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International Journal of Molecular Sciences (ISSN 1422-0067; CODEN: IJMCFK; ISSN 1661-6596 for printed edition) is an international peer-reviewed open access journal providing an advanced forum for biochemistry, molecular and cell biology, and molecular biophysics, and is published monthly online by MDPI. The Australian Society of Plant Scientists (ASPS) and Epigenetics Society are affiliated with IJMS and their members receive a discount on the article processing charges.
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Impact Factor: 3.687 (2017) ; 5-Year Impact Factor: 3.878 (2017)
Latest Articles
Ginsenoside Rg1 Prevents Doxorubicin-Induced Cardiotoxicity through the Inhibition of Autophagy and Endoplasmic Reticulum Stress in Mice
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Int. J. Mol. Sci. 2018, 19(11), 3658; https://doi.org/10.3390/ijms19113658 (registering DOI) - 20 November 2018
Abstract
Ginsenoside Rg1, a saponin that is a primary component of ginseng, has been demonstrated to protect hearts from diverse cardiovascular diseases with regulating multiple cellular signal pathways. In the present study, we investigated the protective role of ginsenoside Rg1 on doxorubicin-induced cardiotoxicity and
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Ginsenoside Rg1, a saponin that is a primary component of ginseng, has been demonstrated to protect hearts from diverse cardiovascular diseases with regulating multiple cellular signal pathways. In the present study, we investigated the protective role of ginsenoside Rg1 on doxorubicin-induced cardiotoxicity and its effects on endoplasmic reticulum stress and autophagy. After pre-treatment with ginsenoside Rg1 (50 mg/kg i.g.) for 7 days, male C57BL/6J mice were intraperitoneally injected with a single dose of doxorubicin (6 mg/kg) every 3 days for four injections. Echocardiographic and pathological findings showed that ginsenoside Rg1 could significantly reduce the cardiotoxicity induced by doxorubicin. Ginsenoside Rg1 significantly inhibited doxorubicin-induced formation of autophagosome. At the same time, ginsenoside Rg1 decreased the doxorubicin-induced cardiac microtubule-associated protein-light chain 3 and autophagy related 5 expression. Ginsenoside Rg1 can reduce endoplasmic reticulum dilation caused by doxorubicin. Compared with the doxorubicin group, the expression of cleaved activating transcription factor 6 and inositol-requiring enzyme 1 decreased in group ginsenoside Rg1. Treatment with ginsenoside Rg1 reduces the expression of TIF1 and increases the expression of glucose-regulated protein 78. In the ginsenoside Rg1 group, the expression of p-P70S6K, c-Jun N-terminal kinases 1 and Beclin1 declined. These results indicate that ginsenoside Rg1 may improve doxorubicin-induced cardiac dysfunction by inhibiting endoplasmic reticulum stress and autophagy.
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The Regulation of JNK Signaling Pathways in Cell Death through the Interplay with Mitochondrial SAB and Upstream Post-Translational Effects
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Int. J. Mol. Sci. 2018, 19(11), 3657; https://doi.org/10.3390/ijms19113657 (registering DOI) - 20 November 2018
Abstract
c-Jun-N-terminal kinase (JNK) activity plays a critical role in modulating cell death, which depends on the level and duration of JNK activation. The kinase cascade from MAPkinase kinase kinase (MAP3K) to MAPkinase kinase (MAP2K) to MAPKinase (MAPK) can be regulated by a number
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c-Jun-N-terminal kinase (JNK) activity plays a critical role in modulating cell death, which depends on the level and duration of JNK activation. The kinase cascade from MAPkinase kinase kinase (MAP3K) to MAPkinase kinase (MAP2K) to MAPKinase (MAPK) can be regulated by a number of direct and indirect post-transcriptional modifications, including acetylation, ubiquitination, phosphorylation, and their reversals. Recently, a JNK-mitochondrial SH3-domain binding protein 5 (SH3BP5/SAB)-ROS activation loop has been elucidated, which is required to sustain JNK activity. Importantly, the level of SAB expression in the outer membrane of mitochondria is a major determinant of the set-point for sustained JNK activation. SAB is a docking protein and substrate for JNK, leading to an intramitochondrial signal transduction pathway, which impairs electron transport and promotes reactive oxygen species (ROS) release to sustain the MAPK cascade.
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Auxin Controlled by Ethylene Steers Root Development
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Int. J. Mol. Sci. 2018, 19(11), 3656; https://doi.org/10.3390/ijms19113656 (registering DOI) - 20 November 2018
Abstract
Roots are important plant ground organs, which absorb water and nutrients to control plant growth and development. Phytohormones have been known to play a crucial role in the regulation of root growth, such as auxin and ethylene, which are central regulators of this
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Roots are important plant ground organs, which absorb water and nutrients to control plant growth and development. Phytohormones have been known to play a crucial role in the regulation of root growth, such as auxin and ethylene, which are central regulators of this process. Recent findings have revealed that root development and elongation regulated by ethylene are auxin dependent through alterations of auxin biosynthesis, transport and signaling. In this review, we focus on the recent advances in the study of auxin and auxin–ethylene crosstalk in plant root development, demonstrating that auxin and ethylene act synergistically to control primary root and root hair growth, but function antagonistically in lateral root formation. Moreover, ethylene modulates auxin biosynthesis, transport and signaling to fine-tune root growth and development. Thus, this review steps up the understanding of the regulation of auxin and ethylene in root growth.
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Identification, Characterization, and Expression Patterns of TCP Genes and microRNA319 in Cotton
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Int. J. Mol. Sci. 2018, 19(11), 3655; https://doi.org/10.3390/ijms19113655 (registering DOI) - 20 November 2018
Abstract
The TEOSINTE BRANCHED 1, CYCLOIDEA, and PROLIFERATING CELL FACTORS (TCP) gene family is a group of plant-specific transcription factors that have versatile functions in developmental processes and stress responses. In this study, a total of 73 TCP genes in upland cotton were identified
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The TEOSINTE BRANCHED 1, CYCLOIDEA, and PROLIFERATING CELL FACTORS (TCP) gene family is a group of plant-specific transcription factors that have versatile functions in developmental processes and stress responses. In this study, a total of 73 TCP genes in upland cotton were identified and characterizated. Phylogenetic analysis classified them into three subgroups: 50 belonged to PCF, 16 to CIN, and 7 to CYC/TB1. GhTCP genes are randomly distributed in 22 of the 26 chromosomes in cotton. Expression patterns of GhTCPs were analyzed in 10 tissues, including different developmental stages of ovule and fiber, as well as under heat, salt, and drought stresses. Transcriptome analysis showed that 44 GhTCP genes exhibited varied transcript accumulation patterns in the tested tissues and 41 GhTCP genes were differentially expressed in response to heat, salt, and drought stresses. Furthermore, three GhTCP genes of the CIN clade were found to contain miR319-binding sites. An anti-correlation expression of GhTCP21 and GhTCP54 was analyzed with miR319 under salt and drought stress. Our results lay the foundation for understanding the complex mechanisms of GhTCP-mediated developmental processes and abiotic stress-signaling transduction pathways in cotton.
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STE20/PAKA Protein Kinase Gene Releases an Autoinhibitory Domain through Pre-mRNA Alternative Splicing in the Dermatophyte Trichophyton rubrum
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Int. J. Mol. Sci. 2018, 19(11), 3654; https://doi.org/10.3390/ijms19113654 (registering DOI) - 20 November 2018
Abstract
Signaling pathways are highly diverse in filamentous fungi, allowing the cells to receive and process ambient information. Interaction of components from different pathways results in signaling networks. The mitogen-activated protein kinase (MAPK) pathway is dependent on phosphorylation that is accomplished by kinase proteins.
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Signaling pathways are highly diverse in filamentous fungi, allowing the cells to receive and process ambient information. Interaction of components from different pathways results in signaling networks. The mitogen-activated protein kinase (MAPK) pathway is dependent on phosphorylation that is accomplished by kinase proteins. Thus, the STE/PAK protein kinase family plays essential roles in MAPK signal transduction, regulating several cellular functions. The STE/PAK protein displays an autoinhibitory (Cdc42/Rac interactive binding—CRIB) domain on its N-terminal portion, which interacts with the C-terminal catalytic kinase domain. Based on current knowledge, for the STE/PAK kinase to be activated, molecular signals (e.g., interaction with the activated form of Rac1 and Cdc42 proteins) or proteolytic cleavage by caspase 3 is necessary. Both mechanisms release the kinase domain from the CRIB interaction. Here, we hypothesize a novel molecular mechanism for the activation of STE20/PAKA kinase in Trichophyton rubrum based on an alternative pre-mRNA splicing process. Our data suggest that, because of the retention of intron 1 of this gene, it is theoretically possible that the translation of STE20/PAKA kinase will be free of its autoinhibitory CRIB domain. These findings indicate a rapid response system to environmental changes. Furthermore, STE20/PAKA may be a potential T. rubrum virulence factor and an interesting target for new drugs against dermatophytes.
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Rex Retroelements and Teleost Genomes: An Overview
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Int. J. Mol. Sci. 2018, 19(11), 3653; https://doi.org/10.3390/ijms19113653 (registering DOI) - 20 November 2018
Abstract
Repetitive DNA is an intriguing portion of the genome still not completely discovered and shows a high variability in terms of sequence, genomic organization, and evolutionary mode. On the basis of the genomic organization, it includes satellite DNAs, which are organized as long
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Repetitive DNA is an intriguing portion of the genome still not completely discovered and shows a high variability in terms of sequence, genomic organization, and evolutionary mode. On the basis of the genomic organization, it includes satellite DNAs, which are organized as long arrays of head-to-tail linked repeats, and transposable elements, which are dispersed throughout the genome. These repeated elements represent a considerable fraction of vertebrate genomes contributing significantly in species evolution. In this review, we focus our attention on Rex1, Rex3 and Rex6, three elements specific of teleost genomes. We report an overview of data available on these retroelements highlighting their significative impact in chromatin and heterochromatin organization, in the differentiation of sex chromosomes, in the formation of supernumerary chromosomes, and in karyotype evolution in teleosts.
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Investigating the Role of MicroRNA and Transcription Factor Co-regulatory Networks in Multiple Sclerosis Pathogenesis
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Int. J. Mol. Sci. 2018, 19(11), 3652; https://doi.org/10.3390/ijms19113652 (registering DOI) - 20 November 2018
Abstract
MicroRNAs (miRNAs) and transcription factors (TFs) play key roles in complex multifactorial diseases like multiple sclerosis (MS). Starting from the miRNomic profile previously associated with a cohort of pediatric MS (PedMS) patients, we applied a combined molecular and computational approach in order to
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MicroRNAs (miRNAs) and transcription factors (TFs) play key roles in complex multifactorial diseases like multiple sclerosis (MS). Starting from the miRNomic profile previously associated with a cohort of pediatric MS (PedMS) patients, we applied a combined molecular and computational approach in order to verify published data in patients with adult-onset MS (AOMS). Six out of the 13 selected miRNAs (miR-320a, miR-125a-5p, miR-652-3p, miR-185-5p, miR-942-5p, miR-25-3p) were significantly upregulated in PedMS and AOMS patients, suggesting that they may be considered circulating biomarkers distinctive of the disease independently from age. A computational and unbiased miRNA-based screening of target genes not necessarily associated to MS was then performed in order to provide an extensive view of the genetic mechanisms underlying the disease. A comprehensive MS-specific miRNA-TF co-regulatory network was hypothesized; among others, SP1, RELA, NF-κB, TP53, AR, MYC, HDAC1, and STAT3 regulated the transcription of 61 targets. Interestingly, NF-κB and STAT3 cooperatively regulate the expression of immune response genes and control the cross-talk between inflammatory and immune cells. Further functional analysis will be performed on the identified critical hubs. Above all, in our view, this approach supports the need for multidisciplinary strategies for shedding light into the pathogenesis of MS.
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Mycobacterium tuberculosis ClpC1 N-Terminal Domain Is Dispensable for Adaptor Protein-Dependent Allosteric Regulation
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Int. J. Mol. Sci. 2018, 19(11), 3651; https://doi.org/10.3390/ijms19113651 (registering DOI) - 19 November 2018
Abstract
ClpC1 hexamers couple the energy of ATP hydrolysis to unfold and, subsequently, translocate specific protein substrates into the associated ClpP protease. Substrate recognition by ATPases associated with various cellular activities (AAA+) proteases is driven by the ATPase component, which selectively determines protein substrates
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ClpC1 hexamers couple the energy of ATP hydrolysis to unfold and, subsequently, translocate specific protein substrates into the associated ClpP protease. Substrate recognition by ATPases associated with various cellular activities (AAA+) proteases is driven by the ATPase component, which selectively determines protein substrates to be degraded. The specificity of these unfoldases for protein substrates is often controlled by an adaptor protein with examples that include MecA regulation of Bacillus subtilis ClpC or ClpS-mediated control of Escherichia coli ClpA. No adaptor protein-mediated control has been reported for mycobacterial ClpC1. Using pulldown and stopped-flow fluorescence methods, we report data demonstrating that Mycobacterium tuberculosis ClpC1 catalyzed unfolding of an SsrA-tagged protein is negatively impacted by association with the ClpS adaptor protein. Our data indicate that ClpS-dependent inhibition of ClpC1 catalyzed SsrA-dependent protein unfolding does not require the ClpC1 N-terminal domain but instead requires the presence of an interaction surface located in the ClpC1 Middle Domain. Taken together, our results demonstrate for the first time that mycobacterial ClpC1 is subject to adaptor protein-mediated regulation in vitro.
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Actions of Brain-Derived Neurotrophin Factor in the Neurogenesis and Neuronal Function, and Its Involvement in the Pathophysiology of Brain Diseases
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Int. J. Mol. Sci. 2018, 19(11), 3650; https://doi.org/10.3390/ijms19113650 (registering DOI) - 19 November 2018
Abstract
It is well known that brain-derived neurotrophic factor, BDNF, has an important role in a variety of neuronal aspects, such as differentiation, maturation, and synaptic function in the central nervous system (CNS). BDNF stimulates mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), phosphoinositide-3kinase (PI3K), and
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It is well known that brain-derived neurotrophic factor, BDNF, has an important role in a variety of neuronal aspects, such as differentiation, maturation, and synaptic function in the central nervous system (CNS). BDNF stimulates mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), phosphoinositide-3kinase (PI3K), and phospholipase C (PLC)-gamma pathways via activation of tropomyosin receptor kinase B (TrkB), a high affinity receptor for BDNF. Evidence has shown significant contributions of these signaling pathways in neurogenesis and synaptic plasticity in in vivo and in vitro experiments. Importantly, it has been demonstrated that dysfunction of the BDNF/TrkB system is involved in the onset of brain diseases, including neurodegenerative and psychiatric disorders. In this review, we discuss actions of BDNF and related signaling molecules on CNS neurons, and their contributions to the pathophysiology of brain diseases.
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Lactate Promotes Myoblast Differentiation and Myotube Hypertrophy via a Pathway Involving MyoD In Vitro and Enhances Muscle Regeneration In Vivo
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Int. J. Mol. Sci. 2018, 19(11), 3649; https://doi.org/10.3390/ijms19113649 (registering DOI) - 19 November 2018
Abstract
Lactate is a metabolic substrate mainly produced in muscles, especially during exercise. Recently, it was reported that lactate affects myoblast differentiation; however, the obtained results are inconsistent and the in vivo effect of lactate remains unclear. Our study thus aimed to evaluate the
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Lactate is a metabolic substrate mainly produced in muscles, especially during exercise. Recently, it was reported that lactate affects myoblast differentiation; however, the obtained results are inconsistent and the in vivo effect of lactate remains unclear. Our study thus aimed to evaluate the effects of lactate on myogenic differentiation and its underlying mechanism. The differentiation of C2C12 murine myogenic cells was accelerated in the presence of lactate and, consequently, myotube hypertrophy was achieved. Gene expression analysis of myogenic regulatory factors showed significantly increased myogenic determination protein (MyoD) gene expression in lactate-treated cells compared with that in untreated ones. Moreover, lactate enhanced gene and protein expression of myosin heavy chain (MHC). In particular, lactate increased gene expression of specific MHC isotypes, MHCIIb and IId/x, in a dose-dependent manner. Using a reporter assay, we showed that lactate increased promoter activity of the MHCIIb gene and that a MyoD binding site in the promoter region was necessary for the lactate-induced increase in activity. Finally, peritoneal injection of lactate in mice resulted in enhanced regeneration and fiber hypertrophy in glycerol-induced regenerating muscles. In conclusion, physiologically high lactate concentrations modulated muscle differentiation by regulating MyoD-associated networks, thereby enhancing MHC expression and myotube hypertrophy in vitro and, potentially, in vivo.
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Endothelial Microsomal Prostaglandin E Synthetase-1 Upregulates Vascularity and Endothelial Interleukin-1β in Deteriorative Progression of Experimental Autoimmune Encephalomyelitis
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Int. J. Mol. Sci. 2018, 19(11), 3647; https://doi.org/10.3390/ijms19113647 (registering DOI) - 19 November 2018
Abstract
Microsomal prostaglandin E synthetase-1 (mPGES-1) is an inducible terminal enzyme for the production of prostaglandin E2 (PGE2). In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mPGES-1 is induced in vascular endothelial cells (VECs) around inflammatory foci and
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Microsomal prostaglandin E synthetase-1 (mPGES-1) is an inducible terminal enzyme for the production of prostaglandin E2 (PGE2). In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mPGES-1 is induced in vascular endothelial cells (VECs) around inflammatory foci and facilitates inflammation, demyelination, and paralysis. Therefore, we investigated the role of CD31-positive VECs in mPGES-1-mediated EAE aggravation using immunohistochemical analysis and imaging of wild-type (wt) and mPGES-1-deficient (mPGES-1−/−) mice. We demonstrated that EAE induction facilitated vascularity in inflammatory lesions in the spinal cord, and this was significantly higher in wt mice than in mPGES-1−/− mice. In addition, endothelial interleukin-1β (IL-1β) production was significantly higher in wt mice than in mPGES-1−/− mice. Moreover, endothelial PGE2 receptors (E-prostanoid (EP) receptors EP1–4) were expressed after EAE induction, and IL-1β was induced in EP receptor-positive VECs. Furthermore, IL-1 receptor 1 expression on VECs was increased upon EAE induction. Thus, increased vascularity is one mechanism involved in EAE aggravation induced by mPGES-1. Furthermore, mPGES-1 facilitated the autocrine function of VECs upon EP receptor induction and IL-1β production, modulating mPGES-1 induction in EAE.
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Comparative Characterization of the Complete Mitochondrial Genomes of the Three Apple Snails (Gastropoda: Ampullariidae) and the Phylogenetic Analyses
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Int. J. Mol. Sci. 2018, 19(11), 3646; https://doi.org/10.3390/ijms19113646 (registering DOI) - 19 November 2018
Abstract
The apple snails Pomacea canaliculata, Pomacea diffusa and Pomacea maculate (Gastropoda: Caenogastropoda: Ampullariidae) are invasive pests causing massive economic losses and ecological damage. We sequenced and characterized the complete mitochondrial genomes of these snails to conduct phylogenetic analyses based on comparisons with
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The apple snails Pomacea canaliculata, Pomacea diffusa and Pomacea maculate (Gastropoda: Caenogastropoda: Ampullariidae) are invasive pests causing massive economic losses and ecological damage. We sequenced and characterized the complete mitochondrial genomes of these snails to conduct phylogenetic analyses based on comparisons with the mitochondrial protein coding sequences of 47 Caenogastropoda species. The gene arrangements, distribution and content were canonically identical and consistent with typical Mollusca except for the tRNA-Gln absent in P. diffusa. An identifiable control region (d-loop) was absent. Bayesian phylogenetic analysis indicated that all the Ampullariidae species clustered on the same branch. The genus Pomacea clustered together and then with the genus Marisa. The orders Architaenioglossa and Sorbeoconcha clustered together and then with the order Hypsogastropoda. Furthermore, the intergenic and interspecific taxonomic positions were defined. Unexpectedly, Ceraesignum maximum, Dendropoma gregarium, Eualetes tulipa and Thylacodes squamigerus, traditionally classified in order Hypsogastropoda, were isolated from the order Hypsogastropoda in the most external branch of the Bayesian inference tree. The divergence times of the Caenogastropoda indicated that their evolutionary process covered four geological epochs that included the Quaternary, Neogene, Paleogene and Cretaceous periods. This study will facilitate further investigation of species identification to aid in the implementation of effective management and control strategies of these invasive species.
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Cystine/Glutamate Antiporter and Aripiprazole Compensate NMDA Antagonist-Induced Dysfunction of Thalamocortical L-Glutamatergic Transmission
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Int. J. Mol. Sci. 2018, 19(11), 3645; https://doi.org/10.3390/ijms19113645 (registering DOI) - 19 November 2018
Abstract
To explore pathophysiology of schizophrenia, this study analyzed the regulation mechanisms that are associated with cystine/glutamate antiporter (Sxc), group-II (II-mGluR), and group-III (III-mGluR) metabotropic glutamate-receptors in thalamo-cortical glutamatergic transmission of MK801-induced model using dual-probe microdialysis. L-glutamate release in medial pre-frontal cortex (mPFC) was
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To explore pathophysiology of schizophrenia, this study analyzed the regulation mechanisms that are associated with cystine/glutamate antiporter (Sxc), group-II (II-mGluR), and group-III (III-mGluR) metabotropic glutamate-receptors in thalamo-cortical glutamatergic transmission of MK801-induced model using dual-probe microdialysis. L-glutamate release in medial pre-frontal cortex (mPFC) was increased by systemic- and local mediodorsal thalamic nucleus (MDTN) administrations of MK801, but was unaffected by local administration into mPFC. Perfusion into mPFC of activators of Sxc, II-mGluR, and III-mGluR, and into the MDTN of activators of Sxc, II-mGluR, and GABAA receptor inhibited MK801-evoked L-glutamate release in mPFC. Perfusion of aripiprazole (APZ) into MDTN and mPFC also inhibited systemic MK801-evoked L-glutamate release in mPFC. Inhibition of II-mGluR in mPFC and MDTN blocked inhibitory effects of Sxc-activator and APZ on MK801-evoked L-glutamate release; however, their inhibitory effects were blocked by the inhibition of III-mGluR in mPFC but not in MDTN. These results indicate that reduced activation of the glutamate/NMDA receptor (NMDAR) in MDTN enhanced L-glutamate release in mPFC possibly through GABAergic disinhibition in MDTN. Furthermore, MDTN-mPFC glutamatergic transmission receives inhibitory regulation of Sxc/II-mGluR/III-mGluR functional complex in mPFC and Sxc/II-mGluR complex in MDTN. Established antipsychotic, APZ inhibits MK801-evoked L-glutamate release through the activation of Sxc/mGluRs functional complexes in both MDTN and mPFC.
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Identification of Arenin, a Novel Kunitz-Like Polypeptide from the Skin Secretions of Dryophytes arenicolor
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Int. J. Mol. Sci. 2018, 19(11), 3644; https://doi.org/10.3390/ijms19113644 (registering DOI) - 19 November 2018
Abstract
Amphibian skin secretions are enriched with complex cocktails of bioactive molecules such as proteins, peptides, biogenic amines, alkaloids guanidine derivatives, steroids and other minor components spanning a wide spectrum of pharmacological actions exploited for centuries in folk medicine. This study presents evidence on
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Amphibian skin secretions are enriched with complex cocktails of bioactive molecules such as proteins, peptides, biogenic amines, alkaloids guanidine derivatives, steroids and other minor components spanning a wide spectrum of pharmacological actions exploited for centuries in folk medicine. This study presents evidence on the protein profile of the skin secretions of the canyon tree frog, Dryophytes arenicolor. At the same time, it presents the reverse-phase liquid chromatography isolation, mass spectrometry characterization and identification at mRNA level of a novel 58 amino acids Kunitz-like polypeptide from the skin secretions of Dryophytes arenicolor, arenin. Cell viability assays performed on HDFa, CaCo2 and MCF7 cells cultured with different concentrations of arenin showed a discrete effect at low concentrations (2, 4, 8 and 16 µg/mL) suggesting a multi-target interaction in a hormetic-like dose-response. Further work is required to investigate the mechanisms underlying the variable effect on cell viability produced by different concentrations of arenin.
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Molecular Mechanism for the Regulation of ABA Homeostasis During Plant Development and Stress Responses
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Int. J. Mol. Sci. 2018, 19(11), 3643; https://doi.org/10.3390/ijms19113643 (registering DOI) - 19 November 2018
Abstract
The plant hormone abscisic acid (ABA) play essential roles in numerous physiological processes such as seed dormancy, seed germination, seeding growth and responses to biotic and abiotic stresses. Such biological processes are tightly controlled by a complicated regulatory network including ABA homoeostasis, signal
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The plant hormone abscisic acid (ABA) play essential roles in numerous physiological processes such as seed dormancy, seed germination, seeding growth and responses to biotic and abiotic stresses. Such biological processes are tightly controlled by a complicated regulatory network including ABA homoeostasis, signal transduction as well as cross-talking among other signaling pathways. It is known that ABA homoeostasis modulated by its production, inactivation, and transport pathways is considered to be of great importance for plant development and stress responses. Most of the enzymes and transporters involved in ABA homoeostasis have been largely characterized and they all work synergistically to maintain ABA level in plants. Increasing evidence have suggested that transcriptional regulation of the genes involved in either ABA production or ABA inactivation plays vital roles in ABA homoeostasis. In addition to transcription factors, such progress is also regulated by microRNAs and newly characterized root to shoot mobile peptide-receptor like kinase (RLKs) mediated long-distance signal transduction. Thus, ABA contents are always kept in a dynamic balance. In this review, we survey recent research on ABA production, inactivation and transport pathways, and summarize some latest findings about the mechanisms that regulate ABA homoeostasis.
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Visfatin Promotes Wound Healing through the Activation of ERK1/2 and JNK1/2 Pathway
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Int. J. Mol. Sci. 2018, 19(11), 3642; https://doi.org/10.3390/ijms19113642 (registering DOI) - 19 November 2018
Abstract
Visfatin, a member of the adipokine family, plays an important role in many metabolic and stress responses. The mechanisms underlying the direct therapeutic effects of visfatin on wound healing have not been reported yet. In this study, we examined the effects of visfatin
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Visfatin, a member of the adipokine family, plays an important role in many metabolic and stress responses. The mechanisms underlying the direct therapeutic effects of visfatin on wound healing have not been reported yet. In this study, we examined the effects of visfatin on wound healing in vitro and in vivo. Visfatin enhanced the proliferation and migration of human dermal fibroblasts (HDFs) and keratinocytes the expression of wound healing-related vascular endothelial growth factor (VEGF) in vitro and in vivo. Treatment of HDFs with visfatin induced activation of both extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases 1 and 2 (JNK1/2) in a time-dependent manner. Inhibition of ERK1/2 and JNK1/2 led to a significant decrease in visfatin-induced proliferation and migration of HDFs. Importantly, blocking VEGF with its neutralizing antibodies suppressed the visfatin-induced proliferation and migration of HDFs and human keratinocytes, indicating that visfatin induces the proliferation and migration of HDFs and human keratinocytes via increased VEGF expression. Moreover, visfatin effectively improved wound repair in vivo, which was comparable to the wound healing activity of epidermal growth factor (EGF). Taken together, we demonstrate that visfatin promotes the proliferation and migration of HDFs and human keratinocytes by inducing VEGF expression and can be used as a potential novel therapeutic agent for wound healing.
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Structure–Activity Relationship Study of Newly Synthesized Iridium-III Complexes as Potential Series for Treating Thrombotic Diseases
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Int. J. Mol. Sci. 2018, 19(11), 3641; https://doi.org/10.3390/ijms19113641 (registering DOI) - 19 November 2018
Abstract
Platelets play a major role in hemostatic events and are associated with various pathological events, such as arterial thrombosis and atherosclerosis. Iridium (Ir) compounds are potential alternatives to platinum compounds, since they exert promising anticancer effects without cellular toxicity. Our recent studies found
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Platelets play a major role in hemostatic events and are associated with various pathological events, such as arterial thrombosis and atherosclerosis. Iridium (Ir) compounds are potential alternatives to platinum compounds, since they exert promising anticancer effects without cellular toxicity. Our recent studies found that Ir compounds show potent antiplatelet properties. In this study, we evaluated the in vitro antiplatelet, in vivo antithrombotic and structure–activity relationship (SAR) of newly synthesized Ir complexes, Ir-1, Ir-2 and Ir-4, in agonists-induced human platelets. Among the tested compounds, Ir-1 was active in inhibiting platelet aggregation induced by collagen; however, Ir-2 and Ir-4 had no effects even at their maximum concentrations of 50 μM against collagen and 500 μM against U46619-induced aggregation. Similarly, Ir-1 was potently inhibiting of adenosine triphosphate (ATP) release, calcium mobilization ([Ca2+]i) and P-selectin expression induced by collagen-induced without cytotoxicity. Likewise, Ir-1 expressively suppressed collagen-induced Akt, PKC, p38MAPKs and JNK phosphorylation. Interestingly, Ir-2 and Ir-4 had no effect on platelet function analyzer (PFA-100) collagen-adenosine diphosphate (C-ADP) and collagen-epinephrine (C-EPI) induced closure times in mice, but Ir-1 caused a significant increase when using C-ADP stimulation. Other in vivo studies revealed that Ir-1 significantly prolonged the platelet plug formation, increased tail bleeding times and reduced the mortality of adenosine diphosphate (ADP)-induced acute pulmonary thromboembolism in mice. Ir-1 has no substitution on its phenyl group, a water molecule (like cisplatin) can replace its chloride ion and, hence, the rate of hydrolysis might be tuned by the substituent on the ligand system. These features might have played a role for the observed effects of Ir-1. These results indicate that Ir-1 may be a lead compound to design new antiplatelet drugs for the treatment of thromboembolic diseases.
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Effects of Enhanced Hydrophilic Titanium Dioxide-Coated Hydroxyapatite on Bone Regeneration in Rabbit Calvarial Defects
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Int. J. Mol. Sci. 2018, 19(11), 3640; https://doi.org/10.3390/ijms19113640 (registering DOI) - 19 November 2018
Abstract
The regeneration of bone defects caused by periodontal disease or trauma is an important goal. Porous hydroxyapatite (HA) is an osteoconductive graft material. However, the hydrophobic properties of HA can be a disadvantage in the initial healing process. HA can be coated with
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The regeneration of bone defects caused by periodontal disease or trauma is an important goal. Porous hydroxyapatite (HA) is an osteoconductive graft material. However, the hydrophobic properties of HA can be a disadvantage in the initial healing process. HA can be coated with TiO2 to improve its hydrophilicity, and ultraviolet irradiation (UV) can further increase the hydrophilicity by photofunctionalization. This study was designed to evaluate the effect of 5% TiO2-coated HA on rabbit calvarial defects and compare it with that of photofunctionalization on new bone in the early stage. The following four study groups were established, negative control, HA, TiO2-coated HA, and TiO2-coated HA with UV. The animals were sacrificed and the defects were assessed by radiography as well as histologic and histomorphometric analyses. At 2 and 8 weeks postoperatively, the TiO2-coated HA with UV group and TiO2-coated HA group showed significantly higher percentages of new bone than the control group (p < 0.05). UV irradiation increased the extent of new bone formation, and there was a significant difference between the TiO2-coated HA group and TiO2-coated HA with UV group. The combination of TiO2/HA and UV irradiation in bone regeneration appears to induce a favorable response.
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Needle-Free Immunization with Chitosan-Based Systems
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Int. J. Mol. Sci. 2018, 19(11), 3639; https://doi.org/10.3390/ijms19113639 (registering DOI) - 19 November 2018
Abstract
Despite successful use, needle-based immunizations have several issues such as the risk of injuries and infections from the reuse of needles and syringes and the low patient compliance due to pain and fear of needles during immunization. In contrast, needle-free immunizations have several
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Despite successful use, needle-based immunizations have several issues such as the risk of injuries and infections from the reuse of needles and syringes and the low patient compliance due to pain and fear of needles during immunization. In contrast, needle-free immunizations have several advantages including ease of administration, high level of patient compliance and the possibility of mass vaccination. Thus, there is an increasing interest on developing effective needle-free immunizations via cutaneous and mucosal approaches. Here, we discuss several methods of needle-free immunizations and provide insights into promising use of chitosan systems for successful immunization.
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