Next Issue
Previous Issue

E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Table of Contents

Int. J. Mol. Sci., Volume 19, Issue 1 (January 2018)

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
Cover Story (view full-size image) The enteric nervous system consists of more neurons than the spinal cord. These neurons generate [...] Read more.
View options order results:
result details:
Displaying articles 1-316
Export citation of selected articles as:
Open AccessArticle Comparative Genomics of the Balsaminaceae Sister Genera Hydrocera triflora and Impatiens pinfanensis
Int. J. Mol. Sci. 2018, 19(1), 319; https://doi.org/10.3390/ijms19010319
Received: 21 December 2017 / Revised: 13 January 2018 / Accepted: 15 January 2018 / Published: 23 January 2018
Cited by 4 | PDF Full-text (2608 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The family Balsaminaceae, which consists of the economically important genus Impatiens and the monotypic genus Hydrocera, lacks a reported or published complete chloroplast genome sequence. Therefore, chloroplast genome sequences of the two sister genera are significant to give insight into the phylogenetic
[...] Read more.
The family Balsaminaceae, which consists of the economically important genus Impatiens and the monotypic genus Hydrocera, lacks a reported or published complete chloroplast genome sequence. Therefore, chloroplast genome sequences of the two sister genera are significant to give insight into the phylogenetic position and understanding the evolution of the Balsaminaceae family among the Ericales. In this study, complete chloroplast (cp) genomes of Impatiens pinfanensis and Hydrocera triflora were characterized and assembled using a high-throughput sequencing method. The complete cp genomes were found to possess the typical quadripartite structure of land plants chloroplast genomes with double-stranded molecules of 154,189 bp (Impatiens pinfanensis) and 152,238 bp (Hydrocera triflora) in length. A total of 115 unique genes were identified in both genomes, of which 80 are protein-coding genes, 31 are distinct transfer RNA (tRNA) and four distinct ribosomal RNA (rRNA). Thirty codons, of which 29 had A/T ending codons, revealed relative synonymous codon usage values of >1, whereas those with G/C ending codons displayed values of <1. The simple sequence repeats comprise mostly the mononucleotide repeats A/T in all examined cp genomes. Phylogenetic analysis based on 51 common protein-coding genes indicated that the Balsaminaceae family formed a lineage with Ebenaceae together with all the other Ericales. Full article
(This article belongs to the Special Issue Chloroplast)
Figures

Figure 1

Open AccessArticle Affinity Purification and Comparative Biosensor Analysis of Citrulline-Peptide-Specific Antibodies in Rheumatoid Arthritis
Int. J. Mol. Sci. 2018, 19(1), 326; https://doi.org/10.3390/ijms19010326
Received: 30 December 2017 / Revised: 15 January 2018 / Accepted: 17 January 2018 / Published: 22 January 2018
PDF Full-text (4391 KB) | HTML Full-text | XML Full-text
Abstract
Background: In rheumatoid arthritis (RA), anti-citrullinated protein/peptide antibodies (ACPAs) are responsible for disease onset and progression, however, our knowledge is limited on ligand binding affinities of autoantibodies with different citrulline-peptide specificity. Methods: Citrulline-peptide-specific ACPA IgGs were affinity purified and tested by ELISA. Binding
[...] Read more.
Background: In rheumatoid arthritis (RA), anti-citrullinated protein/peptide antibodies (ACPAs) are responsible for disease onset and progression, however, our knowledge is limited on ligand binding affinities of autoantibodies with different citrulline-peptide specificity. Methods: Citrulline-peptide-specific ACPA IgGs were affinity purified and tested by ELISA. Binding affinities of ACPA IgGs and serum antibodies were compared by surface plasmon resonance (SPR) analysis. Bifunctional nanoparticles harboring a multi-epitope citrulline-peptide and a complement-activating peptide were used to induce selective depletion of ACPA-producing B cells. Results: KD values of affinity-purified ACPA IgGs varied between 10−6 and 10−8 M and inversely correlated with disease activity. Based on their cross-reaction with citrulline-peptides, we designed a novel multi-epitope peptide, containing Cit-Gly and Ala-Cit motifs in two–two copies, separated with a short, neutral spacer. This peptide detected antibodies in RA sera with 66% sensitivity and 98% specificity in ELISA and was recognized by 90% of RA sera, while none of the healthy samples in SPR. When coupled to nanoparticles, the multi-epitope peptide specifically targeted and depleted ACPA-producing B cells ex vivo. Conclusions: The unique multi-epitope peptide designed based on ACPA cross-reactivity might be suitable to develop better diagnostics and novel therapies for RA. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases Therapy)
Figures

Graphical abstract

Open AccessReview Heat Shock Proteins and Autophagy Pathways in Neuroprotection: From Molecular Bases to Pharmacological Interventions
Int. J. Mol. Sci. 2018, 19(1), 325; https://doi.org/10.3390/ijms19010325
Received: 22 December 2017 / Revised: 15 January 2018 / Accepted: 18 January 2018 / Published: 22 January 2018
Cited by 1 | PDF Full-text (2232 KB) | HTML Full-text | XML Full-text
Abstract
Neurodegenerative diseases (NDDs) such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease (HD), amyotrophic lateral sclerosis, and prion diseases are all characterized by the accumulation of protein aggregates (amyloids) into inclusions and/or plaques. The ubiquitous presence of amyloids in NDDs suggests the involvement
[...] Read more.
Neurodegenerative diseases (NDDs) such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease (HD), amyotrophic lateral sclerosis, and prion diseases are all characterized by the accumulation of protein aggregates (amyloids) into inclusions and/or plaques. The ubiquitous presence of amyloids in NDDs suggests the involvement of disturbed protein homeostasis (proteostasis) in the underlying pathomechanisms. This review summarizes specific mechanisms that maintain proteostasis, including molecular chaperons, the ubiquitin-proteasome system (UPS), endoplasmic reticulum associated degradation (ERAD), and different autophagic pathways (chaperon mediated-, micro-, and macro-autophagy). The role of heat shock proteins (Hsps) in cellular quality control and degradation of pathogenic proteins is reviewed. Finally, putative therapeutic strategies for efficient removal of cytotoxic proteins from neurons and design of new therapeutic targets against the progression of NDDs are discussed. Full article
(This article belongs to the collection Neuroprotective Strategies)
Figures

Figure 1

Open AccessArticle Overall Survival of Ovarian Cancer Patients Is Determined by Expression of Galectins-8 and -9
Int. J. Mol. Sci. 2018, 19(1), 323; https://doi.org/10.3390/ijms19010323
Received: 28 November 2017 / Revised: 16 January 2018 / Accepted: 18 January 2018 / Published: 22 January 2018
PDF Full-text (1265 KB) | HTML Full-text | XML Full-text
Abstract
The evaluation of new prognostic factors that can be targeted in ovarian cancer diagnosis and therapy is of the utmost importance. Galectins are a family of carbohydrate binding proteins with various implications in cancer biology. In this study, the presence of galectin (Gal)-8
[...] Read more.
The evaluation of new prognostic factors that can be targeted in ovarian cancer diagnosis and therapy is of the utmost importance. Galectins are a family of carbohydrate binding proteins with various implications in cancer biology. In this study, the presence of galectin (Gal)-8 and -9 was investigated in 156 ovarian cancer samples using immunohistochemistry (IHC). Staining was evaluated using semi-quantitative immunoreactivity (IR) scores and correlated to clinical and pathological data. Different types of galectin expression were compared with respect to disease-free survival (DFS) and overall survival (OS). Gal-8 served as a new positive prognostic factor for the OS and DFS of ovarian cancer patients. Gal-9 expression determined the DFS and OS of ovarian cancer patients in two opposing ways—moderate Gal-9 expression was correlated with a reduced outcome as compared to Gal-9 negative cases, while patients with high Gal-9 expression showed the best outcome. Full article
(This article belongs to the Special Issue Galectins in Cancer and Translational Medicine)
Figures

Graphical abstract

Open AccessReview Role of 3-Hydroxy Fatty Acid-Induced Hepatic Lipotoxicity in Acute Fatty Liver of Pregnancy
Int. J. Mol. Sci. 2018, 19(1), 322; https://doi.org/10.3390/ijms19010322
Received: 1 January 2018 / Revised: 16 January 2018 / Accepted: 16 January 2018 / Published: 22 January 2018
PDF Full-text (1609 KB) | HTML Full-text | XML Full-text
Abstract
Acute fatty liver of pregnancy (AFLP), a catastrophic illness for both the mother and the unborn offspring, develops in the last trimester of pregnancy with significant maternal and perinatal mortality. AFLP is also recognized as an obstetric and medical emergency. Maternal AFLP is
[...] Read more.
Acute fatty liver of pregnancy (AFLP), a catastrophic illness for both the mother and the unborn offspring, develops in the last trimester of pregnancy with significant maternal and perinatal mortality. AFLP is also recognized as an obstetric and medical emergency. Maternal AFLP is highly associated with a fetal homozygous mutation (1528G>C) in the gene that encodes for mitochondrial long-chain hydroxy acyl-CoA dehydrogenase (LCHAD). The mutation in LCHAD results in the accumulation of 3-hydroxy fatty acids, such as 3-hydroxy myristic acid, 3-hydroxy palmitic acid and 3-hydroxy dicarboxylic acid in the placenta, which are then shunted to the maternal circulation leading to the development of acute liver injury observed in patients with AFLP. In this review, we will discuss the mechanistic role of increased 3-hydroxy fatty acid in causing lipotoxicity to the liver and in inducing oxidative stress, mitochondrial dysfunction and hepatocyte lipoapoptosis. Further, we also review the role of 3-hydroxy fatty acids in causing placental damage, pancreatic islet β-cell glucolipotoxicity, brain damage, and retinal epithelial cells lipoapoptosis in patients with LCHAD deficiency. Full article
(This article belongs to the Special Issue Hepatotoxicity: Molecular Mechanisms and Pathophysiology)
Figures

Graphical abstract

Open AccessCommunication Identification of a Rare Germline Heterozygous Deletion Involving the Polycistronic miR-17–92 Cluster in Two First-Degree Relatives from a BRCA 1/2 Negative Chilean Family with Familial Breast Cancer: Possible Functional Implications
Int. J. Mol. Sci. 2018, 19(1), 321; https://doi.org/10.3390/ijms19010321
Received: 10 November 2017 / Revised: 11 January 2018 / Accepted: 18 January 2018 / Published: 22 January 2018
PDF Full-text (2951 KB) | HTML Full-text | XML Full-text
Abstract
Micro-RNAs (miRNAs) have emerged as novel gene expression regulators. Recent evidence strongly suggests a role for miRNAs in a large variety of cancer-related pathways. Different studies have shown that 18.7 to 37% of all human miRNA genes are clustered. miR-17–92 polycistronic cluster overexpression
[...] Read more.
Micro-RNAs (miRNAs) have emerged as novel gene expression regulators. Recent evidence strongly suggests a role for miRNAs in a large variety of cancer-related pathways. Different studies have shown that 18.7 to 37% of all human miRNA genes are clustered. miR-17–92 polycistronic cluster overexpression is associated with human hematolymphoid and solid malignancies including breast cancer (BC). Here, we report the identification of rs770419845, a rare 6 bp deletion located within the polycistronic miR-17–92 cluster, in two first-degree relatives from a Chilean family with familial BC and negative for point mutations in BRCA 1/2 genes. The deletion was identified by Sanger sequencing when 99 BRCA1/2 mutation-negative BC cases with a strong family history were initially screened. In silico analysis predicts that rs770419845 affects the secondary structure and stability of the pre-miR-17–pre-miR-18 region and the entire 17–92 cluster. The deletion was screened in 458 high-risk BRCA1/2-negative Chilean families and 480 controls. rs770419845 was not detected in any control but identified in a single family with two cases of BC and other cancers. Both BC cases, the mother and her daughter, carried the deletion. Based on bioinformatic analyses, the location of the deletion and its low frequency, we presume rs770419845 may be a pathogenic variant. Functional studies are needed to support this hypothesis. Full article
(This article belongs to the collection Advances in Molecular Oncology)
Figures

Graphical abstract

Open AccessReview Hereditary Fibrinogen Aα-Chain Amyloidosis in Asia: Clinical and Molecular Characteristics
Int. J. Mol. Sci. 2018, 19(1), 320; https://doi.org/10.3390/ijms19010320
Received: 26 December 2017 / Revised: 18 January 2018 / Accepted: 19 January 2018 / Published: 22 January 2018
PDF Full-text (1607 KB) | HTML Full-text | XML Full-text
Abstract
Hereditary fibrinogen Aα-chain amyloidosis (Aα-chain amyloidosis) is a type of autosomal dominant systemic amyloidosis caused by mutations in fibrinogen Aα-chain gene (FGA). Patients with Aα-chain amyloidosis have been mainly reported in Western countries but have been rarely reported in
[...] Read more.
Hereditary fibrinogen Aα-chain amyloidosis (Aα-chain amyloidosis) is a type of autosomal dominant systemic amyloidosis caused by mutations in fibrinogen Aα-chain gene (FGA). Patients with Aα-chain amyloidosis have been mainly reported in Western countries but have been rarely reported in Asia, with only five patients with Aα-chain amyloidosis being reported in Korea, China, and Japan. Clinically, the most prominent manifestation in Asian patients with Aα-chain amyloidosis is progressive nephropathy caused by excessive amyloid deposition in the glomeruli, which is similar to that observed in patients with Aα-chain amyloidosis in Western countries. In molecular features in Asian Aα-chain amyloidosis, the most common variant, E526V, was found in only one Chinese kindred, and other four kindred each had a different variant, which have not been identified in other countries. These variants are located in the C-terminal region (amino acid residues 517–555) of mature Aα-chain, which was similar to that observed in patients with Aα-chain amyloidosis in other countries. The precise number of Asian patients with Aα-chain amyloidosis is unclear. However, patients with Aα-chain amyloidosis do exist in Asian countries, and the majority of these patients may be diagnosed with other types of systemic amyloidosis. Full article
(This article belongs to the Special Issue Genetic Basis of Fibrinogen Disorders)
Figures

Figure 1

Open AccessReview Microglia and Aging: The Role of the TREM2–DAP12 and CX3CL1-CX3CR1 Axes
Int. J. Mol. Sci. 2018, 19(1), 318; https://doi.org/10.3390/ijms19010318
Received: 20 November 2017 / Revised: 17 January 2018 / Accepted: 18 January 2018 / Published: 22 January 2018
Cited by 3 | PDF Full-text (2924 KB) | HTML Full-text | XML Full-text
Abstract
Depending on the species, microglial cells represent 5–20% of glial cells in the adult brain. As the innate immune effector of the brain, microglia are involved in several functions: regulation of inflammation, synaptic connectivity, programmed cell death, wiring and circuitry formation, phagocytosis of
[...] Read more.
Depending on the species, microglial cells represent 5–20% of glial cells in the adult brain. As the innate immune effector of the brain, microglia are involved in several functions: regulation of inflammation, synaptic connectivity, programmed cell death, wiring and circuitry formation, phagocytosis of cell debris, and synaptic pruning and sculpting of postnatal neural circuits. Moreover, microglia contribute to some neurodevelopmental disorders such as Nasu-Hakola disease (NHD), and to aged-associated neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and others. There is evidence that human and rodent microglia may become senescent. This event determines alterations in the microglia activation status, associated with a chronic inflammation phenotype and with the loss of neuroprotective functions that lead to a greater susceptibility to the neurodegenerative diseases of aging. In the central nervous system (CNS), Triggering Receptor Expressed on Myeloid Cells 2-DNAX activation protein 12 (TREM2-DAP12) is a signaling complex expressed exclusively in microglia. As a microglial surface receptor, TREM2 interacts with DAP12 to initiate signal transduction pathways that promote microglial cell activation, phagocytosis, and microglial cell survival. Defective TREM2-DAP12 functions play a central role in the pathogenesis of several diseases. The CX3CL1 (fractalkine)-CX3CR1 signaling represents the most important communication channel between neurons and microglia. The expression of CX3CL1 in neurons and of its receptor CX3CR1 in microglia determines a specific interaction, playing fundamental roles in the regulation of the maturation and function of these cells. Here, we review the role of the TREM2-DAP12 and CX3CL1-CX3CR1 axes in aged microglia and the involvement of these pathways in physiological CNS aging and in age-associated neurodegenerative diseases. Full article
(This article belongs to the Special Issue Microglia in Aging and Neurodegenerative Disease)
Figures

Figure 1

Open AccessReview Human MHC-II with Shared Epitope Motifs Are Optimal Epstein-Barr Virus Glycoprotein 42 Ligands—Relation to Rheumatoid Arthritis
Int. J. Mol. Sci. 2018, 19(1), 317; https://doi.org/10.3390/ijms19010317
Received: 30 December 2017 / Revised: 15 January 2018 / Accepted: 17 January 2018 / Published: 21 January 2018
Cited by 1 | PDF Full-text (958 KB) | HTML Full-text | XML Full-text
Abstract
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder of unknown etiology, which is characterized by inflammation in the synovium and joint damage. Although the pathogenesis of RA remains to be determined, a combination of environmental (e.g., viral infections) and genetic factors influence
[...] Read more.
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder of unknown etiology, which is characterized by inflammation in the synovium and joint damage. Although the pathogenesis of RA remains to be determined, a combination of environmental (e.g., viral infections) and genetic factors influence disease onset. Especially genetic factors play a vital role in the onset of disease, as the heritability of RA is 50–60%, with the human leukocyte antigen (HLA) alleles accounting for at least 30% of the overall genetic risk. Some HLA-DR alleles encode a conserved sequence of amino acids, referred to as the shared epitope (SE) structure. By analyzing the structure of a HLA-DR molecule in complex with Epstein-Barr virus (EBV), the SE motif is suggested to play a vital role in the interaction of MHC II with the viral glycoprotein (gp) 42, an essential entry factor for EBV. EBV has been repeatedly linked to RA by several lines of evidence and, based on several findings, we suggest that EBV is able to induce the onset of RA in predisposed SE-positive individuals, by promoting entry of B-cells through direct contact between SE and gp42 in the entry complex. Full article
(This article belongs to the Special Issue Research of Pathogenesis and Novel Therapeutics in Arthritis)
Figures

Figure 1

Open AccessArticle Effects of Exogenous Melatonin on Methyl Viologen-Mediated Oxidative Stress in Apple Leaf
Int. J. Mol. Sci. 2018, 19(1), 316; https://doi.org/10.3390/ijms19010316
Received: 21 November 2017 / Revised: 10 January 2018 / Accepted: 17 January 2018 / Published: 21 January 2018
PDF Full-text (2707 KB) | HTML Full-text | XML Full-text
Abstract
Oxidative stress is a major source of damage of plants exposed to adverse environments. We examined the effect of exogenous melatonin (MT) in limiting of oxidative stress caused by methyl viologen (MV; paraquatin) in apple leaves (Malus domestica Borkh.). When detached leaves
[...] Read more.
Oxidative stress is a major source of damage of plants exposed to adverse environments. We examined the effect of exogenous melatonin (MT) in limiting of oxidative stress caused by methyl viologen (MV; paraquatin) in apple leaves (Malus domestica Borkh.). When detached leaves were pre-treated with melatonin, their level of stress tolerance increased. Under MV treatment, melatonin effectively alleviated the decrease in chlorophyll concentrations and maximum potential Photosystem II efficiency while also mitigating membrane damage and lipid peroxidation when compared with control leaves that were sprayed only with water prior to the stress experiment. The melatonin-treated leaves also showed higher activities and transcripts of antioxidant enzymes superoxide dismutase, peroxidase, and catalase. In addition, the expression of genes for those enzymes was upregulated. Melatonin-synthesis genes MdTDC1, MdT5H4, MdAANAT2, and MdASMT1 were also upregulated under oxidative stress in leaves but that expression was suppressed in response to 1 mM melatonin pretreatment during the MV treatments. Therefore, we conclude that exogenous melatonin mitigates the detrimental effects of oxidative stress, perhaps by slowing the decline in chlorophyll concentrations, moderating membrane damage and lipid peroxidation, increasing the activities of antioxidant enzymes, and changing the expression of genes for melatonin synthesis. Full article
(This article belongs to the Section Molecular Plant Sciences)
Figures

Figure 1

Open AccessReview Endothelium-Dependent Hyperpolarization (EDH) in Hypertension: The Role of Endothelial Ion Channels
Int. J. Mol. Sci. 2018, 19(1), 315; https://doi.org/10.3390/ijms19010315
Received: 25 December 2017 / Revised: 18 January 2018 / Accepted: 19 January 2018 / Published: 21 January 2018
Cited by 1 | PDF Full-text (1463 KB) | HTML Full-text | XML Full-text
Abstract
Upon stimulation with agonists and shear stress, the vascular endothelium of different vessels selectively releases several vasodilator factors such as nitric oxide and prostacyclin. In addition, vascular endothelial cells of many vessels regulate the contractility of the vascular smooth muscle cells through the
[...] Read more.
Upon stimulation with agonists and shear stress, the vascular endothelium of different vessels selectively releases several vasodilator factors such as nitric oxide and prostacyclin. In addition, vascular endothelial cells of many vessels regulate the contractility of the vascular smooth muscle cells through the generation of endothelium-dependent hyperpolarization (EDH). There is a general consensus that the opening of small- and intermediate-conductance Ca2+-activated K+ channels (SKCa and IKCa) is the initial mechanistic step for the generation of EDH. In animal models and humans, EDH and EDH-mediated relaxations are impaired during hypertension, and anti-hypertensive treatments restore such impairments. However, the underlying mechanisms of reduced EDH and its improvement by lowering blood pressure are poorly understood. Emerging evidence suggests that alterations of endothelial ion channels such as SKCa channels, inward rectifier K+ channels, Ca2+-activated Cl channels, and transient receptor potential vanilloid type 4 channels contribute to the impaired EDH during hypertension. In this review, we attempt to summarize the accumulating evidence regarding the pathophysiological role of endothelial ion channels, focusing on their relationship with EDH during hypertension. Full article
(This article belongs to the Special Issue Ion Transporters and Channels in Physiology and Pathophysiology)
Figures

Figure 1

Open AccessReview Deregulation of Frizzled Receptors in Hepatocellular Carcinoma
Int. J. Mol. Sci. 2018, 19(1), 313; https://doi.org/10.3390/ijms19010313
Received: 22 December 2017 / Revised: 14 January 2018 / Accepted: 19 January 2018 / Published: 21 January 2018
PDF Full-text (517 KB) | HTML Full-text | XML Full-text
Abstract
G protein-coupled receptors (GPCRs) have a substantial role in tumorigenesis and are described as a “cancer driver”. Aberrant expression or activation of GPCRs leads to the deregulation of downstream signaling pathways, thereby promoting cancer progression. In hepatocellular carcinoma (HCC), the Wnt signaling pathway
[...] Read more.
G protein-coupled receptors (GPCRs) have a substantial role in tumorigenesis and are described as a “cancer driver”. Aberrant expression or activation of GPCRs leads to the deregulation of downstream signaling pathways, thereby promoting cancer progression. In hepatocellular carcinoma (HCC), the Wnt signaling pathway is frequently activated and it is associated with an aggressive HCC phenotype. Frizzled (FZD) receptors, a family member of GPCRs, are known to mediate Wnt signaling. Accumulating findings have revealed the deregulation of FZD receptors in HCC and their functional roles have been implicated in HCC progression. Given the important role of FZD receptors in HCC, we summarize here the expression pattern of FZD receptors in HCC and their corresponding functional roles during HCC progression. We also further review and highlight the potential targeting of FZD receptors as an alternative therapeutic strategy in HCC. Full article
(This article belongs to the Special Issue Cancer-Driver G Protein-Coupled Receptors as Therapeutic Targets)
Figures

Figure 1

Open AccessArticle In Vitro Antitumor Activity of Aloperine on Human Thyroid Cancer Cells through Caspase-Dependent Apoptosis
Int. J. Mol. Sci. 2018, 19(1), 312; https://doi.org/10.3390/ijms19010312
Received: 30 November 2017 / Revised: 4 January 2018 / Accepted: 17 January 2018 / Published: 21 January 2018
PDF Full-text (5291 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The global incidence of thyroid cancer, one of the most common endocrine malignancies, is especially high among women. Although most patients with thyroid cancers exhibit a good prognosis with standard treatment, there are no effective therapies for patients with anaplastic thyroid cancers or
[...] Read more.
The global incidence of thyroid cancer, one of the most common endocrine malignancies, is especially high among women. Although most patients with thyroid cancers exhibit a good prognosis with standard treatment, there are no effective therapies for patients with anaplastic thyroid cancers or cancers that have reached an advanced or recurrent level. Therefore, it is important to develop highly effective compounds for treating such patients. Aloperine, a natural compound isolated from Sophora alopecuroides, has been reported to possess antioxidant, anti-inflammatory, anti-neuronal injury, anti-renal injury, antitumor, anti-allergic, and antiviral properties. In this study, we show that aloperine can inhibit cell growth in human anaplastic thyroid cancers and multidrug-resistant papillary thyroid cancers. Moreover, it could suppress in vitro tumorigenesis and promote cellular apoptosis. Further analysis demonstrated the involvement of caspase-dependent apoptosis, including intrinsic and/or extrinsic pathways, in aloperine-induced cellular apoptosis. However, cell cycle regulation was not detected with aloperine treatment. This study suggests the potential therapeutic use of aloperine in human anaplastic thyroid cancers and multidrug-resistant papillary thyroid cancers. Full article
(This article belongs to the collection Programmed Cell Death and Apoptosis)
Figures

Figure 1

Open AccessReview Chondrosarcoma: A Rare Misfortune in Aging Human Cartilage? The Role of Stem and Progenitor Cells in Proliferation, Malignant Degeneration and Therapeutic Resistance
Int. J. Mol. Sci. 2018, 19(1), 311; https://doi.org/10.3390/ijms19010311
Received: 16 December 2017 / Revised: 7 January 2018 / Accepted: 18 January 2018 / Published: 21 January 2018
PDF Full-text (3155 KB) | HTML Full-text | XML Full-text
Abstract
Unlike other malignant bone tumors including osteosarcomas and Ewing sarcomas with a peak incidence in adolescents and young adults, conventional and dedifferentiated chondrosarcomas mainly affect people in the 4th to 7th decade of life. To date, the cell type of chondrosarcoma origin is
[...] Read more.
Unlike other malignant bone tumors including osteosarcomas and Ewing sarcomas with a peak incidence in adolescents and young adults, conventional and dedifferentiated chondrosarcomas mainly affect people in the 4th to 7th decade of life. To date, the cell type of chondrosarcoma origin is not clearly defined. However, it seems that mesenchymal stem and progenitor cells (MSPC) in the bone marrow facing a pro-proliferative as well as predominantly chondrogenic differentiation milieu, as is implicated in early stage osteoarthritis (OA) at that age, are the source of chondrosarcoma genesis. But how can MSPC become malignant? Indeed, only one person in 1,000,000 will develop a chondrosarcoma, whereas the incidence of OA is a thousandfold higher. This means a rare coincidence of factors allowing escape from senescence and apoptosis together with induction of angiogenesis and migration is needed to generate a chondrosarcoma. At early stages, chondrosarcomas are still assumed to be an intermediate type of tumor which rarely metastasizes. Unfortunately, advanced stages show a pronounced resistance both against chemo- and radiation-therapy and frequently metastasize. In this review, we elucidate signaling pathways involved in the genesis and therapeutic resistance of chondrosarcomas with a focus on MSPC compared to signaling in articular cartilage (AC). Full article
(This article belongs to the Special Issue Current Advances in Soft Tissue and Bone Sarcoma)
Figures

Graphical abstract

Open AccessArticle Abscisic Acid (ABA ) Promotes the Induction and Maintenance of Pear (Pyrus pyrifolia White Pear Group) Flower Bud Endodormancy
Int. J. Mol. Sci. 2018, 19(1), 310; https://doi.org/10.3390/ijms19010310
Received: 3 December 2017 / Revised: 14 January 2018 / Accepted: 16 January 2018 / Published: 20 January 2018
Cited by 2 | PDF Full-text (3362 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Dormancy is an adaptive mechanism that allows temperate deciduous plants to survive unfavorable winter conditions. In the present work, we investigated the possible function of abscisic acid (ABA) on the endodormancy process in pear. The ABA content increased during pear flower bud endodormancy
[...] Read more.
Dormancy is an adaptive mechanism that allows temperate deciduous plants to survive unfavorable winter conditions. In the present work, we investigated the possible function of abscisic acid (ABA) on the endodormancy process in pear. The ABA content increased during pear flower bud endodormancy establishment and decreased towards endodormancy release. In total, 39 putative genes related to ABA metabolism and signal transductions were identified from pear genome. During the para- to endodormancy transition, PpNCED-2 and PpNCED-3 had high expression levels, while PpCYP707As expression levels were low. However, during endodormancy, the expression of PpCYP707A-3 sharply increased with increasing cold accumulation. At the same time, the ABA content of pear buds declined, and the percentage of bud breaks rapidly increased. On the other hand, the expression levels of PpPYLs, PpPP2Cs, PpSnRK2s, and PpABI4/ABI5s were also changed during the pear flower bud dormancy cycle. Furthermore, exogenous ABA application to para-dormant buds significantly reduced the bud breaks and accelerated the transition to endodormancy. During the whole treatment time, the expression level of PpPP2C-12 decreased to a greater extent in ABA-treated buds than in control. However, the expression levels of PpSnRK2-1, PpSnRK2-4, and PpABI5-1 were higher in ABA-treated buds. Our results indicated that PpCYP707A-3 and PpNCEDs play pivotal roles on the regulation of endodormancy release, while ABA signal transduction pathway also appears to be involved in the process. The present work provided the basic information about the function of ABA-related genes during pear flower bud dormancy process. Full article
Figures

Graphical abstract

Back to Top