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Int. J. Mol. Sci., Volume 18, Issue 8 (August 2017)

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Open AccessArticle Circadian and Light Regulated Expression of CBFs and their Upstream Signalling Genes in Barley
Int. J. Mol. Sci. 2017, 18(8), 1828; https://doi.org/10.3390/ijms18081828
Received: 5 July 2017 / Revised: 10 August 2017 / Accepted: 19 August 2017 / Published: 22 August 2017
Cited by 2 | PDF Full-text (2479 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
CBF (C-repeat binding factor) transcription factors show high expression levels in response to cold; moreover, they play a key regulatory role in cold acclimation processes. Recently, however, more and more information has led to the conclusion that, apart from cold, light—including its spectra—also
[...] Read more.
CBF (C-repeat binding factor) transcription factors show high expression levels in response to cold; moreover, they play a key regulatory role in cold acclimation processes. Recently, however, more and more information has led to the conclusion that, apart from cold, light—including its spectra—also has a crucial role in regulating CBF expression. Earlier, studies established that the expression patterns of some of these regulatory genes follow circadian rhythms. To understand more of this complex acclimation process, we studied the expression patterns of the signal transducing pathways, including signal perception, the circadian clock and phospholipid signalling pathways, upstream of the CBF gene regulatory hub. To exclude the confounding effect of cold, experiments were carried out at 22 °C. Our results show that the expression of genes implicated in the phospholipid signalling pathway follow a circadian rhythm. We demonstrated that, from among the tested CBF genes expressed in Hordeum vulgare (Hv) under our conditions, only the members of the HvCBF4-phylogenetic subgroup showed a circadian pattern. We found that the HvCBF4-subgroup genes were expressed late in the afternoon or early in the night. We also determined the expression changes under supplemental far-red illumination and established that the transcript accumulation had appeared four hours earlier and more intensely in several cases. Based on our results, we propose a model to illustrate the effect of the circadian clock and the quality of the light on the elements of signalling pathways upstream of the HvCBFs, thus integrating the complex regulation of the early cellular responses, which finally lead to an elevated abiotic stress tolerance. Full article
(This article belongs to the Special Issue Abiotic Stress and Gene Networks in Plants 2017)
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Open AccessArticle Systemic Chemokine Levels with “Gut-Specific” Vedolizumab in Patients with Inflammatory Bowel Disease—A Pilot Study
Int. J. Mol. Sci. 2017, 18(8), 1827; https://doi.org/10.3390/ijms18081827
Received: 31 July 2017 / Revised: 15 August 2017 / Accepted: 17 August 2017 / Published: 22 August 2017
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Abstract
Vedolizumab, a gut-specific biological treatment for inflammatory bowel disease (IBD), is an antibody that binds to the α4β7 integrin and blocks T-cell migration into intestinal mucosa. We aimed to investigate chemokine levels in serum of IBD-patients treated with vedolizumab. In
[...] Read more.
Vedolizumab, a gut-specific biological treatment for inflammatory bowel disease (IBD), is an antibody that binds to the α4β7 integrin and blocks T-cell migration into intestinal mucosa. We aimed to investigate chemokine levels in serum of IBD-patients treated with vedolizumab. In this pilot study, we included 11 IBD patients (8 Crohn’s disease, 3 ulcerative colitis) previously non-respondent to anti-tumor necrosis factor (TNF)-agents. Patients received vedolizumab at week 0, 2 and 6 and were evaluated for clinical efficacy at week 10. Clinical characteristics and routine laboratory parameters were obtained and patients were classified as responders or non-responders. Expression of 21 chemokines in serum was measured using Proximity Extension Assay and related to clinical outcome. At week 10, 6 out of 11 patients had clinically responded. Overall expression of CCL13 increased after treatment. In non-responders, expression of CCL13 and CXCL8 increased after treatment, and CCL20 and CXCL1 expressions were higher compared to responders. In responders, CCL28 decreased after treatment. C-reactive protein (CRP) correlated negatively with 6 chemokines before therapy, but not after therapy. Systemic CCL13 expression increases in IBD-patients after vedolizumab therapy and several chemokine levels differ between responders and non-responders. An increased CCL13-level when starting vedolizumab treatment, might indicate potential prognostic value of measuring chemokine levels when starting therapy with vedolizumab. This study provides new information on modulation of systemic chemokine levels after vedolizumab treatment. Full article
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Open AccessArticle MiR-30a-5p Inhibits Epithelial-to-Mesenchymal Transition and Upregulates Expression of Tight Junction Protein Claudin-5 in Human Upper Tract Urothelial Carcinoma Cells
Int. J. Mol. Sci. 2017, 18(8), 1826; https://doi.org/10.3390/ijms18081826
Received: 13 July 2017 / Revised: 14 August 2017 / Accepted: 18 August 2017 / Published: 22 August 2017
Cited by 4 | PDF Full-text (17895 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The involvement of microRNAs (miRNAs) in cancer development and their potential as prognostic biomarkers are becoming increasingly known. However, the signature of miRNAs and their regulatory roles in tumorigenesis of upper tract urothelial carcinoma (UTUC) remain to be elucidated. This study aimed to
[...] Read more.
The involvement of microRNAs (miRNAs) in cancer development and their potential as prognostic biomarkers are becoming increasingly known. However, the signature of miRNAs and their regulatory roles in tumorigenesis of upper tract urothelial carcinoma (UTUC) remain to be elucidated. This study aimed to profile the miRNA expression pattern in UTUC tumor tissues and identify candidate miRNAs with prognostic and/or therapeutic functions. Methods and Results: We collected 22 UTUC tissue and adjacent normal tissues samples from patients who underwent nephroureterectomy. The miRNAs signatures of three selected UTUC samples using next-generation sequencing showed that miR-30a-5p was significantly downregulated in UTUC tumors compared to adjacent normal tissues. The differentially-expressed miRNAs were specifically validated by quantitative real-time polymerase chain reaction. In addition, the miRNA expression signatures were analyzed with the transcriptome profile characterized by microarray. Further in vitro studies indicated that overexpression of miR-30a-5p significantly suppressed proliferation, migration, and epithelial-to-mesenchymal transition (EMT) in cultured BFTC-909 UTUC cells. As a potential target gene of miR-30a-5p in the tight junction pathway suggested by the pathway enrichment analysis, the reduced expression of tight junction protein claudin-5 in UTUC cells was demonstrated to be upregulated by miR-30a-5p genetic delivery. Conclusions: Taken together, our findings demonstrated that miR-30a-5p inhibits proliferation, metastasis, and EMT, and upregulates the expression of tight junction claudin-5 in UTUC cells. Thus, miR-30a-5p may provide a promising therapeutic strategy for UTUC treatment. Full article
(This article belongs to the collection Regulation by Non-Coding RNAs)
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Open AccessReview Chemokines as a Conductor of Bone Marrow Microenvironment in Chronic Myeloid Leukemia
Int. J. Mol. Sci. 2017, 18(8), 1824; https://doi.org/10.3390/ijms18081824
Received: 19 July 2017 / Revised: 19 August 2017 / Accepted: 20 August 2017 / Published: 22 August 2017
Cited by 3 | PDF Full-text (1361 KB) | HTML Full-text | XML Full-text
Abstract
All blood lineage cells are generated from hematopoietic stem cells (HSCs), which reside in bone marrow after birth. HSCs self-renew, proliferate, and differentiate into mature progeny under the control of local microenvironments including hematopoietic niche, which can deliver regulatory signals in the form
[...] Read more.
All blood lineage cells are generated from hematopoietic stem cells (HSCs), which reside in bone marrow after birth. HSCs self-renew, proliferate, and differentiate into mature progeny under the control of local microenvironments including hematopoietic niche, which can deliver regulatory signals in the form of bound or secreted molecules and from physical cues such as oxygen tension and shear stress. Among these mediators, accumulating evidence indicates the potential involvement of several chemokines, particularly CXCL12, in the interaction between HSCs and bone marrow microenvironments. Fusion between breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog (ABL)-1 gene gives rise to BCR-ABL protein with a constitutive tyrosine kinase activity and transforms HSCs and/or hematopoietic progenitor cells (HPCs) into disease-propagating leukemia stem cells (LSCs) in chronic myeloid leukemia (CML). LSCs can self-renew, proliferate, and differentiate under the influence of the signals delivered by bone marrow microenvironments including niche, as HSCs can. Thus, the interaction with bone marrow microenvironments is indispensable for the initiation, maintenance, and progression of CML. Moreover, the crosstalk between LSCs and bone marrow microenvironments can contribute to some instances of therapeutic resistance. Furthermore, evidence is accumulating to indicate the important roles of bone marrow microenvironment-derived chemokines. Hence, we will herein discuss the roles of chemokines in CML with a focus on bone marrow microenvironments. Full article
(This article belongs to the Special Issue Tumor Microenvironment)
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Open AccessArticle Identification of Reference and Biomarker Proteins in Chlamydomonas reinhardtii Cultured under Different Stress Conditions
Int. J. Mol. Sci. 2017, 18(8), 1822; https://doi.org/10.3390/ijms18081822
Received: 25 May 2017 / Revised: 16 August 2017 / Accepted: 17 August 2017 / Published: 22 August 2017
Cited by 2 | PDF Full-text (2763 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Reference proteins and biomarkers are important for the quantitative evaluation of protein abundance. Chlamydomonas reinhardtii was grown under five stress conditions (dark, cold, heat, salt, and glucose supplementation), and the OD750 and total protein contents were evaluated on days 0, 1, 2,
[...] Read more.
Reference proteins and biomarkers are important for the quantitative evaluation of protein abundance. Chlamydomonas reinhardtii was grown under five stress conditions (dark, cold, heat, salt, and glucose supplementation), and the OD750 and total protein contents were evaluated on days 0, 1, 2, 4, and 6 of culture. Antibodies for 20 candidate proteins were generated, and the protein expression patterns were examined by western blotting. Reference protein(s) for each treatment were identified by calculating the Pearson’s correlation coefficient (PCC) between target protein abundance and total protein content. Histone H3, beta tubulin 1 (TUB-1), ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (RBCL), and mitochondrial F1F0 ATP synthase subunit 6 (ATPs-6) were the top reference proteins, because they were expressed stably under multiple stress conditions. The average relative-fold change (ARF) value of each protein was calculated to identify biomarkers. Heat shock protein 90B (HSP90B), flagellar associated protein (FAP127) and ATP synthase CF0 A subunit (ATPs-A) were suitable biomarkers for multiple treatments, while receptor of activated protein kinase C1 (RCK1), biotin carboxylase (BCR1), mitochondrial phosphate carrier protein (MPC1), and rubisco large subunit N-methyltransferase (RMT1) were suitable biomarkers for the dark, cold, heat, and glucose treatments, respectively. Full article
(This article belongs to the Special Issue Selected Papers from the 6th National Plant Protein Research Congress)
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Open AccessReview Principal Aspects Regarding the Maintenance of Mammalian Mitochondrial Genome Integrity
Int. J. Mol. Sci. 2017, 18(8), 1821; https://doi.org/10.3390/ijms18081821
Received: 10 July 2017 / Revised: 11 August 2017 / Accepted: 14 August 2017 / Published: 22 August 2017
Cited by 2 | PDF Full-text (945 KB) | HTML Full-text | XML Full-text
Abstract
Mitochondria have emerged as key players regarding cellular homeostasis not only due to their contribution regarding energy production through oxidative phosphorylation, but also due to their involvement in signaling, ion regulation, and programmed cell death. Indeed, current knowledge supports the notion that mitochondrial
[...] Read more.
Mitochondria have emerged as key players regarding cellular homeostasis not only due to their contribution regarding energy production through oxidative phosphorylation, but also due to their involvement in signaling, ion regulation, and programmed cell death. Indeed, current knowledge supports the notion that mitochondrial dysfunction is a hallmark in the pathogenesis of various diseases. Mitochondrial biogenesis and function require the coordinated action of two genomes: nuclear and mitochondrial. Unfortunately, both intrinsic and environmental genotoxic insults constantly threaten the integrity of nuclear as well as mitochondrial DNA. Despite the extensive research that has been made regarding nuclear genome instability, the importance of mitochondrial genome integrity has only recently begun to be elucidated. The specific architecture and repair mechanisms of mitochondrial DNA, as well as the dynamic behavior that mitochondria exert regarding fusion, fission, and autophagy participate in mitochondrial genome stability, and therefore, cell homeostasis. Full article
(This article belongs to the Special Issue Mechanisms Leading to Genomic Instability)
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Open AccessArticle GLUT10—Lacking in Arterial Tortuosity Syndrome—Is Localized to the Endoplasmic Reticulum of Human Fibroblasts
Int. J. Mol. Sci. 2017, 18(8), 1820; https://doi.org/10.3390/ijms18081820
Received: 28 July 2017 / Revised: 13 August 2017 / Accepted: 13 August 2017 / Published: 22 August 2017
Cited by 1 | PDF Full-text (3959 KB) | HTML Full-text | XML Full-text
Abstract
GLUT10 belongs to a family of transporters that catalyze the uptake of sugars/polyols by facilitated diffusion. Loss-of-function mutations in the SLC2A10 gene encoding GLUT10 are responsible for arterial tortuosity syndrome (ATS). Since subcellular distribution of the transporter is dubious, we aimed to clarify
[...] Read more.
GLUT10 belongs to a family of transporters that catalyze the uptake of sugars/polyols by facilitated diffusion. Loss-of-function mutations in the SLC2A10 gene encoding GLUT10 are responsible for arterial tortuosity syndrome (ATS). Since subcellular distribution of the transporter is dubious, we aimed to clarify the localization of GLUT10. In silico GLUT10 localization prediction suggested its presence in the endoplasmic reticulum (ER). Immunoblotting showed the presence of GLUT10 protein in the microsomal, but not in mitochondrial fractions of human fibroblasts and liver tissue. An even cytosolic distribution with an intense perinuclear decoration of GLUT10 was demonstrated by immunofluorescence in human fibroblasts, whilst mitochondrial markers revealed a fully different decoration pattern. GLUT10 decoration was fully absent in fibroblasts from three ATS patients. Expression of exogenous, tagged GLUT10 in fibroblasts from an ATS patient revealed a strict co-localization with the ER marker protein disulfide isomerase (PDI). The results demonstrate that GLUT10 is present in the ER. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Open AccessCommunication Impact of Platelet-Rich Plasma on Viability and Proliferation in Wound Healing Processes after External Radiation
Int. J. Mol. Sci. 2017, 18(8), 1819; https://doi.org/10.3390/ijms18081819
Received: 12 July 2017 / Revised: 7 August 2017 / Accepted: 17 August 2017 / Published: 22 August 2017
Cited by 1 | PDF Full-text (743 KB) | HTML Full-text | XML Full-text
Abstract
Platelet-rich plasma is a current subject of studies on chronic wound healing therapy due to possible pro-angiogenic effects. Microvascular compromise represents the major component in radiogenic wound healing complications. The effects of platelet-rich plasma on irradiated cells of the cutaneous wound healing process
[...] Read more.
Platelet-rich plasma is a current subject of studies on chronic wound healing therapy due to possible pro-angiogenic effects. Microvascular compromise represents the major component in radiogenic wound healing complications. The effects of platelet-rich plasma on irradiated cells of the cutaneous wound healing process are poorly understood so far. In this study, the interaction of endothelial cells and adipose-derived stem cells in conjunction with treatment with platelet-rich plasma is investigated in the context of radiation effects. Therefore, the expression of surface-marker CD90 and CD31 was determined. Moreover, cell proliferation and viability after external radiation was analyzed with and without treatment by platelet-rich plasma. Full article
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells 2017)
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Open AccessCase Report Peritoneal Mesothelioma with Residential Asbestos Exposure. Report of a Case with Long Survival (Seventeen Years) Analyzed by Cgh-Array
Int. J. Mol. Sci. 2017, 18(8), 1818; https://doi.org/10.3390/ijms18081818
Received: 27 June 2017 / Revised: 17 August 2017 / Accepted: 18 August 2017 / Published: 22 August 2017
Cited by 1 | PDF Full-text (912 KB) | HTML Full-text | XML Full-text
Abstract
Malignant mesothelioma is a rare and aggressive tumor with limited therapeutic options. We report a case of a malignant peritoneal mesothelioma (MPM) epithelioid type, with environmental asbestos exposure, in a 36-year-old man, with a long survival (17 years). The patient received standard treatment
[...] Read more.
Malignant mesothelioma is a rare and aggressive tumor with limited therapeutic options. We report a case of a malignant peritoneal mesothelioma (MPM) epithelioid type, with environmental asbestos exposure, in a 36-year-old man, with a long survival (17 years). The patient received standard treatment which included cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods and Results: Molecular analysis with comparative genomic hybridization (CGH)-array was performed on paraffin-embedded tumoral samples. Multiple chromosomal imbalances were detected. The gains were prevalent. Losses at 1q21, 2q11.1→q13, 8p23.1, 9p12→p11, 9q21.33→q33.1, 9q12→q21.33, and 17p12→p11.2 are observed. Chromosome band 3p21 (BAP1), 9p21 (CDKN2A) and 22q12 (NF2) are not affected. Conclusions: the defects observed in this case are uncommon in malignant peritoneal mesothelioma. Some chromosomal aberrations that appear to be random here, might actually be relevant events explaining the response to therapy, the long survival and, finally, may be considered useful prognostic factors in peritoneal malignant mesothelioma (PMM). Full article
(This article belongs to the Special Issue Mesothelioma Heterogeneity: Potential Mechanisms)
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Open AccessReview Current Advances in Thyroid Cancer Management. Are We Ready for the Epidemic Rise of Diagnoses?
Int. J. Mol. Sci. 2017, 18(8), 1817; https://doi.org/10.3390/ijms18081817
Received: 31 July 2017 / Revised: 16 August 2017 / Accepted: 16 August 2017 / Published: 22 August 2017
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Abstract
A rising incidence of thyroid cancers (TCs) mainly small tumors, observed during recent years, lead to many controversies regarding treatment strategies. TCs represent a distinct molecular background and clinical outcome. Although in most cases TCs are characterized by a good prognosis, there are
[...] Read more.
A rising incidence of thyroid cancers (TCs) mainly small tumors, observed during recent years, lead to many controversies regarding treatment strategies. TCs represent a distinct molecular background and clinical outcome. Although in most cases TCs are characterized by a good prognosis, there are some aggressive forms, which do not respond to standard treatment. There are still some questions, which have to be resolved to avoid dangerous simplifications in the clinical management. In this article, we focused on the current advantages in preoperative molecular diagnostic tests and histopathological examination including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). We discussed the controversies regarding the extent of thyroid surgery and adjuvant radioiodine therapy, as well as new treatment modalities for radioiodine-refractory differentiated thyroid cancer (RR-DTC). Considering medullary thyroid cancer (MTC), we analyzed a clinical management based on histopathology and RET (ret proto-oncogene) mutation genotype, disease follow-up with a special attention to serum calcitonin doubling time as an important prognostic marker, and targeted therapy applied in advanced MTC. In addition, we provided some data regarding anaplastic thyroid cancer (ATC), a highly lethal neoplasm, which lead to death in nearly 100% of patients due to the lack of effective treatment options. Full article
(This article belongs to the Special Issue Cell and Molecular Biology of Thyroid Disorders)
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Open AccessArticle Bioaccessibility, Intestinal Permeability and Plasma Stability of Isorhamnetin Glycosides from Opuntia ficus-indica (L.)
Int. J. Mol. Sci. 2017, 18(8), 1816; https://doi.org/10.3390/ijms18081816
Received: 3 August 2017 / Revised: 14 August 2017 / Accepted: 16 August 2017 / Published: 22 August 2017
Cited by 3 | PDF Full-text (1292 KB) | HTML Full-text | XML Full-text
Abstract
Isorhamnetin glycosides are representative compounds of Opuntia ficus-indica that possess different biological activities. There is slight information about the changes in bioaccessibility induced by the glycosylation pattern of flavonoids, particularly for isorhamnetin. In this study, the bioaccessibility and permeability of isorhamnetin glycosides extracted
[...] Read more.
Isorhamnetin glycosides are representative compounds of Opuntia ficus-indica that possess different biological activities. There is slight information about the changes in bioaccessibility induced by the glycosylation pattern of flavonoids, particularly for isorhamnetin. In this study, the bioaccessibility and permeability of isorhamnetin glycosides extracted from O. ficus-indica were contrasted with an isorhamnetin standard. Also, the plasma stability of these isorhamnetin glycosides after intravenous administration in rats was evaluated. Recoveries of isorhamnetin after oral and gastric digestion were lower than that observed for its glycosides. After intestinal digestion, isorhamnetin glycosides recoveries were reduced to less than 81.0%. The apparent permeability coefficient from apical (AP) to basolateral (BL) direction (Papp(AP-BL)) of isorhamnetin was 2.6 to 4.6-fold higher than those obtained for its glycosides. Isorhamnetin diglycosides showed higher Papp(AP-BL) values than triglycosides. Sugar substituents affected the Papp(AP-BL) of the triglycosides. Isorhamnetin glycosides were better retained in the circulatory system than the aglycone. After intravenous dose of the isorhamnetin standard, the elimination half-life was 0.64 h but increased to 1.08 h when the O. ficus-indica extract was administered. These results suggest that isorhamnetin glycosides naturally found in O. ficus-indica could be a controlled delivery system to maintain a constant plasmatic concentration of this important flavonoid to exert its biological effects in vivo. Full article
(This article belongs to the Special Issue Bioactive Phenolics and Polyphenols 2018)
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Open AccessArticle Successive Onset of Molecular, Cellular and Tissue-Specific Responses in Midgut Gland of Littorina littorea Exposed to Sub-Lethal Cadmium Concentrations
Int. J. Mol. Sci. 2017, 18(8), 1815; https://doi.org/10.3390/ijms18081815
Received: 4 July 2017 / Revised: 17 August 2017 / Accepted: 18 August 2017 / Published: 22 August 2017
Cited by 2 | PDF Full-text (6958 KB) | HTML Full-text | XML Full-text
Abstract
Cadmium (Cd) is one of the most harmful metals, being toxic to most animal species, including marine invertebrates. Among marine gastropods, the periwinkle (Littorina littorea) in particular can accumulate high amounts of Cd in its midgut gland. In this organ, the
[...] Read more.
Cadmium (Cd) is one of the most harmful metals, being toxic to most animal species, including marine invertebrates. Among marine gastropods, the periwinkle (Littorina littorea) in particular can accumulate high amounts of Cd in its midgut gland. In this organ, the metal can elicit extensive cytological and tissue-specific alterations that may reach, depending on the intensity of Cd exposure, from reversible lesions to pathological cellular disruptions. At the same time, Littorina littorea expresses a Cd-specific metallothionein (MT) that, due to its molecular features, expectedly exerts a protective function against the adverse intracellular effects of this metal. The aim of the present study was, therefore, to assess the time course of MT induction in the periwinkle’s midgut gland on the one hand, and cellular and tissue-specific alterations in the digestive organ complex (midgut gland and digestive tract) on the other, upon exposure to sub-lethal Cd concentrations (0.25 and 1 mg Cd/L) over 21 days. Depending on the Cd concentrations applied, the beginning of alterations of the assessed parameters followed distinct concentration-dependent and time-dependent patterns, where the timeframe for the onset of the different response reactions became narrower at higher Cd concentrations compared to lower exposure concentrations. Full article
(This article belongs to the Special Issue Metal Metabolism in Animals II)
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Open AccessArticle The Herbal Bitter Drug Gentiana lutea Modulates Lipid Synthesis in Human Keratinocytes In Vitro and In Vivo
Int. J. Mol. Sci. 2017, 18(8), 1814; https://doi.org/10.3390/ijms18081814
Received: 28 June 2017 / Revised: 26 July 2017 / Accepted: 15 August 2017 / Published: 22 August 2017
Cited by 1 | PDF Full-text (2809 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Gentiana lutea is a herbal bitter drug that is used to enhance gastrointestinal motility and secretion. Recently we have shown that amarogentin, a characteristic bitter compound of Gentiana lutea extract (GE), binds to the bitter taste receptors TAS2R1 and TAS2R38 in human keratinocytes,
[...] Read more.
Gentiana lutea is a herbal bitter drug that is used to enhance gastrointestinal motility and secretion. Recently we have shown that amarogentin, a characteristic bitter compound of Gentiana lutea extract (GE), binds to the bitter taste receptors TAS2R1 and TAS2R38 in human keratinocytes, and stimulates the synthesis of epidermal barrier proteins. Here, we wondered if GE also modulates lipid synthesis in human keratinocytes. To address this issue, human primary keratinocytes were incubated for 6 days with GE. Nile Red labeling revealed that GE significantly increased lipid synthesis in keratinocytes. Similarly, gas chromatography with flame ionization detector indicated that GE increases the amount of triglycerides in keratinocytes. GE induced the expression of epidermal ceramide synthase 3, but not sphingomyelinase. Lipid synthesis, as well as ceramide synthase 3 expression, could be specifically blocked by inhibitors of the p38 MAPK and PPARγ signaling pathway. To assess if GE also modulates lipid synthesis in vivo, we performed a proof of concept half side comparison on the volar forearms of 33 volunteers. In comparison to placebo, GE significantly increased the lipid content of the treated skin areas, as measured with a sebumeter. Thus, GE enhances lipid synthesis in human keratinocytes that is essential for building an intact epidermal barrier. Therefore, GE might be used to improve skin disorders with an impaired epidermal barrier, e.g., very dry skin and atopic eczema. Full article
(This article belongs to the Special Issue Inflammatory Skin Conditions 2017)
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Open AccessReview Towards a Better Understanding of GABAergic Remodeling in Alzheimer’s Disease
Int. J. Mol. Sci. 2017, 18(8), 1813; https://doi.org/10.3390/ijms18081813
Received: 31 July 2017 / Revised: 16 August 2017 / Accepted: 17 August 2017 / Published: 21 August 2017
Cited by 3 | PDF Full-text (1063 KB) | HTML Full-text | XML Full-text
Abstract
γ-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the vertebrate brain. In the past, there has been a major research drive focused on the dysfunction of the glutamatergic and cholinergic neurotransmitter systems in Alzheimer’s disease (AD). However, there is now growing evidence
[...] Read more.
γ-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the vertebrate brain. In the past, there has been a major research drive focused on the dysfunction of the glutamatergic and cholinergic neurotransmitter systems in Alzheimer’s disease (AD). However, there is now growing evidence in support of a GABAergic contribution to the pathogenesis of this neurodegenerative disease. Previous studies paint a complex, convoluted and often inconsistent picture of AD-associated GABAergic remodeling. Given the importance of the GABAergic system in neuronal function and homeostasis, in the maintenance of the excitatory/inhibitory balance, and in the processes of learning and memory, such changes in GABAergic function could be an important factor in both early and later stages of AD pathogenesis. Given the limited scope of currently available therapies in modifying the course of the disease, a better understanding of GABAergic remodeling in AD could open up innovative and novel therapeutic opportunities. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Open AccessReview Regulation of Mitochondrial Structure and Dynamics by the Cytoskeleton and Mechanical Factors
Int. J. Mol. Sci. 2017, 18(8), 1812; https://doi.org/10.3390/ijms18081812
Received: 19 July 2017 / Revised: 9 August 2017 / Accepted: 18 August 2017 / Published: 21 August 2017
Cited by 2 | PDF Full-text (1706 KB) | HTML Full-text | XML Full-text
Abstract
Mitochondria supply cells with energy in the form of ATP, guide apoptosis, and contribute to calcium buffering and reactive oxygen species production. To support these diverse functions, mitochondria form an extensive network with smaller clusters that are able to move along microtubules aided
[...] Read more.
Mitochondria supply cells with energy in the form of ATP, guide apoptosis, and contribute to calcium buffering and reactive oxygen species production. To support these diverse functions, mitochondria form an extensive network with smaller clusters that are able to move along microtubules aided by motor proteins. Mitochondria are also associated with the actin network, which is involved in cellular responses to various mechanical factors. In this review, we discuss mitochondrial structure and function in relation to the cytoskeleton and various mechanical factors influencing cell functions. We first summarize the morphological features of mitochondria with an emphasis on fission and fusion as well as how network properties govern function. We then review the relationship between the mitochondria and the cytoskeletal structures, including mechanical interactions. We also discuss how stretch and its dynamic pattern affect mitochondrial structure and function. Finally, we present preliminary data on how extracellular matrix stiffness influences mitochondrial morphology and ATP generation. We conclude by discussing the more general role that mitochondria may play in mechanobiology and how the mechanosensitivity of mitochondria may contribute to the development of several diseases and aging. Full article
(This article belongs to the Special Issue Mitochondria Crosstalks with other Organelles in Pathophysiology)
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