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Int. J. Mol. Sci., Volume 19, Issue 8 (August 2018)

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Open AccessArticle Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice
Int. J. Mol. Sci. 2018, 19(8), 2428; https://doi.org/10.3390/ijms19082428 (registering DOI)
Received: 16 July 2018 / Revised: 9 August 2018 / Accepted: 15 August 2018 / Published: 17 August 2018
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Abstract
Strokes are one of the leading causes of mortality and chronic morbidity in the world, yet with only limited successful interventions available at present. Our previous studies revealed the potential role of the glucocorticoid receptor (GR) in the pathogenesis of neonatal hypoxic-ischemic encephalopathy
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Strokes are one of the leading causes of mortality and chronic morbidity in the world, yet with only limited successful interventions available at present. Our previous studies revealed the potential role of the glucocorticoid receptor (GR) in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (HIE). In the present study, we investigate the effect of GR knockdown on acute ischemic brain injuries in a model of focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) in adult male CD1 mice. GR siRNAs and the negative control were administered via intracerebroventricular (i.c.v.) injection 48 h prior to MCAO. The cerebral infarction volume and neurobehavioral deficits were determined 48 h after MCAO. RT-qPCR was employed to assess the inflammation-related gene expression profiles in the brain before and after MCAO. Western Blotting was used to evaluate the expression levels of GR, the mineralocorticoid receptor (MR) and the brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling. The siRNAs treatment decreased GR, but not MR, protein expression, and significantly enhanced expression levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in the brain. Of interest, GR knockdown suppressed BDNF/TrkB signaling in adult mice brains. Importantly, GR siRNA pretreatment significantly increased the infarction size and exacerbated the neurobehavioral deficits induced by MCAO in comparison to the control group. Thus, the present study demonstrates the important role of GR in the regulation of the inflammatory responses and neurotrophic BDNF/TrkB signaling pathway in acute ischemic brain injuries in adult mice, revealing a new insight into the pathogenesis and therapeutic potential in acute ischemic strokes. Full article
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Open AccessArticle Interaction between Tumor-Associated Dendritic Cells and Colon Cancer Cells Contributes to Tumor Progression via CXCL1
Int. J. Mol. Sci. 2018, 19(8), 2427; https://doi.org/10.3390/ijms19082427
Received: 2 July 2018 / Revised: 27 July 2018 / Accepted: 13 August 2018 / Published: 16 August 2018
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Abstract
Crosstalk of a tumor with its microenvironment is a critical factor contributing to cancer development. This study investigates the soluble factors released by tumor-associated dendritic cells (TADCs) responsible for increasing cancer stem cell (CSC) properties, cell mobility, and epithelial-to-mesenchymal transition (EMT). Dendritic cells
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Crosstalk of a tumor with its microenvironment is a critical factor contributing to cancer development. This study investigates the soluble factors released by tumor-associated dendritic cells (TADCs) responsible for increasing cancer stem cell (CSC) properties, cell mobility, and epithelial-to-mesenchymal transition (EMT). Dendritic cells (DCs) of colon cancer patients were collected for phenotype and CXCL1 expression by flow cytometry and Luminex assays. The transcriptome of CXCL1-treated cancer cells was established by next generation sequencing. Inflammatory chemokine CXCL1, present in large amounts in DCs isolated from colon cancer patients, and SW620-conditioned TADCs, enhance CSC characteristics in cancer, supported by enhanced anchorage-independent growth, CD133 expression and aldehyde dehydrogenase activity. Additionally, CXCL1 increases the metastatic ability of a cancer by enhancing cell migration, matrix metalloproteinase-7 expression and EMT. The enhanced CXCL1 expression in DCs is also noted in mice transplanted with colon cancer cells. Transcriptome analysis of CXCL1-treated SW620 cells indicates that CXCL1 increases potential oncogene expression in colon cancer, including PTHLH, TYRP1, FOXO1, TCF4 and ZNF880. Concurrently, CXCL1 displays a specific microRNA (miR) upregulated by the prototypical colon cancer onco-miR miR-105. Analysis of publicly available data reveals CXCL1-driven oncogenes and miR-105 have a negative prognostic impact on the outcome of colon cancer. This study indicates a new mechanism by which the colon cancer milieu exploits DC plasticity to support cancer progression. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Open AccessArticle Suppression of Schistosoma japonicum Acetylcholinesterase Affects Parasite Growth and Development
Int. J. Mol. Sci. 2018, 19(8), 2426; https://doi.org/10.3390/ijms19082426
Received: 31 July 2018 / Revised: 10 August 2018 / Accepted: 11 August 2018 / Published: 16 August 2018
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Abstract
To further investigate the importance of Schistosoma japonicum acetylcholinesterase (SjAChE) in cholinergic signaling for parasite growth and development, we used RNA interference (RNAi) to knock-down its expression in adults and eggs in vitro. This resulted in its reduced transcription but also expression of
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To further investigate the importance of Schistosoma japonicum acetylcholinesterase (SjAChE) in cholinergic signaling for parasite growth and development, we used RNA interference (RNAi) to knock-down its expression in adults and eggs in vitro. This resulted in its reduced transcription but also expression of other important genes involved both in cholinergic signaling and glucose uptake were impacted substantially. Significant decreases in AChE protein expression, AChE enzymatic activity, and glucose uptake were observed in the SjAChE-knockdown parasites compared with luciferase controls. In vaccine/challenge experiments, we found that immunization of mice with recombinant SjAChE (rSjAChE) expressed in Escherichia coli elicited reductions in male worm numbers (33%), liver granuloma density (41%), and reduced numbers of mature intestinal eggs (73%) in the vaccinated group compared with the control group. These results indicate AChE plays an important role in the metabolism of male worms, and impacts indirectly on female fecundity leading to increased numbers of immature eggs being released and reduced sizes of liver granulomas. Furthermore, cytokine analysis showed that immunization of mice with rSjAChE elicited a predominantly Th1-type immune response characterized by increased production of IFNγ in splenic CD4+ T cells of vaccinated mice. The study confirms the potential of SjAChE as a vaccine/drug candidate against zoonotic schistosomiasis japonica. Full article
(This article belongs to the Special Issue Nanomedicine/Molecular Medicine)
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Open AccessArticle Deacetylation of Histone H4 Accompanying Cardiomyogenesis is Weakened in HDAC1-Depleted ES Cells
Int. J. Mol. Sci. 2018, 19(8), 2425; https://doi.org/10.3390/ijms19082425
Received: 10 July 2018 / Revised: 9 August 2018 / Accepted: 14 August 2018 / Published: 16 August 2018
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Abstract
Cell differentiation into cardiomyocytes requires activation of differentiation-specific genes and epigenetic factors that contribute to these physiological processes. This study is focused on the in vitro differentiation of mouse embryonic stem cells (mESCs) induced into cardiomyocytes. The effects of clinically promising inhibitors of
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Cell differentiation into cardiomyocytes requires activation of differentiation-specific genes and epigenetic factors that contribute to these physiological processes. This study is focused on the in vitro differentiation of mouse embryonic stem cells (mESCs) induced into cardiomyocytes. The effects of clinically promising inhibitors of histone deacetylases (HDACi) on mESC cardiomyogenesis and on explanted embryonic hearts were also analyzed. HDAC1 depletion caused early beating of cardiomyocytes compared with those of the wild-type (wt) counterpart. Moreover, the adherence of embryonic bodies (EBs) was reduced in HDAC1 double knockout (dn) mESCs. The most important finding was differentiation-specific H4 deacetylation observed during cardiomyocyte differentiation of wt mESCs, while H4 deacetylation was weakened in HDAC1-depleted cells induced to the cardiac pathway. Analysis of the effect of HDACi showed that Trichostatin A (TSA) is a strong hyperacetylating agent, especially in wt mESCs, but only SAHA reduced the size of the beating areas in EBs that originated from HDAC1 dn mESCs. Additionally, explanted embryonic hearts (e15) responded to treatment with HDACi: all of the tested HDACi (TSA, SAHA, VPA) increased the levels of H3K9ac, H4ac, H4K20ac, and pan-acetylated lysines in embryonic hearts. This observation shows that explanted tissue can be maintained in a hyperacetylation state several hours after excision, which appears to be useful information from the view of transplantation strategy and the maintenance of gene upregulation via acetylation in tissue intended for transplantation. Full article
(This article belongs to the Special Issue Histone Deacetylase Inhibitors in Health and Disease)
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Open AccessReview Diffuse Gastric Cancer: A Summary of Analogous Contributing Factors for Its Molecular Pathogenicity
Int. J. Mol. Sci. 2018, 19(8), 2424; https://doi.org/10.3390/ijms19082424
Received: 4 July 2018 / Revised: 8 August 2018 / Accepted: 14 August 2018 / Published: 16 August 2018
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Abstract
Gastric cancer is the third leading cause of cancer-related deaths and ranks as the fifth most common cancer worldwide. Incidence and mortality differ depending on the geographical region and gastric cancer ranks first in East Asian countries. Although genetic factors, gastric environment, and
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Gastric cancer is the third leading cause of cancer-related deaths and ranks as the fifth most common cancer worldwide. Incidence and mortality differ depending on the geographical region and gastric cancer ranks first in East Asian countries. Although genetic factors, gastric environment, and Helicobacter pylori infection have been associated with the pathogenicity and development of intestinal-type gastric cancer that follows the Correa’s cascade, the pathogenicity of diffuse-type gastric cancer remains mostly unknown and undefined. However, genetic abnormalities in the cell adherence factors, such as E-cadherin and cellular activities that cause impaired cell integrity and physiology, have been documented as contributing factors. In recent years, H. pylori infection has been also associated with the development of diffuse-type gastric cancer. Therefore, in this report, we discuss the host factors as well as the bacterial factors that have been reported as associated factors contributing to the development of diffuse-type gastric cancer. Full article
(This article belongs to the Special Issue Molecular Features Distinguishing Gastric Cancer Subtypes)
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Open AccessReview Emerging Roles of Sonic Hedgehog in Adult Neurological Diseases: Neurogenesis and Beyond
Int. J. Mol. Sci. 2018, 19(8), 2423; https://doi.org/10.3390/ijms19082423
Received: 8 July 2018 / Revised: 10 August 2018 / Accepted: 13 August 2018 / Published: 16 August 2018
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Abstract
Sonic hedgehog (Shh), a member of the hedgehog (Hh) family, was originally recognized as a morphogen possessing critical characters for neural development during embryogenesis. Recently, however, Shh has emerged as an important modulator in adult neural tissues through different mechanisms such as neurogenesis,
[...] Read more.
Sonic hedgehog (Shh), a member of the hedgehog (Hh) family, was originally recognized as a morphogen possessing critical characters for neural development during embryogenesis. Recently, however, Shh has emerged as an important modulator in adult neural tissues through different mechanisms such as neurogenesis, anti-oxidation, anti-inflammation, and autophagy. Therefore, Shh may potentially have clinical application in neurodegenerative diseases and brain injuries. In this article, we present some examples, including ours, to show different aspects of Shh signaling and how Shh agonists or mimetics are used to alter the neuronal fates in various disease models, both in vitro and in vivo. Other potential mechanisms that are discussed include alteration of mitochondrial function and anti-aging effect; both are critical for age-related neurodegenerative diseases. A thorough understanding of the protective mechanisms elicited by Shh may provide a rationale to design innovative therapeutic regimens for various neurodegenerative diseases. Full article
(This article belongs to the Special Issue Hedgehog Signaling)
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Open AccessArticle Prenylated Flavonoids from Roots of Glycyrrhiza uralensis Induce Differentiation of B16-F10 Melanoma Cells
Int. J. Mol. Sci. 2018, 19(8), 2422; https://doi.org/10.3390/ijms19082422
Received: 12 July 2018 / Revised: 7 August 2018 / Accepted: 8 August 2018 / Published: 16 August 2018
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Abstract
Roots of Glycyrrhiza uralensis have been used as herbal medicine and natural sweetener. By activity-guided phytochemical investigation of the extracts from G.uralensis root, ten flavonoids, namely GF-1–GF-10, of which five were prenylated flavonoids, were found to show antiproliferative effects in melanoma B16-F10 cells.
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Roots of Glycyrrhiza uralensis have been used as herbal medicine and natural sweetener. By activity-guided phytochemical investigation of the extracts from G.uralensis root, ten flavonoids, namely GF-1–GF-10, of which five were prenylated flavonoids, were found to show antiproliferative effects in melanoma B16-F10 cells. Three of the prenylated flavonoids, namely GF-1, GF-4 and GF-9, significantly induced the differentiation of B16-F10 cells; the inductions included increase of tyrosinase activity, tyrosinase protein, and melanin content. In GF-1 and GF-9 induced melanoma differentiation, the phosphorylation of p38 MAPK (mitogen activated potein kinase) was identified; while GF-4 could trigger the phosphorylation of PI3K/AKT (phosphatidylinositol 3-kinase/Protein Kinase B) signaling. However, application of GF-6 to the melanoma cells did not induce differentiation; but which promoted cell apoptotic signaling, i.e., increase levels of cleaved-PRAP, cleaved-caspase 3, and cleaved-caspase 9. These results suggested that different types of prenylated flavonoids from G. uralensis might have potential anticancer effects against melanoma cells by acting through different signaling pathways. Full article
(This article belongs to the Special Issue Plant Natural Products for Human Health)
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Open AccessArticle Intrathecal Injection of Dual Zipper Kinase shRNA Alleviating the Neuropathic Pain in a Chronic Constrictive Nerve Injury Model
Int. J. Mol. Sci. 2018, 19(8), 2421; https://doi.org/10.3390/ijms19082421
Received: 26 July 2018 / Revised: 8 August 2018 / Accepted: 11 August 2018 / Published: 16 August 2018
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Abstract
Dual leucine zipper kinase (DLK) is a member of mitogen-activated protein kinase kinase kinase (MAP3K) family mainly involved in neuronal degeneration. However, the role of DLK signaling in the neuropathic pain has not yet been fully determined. Chronic constrictive injury (CCI) was conducted
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Dual leucine zipper kinase (DLK) is a member of mitogen-activated protein kinase kinase kinase (MAP3K) family mainly involved in neuronal degeneration. However, the role of DLK signaling in the neuropathic pain has not yet been fully determined. Chronic constrictive injury (CCI) was conducted by four 3-0 chromic gut ligatures loosely ligated around the sciatic nerve. Escalated DLK expression over the dorsal root ganglion was observed from one to four rings of CCI. Remarkable expression of DLK was observed in primary dorsal root ganglion cells culture subjected to electrical stimulation and attenuated by DLK short hairpin RNA (shRNA) treatment. Intrathecal injection of DLK shRNA attenuates the expression of DLK over the dorsal root ganglion and hippocampus neurons and increased the threshold of mechanical allodynia and decreased thermal hyperalgesia. In CatWalk gait analysis, significant decreases of print area, maximum contact maximum intensity, stand phase, single stance, and regular index by CCI were alleviated by the DLK shRNA administration. In conclusion, the expression of DLK was up-regulated in chronic constrictive injury and attenuated by the administration of DLK shRNA, which paralleled the improvement of neurobehavior of neuropathic pain. The modulation of DLK expression is a potential clinic treatment option for neuropathic pain. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Open AccessArticle Enhancement of Radiation Effectiveness in Cervical Cancer Cells by Combining Ionizing Radiation with Hyperthermia and Molecular Targeting Agents
Int. J. Mol. Sci. 2018, 19(8), 2420; https://doi.org/10.3390/ijms19082420
Received: 27 July 2018 / Revised: 15 August 2018 / Accepted: 15 August 2018 / Published: 16 August 2018
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Abstract
Hyperthermia (HT) and molecular targeting agents can be used to enhance the effect of radiotherapy (RT). The purpose of this paper is to evaluate radiation sensitization by HT and different molecular targeting agents (Poly [ADP-ribose] polymerase 1 inhibitor, PARP1-i; DNA-dependent protein
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Hyperthermia (HT) and molecular targeting agents can be used to enhance the effect of radiotherapy (RT). The purpose of this paper is to evaluate radiation sensitization by HT and different molecular targeting agents (Poly [ADP-ribose] polymerase 1 inhibitor, PARP1-i; DNA-dependent protein kinase catalytic subunit inhibitor, DNA-PKcs-i and Heat Shock Protein 90 inhibitor, HSP90-i) in cervical cancer cell lines. Survival curves of SiHa and HeLa cells, concerning the combined effects of radiation with hyperthermia and PARP1-i, DNA-PKcs-i or HSP90-i, were analyzed using the linear-quadratic model: S(D)/S(0) = exp − (αD + βD2). The values of the linear-quadratic (LQ) parameters α and β, determine the effectiveness at low and high doses, respectively. The effects of these sensitizing agents on the LQ parameters are compared to evaluate dose-dependent differences in radio enhancement. Combination of radiation with hyperthermia, PARP1-i and DNA-PKcs-i significantly increased the value of the linear parameter α. Both α and β were significantly increased for HSP90-i combined with hyperthermia in HeLa cells, though not in SiHa cells. The Homologous Recombination pathway is inhibited by hyperthermia. When hyperthermia is combined with DNA-PKcs-i and PARP1-i, the Non-Homologous End Joining or Alternative Non-Homologous End Joining pathway is also inhibited, leading to a more potent radio enhancement. The observed increments of the α value imply that significant radio enhancement is obtained at clinically-used radiotherapy doses. Furthermore, the sensitizing effects of hyperthermia can be even further enhanced when combined with other molecular targeting agents. Full article
(This article belongs to the Special Issue Partnership of Radiotherapy and Immunotherapy)
Open AccessReview Vitamin D and Influenza—Prevention or Therapy?
Int. J. Mol. Sci. 2018, 19(8), 2419; https://doi.org/10.3390/ijms19082419
Received: 28 June 2018 / Revised: 24 July 2018 / Accepted: 1 August 2018 / Published: 16 August 2018
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Abstract
Vitamin D generates many extraskeletal effects due to the vitamin D receptor (VDR) which is present in most tissues throughout the body. The possible role of vitamin D in infections is implied from its impact on the innate and adaptive immune responses. A
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Vitamin D generates many extraskeletal effects due to the vitamin D receptor (VDR) which is present in most tissues throughout the body. The possible role of vitamin D in infections is implied from its impact on the innate and adaptive immune responses. A significant effect is also the suppression of inflammatory processes. Because vitamin D could be acknowledged as a “seasonal stimulus”, as defined by R. Edgar Hope-Simpson, it would be crucial to prove it from a potential easy and cheap prophylaxis or therapy support perspective as far as influenza infections are concerned. The survey of the literature data generates some controversies and doubts about the possible role of vitamin D in the prevention of influenza virus. The most important point is to realise that the broad spectrum of this vitamin’s activity does not exclude such a possibility. According to most of the authors, more randomized controlled trials with effective, large populations are needed to explore the preventive effect of vitamin D supplementation on viral influenza infections. Full article
(This article belongs to the Special Issue Vitamin D and Human Health)
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Open AccessArticle Metronidazole Causes Skeletal Muscle Atrophy and Modulates Muscle Chronometabolism
Int. J. Mol. Sci. 2018, 19(8), 2418; https://doi.org/10.3390/ijms19082418
Received: 24 July 2018 / Revised: 13 August 2018 / Accepted: 14 August 2018 / Published: 16 August 2018
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Abstract
Antibiotics lead to increased susceptibility to colonization by pathogenic organisms, with different effects on the host-microbiota relationship. Here, we show that metronidazole treatment of specific pathogen-free (SPF) mice results in a significant increase of the bacterial phylum Proteobacteria in fecal pellets. Furthermore, metronidazole
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Antibiotics lead to increased susceptibility to colonization by pathogenic organisms, with different effects on the host-microbiota relationship. Here, we show that metronidazole treatment of specific pathogen-free (SPF) mice results in a significant increase of the bacterial phylum Proteobacteria in fecal pellets. Furthermore, metronidazole in SPF mice decreases hind limb muscle weight and results in smaller fibers in the tibialis anterior muscle. In the gastrocnemius muscle, metronidazole causes upregulation of Hdac4, myogenin, MuRF1, and atrogin1, which are implicated in skeletal muscle neurogenic atrophy. Metronidazole in SPF mice also upregulates skeletal muscle FoxO3, described as involved in apoptosis and muscle regeneration. Of note, alteration of the gut microbiota results in increased expression of the muscle core clock and effector genes Cry2, Ror-β, and E4BP4. PPARγ and one of its important target genes, adiponectin, are also upregulated by metronidazole. Metronidazole in germ-free (GF) mice increases the expression of other core clock genes, such as Bmal1 and Per2, as well as the metabolic regulators FoxO1 and Pdk4, suggesting a microbiota-independent pharmacologic effect. In conclusion, metronidazole in SPF mice results in skeletal muscle atrophy and changes the expression of genes involved in the muscle peripheral circadian rhythm machinery and metabolic regulation. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Open AccessArticle In Vivo Analysis of miR-34a Regulated Glucose Metabolism Related Genes in Megalobrama amblycephala
Int. J. Mol. Sci. 2018, 19(8), 2417; https://doi.org/10.3390/ijms19082417
Received: 17 July 2018 / Revised: 27 July 2018 / Accepted: 8 August 2018 / Published: 16 August 2018
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Abstract
The Megalobrama amblycephala (M. amblycephala) is one of the most important economic freshwater fish in China. The molecular mechanism under the glucose intolerance responses which affects the growth performance and feed utilization is still confused. miR-34a was reported as a key
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The Megalobrama amblycephala (M. amblycephala) is one of the most important economic freshwater fish in China. The molecular mechanism under the glucose intolerance responses which affects the growth performance and feed utilization is still confused. miR-34a was reported as a key regulator in the glucose metabolism, but how did the miR-34a exert its function in the metabolism of glucose/insulin in M. amblycephala was still unclear. In this study, we intraperitoneally injected the miR-34a inhibitor (80 nmol/100 g body weight) into M. amblycephala (fed with high starch diet, 45% starch) for 12 h, and then analyzed the gene expression profiling in livers by RNA-seq. The results showed that miR-34a expression in M. amblycephala livers was inhibited by injection of miR-34a inhibitor, and a total of 2212 differentially expressed genes (DEGs) were dysregulated (including 1183 up- and 1029 downregulated DEGs). Function enrichment analysis of DEGs showed that most of them were enriched in the peroxisome proliferator-activated receptor (PPAR), insulin, AMP-activated protein kinase (AMPK) and janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways, which were all associated with the glucose/lipid metabolic and biosynthetic processes. In addition, we examined and verified the differential expression levels of some genes involved in AMPK signaling pathway by qRT-PCR. These results demonstrated that the inhibition of miR-34a might regulate glucose metabolism in M. amblycephala through downstream target genes. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Open AccessArticle Long-Term Effects of Cold on Growth, Development and Yield of Narrow-Leaf Lupine May Be Alleviated by Seed Hydropriming or Butenolide
Int. J. Mol. Sci. 2018, 19(8), 2416; https://doi.org/10.3390/ijms19082416
Received: 19 July 2018 / Revised: 2 August 2018 / Accepted: 8 August 2018 / Published: 16 August 2018
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Abstract
In this article, the effects of cold on the development of Lupine angustifolius and the possibility of mitigating it, via seed hydropriming or pre-treatment with butenolide (10−6 M–10−4 M), are investigated in two cultivars, differing in their ability to germinate at
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In this article, the effects of cold on the development of Lupine angustifolius and the possibility of mitigating it, via seed hydropriming or pre-treatment with butenolide (10−6 M–10−4 M), are investigated in two cultivars, differing in their ability to germinate at low temperature. Physiological background of plant development after cold stress was investigated in imbibed seeds. For the first four weeks, the seedlings grew at 7 °C or 13 °C. Seeds well germinating at 7 °C demonstrated higher activity of α-amylase and higher levels of gibberellins, IAA and kinetin. Germination ability at low temperature correlated with dehydrogenase activity and membrane permeability. Seed pre-treatment improved germination at low temperature by decreasing abscisic acid content. Seed hydropriming alleviated cold effects on plant development rate and yield, while butenolide accelerated vegetative development but delayed the generative phase. Potential seed yield may be predicted based on the seed germination vigour and the photosynthetic efficiency measured before flowering. Full article
(This article belongs to the Special Issue Seed Development, Dormancy and Germination)
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Open AccessReview Recent Advances by In Silico and In Vitro Studies of Amyloid-β 1-42 Fibril Depicted a S-Shape Conformation
Int. J. Mol. Sci. 2018, 19(8), 2415; https://doi.org/10.3390/ijms19082415
Received: 14 July 2018 / Revised: 9 August 2018 / Accepted: 10 August 2018 / Published: 16 August 2018
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Abstract
The amyloid-β 1-42 (Aβ1-42) peptide is produced by proteolytic cleavage of the amyloid precursor protein (APP) by sequential reactions that are catalyzed by γ and β secretases. Aβ1-42, together with the Tau protein are two principal hallmarks of Alzheimer’s disease (AD) that are
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The amyloid-β 1-42 (Aβ1-42) peptide is produced by proteolytic cleavage of the amyloid precursor protein (APP) by sequential reactions that are catalyzed by γ and β secretases. Aβ1-42, together with the Tau protein are two principal hallmarks of Alzheimer’s disease (AD) that are related to disease genesis and progression. Aβ1-42 possesses a higher aggregation propensity, and it is able to form fibrils via nucleated fibril formation. To date, there are compounds available that prevent Aβ1-42 aggregation, but none have been successful in clinical trials, possibly because the Aβ1-42 structure and aggregation mechanisms are not thoroughly understood. New molecules have been designed, employing knowledge of the Aβ1-42 structure and are based on preventing or breaking the ionic interactions that have been proposed for formation of the Aβ1-42 fibril U-shaped structure. Recently, a new Aβ1-42 fibril S-shaped structure was reported that, together with its aggregation and catalytic properties, could be helpful in the design of new inhibitor molecules. Therefore, in silico and in vitro methods have been employed to analyze the Aβ1-42 fibril S-shaped structure and its aggregation to obtain more accurate Aβ1-42 oligomerization data for the design and evaluation of new molecules that can prevent the fibrillation process. Full article
(This article belongs to the Special Issue Amyloid Fibrils and Methods for Their Study)
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Open AccessArticle Two New Polyphenol Oxidase Genes of Tea Plant (Camellia sinensis) Respond Differentially to the Regurgitant of Tea Geometrid, Ectropis obliqua
Int. J. Mol. Sci. 2018, 19(8), 2414; https://doi.org/10.3390/ijms19082414
Received: 15 July 2018 / Revised: 9 August 2018 / Accepted: 13 August 2018 / Published: 16 August 2018
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Abstract
Polyphenol oxidases (PPOs) have been reported to play an important role in protecting plants from attacks by herbivores. Though PPO genes in other plants have been extensively studied, research on PPO genes in the tea plant (Camellia sinensis) is lacking. In
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Polyphenol oxidases (PPOs) have been reported to play an important role in protecting plants from attacks by herbivores. Though PPO genes in other plants have been extensively studied, research on PPO genes in the tea plant (Camellia sinensis) is lacking. In particular, which members of the PPO gene family elicit the defense response of the tea plant are as yet unknown. Here, two new PPO genes, CsPPO1 and CsPPO2, both of which had high identity with PPOs from other plants, were obtained from tea leaves. The full length of CsPPO1 contained an open reading frame (ORF) of 1740 bp that encoded a protein of 579 amino acids, while CsPPO2 contained an ORF of 1788 bp that encoded a protein of 595 amino acids. The deduced CsPPO1 and CsPPO2 proteins had calculated molecular masses of 64.6 and 65.9 kDa; the isoelectric points were 6.94 and 6.48, respectively. The expression products of recombinant CsPPO1 and CsPPO2 in Escherichia coli were about 91 and 92 kDa, respectively, but the recombinant proteins existed in the form of an inclusion body. Whereas CsPPO1 is highly expressed in stems, CsPPO2 is highly expressed in roots. Further results showed that the expression of CsPPO1 and CsPPO2 was wound- and Ectropis obliqua-induced, and that regurgitant, unlike treatment with wounding plus deionized water, significantly upregulated the transcriptional expression of CsPPO2 but not of CsPPO1. The difference between regurgitant and wounding indicates that CsPPO2 may play a more meaningful defensive role against E. obliqua than CsPPO1. Meanwhile, we found the active component(s) of the regurgitant elicited by the expression of CsPPO may contain small molecules (under 3-kDa molecular weight). These conclusions advance the understanding of the biological function of two new PPO genes and show that one of these, CsPPO2, may be a promising gene for engineering tea plants that are resistant to E. obliqua. Full article
(This article belongs to the Special Issue Plant Innate Immunity 2.0)
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Open AccessReview Hallmarks of Cancer-Related Newly Prognostic Factors of Oral Squamous Cell Carcinoma
Int. J. Mol. Sci. 2018, 19(8), 2413; https://doi.org/10.3390/ijms19082413
Received: 28 July 2018 / Revised: 13 August 2018 / Accepted: 15 August 2018 / Published: 16 August 2018
PDF Full-text (627 KB)
Abstract
Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth leading malignancy worldwide. OSCC is an aggressive tumor and its prognosis has exhibited little improvement in the last three decades. Comprehensive elucidation of OSCC’s molecular mechanism is imperative for early
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Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth leading malignancy worldwide. OSCC is an aggressive tumor and its prognosis has exhibited little improvement in the last three decades. Comprehensive elucidation of OSCC’s molecular mechanism is imperative for early detection and treatment, improving patient survival. Based on broadly accepted notions, OSCC arises from multiple genetic alterations caused by chronic exposure to carcinogens. In 2011, research revealed 10 key alterations fundamental to cancer cell development: sustaining proliferative signaling, evading growth suppressors, avoiding immune destruction, activating invasion and metastasis, tumor-promoting inflammation, enabling replicative immortality, inducing angiogenesis, genome instability and mutation, resisting cell death, and deregulating energetics. This review describes molecular pathological findings on conventional and novel hallmarks of OSCC prognostic factors. In addition, the review summarizes the functions and roles of several molecules as novel OSCC prognosticators. Full article
(This article belongs to the Special Issue Oral Cancer—Diagnosis and Therapeutics)
Open AccessReview Is TAK1 a Direct Upstream Kinase of AMPK?
Int. J. Mol. Sci. 2018, 19(8), 2412; https://doi.org/10.3390/ijms19082412
Received: 29 June 2018 / Revised: 13 August 2018 / Accepted: 14 August 2018 / Published: 15 August 2018
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Abstract
Alongside Liver kinase B1 (LKB1) and Ca2+/Calmodulin-dependent protein kinase kinase 2 (CaMKK2), Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) has been suggested as a direct upstream kinase of AMP-activated protein kinase (AMPK). Several subsequent studies have reported on the TAK1-AMPK relationship,
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Alongside Liver kinase B1 (LKB1) and Ca2+/Calmodulin-dependent protein kinase kinase 2 (CaMKK2), Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) has been suggested as a direct upstream kinase of AMP-activated protein kinase (AMPK). Several subsequent studies have reported on the TAK1-AMPK relationship, but the interpretation of the respective data has led to conflicting views. Therefore, to date the acceptance of TAK1 as a genuine AMPK kinase is lagging behind. This review provides with argumentation, whether or not TAK1 functions as a direct upstream kinase of AMPK. Several specific open questions that may have precluded the consensus are discussed based on available data. In brief, TAK1 can function as direct AMPK upstream kinase in specific contexts and in response to a subset of TAK1 activating stimuli. Further research is needed to define the intricate signals that are conditional for TAK1 to phosphorylate and activate AMPKα at T172. Full article
(This article belongs to the Special Issue AMP-Activated Protein Kinase Signalling)
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Open AccessReview Molecular Signatures of the Insulin-Like Growth Factor 1-Mediated Epithelial-Mesenchymal Transition in Breast, Lung and Gastric Cancers
Int. J. Mol. Sci. 2018, 19(8), 2411; https://doi.org/10.3390/ijms19082411
Received: 29 June 2018 / Revised: 13 August 2018 / Accepted: 14 August 2018 / Published: 15 August 2018
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Abstract
The insulin-like growth factor (IGF) system, which is constituted by the IGF-1 and IGF-2 peptide hormones, their corresponding receptors and several IGF binding proteins, is involved in physiological and pathophysiological processes. The IGF system promotes cancer proliferation/survival and its signaling induces the epithelial-mesenchymal
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The insulin-like growth factor (IGF) system, which is constituted by the IGF-1 and IGF-2 peptide hormones, their corresponding receptors and several IGF binding proteins, is involved in physiological and pathophysiological processes. The IGF system promotes cancer proliferation/survival and its signaling induces the epithelial-mesenchymal transition (EMT) phenotype, which contributes to the migration, invasiveness, and metastasis of epithelial tumors. These cancers share two major IGF-1R signaling transduction pathways, PI3K/AKT and RAS/MEK/ERK. However, as far as we could review at this time, each type of cancer cell undergoes EMT through tumor-specific routes. Here, we review the tumor-specific molecular signatures of IGF-1-mediated EMT in breast, lung, and gastric cancers. Full article
(This article belongs to the Special Issue Inflammation and Cancer 2018)
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Open AccessReview The Efficacy of Buprenorphine in Major Depression, Treatment-Resistant Depression and Suicidal Behavior: A Systematic Review
Int. J. Mol. Sci. 2018, 19(8), 2410; https://doi.org/10.3390/ijms19082410
Received: 2 July 2018 / Revised: 31 July 2018 / Accepted: 8 August 2018 / Published: 15 August 2018
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Abstract
Although several pharmacological options to treat depression are currently available, approximately one third of patients who receive antidepressant medications do not respond adequately or achieve a complete remission. Thus, novel strategies are needed to successfully address those who did not respond, or partially
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Although several pharmacological options to treat depression are currently available, approximately one third of patients who receive antidepressant medications do not respond adequately or achieve a complete remission. Thus, novel strategies are needed to successfully address those who did not respond, or partially respond, to available antidepressant pharmacotherapy. Research findings revealed that the opioid system is significantly involved in the regulation of mood and incentives salience and may be an appropriate target for novel therapeutic agents. The present study aimed to systematically review the current literature about the use of buprenorphine (BUP) for major depression, treatment-resistant depression (TRD), non-suicidal self-injury (NSSI) behavior, and suicidal behavior. We investigated Pubmed and Scopus databases using the following keywords: “buprenorphine AND depression”, “buprenorphine AND treatment resistant depression”, “buprenorphine AND suicid*”, “buprenorphine AND refractory depression”. Several evidence demonstrate that, at low doses, BUP is an efficacious, well-tolerated, and safe option in reducing depressive symptoms, serious suicidal ideation, and NSSI, even in patients with TRD. However, more studies are needed to evaluate the long-term effects, and relative efficacy of specific combinations (e.g., BUP + samidorphan (BUP/SAM), BUP + naloxone (BUP/NAL), BUP + naltrexone) over BUP monotherapy or adjunctive BUP treatment with standard antidepressants, as well as to obtain more uniform guidance about the optimal BUP dosing interval. Full article
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Open AccessArticle Combination ART-Induced Oxidative/Nitrosative Stress, Neurogenic Inflammation and Cardiac Dysfunction in HIV-1 Transgenic (Tg) Rats: Protection by Mg
Int. J. Mol. Sci. 2018, 19(8), 2409; https://doi.org/10.3390/ijms19082409
Received: 28 June 2018 / Revised: 4 August 2018 / Accepted: 13 August 2018 / Published: 15 August 2018
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Abstract
Chronic effects of a combination antiretroviral therapy (cART = tenofovir/emtricitatine + atazanavir/ritonavir) on systemic and cardiac oxidative stress/injury in HIV-1 transgenic (Tg) rats and protection by Mg-supplementation were assessed. cART (low doses) elicited no significant effects in normal rats, but induced time-dependent oxidative/nitrosative
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Chronic effects of a combination antiretroviral therapy (cART = tenofovir/emtricitatine + atazanavir/ritonavir) on systemic and cardiac oxidative stress/injury in HIV-1 transgenic (Tg) rats and protection by Mg-supplementation were assessed. cART (low doses) elicited no significant effects in normal rats, but induced time-dependent oxidative/nitrosative stresses: 2.64-fold increased plasma 8-isoprostane, 2.0-fold higher RBC oxidized glutathione (GSSG), 3.2-fold increased plasma 3-nitrotyrosine (NT), and 3-fold elevated basal neutrophil superoxide activity in Tg rats. Increased NT staining occurred within cART-treated HIV-Tg hearts, and significant decreases in cardiac systolic and diastolic contractile function occurred at 12 and 18 weeks. HIV-1 expression alone caused modest levels of oxidative stress and cardiac dysfunction. Significantly, cART caused up to 24% decreases in circulating Mg in HIV-1-Tg rats, associated with elevated renal NT staining, increased creatinine and urea levels, and elevated plasma substance P levels. Strikingly, Mg-supplementation (6-fold) suppressed all oxidative/nitrosative stress indices in the blood, heart and kidney and substantially attenuated contractile dysfunction (>75%) of cART-treated Tg rats. In conclusion, cART caused significant renal and cardiac oxidative/nitrosative stress/injury in Tg-rats, leading to renal Mg wasting and hypomagnesemia, triggering substance P-dependent neurogenic inflammation and cardiac dysfunction. These events were effectively attenuated by Mg-supplementation likely due to its substance P-suppressing and Mg’s intrinsic anti-peroxidative/anti-calcium properties. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2018)
Open AccessReview Tau in Oligodendrocytes Takes Neurons in Sickness and in Health
Int. J. Mol. Sci. 2018, 19(8), 2408; https://doi.org/10.3390/ijms19082408
Received: 9 July 2018 / Revised: 5 August 2018 / Accepted: 6 August 2018 / Published: 15 August 2018
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Abstract
Oligodendrocytes (OLGs), the myelin-forming cells of the central nervous system (CNS), are lifelong partners of neurons. They adjust to the functional demands of neurons over the course of a lifetime to meet the functional needs of a healthy CNS. When this functional interplay
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Oligodendrocytes (OLGs), the myelin-forming cells of the central nervous system (CNS), are lifelong partners of neurons. They adjust to the functional demands of neurons over the course of a lifetime to meet the functional needs of a healthy CNS. When this functional interplay breaks down, CNS degeneration follows. OLG processes are essential features for OLGs being able to connect with the neurons. As many as fifty cellular processes from a single OLG reach and wrap an equal number of axonal segments. The cellular processes extend to meet and wrap axonal segments with myelin. Further, transport regulation, which is critical for myelination, takes place within the cellular processes. Because the microtubule-associated protein tau plays a crucial role in cellular process extension and myelination, alterations of tau in OLGs have deleterious effects, resulting in neuronal malfunction and CNS degeneration. Here, we review current concepts on the lifelong role of OLGs and myelin for brain health and plasticity. We present key studies of tau in OLGs and select important studies of tau in neurons. The extensive work on tau in neurons has considerably advanced our understanding of how tau promotes either health or disease. Because OLGs are crucial to neuronal health at any age, an understanding of the functions and regulation of tau in OLGs could uncover new therapeutics for selective CNS neurodegenerative diseases. Full article
(This article belongs to the Special Issue Tau Function and Dysfunctional Tauopathies)
Open AccessArticle Effects of Oat Bran on Nutrient Digestibility, Intestinal Microbiota, and Inflammatory Responses in the Hindgut of Growing Pigs
Int. J. Mol. Sci. 2018, 19(8), 2407; https://doi.org/10.3390/ijms19082407
Received: 8 July 2018 / Revised: 9 August 2018 / Accepted: 10 August 2018 / Published: 15 August 2018
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Abstract
Oat bran has drawn great attention within human research for its potential role in improving gut health. However, research regarding the impact of oat bran on nutrient utilization and intestinal functions in pigs is limited. The purpose of this study was to investigate
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Oat bran has drawn great attention within human research for its potential role in improving gut health. However, research regarding the impact of oat bran on nutrient utilization and intestinal functions in pigs is limited. The purpose of this study was to investigate the effects of oat bran on nutrient digestibility, intestinal microbiota, and inflammatory responses in the hindgut of growing pigs. Twenty-six growing pigs were fed either a basal diet (CON) or a basal diet supplemented with 10% oat bran (OB) within a 28 day feeding trial. Results showed that digestibility of dietary gross energy, dry matter, organic matter, and crude protein were lower in the OB group compared to the CON group on day 14, but no differences were observed between the two groups on day 28. In the colon, the relative abundance of operational taxonomic units (OTUs) associated with Prevotella, Butyricicoccus, and Catenibacterium were higher, while those associated with Coprococcus and Desulfovibrio were lower in the OB group compared to the CON group. Oat bran decreased mRNA expression of caecal interleukin-8 (IL-8), as well as colonic IL-8, nuclear factor-κB (NF-κB), and tumor necrosis factor-α (TNF-α) of the pigs. In summary, oat bran treatment for 28 day did not affect dietary nutrient digestibility, but promoted the growth of cellulolytic bacteria and ameliorated inflammatory reactions in the hindgut of growing pigs. Full article
(This article belongs to the Special Issue Nutrition and Gut Health)
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Open AccessArticle Responses of Transgenic Melatonin-Enriched Goats on LPS Stimulation and the Proteogenomic Profiles of Their PBMCs
Int. J. Mol. Sci. 2018, 19(8), 2406; https://doi.org/10.3390/ijms19082406
Received: 16 July 2018 / Revised: 4 August 2018 / Accepted: 10 August 2018 / Published: 15 August 2018
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Abstract
The anti-inflammatory activity of melatonin (MT) has been well documented; however, little is known regarding endogenously occurring MT in this respect, especially for large animals. In the current study, we created a MT-enriched animal model (goats) overexpressing the MT synthetase gene Aanat.
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The anti-inflammatory activity of melatonin (MT) has been well documented; however, little is known regarding endogenously occurring MT in this respect, especially for large animals. In the current study, we created a MT-enriched animal model (goats) overexpressing the MT synthetase gene Aanat. The responses of these animals to lipopolysaccharide (LPS) stimulation were systematically studied. It was found that LPS treatment exacerbated the inflammatory response in wild-type (WT) goats and increased their temperature to 40 °C. In addition, their granulocyte counts were also significantly elevated. In contrast, these symptoms were not observed in transgenic goats with LPS treatment. The rescue study with MT injection into WT goats who were treated with LPS confirmed that the protective effects in transgenic goats against LPS were attributed to a high level of endogenously produced MT. The proteomic analysis in the peripheral blood mononuclear cells (PBMCs) isolated from the transgenic animals uncovered several potential mechanisms. MT suppressed the lysosome formation as well as its function by downregulation of the lysosome-associated genes Lysosome-associated membrane protein 2 (LAMP2), Insulin-like growth factor 2 receptor (IGF2R), and Arylsulfatase B (ARSB). A high level of MT enhanced the antioxidant capacity of these cells to reduce the cell apoptosis induced by the LPS. In addition, the results also uncovered previously unknown information that showed that MT may have protective effects on some human diseases, including tuberculosis, bladder cancer, and rheumatoid arthritis, by downregulation of these disease-associated genes. All these observations warranted further investigations. Full article
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Open AccessArticle Edema Induced by a Crotalus durissus terrificus Venom Serine Protease (Cdtsp 2) Involves the PAR Pathway and PKC and PLC Activation
Int. J. Mol. Sci. 2018, 19(8), 2405; https://doi.org/10.3390/ijms19082405
Received: 17 May 2018 / Revised: 3 August 2018 / Accepted: 5 August 2018 / Published: 15 August 2018
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Abstract
Snake venom serine proteases (SVSPs) represent an essential group of enzymatic toxins involved in several pathophysiological effects on blood homeostasis. Some findings suggest the involvement of this class of enzymatic toxins in inflammation. In this paper, we purified and isolated a new gyroxin
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Snake venom serine proteases (SVSPs) represent an essential group of enzymatic toxins involved in several pathophysiological effects on blood homeostasis. Some findings suggest the involvement of this class of enzymatic toxins in inflammation. In this paper, we purified and isolated a new gyroxin isoform from the Crotalus durissus terrificus (Cdt) venom, designated as Cdtsp 2, which showed significant proinflammatory effects in a murine model. In addition, we performed several studies to elucidate the main pathway underlying the edematogenic effect induced by Cdtsp 2. Enzymatic assays and structural analysis (primary structure analysis and three-dimensional modeling) were closely performed with pharmacological assays. The determination of edematogenic activity was performed using Cdtsp 2 isolated from snake venom, and was applied to mice treated with protein kinase C (PKC) inhibitor, phospholipase C (PLC) inhibitor, dexamethasone (Dexa), antagonists for protease-activated receptors (PARs), or saline (negative control). Additionally, we measured the levels of cyclooxygenase 2 (COX-2), malondialdehyde (MDA), and prostaglandin E2 (PGE2). Cdtsp 2 is characterized by an approximate molecular mass of 27 kDa, an isoelectric point (pI) of 4.5, and significant fibrinolytic activity, as well as the ability to hydrolyze Nα-benzoyl-l-arginine 4-nitroanilide (BAPNA). Its primary and three-dimensional structures revealed Cdtsp 2 as a typical snake venom serine protease that induces significant edema via the metabolism of arachidonic acid (AA), involving PARs, PKC, PLC, and COX-2 receptors, as well as inducing a significant increase in MDA levels. Our results showed that Cdtsp 2 is a serine protease with significant enzymatic activity, and it may be involved in the degradation of PAR1 and PAR2, which activate PLC and PKC to mobilize AA, while increasing oxidative stress. In this article, we provide a new perspective for the role of SVSPs beyond their effects on blood homeostasis. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Open AccessArticle NOX Inhibition Improves β-Adrenergic Stimulated Contractility and Intracellular Calcium Handling in the Aged Rat Heart
Int. J. Mol. Sci. 2018, 19(8), 2404; https://doi.org/10.3390/ijms19082404
Received: 27 June 2018 / Revised: 28 July 2018 / Accepted: 1 August 2018 / Published: 15 August 2018
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Abstract
Cardiac aging is characterized by alterations in contractility and intracellular calcium ([Ca2+]i) homeostasis. It has been suggested that oxidative stress may be involved in this process. We and others have reported that in cardiomyopathies the NADPH oxidase (NOX)-derived superoxide
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Cardiac aging is characterized by alterations in contractility and intracellular calcium ([Ca2+]i) homeostasis. It has been suggested that oxidative stress may be involved in this process. We and others have reported that in cardiomyopathies the NADPH oxidase (NOX)-derived superoxide is increased, with a negative impact on [Ca2+]i and contractility. We tested the hypothesis that in the aged heart, [Ca2+]i handling and contractility are disturbed by NOX-derived superoxide. For this we used adults (≈5 month-old) and aged (20–24 month-old) rats. Contractility was evaluated in isolated hearts, challenged with isoproterenol. To assess [Ca2+]i, isolated cardiac myocytes were field-stimulated and [Ca2+]i was monitored with fura-2. Cardiac concentration-response to isoproterenol was depressed in aged compared to adults hearts (p < 0.005), but was restored by NOX inhibitors apocynin and VAS2870. In isolated cardiomyocytes, apocynin increased the amplitude of [Ca2+]i in aged myocytes (p < 0.05). Time-50 [Ca2+]i decay was increased in aged myocytes (p < 0.05) and reduced towards normal by NOX inhibition. In addition, we found that myofilaments Ca2+ sensitivity was reduced in aged myocytes (p < 0.05), and was further reduced by apocynin. NOX2 expression along with NADPH oxidase activity was increased in aged hearts. Phospholamban phosphorylation (Ser16/Thr17) after isoproterenol treatment was reduced in aged hearts compared to adults and was restored by apocynin treatment (p < 0.05). In conclusion, β-adrenergic-induced contractility was depressed in aged hearts, and NOX inhibition restored back to normal. Moreover, altered Ca2+ handling in aged myocytes was also improved by NOX inhibition. These results suggest a NOX-dependent effect in aged myocytes at the level of Ca2+ handling proteins and myofilaments. Full article
(This article belongs to the Special Issue The Impact of Aging on Cardio and Cerebrovascular Diseases)
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Open AccessArticle Seed-Specific Gene MOTHER of FT and TFL1(MFT) Involved in Embryogenesis, Hormones and Stress Responses in Dimocarpus longan Lour.
Int. J. Mol. Sci. 2018, 19(8), 2403; https://doi.org/10.3390/ijms19082403
Received: 12 July 2018 / Revised: 9 August 2018 / Accepted: 10 August 2018 / Published: 14 August 2018
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Abstract
Mother of FT and TFL1 (MFT) belongs to phosphatidylethanolamine-binding protein (PEBP) family, which plays an important role in flowering time regulation, seed development, and germination. To gain insight into the molecular function of DlMFT in Dimocarpus longan Lour., we isolated DlMFT
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Mother of FT and TFL1 (MFT) belongs to phosphatidylethanolamine-binding protein (PEBP) family, which plays an important role in flowering time regulation, seed development, and germination. To gain insight into the molecular function of DlMFT in Dimocarpus longan Lour., we isolated DlMFT and its promoter sequence from longan embryogenic callus (EC). Bioinformatic analysis indicated that the promoter contained multiphytohormones and light responsive regulatory elements. Subcellular localization showed that the given the DlMFT signal localized in the nucleus, expression profiling implied that DlMFT showed significant upregulation during somatic embryogenesis (SE) and zygotic embryogenesis (ZE), and particular highly expressed in late or maturation stages. The accumulation of DlMFT was mainly detected in mature fruit and seed, while it was undetected in abortive seeds, and notably decreased during seed germination. DlMFT responded differentially to exogenous hormones in longan EC. Auxins, salicylic acid (SA) and methyl jasmonate (MeJa) suppressed its expression, however, abscisic acid (ABA), brassinosteroids (BR) showed the opposite function. Meanwhile, DlMFT differentially responded to various abiotic stresses. Our study revealed that DlMFT might be a key regulator of longan somatic and zygotic embryo development, and in seed germination, it is involved in complex plant hormones and abiotic stress signaling pathways. Full article
(This article belongs to the Section Molecular Plant Sciences)
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Open AccessArticle Comparative Transcriptome Profiling of Two Tomato Genotypes in Response to Potassium-Deficiency Stress
Int. J. Mol. Sci. 2018, 19(8), 2402; https://doi.org/10.3390/ijms19082402
Received: 14 June 2018 / Revised: 9 August 2018 / Accepted: 10 August 2018 / Published: 14 August 2018
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Abstract
Tomato is a crop that requires a sufficient supply of potassium (K) for optimal productivity and quality. K+-deficiency stress decreases tomato yield and quality. To further delve into the mechanism of the response to K+-deficiency and to screen out
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Tomato is a crop that requires a sufficient supply of potassium (K) for optimal productivity and quality. K+-deficiency stress decreases tomato yield and quality. To further delve into the mechanism of the response to K+-deficiency and to screen out low-K+ tolerant genes in tomatoes, BGISEQ-500-based RNA sequencing was performed using two tomato genotypes (low-K+ tolerant JZ34 and low-K+ sensitive JZ18). We identified 1936 differentially expressed genes (DEGs) in JZ18 and JZ34 at 12 and 24 h after K+-deficiency treatment. According to the Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses, the DEGs that changed significantly primarily included transcription factors, transporters, kinases, oxidative stress proteins, and hormone signaling-and glycometabolism-related genes. The experimental results confirmed the induced expression of the responsive genes in the low-K+ signaling pathway. The largest group of DEGs comprised up to 110 oxidative stress-related genes. In total, 19 ethylene response factors (ERFs) demonstrated differential expression between JZ18 and JZ34 in response to K+-deficiency. Furthermore, we confirmed 20 DEGs closely related to K+-deficiency stress by quantitative RT-PCR (qRT-PCR), some of which affected the root configuration, these DEGs could be further studied for use as molecular targets to explore novel approaches, and to acquire more effective K acquisition efficiencies for tomatoes. A hypothesis involving possible cross-talk between phytohormone signaling cues and reactive oxygen species (ROS) leading to root growth in JZ34 is proposed. The results provide a comprehensive foundation for the molecular mechanisms involved in the response of tomatoes to low K+ stress. Full article
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Open AccessArticle Assessment of Genetic Diversity, Population Structure, and Evolutionary Relationship of Uncharacterized Genes in a Novel Germplasm Collection of Diploid and Allotetraploid Gossypium Accessions Using EST and Genomic SSR Markers
Int. J. Mol. Sci. 2018, 19(8), 2401; https://doi.org/10.3390/ijms19082401
Received: 23 June 2018 / Revised: 8 August 2018 / Accepted: 13 August 2018 / Published: 14 August 2018
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Abstract
This study evaluated the genetic diversity and population structures in a novel cotton germplasm collection comprising 132 diploids, including Glossypium klotzschianum and allotetraploid cotton accessions, including Glossypium barbadense, Glossypium darwinii, Glossypium tomentosum, Glossypium ekmanianum, and Glossypium stephensii, from
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This study evaluated the genetic diversity and population structures in a novel cotton germplasm collection comprising 132 diploids, including Glossypium klotzschianum and allotetraploid cotton accessions, including Glossypium barbadense, Glossypium darwinii, Glossypium tomentosum, Glossypium ekmanianum, and Glossypium stephensii, from Santa Cruz, Isabella, San Cristobal, Hawaiian, Dominican Republic, and Wake Atoll islands. A total of 111 expressed sequence tag (EST) and genomic simple sequence repeat (gSSR) markers produced 382 polymorphic loci with an average of 3.44 polymorphic alleles per SSR marker. Polymorphism information content values counted 0.08 to 0.82 with an average of 0.56. Analysis of a genetic distance matrix revealed values of 0.003 to 0.53 with an average of 0.33 in the wild cotton collection. Phylogenetic analysis supported the subgroups identified by STRUCTURE and corresponds well with the results of principal coordinate analysis with a cumulative variation of 45.65%. A total of 123 unique alleles were observed among all accessions and 31 identified only in G. ekmanianum. Analysis of molecular variance revealed highly significant variation between the six groups identified by structure analysis with 49% of the total variation and 51% of the variation was due to diversity within the groups. The highest genetic differentiation among tetraploid populations was observed between accessions from the Hawaiian and Santa Cruz regions with a pairwise FST of 0.752 (p < 0.001). DUF819 containing an uncharacterized gene named yjcL linked to genomic markers has been found to be highly related to tryptophan-aspartic acid (W-D) repeats in a superfamily of genes. The RNA sequence expression data of the yjcL-linked gene Gh_A09G2500 was found to be upregulated under drought and salt stress conditions. The existence of genetic diversity, characterization of genes and variation in novel germplasm collection will be a landmark addition to the genetic study of cotton germplasm. Full article
(This article belongs to the Special Issue Plant Genomics)
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Open AccessArticle Photothermally Triggered Endosomal Escape and Its Influence on Transfection Efficiency of Gold-Functionalized JetPEI/pDNA Nanoparticles
Int. J. Mol. Sci. 2018, 19(8), 2400; https://doi.org/10.3390/ijms19082400
Received: 7 August 2018 / Accepted: 11 August 2018 / Published: 14 August 2018
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Abstract
Plasmonic nanoparticles for drug delivery have attracted increasing interest over the last few years. Their localized surface plasmon resonance causes photothermal effects on laser irradiation, which allows for delivering drugs in a spatio-temporally controlled manner. Here, we explore the use of gold nanoparticles
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Plasmonic nanoparticles for drug delivery have attracted increasing interest over the last few years. Their localized surface plasmon resonance causes photothermal effects on laser irradiation, which allows for delivering drugs in a spatio-temporally controlled manner. Here, we explore the use of gold nanoparticles (AuNP) as carriers for pDNA in combination with pulsed laser irradiation to induce endosomal escape, which is currently considered to be one of the major bottlenecks in macromolecular drug delivery on the intracellular level. In particular, we evaluate nanocomplexes composed of JetPEI (polyethylenimine)pDNA and 10 nm AuNP, which do not exhibit endosomal escape by themselves. After incubating HeLa cells with these complexes, we evaluated endosomal escape and transfection efficiency using low- and high-energy laser pulses. At low laser energy heat is produced by the nanocomplexes, while, at higher laser energy, explosive vapour nanobubbles (VNB) are formed. We investigated the ability of heat transfer and VNB formation to induce endosomal escape and we examine the integrity of pDNA cargo after inducing both photothermal effects. We conclude that JetPEI/pDNA/AuNP complexes are unable to induce meaningful transfection efficiencies because laser treatment causes either dysfunctionality of the cargo when VNB are formed or forms too small pores in the endosomal membrane to allow pDNA to escape in case of heating. We conclude that laser-induced VNB is the most suitable to induce effective pDNA endosomal escape, but a different nanocomplex structure will be required to keep the pDNA intact. Full article
(This article belongs to the Special Issue Nanomedicine/Molecular Medicine)
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Open AccessArticle Application of fluorescence lifetime imaging microscopy of DNA binding dyes to assess radiation-induced chromatin compaction changes
Int. J. Mol. Sci. 2018, 19(8), 2399; https://doi.org/10.3390/ijms19082399
Received: 2 July 2018 / Revised: 2 August 2018 / Accepted: 10 August 2018 / Published: 14 August 2018
PDF Full-text (762 KB) | Supplementary Files
Abstract
In recent years several approaches have been developed to address the chromatin status and its changes in eukaryotic cells under different conditions—but only few are applicable in living cells. Fluorescence lifetime imaging microscopy (FLIM) is a functional tool that can be used for
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In recent years several approaches have been developed to address the chromatin status and its changes in eukaryotic cells under different conditions—but only few are applicable in living cells. Fluorescence lifetime imaging microscopy (FLIM) is a functional tool that can be used for the inspection of the molecular environment of fluorophores in living cells. Here, we present the use of single organic minor groove DNA binder dyes in FLIM for measuring chromatin changes following modulation of chromatin structure in living cells. Treatment with histone deacetylase inhibitors led to an increased fluorescence lifetime indicating global chromatin decompaction, whereas hyperosmolarity decreased the lifetime of the used dyes, thus reflecting the expected compaction. In addition, we demonstrate that time domain FLIM data based on single photon counting should be optimized using pile-up and counting loss correction, which affect the readout even at moderate average detector count rates in inhomogeneous samples. Using these corrections and utilizing Hoechst 34580 as chromatin compaction probe, we measured a pan nuclear increase in the lifetime following irradiation with X-rays in living NIH/3T3 cells thus providing a method to measure radiation-induced chromatin decompaction. Full article
(This article belongs to the Special Issue Advances and Challenges in Biomolecular Radiation Research)
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