carry bioactive molecules within their membranes which are delivered to target cells. Reproducible isolation and enrichment of these exosomes will aid in evaluation of cellular communication. We present an approach that involved the pre-processing of plasma, combined with ultracentrifugation (UC) and size exclusion chromatography (SEC) to isolate EVs and subsequently enrich exosomes. Four variations of this approach (denoted methods I to IV) were compared. Coupling an ultracentrifugation method with size exclusion chromatography (Method II) provided the best yield by nanoparticle tracking analyses (NTA), the presence of the exosomal markers CD63, Flotillin-1 and TSG-101 (immunoblotting) and showed exosome morphology using transmission electron microscopy (TEM). This method provides an efficient way to enrich the exosomes from blood (plasma), which could be potentially employed for clinical diagnostic assessment and therapeutic intervention.

95 citations


Journal ArticleDOI
TL;DR: An overview of the nexus between these two prominent systems (Bone and Immune system) of an organism, which reside in a common niche (bone marrow) and thus cross-communicate to modulate their respective development are provided.
Abstract: Osteoimmunology is an interdisciplinary research field which combines the existing fields of osteology (bone biology) and immunology under one umbrella. The observation that contributed enormously to the emergence of osteoimmunology as an independent field of investigation was the enhanced bone loss in various inflammatory bone diseases such as rheumatoid arthritis, osteoporosis and periodontitis. T helper cells (Th1, Th2, Treg and Th17) along with various other immune cells (B cells, DC, macrophages etc.) are actively involved in bone homeostasis. The present review thus provides an overview of the nexus between these two prominent systems (Bone and Immune system) of an organism, which reside in a common niche (bone marrow) and thus cross-communicate to modulate their respective development. Investigations in the field of osteoimmunology thus promise the advent of new era in the field with novel therapeutics for bone loss in various inflammatory conditions. A molecular insight into the field of osteoimmunology can lead to novel approaches for the prevention and treatment of diverse inflammatory conditions such as osteoporosis, rheumatoid arthritis and osteoarthritis.

92 citations


Journal ArticleDOI
TL;DR: It is postulated that anhedonia is not a distinct entity but is rather an epiphenomenon of hypodopaminergic states and traits arising from the interaction of genetic traits and epigenetic neurobiological alterations in response to environmental influences.
Abstract: Anhedonia is a condition that leads to the loss of feelings pleasure in response to natural reinforcers like food, sex, exercise, and social activities. This disorder occurs in addiction, and an array of related neuropsychiatric syndromes, including schizophrenia, depression, and Post Traumatic Stress Disorder (PTSD). Anhedonia may by due to derangements in mesolimbic dopaminergic pathways and their terminal fields (e.g., striatum, amygdala, and prefrontal cortex) that persist long after the traces of the causative drugs are eliminated (pharmacokinetically). Here we postulate that anhedonia is not a distinct entity but is rather an epiphenomenon of hypodopaminergic states and traits arising from the interaction of genetic traits and epigenetic neurobiological alterations in response to environmental influences. Moreover, dopaminergic activity is rather complex, and so it may give rise to differential pathophysiological processes such as incentive sensitization, aberrant learning and stress-like "anti-reward" phenomena. These processes may have additive, synergistic or antagonistic interactions with the concurrent reward deficiency states leading in some instances to more severe and long-lasting symptoms. Operant understanding of the neurogenetic antecedents to reward deficiency syndrome (RDS) and the elucidation of reward gene polymorphisms may provide a map for accessing an individual's genetic risk for developing Anhedonia. Prevention techniques that can restore homeostatic balance via physiological activation of dopaminergic receptors (D2/D3) may be instrumental for targeting not only anhedonia per se but also drug craving and relapse.

91 citations


Journal ArticleDOI
TL;DR: Findings from Positron Emission Tomography (PET), functional Magnetic Resonance Imaging (fMRI) and structural imaging studies, as well as evidence from neuroimaging studies of bariatric surgery and pharmacological interventions on obese individuals are examined.
Abstract: Drugs and food both exert a rewarding effect through the firing of dopamine neurons in the ventral tegmental area, resulting in the release of dopamine into the nucleus accumbens and effects on the mesolimbic pathway. Here, we review the neuroimaging literature to consider the validity of food addiction and the common neurobiological mechanisms that overlap in food and drug addiction. This review paper focuses on findings from Positron Emission Tomography (PET), functional Magnetic Resonance Imaging (fMRI) and structural imaging studies, as well as evidence from neuroimaging studies of bariatric surgery and pharmacological interventions on obese individuals. We examine not only functional and structural changes in the mesolimbic pathways, but also in other frontal areas shown to be involved in drug addiction, including the prefrontal cortex, orbitofrontal cortex and anterior cingulate cortex, as well as changes in neurotransmitter systems beyond dopaminergic systems.

90 citations


Journal ArticleDOI
TL;DR: This review is aimed to present a global picture of multifaceted platelet biology and platelet involvement in selected non-hemostatic events.
Abstract: While platelets have long been known to be essential for maintaining hemostasis in the vasculature, their role in tissue repair, inflammation and innate and adaptive immunity is a more recent science The ability of platelets to attach to the vessel wall, form aggregates and promote fibrin formation, key elements of blood clotting, has been said to both favor and dampen inflammation, to fight infection and to assure an adequate immune response To fulfill their different roles platelets often synchronize with leukocytes and cells of the immune system But just as the molecular pathways of platelets in preventing blood loss can lead to arterial thrombosis and stroke if occurring in an uncontrolled manner, the failure to control inflammation can lead to sepsis and inadequate platelet function and can aggravate many major illnesses This review is aimed to present a global picture of multifaceted platelet biology and platelet involvement in selected non-hemostatic events

87 citations


Journal ArticleDOI
TL;DR: It is indicated that H19 is associated with growth, migration, invasion, and/or metastasis in many cancers; however, its reported functional mechanisms vary among cancer types.
Abstract: With the recent advent of whole genome and transcriptome sequencing technologies, long non-coding RNAs have been brought into the spotlight in molecular biology H19 was one of the first reported long non-coding RNAs; its expression is high in embryonic organs and absent or greatly reduced in most adult tissues Accumulating evidence suggests that H19 plays crucial roles in embryogenesis However, its levels are increased in different cancers, including breast, hepato-gastrointestinal, urological, respiratory, and brain tumors Although there have been several controversial reports as to whether H19 is oncogenic or tumor-suppressive, most studies have indicated that H19 is associated with growth, migration, invasion, and/or metastasis in many cancers; however, its reported functional mechanisms vary among cancer types Furthermore, serum H19 levels in patients with certain cancers have been suggested to be useful for diagnosis and prognosis Thus, H19 long non-coding RNA might be a candidate for development of promising therapeutic and diagnostic modalities for several cancers The purpose of this review is to provide an inclusive report on the functional role of H19 in different cancers

81 citations


Journal ArticleDOI
TL;DR: Deep brain stimulation will continue to offer a reversible and safe therapeutic option for a host of neurological conditions and remains one of the best windows into human brain physiology.
Abstract: Deep brain stimulation (DBS) has emerged as a revolutionary treatment option for essential tremor (ET), Parkinson's disease (PD), idiopathic dystonia, and severe obsessive-compulsive disorder (OCD) This article reviews the historical foundations of DBS including basal ganglia pathophysiological models, classic principles of electrical stimulation, technical components of the DBS system, treatment risks, and future directions for DBS Chronic high frequency stimulation induces a number of functional changes from fast physiological to slower metabolic effects and ultimately leads to structural reorganization of the brain, so-called neuroplasticity Examples of each of these fast, slow, and long-term changes are given in the context of Parkinson's disease where these mechanisms have perhaps been the most intensely investigated In particular, details of striatal dopamine release, expression of trophic factors, and a possible neuroprotective mechanism of DBS are highlighted We close with a brief discussion of technical and clinical considerations for improvement Deep brain stimulation will continue to offer a reversible and safe therapeutic option for a host of neurological conditions and remains one of the best windows into human brain physiology

Journal ArticleDOI
TL;DR: This review provides a detailed view about the role of metal and metal oxide nanoparticles in the treatment of infections in conjunction with antibiotics, their modes of action, and synergism, and the problems of multidrug resistance are addressed to allow the development of a comprehensive, reliable, and rational treatment plan.
Abstract: The discovery of antibiotics was hailed as a historic breakthrough for the human race in the fight against bacterial and malignant infections. However, in a very short time, owing to their acute and aggressive nature, bacteria have developed resistance against antibiotics and other chemotherapeutics agents. Potentially, this situation could again result in bacterial infection outbreaks. Metal and metal oxide nanoparticles have been proven as better alternatives; the combination of antibiotics and metal oxide nanoparticles was shown to decrease the toxicity and enhance the antibacterial, antiviral, and anticancer efficacy of the agents. This review provides a detailed view about the role of metal and metal oxide nanoparticles in the treatment of infections in conjunction with antibiotics, their modes of action, and synergism. In addition, the problems of multidrug resistance are addressed and will allow the development of a comprehensive, reliable, and rational treatment plan. It is expected that this comprehensive review will lead to new research opportunities, which should be helpful for future applications in biomedical science.

Journal ArticleDOI
TL;DR: Viral infection mediated TLRs activation is both cell type- and species-specific and explains the difficulties in correlating murine model data with the human data, and their contributions to the procoagulant response.
Abstract: The abundance of evidence suggest that inflammation of immune and non-immune cells may lead to an imbalance of the pro- and anti-coagulant state during viral infections. During systemic infections, the endothelium plays a critical role in regulating hemostasis, and severe imbalances of endothelial function and activation can contribute to organ failure. Viral infections may elevate plasma levels of procoagulant markers such as TAT and D-dimer TF-positive MPs as well as von Willebrand factor (vWF). Although multiple clinical studies are showing the association of viral infection and increased prothrombotic risk, the pathological mechanisms have not been fully identified for most viral infections. Viral infection mediated TLRs activation is both cell type- and species-specific and explains the difficulties in correlating murine model data with the human data. In this review, we briefly discuss the TF-dependent coagulation activation, Toll-like receptors (TLRs) signaling during viral infections, and their contributions to the procoagulant response.

Journal ArticleDOI
TL;DR: The Genetic Addiction Risk Score (GARS) is examined, the first test to accurately predict vulnerability to pain, addiction, and other compulsive behaviors, defined as Reward Deficiency Syndrome (RDS).
Abstract: The interaction of neurotransmitters and genes that control the release of dopamine is the Brain Reward Cascade (BRC). Variations within the BRC, whether genetic or epigenetic, may predispose individuals to addictive behaviors and altered pain tolerance. This discussion authored by a group of concerned scientists and clinicians examines the Genetic Addiction Risk Score (GARS), the first test to accurately predict vulnerability to pain, addiction, and other compulsive behaviors, defined as Reward Deficiency Syndrome (RDS). Innovative strategies to combat epidemic opioid, iatrogenic prescription drug abuse and death, based on the role of dopaminergic tone in pain pathways, are proposed. Sensitivity to pain may reside in the mesolimbic projection system, where genetic polymorphisms associate with a predisposition to pain vulnerability or tolerance. They provide unique therapeutic targets that could assist in the treatment of pain, and identify risk for subsequent addiction. Pharmacogenomic testing of candidate genes like CB1, mu receptors, and PENK might result in pharmacogenomic, personalized solutions, and improved clinical outcomes. Genetically identifying risk for all RDS behaviors, especially in compromised populations, may be a frontline tool to assist municipalities to provide better resource allocation.

Journal ArticleDOI
TL;DR: This work highlights the bioactive compounds that are isolated from microalgae for the purpose of using them as food, and as chemicals in pharmaceutical industry as new agents with therapeutic benefits.
Abstract: Microalgae are one of the oldest microorganisms, that grow in various hostile environments, ranging from deserts to Antarctica. The microalgae sustain life in such harsh environments through generation of secondary metabolites. Microalgae biosynthesize a large number of diverse bioactive metabolites with activities on cancer, neurodegenerative diseases, and infectious diseases. Here, we highlight the bioactive compounds that are isolated from microalgae for the purpose of using them as food, and as chemicals in pharmaceutical industry as new agents with therapeutic benefits.

Journal ArticleDOI
TL;DR: This review aims to use recent evidence to connect sugar's impact on the body, brain, and behavior to elucidate how and why sugar consumption has been implicated in addictive behaviors and poor health outcomes.
Abstract: Sugar is highly palatable and rewarding, both in its taste and nutritive input. Excessive sugar consumption, however, may trigger neuroadaptations in the reward system that decouple eating behavior from caloric needs and leads to compulsive overeating. Excessive sugar intake is in turn associated with adverse health conditions, including obesity, metabolic syndrome, and inflammatory diseases. This review aims to use recent evidence to connect sugar's impact on the body, brain, and behavior to elucidate how and why sugar consumption has been implicated in addictive behaviors and poor health outcomes.

Journal ArticleDOI
TL;DR: The purpose of this review is to emphasize age-related physiological adaptations occurring with regular exercise training, with specific reference to the main organs involved in oxygen delivery and utilization as well as the importance of exercise training for promoting life expectancy in clinically referred populations.
Abstract: Cardiorespiratory fitness, as measured by maximal oxygen uptake (VO2max), is related to functional capacity and human performance and has been shown to be a strong and independent predictor of all-cause and disease-specific mortality. The purpose of this review is to emphasize age-related physiological adaptations occurring with regular exercise training, with specific reference to the main organs (lung, heart, skeletal muscles) involved in oxygen delivery and utilization as well as the importance of exercise training for promoting life expectancy in clinically referred populations. As yet, it is not possible to extend the genetically fixed lifespan with regular exercise training, but to give the years more life. This is where physical fitness plays an important role.

Journal ArticleDOI
TL;DR: The hyperactive SOCE may promote metastatic dissemination and colonization by reorganizing the actin cytoskeleton, degrading the extracellular matrix and remodeling the tumor microenvironment.
Abstract: Store-operated calcium entry (SOCE) is the predominant calcium entry mechanism in most cancer cells. SOCE is mediated by the endoplasmic reticulum calcium sensor STIMs (STIM1 and 2) and plasma membrane channel forming unit Orais (Orai 1-3). In recent years there is increasing evidence indicating that SOCE in cancer cells is dysregulated to promote cancer cell migration, invasion and metastasis. The overexpression of STIM and Orai proteins has been reported to correlate with the metastatic progression of various cancers. The hyperactive SOCE may promote metastatic dissemination and colonization by reorganizing the actin cytoskeleton, degrading the extracellular matrix and remodeling the tumor microenvironment. Here we discuss how these recent progresses provide novel insights to our understanding of tumor metastasis.

Journal ArticleDOI
TL;DR: Observations suggested that AA treatment mitigated AlCl3 induced AD associated pathologies, which might be due to its multiple pharmacological actions, which are necessary to establish its neuroprotective role in AD.
Abstract: Alzheimer's disease (AD) is the most common form of dementia, characterized by memory loss, cognitive impairment and personality disorders accompanied by diffuse structural abnormalities in the brain of elderly people. The current investigation explored the neuroprotective potential of asiatic acid (AA), a natural triterpene of Centella asiatica on aluminium chloride (AlCl3) induced rat model of AD. Oral administration of AlCl3 (100 mg/kg b.w.) for 42 days significantly elevated the levels of Al, activity of acetyl cholinesterase and expressions of amyloid precursor protein, amyloid beta1-42, beta and gamma secretases, glial fibrillary acidic protein, ionized calcium binding adaptor molecule 1, interleukins -1β, 6, 4, 2, tumor necrosis factor alpha, inducible nitric oxide synthase, nuclear factor- k beta and cyclooxygenase-2 in the hippocampus and cortex compared to the control group. Our observations suggested that AA treatment mitigated AlCl3 induced AD associated pathologies, which might be due to its multiple pharmacological actions. Further studies are necessary in order to explore the link between AlCl3-mediated oxidative stress and associated apoptosis to establish its neuroprotective role in AD.

Journal ArticleDOI
TL;DR: In this paper, a broad analysis of the different aspects of this approach for anti-leishmanial treatment is presented, as well as a broad review of the use of drugs that are already used for other diseases.
Abstract: The leishmaniases represent a public health problem in under-developed countries and are considered a neglected disease by the World Health Organization (WHO) They are cuased by Leishmania parasites with different clinical manifestations Currently, there is no vaccine, and treatment is in-efficient and is associated with both serious side effects often leading to resistance to the parasites Thus, it is essential to search for new treatment strategies, such as drug repurposing, ie, the use of drugs that are already used for other diseases The discovery of new clinical applications for approved drugs is strategic for lowering the cost of drug discovery since human toxicity assays are already conducted Here, we review a broad analysis of the different aspects of this approach for anti-leishmanial treatment

Journal ArticleDOI
TL;DR: The role of nanotechnology in promoting the wound healing process is critically reviewed and nanoparticles affect wound healing by influencing collagen deposition and realignment and provide approaches for skin regeneration and wound healing.
Abstract: Chronic non-healing wounds represent a growing problem due to their high morbidity and cost. Despite recent advances in wound healing, several systemic and local factors can disrupt the weighed physiologic healing process. This paper critically reviews and discusses the role of nanotechnology in promoting the wound healing process. Nanotechnology-based materials have physicochemical, optical and biological properties unique from their bulk equivalent. These nanoparticles can be incorporated into scaffolds to create nanocomposite smart materials, which promote wound healing through their antimicrobial, as well as selective anti- and pro-inflammatory, and pro-angiogenic properties. Owed to their high surface area, nanoparticles have also been used for drug delivery as well as gene delivery vectors. In addition, nanoparticles affect wound healing by influencing collagen deposition and realignment and provide approaches for skin regeneration and wound healing.

Journal ArticleDOI
TL;DR: The biofuels produced by microbial biotechnology might substitute the crop-based bio-ethanol and bio-diesel production because of importance of high-value compounds in aquaculture and bioremediation, and the potential to reduce carbon emissions and energy security.
Abstract: Increasing energy demand, limited fossil fuel resources and climate change have prompted development of alternative sustainable and economical fuel resources such as crop-based bio-ethanol and bio-diesel. However, there is concern over use of arable land that is used for food agriculture for creation of biofuel. Thus, there is a renewed interest in the use of microbes particularly microalgae for bio-fuel production. Microbes such as micro-algae and cyanobacteria that are used for biofuel production also produce other bioactive compounds under stressed conditions. Microbial agents used for biofuel production also produce bioactive compounds with antimicrobial, antiviral, anticoagulant, antioxidant, antifungal, anti-inflammatory and anticancer activity. Because of importance of such high-value compounds in aquaculture and bioremediation, and the potential to reduce carbon emissions and energy security, the biofuels produced by microbial biotechnology might substitute the crop-based bio-ethanol and bio-diesel production.

Journal ArticleDOI
TL;DR: Recent findings regarding the concerted mechanism of action of Polycomb group proteins (PcG), acting together with some classically defined lncRNAs including X-inactive specific transcript (XIST), antisense non-coding RNA in the INK4 locus (ANRIL), metastasis associated lung adenocarcinoma transcript 1 (MALAT1), and HOX transcript antisense RNA (HOTAIR).
Abstract: High-throughput analyses have revealed that the vast majority of the transcriptome does not code for proteins. These non-translated transcripts, when larger than 200 nucleotides, are termed long non-coding RNAs (lncRNAs), and play fundamental roles in diverse cellular processes. LncRNAs are subject to dynamic chemical modification, adding another layer of complexity to our understanding of the potential roles that lncRNAs play in health and disease. Many lncRNAs regulate transcriptional programs by influencing the epigenetic state through direct interactions with chromatin-modifying proteins. Among these proteins, Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) have been shown to be recruited by lncRNAs to silence target genes. Aberrant expression, deficiency or mutation of both lncRNA and Polycomb have been associated with numerous human diseases, including cancer. In this review, we have highlighted recent findings regarding the concerted mechanism of action of Polycomb group proteins (PcG), acting together with some classically defined lncRNAs including X-inactive specific transcript (XIST), antisense non-coding RNA in the INK4 locus (ANRIL), metastasis associated lung adenocarcinoma transcript 1 (MALAT1), and HOX transcript antisense RNA (HOTAIR).

Journal ArticleDOI
TL;DR: The expression, role, and regulatory mechanisms of IIIb and IIIc variants of FGFR in cancers are discussed.
Abstract: Types 1-4 of fibroblast growth factor receptors (FGFR) are all expressed in various cancers Because of its prominent role in carcinogenesis and cancer progression, FGFR-2, is being considered as a novel target in cancer treatment Owing to the alternative splicing of its extracellular domain, FGFR-2 exists in two variants: IIIb and IIIc FGFR-2 IIIb is mainly expressed in normal epithelial cells, as well as in oral mucosal, esophageal, gastric, colorectal, pancreatic, pulmonary, breast, endometrial, cervical, and prostate cancers The IIIc variant of FGFR is expressed in mesenchymal cells, and during epithelial-mesenchymal transition (EMT), is expressed in colorectal, pancreatic, bladder, cervical, and prostate cancers The FGFR IIIb and IIIc variants bind different forms of FGFs and exert autocrine and/or paracrine effects in cancers Recent reports indicate that switching from IIIb to IIIc variants correlates with the aggressiveness of the cancers via EMT Here, we discuss the expression, role, and regulatory mechanisms of IIIb and IIIc variants of FGFR in cancers

Journal ArticleDOI
TL;DR: Current knowledge about the association of Cd exposure and prostate cancer is summarized, that suggests that new studies to show the role of C d in the pathogenesis of prostatate cancer are needed.
Abstract: Cadmium (Cd) is a metal found in group 12 (IIB) of the periodic table of elements together with zinc, a metal with which it is often conjugated in nature. Occupational exposure to Cd occurs in many industrial settings, by cigarette smoking, diet and due to environmental pollution. International Agency for Research on Cancer and other epidemiological studies suggested that Cd can lead to prostate cancer and likely to kidney and lung cancers. Although epidemiological studies seem to point towards such an association, the in vitro studies have not been compelling. The aim of this article is to summarize current knowledge about the association of Cd exposure and prostate cancer, that suggests that new studies to show the role of Cd in the pathogenesis of prostatate cancer.

Journal ArticleDOI
TL;DR: The most recent drug repurposing approaches to fight DENV infection and their implications in antiviral drug-discovery are described.
Abstract: Dengue is a mosquito-borne viral disease caused by four antigenically distinct serotypes of Dengue Virus (DENV), namely DENV1-4 and is currently considered the most important arthropod-born viral disease in the world. An effective antiviral therapy to treat Dengue Virus infection is still missing and a number of replicative cycle inhibitors are currently under study. Considering the rapid spreading of DENV and the common timeframe required for bringing a new drug on the market, the repurposing of approved drugs used for different diseases to identify novel inhibitors of this pathogen represents an attractive approach for a rapid therapeutic intervention. Herein, we will describe the most recent drug repurposing approaches to fight DENV infection and their implications in antiviral drug-discovery.

Journal ArticleDOI
TL;DR: This review examines glucose and amino acid transporters expressed in the apical membrane, basolateral membrane, or the inside of the absorptive enterocytes, and shows how these nutrients influence the proliferation and differentiation of an intestinal stem cell into one specialized cell type when they migrate from the bottom of the crypt to the tip of the villus.
Abstract: The main function of the porcine intestinal tract is nutrient digestion and absorption. This function is performed by the absorptive enterocytes, which are differentiated from the intestinal stem cells residing at the bottom of the crypt. Nutrients such as glucose and amino acids are transported, absorbed by various transporters embedded on the membranes of these enterocytes. Metabolism occurs in each cell along the crypt-villus axis (CVA). Because the intestinal epithelial cells are the most vigorous, self-renewing cells, regenerating from the crypt bottom to the villus tip in only three to five days, the CVA is an appealing organ for studying cell maturation. In this review, we examine the glucose and amino acid transporters expressed in the apical membrane, basolateral membrane, or the inside of the absorptive enterocytes. We also discuss glucose and amino acid metabolism in small epithelial cells, and show how these nutrients influence the proliferation and differentiation of an intestinal stem cell into one specialized cell type when they migrate from the bottom of the crypt to the tip of the villus.

Journal ArticleDOI
TL;DR: The current techniques that are developed to determine the ability of OCT images for early detection/diagnosis of retinal diseases and several challenges that face the researchers in the analysis of the OCT retinal images are overviewed.
Abstract: Optical Coherence Topography (OCT) is an emerging biomedical imaging technology that offers non-invasive real-time, high-resolution imaging of highly scattering tissues. It is widely used in ophthalmology to perform diagnostic imaging on the structure of the anterior eye and the retina. Clinical studies are carried out to assess the application of OCT for some retinal diseases. OCT can provide means for early detection for various types of diseases because morphological changes often occur before the physical symptoms of these diseases. In addition, follow-up imaging can assess treatment effectiveness and recurrence of a disease. A review in this area is needed to identify the results and the findings from OCT images in the field of retinal diseases and how to use these findings to help in clinical applications. This paper overviews the current techniques that are developed to determine the ability of OCT images for early detection/diagnosis of retinal diseases. Also, the paper remarks several challenges that face the researchers in the analysis of the OCT retinal images.

Journal ArticleDOI
TL;DR: Cell culture systems using McCoy cells and subsequent immunofluorescent staining are still the most common methodology used for antimicrobial susceptibility testing, but the presence of resistance markers should be appraised by further genetic analysis.
Abstract: Chlamydia trachomatis (C. trachomatis) is a leading cause of bacterial sexually transmitted infections in developed and undeveloped countries, and therefore a global public health issue. In an era of increasing bacterial resistance to antibiotics, resistance has been an exceedingly rare phenomenon in C. trachomatis; however, clinical treatment failures attributed to multidrug-resistant C. trachomatis strains have been described on several occasions. Cell culture systems using McCoy cells and subsequent immunofluorescent staining are still the most common methodology used for antimicrobial susceptibility testing, but the presence of resistance markers should be appraised by further genetic analysis. Azithromycin resistance of C. trachomatis is often a result of the mutations in the peptidyl transferase region of 23S rRNA genes, tetracycline resistance is usually linked to the presence of foreign genomic islands integrated in chlamydial chromosome, whereas a predominant mechanism of fluoroquinolone resistance is a point mutation in the gyrA quinolone-resistance-determining region. A nucleotide substitution in rpoB gene is responsible for rifampin resistance, and different mechanisms have been involved in the development of resistance to aminoglycosides, lincomycin and sulphonamide/trimethoprim combinations.

Journal ArticleDOI
TL;DR: Various Omics research efforts are reviewed in light of research on anti-tick vaccines to develop new vaccine antigens and adjuvants to assist tick control programs.
Abstract: Tick vaccines have been available for more than 20 years. They are useful and effective control agents when used properly. However, no new products have emerged since the Bm86-based Gavac vaccine was commercialized. Acaricide resistance is a problem with no abatement in sight and anti-tick vaccines are likely to be relied upon even more in the coming years. As human medicine and plant agriculture has embraced the various Omics technologies, the search for anti-tick vaccines would be well served to follow; so that new vaccine antigens and adjuvants might be developed to assist tick control programs. However, the simple outward appearance of ticks and their life cycle belies the complexity of their genomes which are computationally challenging to sequence and annotate. We review various Omics research efforts in light of research on anti-tick vaccines.