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Int. J. Mol. Sci., Volume 19, Issue 3 (March 2018)

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Cover Story (view full-size image) Tyrosinase is the key enzyme of melanin production in melanosomes, which are transferred from [...] Read more.
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Open AccessReview p53 as a Dichotomous Regulator of Liver Disease: The Dose Makes the Medicine
Int. J. Mol. Sci. 2018, 19(3), 921; https://doi.org/10.3390/ijms19030921
Received: 7 February 2018 / Revised: 16 March 2018 / Accepted: 17 March 2018 / Published: 20 March 2018
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Abstract
Lifestyle-related disorders, such as the metabolic syndrome, have become a primary risk factor for the development of liver pathologies that can progress from hepatic steatosis, hepatic insulin resistance, steatohepatitis, fibrosis and cirrhosis, to the most severe condition of hepatocellular carcinoma (HCC). While the
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Lifestyle-related disorders, such as the metabolic syndrome, have become a primary risk factor for the development of liver pathologies that can progress from hepatic steatosis, hepatic insulin resistance, steatohepatitis, fibrosis and cirrhosis, to the most severe condition of hepatocellular carcinoma (HCC). While the prevalence of liver pathologies is steadily increasing in modern societies, there are currently no approved drugs other than chemotherapeutic intervention in late stage HCC. Hence, there is a pressing need to identify and investigate causative molecular pathways that can yield new therapeutic avenues. The transcription factor p53 is well established as a tumor suppressor and has recently been described as a central metabolic player both in physiological and pathological settings. Given that liver is a dynamic tissue with direct exposition to ingested nutrients, hepatic p53, by integrating cellular stress response, metabolism and cell cycle regulation, has emerged as an important regulator of liver homeostasis and dysfunction. The underlying evidence is reviewed herein, with a focus on clinical data and animal studies that highlight a direct influence of p53 activity on different stages of liver diseases. Based on current literature showing that activation of p53 signaling can either attenuate or fuel liver disease, we herein discuss the hypothesis that, while hyper-activation or loss of function can cause disease, moderate induction of hepatic p53 within physiological margins could be beneficial in the prevention and treatment of liver pathologies. Hence, stimuli that lead to a moderate and temporary p53 activation could present new therapeutic approaches through several entry points in the cascade from hepatic steatosis to HCC. Full article
(This article belongs to the collection Molecular Mechanisms of Human Liver Diseases)
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Open AccessArticle CpG ODN1826 as a Promising Mucin1-Maltose-Binding Protein Vaccine Adjuvant Induced DC Maturation and Enhanced Antitumor Immunity
Int. J. Mol. Sci. 2018, 19(3), 920; https://doi.org/10.3390/ijms19030920
Received: 13 February 2018 / Revised: 13 March 2018 / Accepted: 15 March 2018 / Published: 20 March 2018
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Abstract
Mucin 1 (MUC1), being an oncogene, is an attractive target in tumor immunotherapy. Maltose binding protein (MBP) is a potent built-in adjuvant to enhance protein immunogenicity. Thus, a recombinant MUC1 and MBP antitumor vaccine (M-M) was constructed in our laboratory. To
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Mucin 1 (MUC1), being an oncogene, is an attractive target in tumor immunotherapy. Maltose binding protein (MBP) is a potent built-in adjuvant to enhance protein immunogenicity. Thus, a recombinant MUC1 and MBP antitumor vaccine (M-M) was constructed in our laboratory. To enhance the antitumor immune activity of M-M, CpG oligodeoxynucleotides 1826 (CpG 1826), a toll-like receptor-9 agonist, was examined in this study as an adjuvant. The combination of M-M and CpG 1826 significantly inhibited MUC1-expressing B16 cell growth and prolonged the survival of tumor-bearing mice. It induced MUC1-specific antibodies and Th1 immune responses, as well as the Cytotoxic T Lymphocytes (CTL) cytotoxicity in vivo. Further studies showed that it promoted the maturation and activation of the dendritic cell (DC) and skewed towards Th1 phenotype in vitro. Thus, our study revealed that CpG 1826 is an efficient adjuvant, laying a foundation for further M-M clinical research. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Open AccessReview Therapeutic Properties and Biological Benefits of Marine-Derived Anticancer Peptides
Int. J. Mol. Sci. 2018, 19(3), 919; https://doi.org/10.3390/ijms19030919
Received: 26 January 2018 / Revised: 7 March 2018 / Accepted: 16 March 2018 / Published: 20 March 2018
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Abstract
Various organisms exist in the oceanic environment. These marine organisms provide an abundant source of potential medicines. Many marine peptides possess anticancer properties, some of which have been evaluated for treatment of human cancer in clinical trials. Marine anticancer peptides kill cancer cells
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Various organisms exist in the oceanic environment. These marine organisms provide an abundant source of potential medicines. Many marine peptides possess anticancer properties, some of which have been evaluated for treatment of human cancer in clinical trials. Marine anticancer peptides kill cancer cells through different mechanisms, such as apoptosis, disruption of the tubulin-microtubule balance, and inhibition of angiogenesis. Traditional chemotherapeutic agents have side effects and depress immune responses. Thus, the research and development of novel anticancer peptides with low toxicity to normal human cells and mechanisms of action capable of avoiding multi-drug resistance may provide a new method for anticancer treatment. This review provides useful information on the potential of marine anticancer peptides for human therapy. Full article
(This article belongs to the Special Issue Natural Bioactives and Phytochemicals in Cancer Prevention)
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Open AccessArticle Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters
Int. J. Mol. Sci. 2018, 19(3), 918; https://doi.org/10.3390/ijms19030918
Received: 11 February 2018 / Revised: 14 March 2018 / Accepted: 15 March 2018 / Published: 20 March 2018
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Abstract
The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously
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The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures (Tms) of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg), agmatine, l-arginine methyl ester, and l-arginine amide. The resulting Tms indicated stabilization of AdiC variants upon ligand binding, in which Tms and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5), an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family. Full article
(This article belongs to the Special Issue Amino Acids Transport and Metabolism)
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Open AccessArticle The Influence of High and Low Doses of Bisphenol A (BPA) on the Enteric Nervous System of the Porcine Ileum
Int. J. Mol. Sci. 2018, 19(3), 917; https://doi.org/10.3390/ijms19030917
Received: 13 February 2018 / Revised: 13 March 2018 / Accepted: 14 March 2018 / Published: 20 March 2018
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Abstract
Bisphenol A, used in the production of plastic, is able to leach from containers into food and cause multidirectional adverse effects in living organisms, including neurodegeneration and metabolic disorders. Knowledge of the impact of BPA on enteric neurons is practically non-existent. The destination
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Bisphenol A, used in the production of plastic, is able to leach from containers into food and cause multidirectional adverse effects in living organisms, including neurodegeneration and metabolic disorders. Knowledge of the impact of BPA on enteric neurons is practically non-existent. The destination of this study was to investigate the influence of BPA at a specific dose (0.05 mg/kg body weight/day) and at a dose ten times higher (0.5 mg/kg body weight/day), given for 28 days, on the porcine ileum. The influence of BPA on enteric neuron immunoreactive to selected neuronal active substances, including substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL), vesicular acetylcholine transporter (VAChT—used here as a marker of cholinergic neurons), and cocaine- and amphetamine-regulated transcript peptide (CART), was studied by the double immunofluorescence method. Both doses of BPA affected the neurochemical characterization of the enteric neurons. The observed changes depended on the type of enteric plexus but were generally characterized by an increase in the number of cells immunoreactive to the particular substances. More visible fluctuations were observed after treatment with higher doses of BPA. The results confirm that even low doses of BPA may influence the neurochemical characterization of the enteric neurons and are not neutral for living organisms. Full article
(This article belongs to the Special Issue Advances in the Research of Endocrine Disrupting Chemicals)
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Open AccessArticle Site-Mutation of Hydrophobic Core Residues Synchronically Poise Super Interleukin 2 for Signaling: Identifying Distant Structural Effects through Affordable Computations
Int. J. Mol. Sci. 2018, 19(3), 916; https://doi.org/10.3390/ijms19030916
Received: 19 February 2018 / Revised: 15 March 2018 / Accepted: 17 March 2018 / Published: 20 March 2018
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Abstract
A superkine variant of interleukin-2 with six site mutations away from the binding interface developed from the yeast display technique has been previously characterized as undergoing a distal structure alteration which is responsible for its super-potency and provides an elegant case study with
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A superkine variant of interleukin-2 with six site mutations away from the binding interface developed from the yeast display technique has been previously characterized as undergoing a distal structure alteration which is responsible for its super-potency and provides an elegant case study with which to get insight about how to utilize allosteric effect to achieve desirable protein functions. By examining the dynamic network and the allosteric pathways related to those mutated residues using various computational approaches, we found that nanosecond time scale all-atom molecular dynamics simulations can identify the dynamic network as efficient as an ensemble algorithm. The differentiated pathways for the six core residues form a dynamic network that outlines the area of structure alteration. The results offer potentials of using affordable computing power to predict allosteric structure of mutants in knowledge-based mutagenesis. Full article
(This article belongs to the collection Proteins and Protein-Ligand Interactions)
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Open AccessArticle Alternative Respiratory Pathway Component Genes (AOX and ND) in Rice and Barley and Their Response to Stress
Int. J. Mol. Sci. 2018, 19(3), 915; https://doi.org/10.3390/ijms19030915
Received: 14 February 2018 / Revised: 15 March 2018 / Accepted: 16 March 2018 / Published: 20 March 2018
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Abstract
Plants have a non-energy conserving bypass of the classical mitochondrial cytochrome c pathway, known as the alternative respiratory pathway (AP). This involves type II NAD(P)H dehydrogenases (NDs) on both sides of the mitochondrial inner membrane, ubiquinone, and the alternative oxidase (AOX). The AP
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Plants have a non-energy conserving bypass of the classical mitochondrial cytochrome c pathway, known as the alternative respiratory pathway (AP). This involves type II NAD(P)H dehydrogenases (NDs) on both sides of the mitochondrial inner membrane, ubiquinone, and the alternative oxidase (AOX). The AP components have been widely characterised from Arabidopsis, but little is known for monocot species. We have identified all the genes encoding components of the AP in rice and barley and found the key genes which respond to oxidative stress conditions. In both species, AOX is encoded by four genes; in rice OsAOX1a, 1c, 1d and 1e representing four clades, and in barley, HvAOX1a, 1c, 1d1 and 1d2, but no 1e. All three subfamilies of plant ND genes, NDA, NDB and NDC are present in both rice and barley, but there are fewer NDB genes compared to Arabidopsis. Cyanide treatment of both species, along with salt treatment of rice and drought treatment of barley led to enhanced expression of various AP components; there was a high level of co-expression of AOX1a and AOX1d, along with NDB3 during the stress treatments, reminiscent of the co-expression that has been well characterised in Arabidopsis for AtAOX1a and AtNDB2. Full article
(This article belongs to the Special Issue Plant Mitochondria)
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Open AccessReview hCG and Its Disruption by Environmental Contaminants during Human Pregnancy
Int. J. Mol. Sci. 2018, 19(3), 914; https://doi.org/10.3390/ijms19030914
Received: 8 March 2018 / Revised: 16 March 2018 / Accepted: 17 March 2018 / Published: 20 March 2018
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Abstract
Human chorionic gonadotropin (hCG) is a hormone of considerable importance in the establishment, promotion and maintenance of human pregnancy. It has been clearly demonstrated that hCG exerts multiple endocrine, paracrine and autocrine actions on a variety of gestational and non-gestational cells and tissues.
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Human chorionic gonadotropin (hCG) is a hormone of considerable importance in the establishment, promotion and maintenance of human pregnancy. It has been clearly demonstrated that hCG exerts multiple endocrine, paracrine and autocrine actions on a variety of gestational and non-gestational cells and tissues. These actions are directed to promote trophoblast invasiveness and differentiation, placental growth, angiogenesis in uterine vasculature, hormone production, modulation of the immune system at the maternal-fetal interface, inhibition of myometrial contractility as well as fetal growth and differentiation. In recent years, considerable interest has been raised towards the biological effects of environmental contaminants, particularly endocrine disrupting chemicals (EDCs). Emerging evidence suggests that prenatal exposure to selected EDCs can have a deleterious impact on the fetus and long-lasting consequences also in adult life. The results of the in vitro effects of commonly found EDCs, particularly Bisphenol A (BPA) and para-Nonylphenol (p-NP), indicate that these substances can alter hCG production and through this action could exert their fetal damage, suggesting that hCG could represent and become a potentially useful clinical biomarker of an inappropriate prenatal exposure to these substances. Full article
(This article belongs to the Special Issue hCG—An Endocrine, Regulator of Gestation and Cancer)
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Open AccessReview PPARβ/δ: A Key Therapeutic Target in Metabolic Disorders
Int. J. Mol. Sci. 2018, 19(3), 913; https://doi.org/10.3390/ijms19030913
Received: 29 January 2018 / Revised: 9 March 2018 / Accepted: 17 March 2018 / Published: 20 March 2018
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Abstract
Research in recent years on peroxisome proliferator-activated receptor (PPAR)β/δ indicates that it plays a key role in the maintenance of energy homeostasis, both at the cellular level and within the organism as a whole. PPARβ/δ activation might help prevent the development of metabolic
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Research in recent years on peroxisome proliferator-activated receptor (PPAR)β/δ indicates that it plays a key role in the maintenance of energy homeostasis, both at the cellular level and within the organism as a whole. PPARβ/δ activation might help prevent the development of metabolic disorders, including obesity, dyslipidaemia, type 2 diabetes mellitus and non-alcoholic fatty liver disease. This review highlights research findings on the PPARβ/δ regulation of energy metabolism and the development of diseases related to altered cellular and body metabolism. It also describes the potential of the pharmacological activation of PPARβ/δ as a treatment for human metabolic disorders. Full article
(This article belongs to the Special Issue PPARs in Cellular and Whole Body Energy Metabolism)
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Open AccessArticle Suppression Effect of Astaxanthin on Osteoclast Formation In Vitro and Bone Loss In Vivo
Int. J. Mol. Sci. 2018, 19(3), 912; https://doi.org/10.3390/ijms19030912
Received: 26 February 2018 / Revised: 15 March 2018 / Accepted: 16 March 2018 / Published: 19 March 2018
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Abstract
Osteoporosis is characterized by a reduction of the bone mineral density (BMD) and microarchitectural deterioration of the bone, which lead to bone fragility and susceptibility to fracture. Astaxanthin (AST) has a variety of biological activities, such as a protective effect against asthma or
[...] Read more.
Osteoporosis is characterized by a reduction of the bone mineral density (BMD) and microarchitectural deterioration of the bone, which lead to bone fragility and susceptibility to fracture. Astaxanthin (AST) has a variety of biological activities, such as a protective effect against asthma or neuroinflammation, antioxidant effect, and decrease of the osteoclast number in the right mandibles in the periodontitis model. Although treatment with AST is known to have an effect on inflammation, no studies on the effect of AST exposure on bone loss have been performed. Thus, in the present study, we examined the antiosteoporotic effect of AST on bone mass in ovariectomized (OVX) mice and its possible mechanism of action. The administration of AST (5, 10 mg/kg) for 6 weeks suppressed the enhancement of serum calcium, inorganic phosphorus, alkaline phosphatase, total cholesterol, and tartrate-resistant acid phosphatase (TRAP) activity. The bone mineral density (BMD) and bone microarchitecture of the trabecular bone in the tibia and femur were recovered by AST exposure. Moreover, in the in vitro experiment, we demonstrated that AST inhibits osteoclast formation through the expression of the nuclear factor of activated T cells (NFAT) c1, dendritic cell-specific transmembrane protein (DC-STAMP), TRAP, and cathepsin K without any cytotoxic effects on bone marrow-derived macrophages (BMMs). Therefore, we suggest that AST may have therapeutic potential for the treatment of postmenopausal osteoporosis. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Open AccessReview Genetic and Epigenetic Regulation in Nonalcoholic Fatty Liver Disease (NAFLD)
Int. J. Mol. Sci. 2018, 19(3), 911; https://doi.org/10.3390/ijms19030911
Received: 27 February 2018 / Revised: 14 March 2018 / Accepted: 15 March 2018 / Published: 19 March 2018
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Abstract
Genetics and epigenetics play a key role in the development of several diseases, including nonalcoholic fatty liver disease (NAFLD). Family studies demonstrate that first degree relatives of patients with NAFLD are at a much higher risk of the disease than the general population.
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Genetics and epigenetics play a key role in the development of several diseases, including nonalcoholic fatty liver disease (NAFLD). Family studies demonstrate that first degree relatives of patients with NAFLD are at a much higher risk of the disease than the general population. The development of the Genome Wide Association Study (GWAS) technology has allowed the identification of numerous genetic polymorphisms involved in the evolution of diseases (e.g., PNPLA3, MBOAT7). On the other hand, epigenetic changes interact with inherited risk factors to determine an individual’s susceptibility to NAFLD. Modifications of the histones amino-terminal ends are key factors in the maintenance of chromatin structure and gene expression (cAMP-responsive element binding protein H (CREBH) or SIRT1). Activation of SIRT1 showed potential against the physiological mechanisms related to NAFLD. Abnormal DNA methylation represents a starting point for cancer development in NAFLD patients. Besides, the evaluation of circulating miRNA profiles represents a promising approach to assess and non-invasively monitor liver disease severity. To date, there is no approved pharmacologic therapy for NAFLD and the current treatment remains weight loss with lifestyle modification and exercise. In this review, the status of research into relevant genetic and epigenetic modifiers of NAFLD progression will be discussed. Full article
(This article belongs to the Special Issue Transcriptional Regulation in Lipid Metabolism)
Open AccessArticle In-Silico Integration Approach to Identify a Key miRNA Regulating a Gene Network in Aggressive Prostate Cancer
Int. J. Mol. Sci. 2018, 19(3), 910; https://doi.org/10.3390/ijms19030910
Received: 28 February 2018 / Revised: 15 March 2018 / Accepted: 16 March 2018 / Published: 19 March 2018
PDF Full-text (2066 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Like other cancer diseases, prostate cancer (PC) is caused by the accumulation of genetic alterations in the cells that drives malignant growth. These alterations are revealed by gene profiling and copy number alteration (CNA) analysis. Moreover, recent evidence suggests that also microRNAs have
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Like other cancer diseases, prostate cancer (PC) is caused by the accumulation of genetic alterations in the cells that drives malignant growth. These alterations are revealed by gene profiling and copy number alteration (CNA) analysis. Moreover, recent evidence suggests that also microRNAs have an important role in PC development. Despite efforts to profile PC, the alterations (gene, CNA, and miRNA) and biological processes that correlate with disease development and progression remain partially elusive. Many gene signatures proposed as diagnostic or prognostic tools in cancer poorly overlap. The identification of co-expressed genes, that are functionally related, can identify a core network of genes associated with PC with a better reproducibility. By combining different approaches, including the integration of mRNA expression profiles, CNAs, and miRNA expression levels, we identified a gene signature of four genes overlapping with other published gene signatures and able to distinguish, in silico, high Gleason-scored PC from normal human tissue, which was further enriched to 19 genes by gene co-expression analysis. From the analysis of miRNAs possibly regulating this network, we found that hsa-miR-153 was highly connected to the genes in the network. Our results identify a four-gene signature with diagnostic and prognostic value in PC and suggest an interesting gene network that could play a key regulatory role in PC development and progression. Furthermore, hsa-miR-153, controlling this network, could be a potential biomarker for theranostics in high Gleason-scored PC. Full article
(This article belongs to the Special Issue The Role of MicroRNAs in Human Diseases)
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Open AccessReview Amino Acid Metabolism and Transport Mechanisms as Potential Antifungal Targets
Int. J. Mol. Sci. 2018, 19(3), 909; https://doi.org/10.3390/ijms19030909
Received: 12 February 2018 / Revised: 13 March 2018 / Accepted: 15 March 2018 / Published: 19 March 2018
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Abstract
Discovering new drugs for treatment of invasive fungal infections is an enduring challenge. There are only three major classes of antifungal agents, and no new class has been introduced into clinical practice in more than a decade. However, recent advances in our understanding
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Discovering new drugs for treatment of invasive fungal infections is an enduring challenge. There are only three major classes of antifungal agents, and no new class has been introduced into clinical practice in more than a decade. However, recent advances in our understanding of the fungal life cycle, functional genomics, proteomics, and gene mapping have enabled the identification of new drug targets to treat these potentially deadly infections. In this paper, we examine amino acid transport mechanisms and metabolism as potential drug targets to treat invasive fungal infections, including pathogenic yeasts, such as species of Candida and Cryptococcus, as well as molds, such as Aspergillus fumigatus. We also explore the mechanisms by which amino acids may be exploited to identify novel drug targets and review potential hurdles to bringing this approach into clinical practice. Full article
(This article belongs to the Special Issue Amino Acids Transport and Metabolism)
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Open AccessArticle HER2-Targeted Multifunctional Silica Nanoparticles Specifically Enhance the Radiosensitivity of HER2-Overexpressing Breast Cancer Cells
Int. J. Mol. Sci. 2018, 19(3), 908; https://doi.org/10.3390/ijms19030908
Received: 26 February 2018 / Revised: 13 March 2018 / Accepted: 13 March 2018 / Published: 19 March 2018
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Abstract
We investigated the effects of targeted functionalized silica nanoparticles on the radiosensitivity of cancer cells. Better control of the local concentration of silica nanoparticles may facilitate their use as an adjuvant in conjunction with ionizing radiation to target cancer cells while preventing damage
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We investigated the effects of targeted functionalized silica nanoparticles on the radiosensitivity of cancer cells. Better control of the local concentration of silica nanoparticles may facilitate their use as an adjuvant in conjunction with ionizing radiation to target cancer cells while preventing damage to normal cells. Hyperbranched polyamidoamine (PAMAM) was grafted onto the surface of amorphous silica nanoparticles to functionalize them. The PAMAM-coated silica nanoparticles (PCSNs) were then conjugated with fluorescent dyes. Anti-HER2 antibodies were covalently attached to the labeled PCSNs. The HER2-overexpressing SK-BR3 breast cancer cell line was incubated in medium containing the PCSN probes. After incubation; the cells were exposed to X-ray radiation. Cells were counted in all samples using cell proliferation assays; and apoptotic cells were detected. The cell survival results showed that the combination of the targeted PCSN probes and radiation reduced the survival rate of SK-BR3 cells to a greater extent than when either PCSN probes, PCSNs or radiation were applied individually. The results also showed an increase in apoptosis in the SK-BR3 cells that internalized the PCSN probes and were then irradiated. Based on these data, PCSN probes act as specific radiosensitizing agents for HER2-overexpressing cells. Full article
(This article belongs to the collection Bioactive Nanoparticles)
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Open AccessReview Amino Acid Transporters and Glutamine Metabolism in Breast Cancer
Int. J. Mol. Sci. 2018, 19(3), 907; https://doi.org/10.3390/ijms19030907
Received: 6 February 2018 / Revised: 15 March 2018 / Accepted: 18 March 2018 / Published: 19 March 2018
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Abstract
Amino acid transporters are membrane transport proteins, most of which are members of the solute carrier families. Amino acids are essential for the survival of all types of cells, including tumor cells, which have an increased demand for nutrients to facilitate proliferation and
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Amino acid transporters are membrane transport proteins, most of which are members of the solute carrier families. Amino acids are essential for the survival of all types of cells, including tumor cells, which have an increased demand for nutrients to facilitate proliferation and cancer progression. Breast cancer is the most common malignancy in women worldwide and is still associated with high mortality rates, despite improved treatment strategies. Recent studies have demonstrated that the amino acid metabolic pathway is altered in breast cancer and that amino acid transporters affect tumor growth and progression. In breast cancer, glutamine is one of the key nutrients, and glutamine metabolism is closely related to the amino acid transporters. In this review, we focus on amino acid transporters and their roles in breast cancer. We also highlight the different subsets of upregulated amino acid transporters in breast cancer and discuss their potential applications as treatment targets, cancer imaging tracers, and drug delivery components. Glutamine metabolism as well as its regulation and therapeutic implication in breast cancer are also discussed. Full article
(This article belongs to the Special Issue Amino Acids Transport and Metabolism)
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