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Int. J. Mol. Sci., Volume 14, Issue 5 (May 2013), Pages 8684-10682

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Open AccessArticle Characterization, Purification of Poncirin from Edible Citrus Ougan (Citrus reticulate cv. Suavissima) and Its Growth Inhibitory Effect on Human Gastric Cancer Cells SGC-7901
Int. J. Mol. Sci. 2013, 14(5), 8684-8697; doi:10.3390/ijms14058684
Received: 20 January 2013 / Revised: 2 April 2013 / Accepted: 17 April 2013 / Published: 24 April 2013
Cited by 8 | PDF Full-text (290 KB) | HTML Full-text | XML Full-text
Abstract
Poncirin is a bitter flavanone glycoside with various biological activities. Poncirin was isolated from four different tissues (flavedo, albedo, segment membrane, and juice sac) of Ougan fruit (Citrus reticulate cv. Suavissima). The highest content of poncirin was found in the albedo of
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Poncirin is a bitter flavanone glycoside with various biological activities. Poncirin was isolated from four different tissues (flavedo, albedo, segment membrane, and juice sac) of Ougan fruit (Citrus reticulate cv. Suavissima). The highest content of poncirin was found in the albedo of Ougan fruit (1.37 mg/g DW). High speed counter-current chromatography (HSCCC) combined with D101 resin chromatography was utilized for the separation and purification of poncirin from the albedo of Ougan fruit. After this two-step purification, poncirin purity increased from 0.14% to 96.56%. The chemical structure of the purified poncirin was identified by both HPLC-PDA and LC-MS. Poncirin showed a significant in vitro inhibitory effect on the growth of the human gastric cancer cells, SGC-7901, in a dose-dependent manner. Thus, poncirin from Ougan fruit, may be beneficial for gastric cancer prevention. The purification method demonstrated here will be useful for further studies on the pharmacological mechanism of poncirin activity, as well as for guiding the consumption of Ougan fruit. Full article
(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism)
Open AccessCommunication Porous Polyimide Membranes Prepared by Wet Phase Inversion for Use in Low Dielectric Applications
Int. J. Mol. Sci. 2013, 14(5), 8698-8707; doi:10.3390/ijms14058698
Received: 30 November 2012 / Revised: 27 March 2013 / Accepted: 27 March 2013 / Published: 24 April 2013
Cited by 8 | PDF Full-text (822 KB) | HTML Full-text | XML Full-text
Abstract
A wet phase inversion process of polyamic acid (PAA) allowed fabrication of a porous membrane of polyimide (PI) with the combination of a low dielectric constant (1.7) and reasonable mechanical properties (Tensile strain: 8.04%, toughness: 3.4 MJ/m3, tensile stress: 39.17 MPa,
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A wet phase inversion process of polyamic acid (PAA) allowed fabrication of a porous membrane of polyimide (PI) with the combination of a low dielectric constant (1.7) and reasonable mechanical properties (Tensile strain: 8.04%, toughness: 3.4 MJ/m3, tensile stress: 39.17 MPa, and young modulus: 1.13 GPa), with further thermal imidization process of PAA. PAA was simply synthesized from purified pyromellitic dianhydride (PMDA) and 4,4-oxydianiline (ODA) in two different reaction solvents such as γ-butyrolactone (GBL) and N-methyl-2-pyrrolidinone (NMP), which produce Mw/PDI of 630,000/1.45 and 280,000/2.0, respectively. The porous PAA membrane was fabricated by the wet phase inversion process based on a solvent/non-solvent system via tailored composition between GBL and NMP. The porosity of PI, indicative of a low electric constant, decreased with increasing concentration of GBL, which was caused by sponge-like formation. However, due to interplay between the low electric constant (structural formation) and the mechanical properties, GBL was employed for further exploration, using toluene and acetone vs. DI-water as a coagulation media. Non-solvents influenced determination of the PAA membrane size and porosity. With this approach, insight into the interplay between dielectric properties and mechanical properties will inform a wide range of potential low-k material applications. Full article
Open AccessArticle Surgical Resection of Brain Metastases—Impact on Neurological Outcome
Int. J. Mol. Sci. 2013, 14(5), 8708-8718; doi:10.3390/ijms14058708
Received: 5 February 2013 / Revised: 13 April 2013 / Accepted: 16 April 2013 / Published: 24 April 2013
Cited by 5 | PDF Full-text (856 KB) | HTML Full-text | XML Full-text
Abstract
Brain metastases (BM) develop in about 30% of all cancer patients. Surgery plays an important role in confirming neuropathological diagnosis, relieving mass effects and improving the neurological status. To select patients with the highest benefit from surgical resection, prognostic indices (RPA, GPA) have
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Brain metastases (BM) develop in about 30% of all cancer patients. Surgery plays an important role in confirming neuropathological diagnosis, relieving mass effects and improving the neurological status. To select patients with the highest benefit from surgical resection, prognostic indices (RPA, GPA) have been formulated which are solely focused on survival without considering neurological improvement. In this study we analyzed the impact of surgical resection on the neurological status in addition to overall survival in 206 BM patients. Surgical mortality and morbidity was 0.0% and 10.3% respectively. New neurologic deficits occurred in 6.3% of all patients. The median overall survival was 6.3 months. Poor RPA class and short time interval between diagnosis of cancer and the occurrence of BM were independent factors predictive for poor survival. Improvement of neurological performance was achieved in 56.8% of all patients, with the highest improvement rate seen in patients presenting with increased intracranial pressure and hemiparesis. Notably, the neurological benefits were independent from RPA class. In conclusion, surgical resection leads to significant neurological improvement despite poor RPA class and short overall survival. Considering the low mortality and morbidity rates, resection should be considered as a valid option to increase neurological function and quality of life for patients with BM. Full article
(This article belongs to the Special Issue Brain Metastasis)
Open AccessArticle The Expression of Millettia pinnata Chalcone Isomerase in Saccharomyces cerevisiae Salt-Sensitive Mutants Enhances Salt-Tolerance
Int. J. Mol. Sci. 2013, 14(5), 8775-8786; doi:10.3390/ijms14058775
Received: 31 January 2013 / Revised: 18 March 2013 / Accepted: 1 April 2013 / Published: 24 April 2013
Cited by 5 | PDF Full-text (586 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The present study demonstrates a new Millettia pinnata chalcone isomerase (MpCHI) whose transcription level in leaf was confirmed to be enhanced after being treated by seawater or NaCl (500 mM) via transcriptome sequencing and Real-Time Quantitative Reverse Transcription PCR (QRT-PCR) analyses. Its full
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The present study demonstrates a new Millettia pinnata chalcone isomerase (MpCHI) whose transcription level in leaf was confirmed to be enhanced after being treated by seawater or NaCl (500 mM) via transcriptome sequencing and Real-Time Quantitative Reverse Transcription PCR (QRT-PCR) analyses. Its full length cDNA (666 bp) was obtained by 3'-end and 5'-end Rapid Amplification of cDNA Ends (RACE). The analysis via NCBI BLAST indicates that both aminoacid sequence and nucleotide sequence of the MpCHI clone share high homology with other leguminous CHIs (73%–86%). Evolutionarily, the phylogenic analysis further revealed that the MpCHI is a close relative of leguminous CHIs. The MpCHI protein consists of 221 aminoacid (23.64 KDa), whose peptide length, amino acid residues of substrate-binding site and reactive site are very similar to other leguminous CHIs reported previously. Two pYES2-MpCHI transformed salt-sensitive Saccharomyces cerevisiae mutants (Δnha1 and Δnhx1) showed improved salt-tolerance significantly compared to pYES2-vector transformed yeast mutants, suggesting the MpCHI or the flavonoid biosynthesis pathway could regulate the resistance to salt stress in M. pinnata. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessArticle The Cloning and Characterization of the Enolase2 Gene of Gekko japonicus and Its Polyclonal Antibody Preparation
Int. J. Mol. Sci. 2013, 14(5), 8787-8800; doi:10.3390/ijms14058787
Received: 6 February 2013 / Revised: 7 April 2013 / Accepted: 16 April 2013 / Published: 24 April 2013
Cited by 5 | PDF Full-text (2178 KB) | HTML Full-text | XML Full-text
Abstract
The enolase2 gene is usually expressed in mature neurons and also named neuron specific enolase (NSE). In the present study, we first obtained the NSE gene cDNA sequence by using the RACE method based on the expressed sequence tag (EST) fragment
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The enolase2 gene is usually expressed in mature neurons and also named neuron specific enolase (NSE). In the present study, we first obtained the NSE gene cDNA sequence by using the RACE method based on the expressed sequence tag (EST) fragment from the cDNA library of Gekko japonicus and identified one transcript of about 2.2 kb in central nervous system of Gekko japonicus by Northern blotting. The open reading frame of NSE is 1305 bp, which encodes a 435 amino-acid protein. We further investigated the multi-tissue expression pattern of NSE by RT-PCR and found that the expression of NSE mRNA was very high in brain, spinal cord and low in heart, while it was not detectable in other tissues. The real-time quantitative PCR was used to investigate the time-dependent change in the expression of the NSE mRNA level after gecko spinal cord transection and found it significantly increased at one day, reaching its highest level three days post-injury and then decreasing at the seventh day of the experiment. The recombinant plasmid of pET-32a-NSE was constructed and induced to express His fused NSE protein. The purified NSE protein was used to immunize rabbits to generate polyclonal antisera. The titer of the antiserum was more than 1:65536 determined by ELISA. Western blotting showed that the prepared antibody could specifically recognize the recombinant and endogenous NSE protein. The result of immunohistochemistry revealed that positive signals were present in neurons of the brain and the spinal cord. This study provided the tools of cDNA and polyclonal antibody for studying NSE function in Gekko japonicus. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Caffeic Acid Phenethyl Ester Suppresses Proliferation and Survival of TW2.6 Human Oral Cancer Cells via Inhibition of Akt Signaling
Int. J. Mol. Sci. 2013, 14(5), 8801-8817; doi:10.3390/ijms14058801
Received: 1 March 2013 / Revised: 2 April 2013 / Accepted: 15 April 2013 / Published: 24 April 2013
Cited by 19 | PDF Full-text (1809 KB) | HTML Full-text | XML Full-text
Abstract
Caffeic acid phenethyl ester (CAPE) is a bioactive component extracted from honeybee hive propolis. Our observations indicated that CAPE treatment suppressed cell proliferation and colony formation of TW2.6 human oral squamous cell carcinoma (OSCC) cells dose-dependently. CAPE treatment decreased G1 phase cell population,
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Caffeic acid phenethyl ester (CAPE) is a bioactive component extracted from honeybee hive propolis. Our observations indicated that CAPE treatment suppressed cell proliferation and colony formation of TW2.6 human oral squamous cell carcinoma (OSCC) cells dose-dependently. CAPE treatment decreased G1 phase cell population, increased G2/M phase cell population, and induced apoptosis in TW2.6 cells. Treatment with CAPE decreased protein abundance of Akt, Akt1, Akt2, Akt3, phospho-Akt Ser473, phospho-Akt Thr 308, GSK3β, FOXO1, FOXO3a, phospho-FOXO1 Thr24, phospho-FoxO3a Thr32, NF-κB, phospho-NF-κB Ser536, Rb, phospho-Rb Ser807/811, Skp2, and cyclin D1, but increased cell cycle inhibitor p27Kip. Overexpression of Akt1 or Akt2 in TW2.6 cells rescued growth inhibition caused by CAPE treatment. Co-treating TW2.6 cells with CAPE and 5-fluorouracil, a commonly used chemotherapeutic drug for oral cancers, exhibited additive cell proliferation inhibition. Our study suggested that administration of CAPE is a potential adjuvant therapy for patients with OSCC oral cancer. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Two Distinct Channels Mediated by m2mAChR and α9nAChR Co-Exist in Type II Vestibular Hair Cells of Guinea Pig
Int. J. Mol. Sci. 2013, 14(5), 8818-8831; doi:10.3390/ijms14058818
Received: 25 February 2013 / Revised: 29 March 2013 / Accepted: 17 April 2013 / Published: 24 April 2013
Cited by 8 | PDF Full-text (1144 KB) | HTML Full-text | XML Full-text
Abstract
Acetylcholine (ACh) is the principal vestibular efferent neurotransmitter among mammalians. Pharmacologic studies prove that ACh activates a small conductance Ca2+-activated K+ channels (KCa) current (SK2), mediated by α9-containing nicotinic ACh receptor (α9nAChR) in mammalian type II vestibular hair cells (VHCs
[...] Read more.
Acetylcholine (ACh) is the principal vestibular efferent neurotransmitter among mammalians. Pharmacologic studies prove that ACh activates a small conductance Ca2+-activated K+ channels (KCa) current (SK2), mediated by α9-containing nicotinic ACh receptor (α9nAChR) in mammalian type II vestibular hair cells (VHCs II). However, our studies demonstrate that the m2 muscarinic ACh receptor (m2mAChR) mediates a big conductance KCa current (BK) in VHCs II. To better elucidate the correlation between these two distinct channels in VHCs II of guinea pig, this study was designed to verify whether these two channels and their corresponding AChR subtypes co-exist in the same VHCs II by whole-cell patch clamp recordings. We found that m2mAChR sensitive BK currents were activated in VHCs II isolated by collagenase IA, while α9nAChR sensitive SK2 currents were activated in VHCs II isolated by trypsin. Interestingly, after exposing the patched cells isolated by trypsin to collagenase IA for 3 min, the α9nAChR sensitive SK2 current was abolished, while m2mAChR-sensitive BK current was activated. Therefore, our findings provide evidence that the two distinct channels and their corresponding AChR subtypes may co-exist in the same VHCs II, and the alternative presence of these two ACh receptors-sensitive currents depended on isolating preparation with different enzymes. Full article
Open AccessArticle LILRA3 Is Associated with Benign Prostatic Hyperplasia Risk in a Chinese Population
Int. J. Mol. Sci. 2013, 14(5), 8832-8840; doi:10.3390/ijms14058832
Received: 21 February 2013 / Revised: 21 March 2013 / Accepted: 8 April 2013 / Published: 24 April 2013
Cited by 2 | PDF Full-text (200 KB) | HTML Full-text | XML Full-text
Abstract
A recent prostate cancer (PCa) genome-wide association study (GWAS) identified rs103294, a single nucleotide polymorphism (SNP) located on LILRA3, a key component in the regulation of inflammatory inhibition, to be significantly associated with PCa risk in a Chinese population. Because inflammation may
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A recent prostate cancer (PCa) genome-wide association study (GWAS) identified rs103294, a single nucleotide polymorphism (SNP) located on LILRA3, a key component in the regulation of inflammatory inhibition, to be significantly associated with PCa risk in a Chinese population. Because inflammation may be a common etiological risk factor between PCa and benign prostatic hyperplasia (BPH), the current study was conducted to investigate the association of rs103294 with BPH risk. rs103294 was genotyped in a Chinese population of 426 BPH cases and 1,008 controls from Xinhua Hospital in Shanghai, China. Association between rs103294, BPH risk and clinicopathological traits were tested with adjustment for age. rs103294 was significantly associated with BPH risk with a p-value of 0.0067. Individuals with risk allele “C” had increased risk for BPH (OR = 1.34, 95% CI: 1.09–1.66). Stratified analysis revealed a stronger association risk for younger patients who are below 72 years old (OR = 1.51, 95% CI: 1.06–2.16). Our study represents the first effort to demonstrate that LILRA3 gene is significantly associated with BPH risk in a Chinese population. Our results support a common role of inflammation in the development of PCa and BPH. Additional studies are needed to further evaluate our results. Full article
(This article belongs to the Special Issue Molecular Research in Urology)
Open AccessArticle Triterpenoids from the Roots of Rhaphiolepis indica var. tashiroi and Their Anti-Inflammatory Activity
Int. J. Mol. Sci. 2013, 14(5), 8890-8898; doi:10.3390/ijms14058890
Received: 22 February 2013 / Revised: 22 March 2013 / Accepted: 26 March 2013 / Published: 24 April 2013
Cited by 7 | PDF Full-text (393 KB) | HTML Full-text | XML Full-text
Abstract
Two new triterpenoids, 2α,3β-dihydroxyolean-11,13(18)-dien-19β,28-olide (1) and 3β,5β-dihydroxyglutinol (2), together with eight known compounds (310) were isolated from the roots of Rhaphiolepis indica var. tashiroi (Rosaceae). The structures of 110 were determined by
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Two new triterpenoids, 2α,3β-dihydroxyolean-11,13(18)-dien-19β,28-olide (1) and 3β,5β-dihydroxyglutinol (2), together with eight known compounds (310) were isolated from the roots of Rhaphiolepis indica var. tashiroi (Rosaceae). The structures of 110 were determined by spectroscopic techniques. Among these isolates, 2α,3β-dihydroxyolean-13(18)-en-28-oic acid (9) exhibited inhibitory effect on N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide production, with an IC50 value of 16.50 μM. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Identification of Plasma Metabolomic Profiling for Diagnosis of Esophageal Squamous-Cell Carcinoma Using an UPLC/TOF/MS Platform
Int. J. Mol. Sci. 2013, 14(5), 8899-8911; doi:10.3390/ijms14058899
Received: 5 March 2013 / Revised: 8 April 2013 / Accepted: 18 April 2013 / Published: 24 April 2013
Cited by 18 | PDF Full-text (450 KB) | HTML Full-text | XML Full-text
Abstract
Epidemiological studies indicated that esophageal squamous-cell carcinoma (ESCC) is still one of the most common causes of cancer incidence in the world. Searching for valuable markers including circulating endogenous metabolites associated with the risk of esophageal cancer, is extremely important A comparative metabolomics
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Epidemiological studies indicated that esophageal squamous-cell carcinoma (ESCC) is still one of the most common causes of cancer incidence in the world. Searching for valuable markers including circulating endogenous metabolites associated with the risk of esophageal cancer, is extremely important A comparative metabolomics study was performed by using ultraperformance liquid chromatography-electrospray ionization-accurate mass time-of-flight mass spectrometry to analyze 53 pairs of plasma samples from ESCC patients and healthy controls recruited in Huaian, China. The result identified a metabolomic profiling of plasma including 25 upregulated metabolites and five downregulated metabolites, for early diagnosis of ESCC. With a database-based verification protocol, 11 molecules were identified, and six upregulated molecules of interest in ESCC were found to belong to phospholipids as follows: phosphatidylserine, phosphatidic acid, phosphatidyl choline, phosphatidylinositol, phosphatidyl ethanolamine, and sphinganine 1-phosphate. Clinical estimation of metabolic biomarkers through hierarchical cluster analysis in plasma samples from 17 ESCC patients and 29 healthy volunteers indicated that the present metabolite profile could distinguish ESCC patients from healthy individuals. The cluster of aberrant expression of these metabolites in ESCC indicates the critical role of phospholipid metabolism in the oncogenesis of ESCC and suggests its potential ability to assess the risk of ESCC development in addition to currently used risk factors. Full article
(This article belongs to the Special Issue Advances in Cancer Diagnosis)
Open AccessArticle New Radioligands for Describing the Molecular Pharmacology of MT1 and MT2 Melatonin Receptors
Int. J. Mol. Sci. 2013, 14(5), 8948-8962; doi:10.3390/ijms14058948
Received: 16 March 2013 / Revised: 14 April 2013 / Accepted: 15 April 2013 / Published: 25 April 2013
Cited by 10 | PDF Full-text (378 KB) | HTML Full-text | XML Full-text
Abstract
Melatonin receptors have been studied for several decades. The low expression of the receptors in tissues led the scientific community to find a substitute for the natural hormone melatonin, the agonist 2-[125I]-iodomelatonin. Using the agonist, several hundreds of studies were conducted,
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Melatonin receptors have been studied for several decades. The low expression of the receptors in tissues led the scientific community to find a substitute for the natural hormone melatonin, the agonist 2-[125I]-iodomelatonin. Using the agonist, several hundreds of studies were conducted, including the discovery of agonists and antagonists for the receptors and minute details about their molecular behavior. Recently, we attempted to expand the panel of radioligands available for studying the melatonin receptors by using the newly discovered compounds SD6, DIV880, and S70254. These compounds were characterized for their affinities to the hMT1 and hMT2 recombinant receptors and their functionality in the classical GTPS system. SD6 is a full agonist, equilibrated between the receptor isoforms, whereas S70254 and DIV880 are only partial MT2 agonists, with Ki in the low nanomolar range while they have no affinity to MT1 receptors. These new tools will hopefully allow for additions to the current body of information on the native localization of the receptor isoforms in tissues. Full article
(This article belongs to the Special Issue Advances in the Research of Melatonin)
Open AccessArticle Characteristic of the Pepper CaRGA2 Gene in Defense Responses against Phytophthora capsici Leonian
Int. J. Mol. Sci. 2013, 14(5), 8985-9004; doi:10.3390/ijms14058985
Received: 25 January 2013 / Revised: 15 April 2013 / Accepted: 16 April 2013 / Published: 25 April 2013
Cited by 13 | PDF Full-text (1174 KB) | HTML Full-text | XML Full-text
Abstract
The most significant threat to pepper production worldwide is the Phytophthora blight, which is caused by the oomycete pathogen, Phytophthora capsici Leonian. In an effort to help control this disease, we isolated and characterized a P. capsici resistance gene, CaRGA2, from a
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The most significant threat to pepper production worldwide is the Phytophthora blight, which is caused by the oomycete pathogen, Phytophthora capsici Leonian. In an effort to help control this disease, we isolated and characterized a P. capsici resistance gene, CaRGA2, from a high resistant pepper (C. annuum CM334) and analyzed its function by the method of real-time PCR and virus-induced gene silencing (VIGS). The CaRGA2 has a full-length cDNA of 3,018 bp with 2,874 bp open reading frame (ORF) and encodes a 957-aa protein. The protein has a predicted molecular weight of 108.6 kDa, and the isoelectric point is 8.106. Quantitative real-time PCR indicated that CaRGA2 expression was rapidly induced by P. capsici. The gene expression pattern was different between the resistant and susceptible cultivars. CaRGA2 was quickly expressed in the resistant cultivar, CM334, and reached to a peak at 24 h after inoculation with P. capsici, five-fold higher than that of susceptible cultivar. Our results suggest that CaRGA2 has a distinct pattern of expression and plays a critical role in P. capsici stress tolerance. When the CaRGA2 gene was silenced via VIGS, the resistance level was clearly suppressed, an observation that was supported by semi-quantitative RT-PCR and detached leave inoculation. VIGS analysis revealed their importance in the surveillance to P. capsici in pepper. Our results support the idea that the CaRGA2 gene may show their response in resistance against P. capsici. These analyses will aid in an effort towards breeding for broad and durable resistance in economically important pepper cultivars. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessArticle The Influence of Polyunsaturated Fatty Acids on the Phospholipase D Isoforms Trafficking and Activity in Mast Cells
Int. J. Mol. Sci. 2013, 14(5), 9005-9017; doi:10.3390/ijms14059005
Received: 26 March 2013 / Revised: 15 April 2013 / Accepted: 18 April 2013 / Published: 25 April 2013
Cited by 2 | PDF Full-text (1099 KB) | HTML Full-text | XML Full-text
Abstract
The impact of polyunsaturated fatty acid (PUFA) supplementation on phospholipase D (PLD) trafficking and activity in mast cells was investigated. The enrichment of mast cells with different PUFA including α-linolenic acid (LNA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LA) or arachidonic
[...] Read more.
The impact of polyunsaturated fatty acid (PUFA) supplementation on phospholipase D (PLD) trafficking and activity in mast cells was investigated. The enrichment of mast cells with different PUFA including α-linolenic acid (LNA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LA) or arachidonic acid (AA) revealed a PUFA-mediated modulation of the mastoparan-stimulated PLD trafficking and activity. All PUFA examined, except AA, prevented the migration of the PLD1 to the plasma membrane. For PLD2 no PUFA effects on trafficking could be observed. Moreover, PUFA supplementation resulted in an increase of mastoparan-stimulated total PLD activity, which correlated with the number of double bonds of the supplemented fatty acids. To investigate, which PLD isoform was affected by PUFA, stimulated mast cells were supplemented with DHA or AA in the presence of specific PLD-isoform inhibitors. It was found that both DHA and AA diminished the inhibition of PLD activity in the presence of a PLD1 inhibitor. By contrast, only AA diminished the inhibition of PLD activity in the presence of a PLD2 inhibitor. Thus, PUFA modulate the trafficking and activity of PLD isoforms in mast cells differently. This may, in part, account for the immunomodulatory effect of unsaturated fatty acids and contributes to our understanding of the modulation of mast cell activity by PUFA. Full article
(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications)
Open AccessArticle IGF-1 Antibody Prolongs the Effective Duration Time of Botulinum Toxin in Decreasing Muscle Strength
Int. J. Mol. Sci. 2013, 14(5), 9051-9061; doi:10.3390/ijms14059051
Received: 18 February 2013 / Revised: 28 March 2013 / Accepted: 15 April 2013 / Published: 25 April 2013
Cited by 2 | PDF Full-text (612 KB) | HTML Full-text | XML Full-text
Abstract
Botulinum toxin type-A (Btx-A), a powerful therapeutic tool in various medical specialties, requires repeated injections to maintain its effect. Therefore, novel methods to prolong the effective duration time of Btx-A are highly needed. Rats were assigned to three major groups: control group (
[...] Read more.
Botulinum toxin type-A (Btx-A), a powerful therapeutic tool in various medical specialties, requires repeated injections to maintain its effect. Therefore, novel methods to prolong the effective duration time of Btx-A are highly needed. Rats were assigned to three major groups: control group (n = 30), Btx-A group (n = 30), and IGF-1 Ab groups. IGF-1 Ab groups were composed by sub-groups A1–A5 (each has 25 rats) for the subsequent IGF-1Ab dose-effect study. Muscle strength was determined by a survey system for rat lower limbs nerve and muscle function. Muscle-specific receptor tyrosine kinase (MuSK), Insulin-like growth factor binding protein-5 (IGFBP5), and growth-associated protein, 43-kDa (GAP43) were determined by real-time polymerase chain reactions (PCRs) and Western blot. We found that Btx-A decreased the muscle strength, with a paralysis maintained for 70 days. IGF-1Ab prolonged the effective duration time of Btx-A. Real-time PCRs and Western blot showed that IGF-1Ab delayed the increase of MuSK and IGFBP5 after Btx-A injection, without affecting GAP43. These results indicate that IGF-1Ab might prolong the effective duration time of Btx-A on muscle strength through delaying the increase of MuSK. It would be interesting to determine whether IGF-1Ab can be used as an auxiliary measure to the Btx-A treatment in the future. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Phylogeography and Genetic Differentiation among Populations of the Moon Turban Snail Lunella granulata Gmelin, 1791 (Gastropoda: Turbinidae)
Int. J. Mol. Sci. 2013, 14(5), 9062-9079; doi:10.3390/ijms14059062
Received: 2 January 2013 / Revised: 11 April 2013 / Accepted: 16 April 2013 / Published: 25 April 2013
Cited by 5 | PDF Full-text (1545 KB) | HTML Full-text | XML Full-text
Abstract
We examined the genetic variation and phylogeographic relationships among 10 populations of Lunella granulata from mainland China, Penghu Archipelago, Taiwan Island, and Japan using mitochondrial COI and 16S markers. A total of 45 haplotypes were obtained in 112 specimens, and relatively high levels
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We examined the genetic variation and phylogeographic relationships among 10 populations of Lunella granulata from mainland China, Penghu Archipelago, Taiwan Island, and Japan using mitochondrial COI and 16S markers. A total of 45 haplotypes were obtained in 112 specimens, and relatively high levels of haplotype diversity (h = 0.903) and low levels of nucleotide diversity (π = 0.0046) were detected. Four major phylogenetic lineage clusters were revealed and were concordant with their geographic distribution, agreeing with the haplotype network. These results suggested that geographic barrier isolating effects were occurring among the populations. This hypothesis was also supported by a significant genetic differentiation index (FST = 0.709) and by a spatial analysis of molecular variance (SAMOVA) analysis. A mismatch distribution analysis, neutrality tests and Bayesian skyline plots found a single significant population expansion. This expansion occurred on the coast of mainland China before 20–17 ka. Consequently, although the dispersal ability of the planktonic stage and the circulation of ocean currents generally promote genetic exchanges among populations, L. granulata has tended to maintain distinct genetic groups that reflect the respective geographic origins of the constituent lineages. Although the circulation of ocean currents, in principle, may still play a role in determining the genetic composition of populations, long-distance migration between regions is difficult even at the planktonic stage. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Transcriptome Analysis of Thapsia laciniata Rouy Provides Insights into Terpenoid Biosynthesis and Diversity in Apiaceae
Int. J. Mol. Sci. 2013, 14(5), 9080-9098; doi:10.3390/ijms14059080
Received: 22 February 2013 / Revised: 21 March 2013 / Accepted: 17 April 2013 / Published: 25 April 2013
Cited by 19 | PDF Full-text (1319 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Thapsia laciniata Rouy (Apiaceae) produces irregular and regular sesquiterpenoids with thapsane and guaiene carbon skeletons, as found in other Apiaceae species. A transcriptomic analysis utilizing Illumina next-generation sequencing enabled the identification of novel genes involved in the biosynthesis of terpenoids in Thapsia.
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Thapsia laciniata Rouy (Apiaceae) produces irregular and regular sesquiterpenoids with thapsane and guaiene carbon skeletons, as found in other Apiaceae species. A transcriptomic analysis utilizing Illumina next-generation sequencing enabled the identification of novel genes involved in the biosynthesis of terpenoids in Thapsia. From 66.78 million HQ paired-end reads obtained from T. laciniata roots, 64.58 million were assembled into 76,565 contigs (N50: 1261 bp). Seventeen contigs were annotated as terpene synthases and five of these were predicted to be sesquiterpene synthases. Of the 67 contigs annotated as cytochromes P450, 18 of these are part of the CYP71 clade that primarily performs hydroxylations of specialized metabolites. Three contigs annotated as aldehyde dehydrogenases grouped phylogenetically with the characterized ALDH1 from Artemisia annua and three contigs annotated as alcohol dehydrogenases grouped with the recently described ADH1 from A. annua. ALDH1 and ADH1 were characterized as part of the artemisinin biosynthesis. We have produced a comprehensive EST dataset for T. laciniata roots, which contains a large sample of the T. laciniata transcriptome. These transcriptome data provide the foundation for future research into the molecular basis for terpenoid biosynthesis in Thapsia and on the evolution of terpenoids in Apiaceae. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Expression Pattern of Small Nucleolar RNA Host Genes and Long Non-Coding RNA in X-rays-Treated Lymphoblastoid Cells
Int. J. Mol. Sci. 2013, 14(5), 9099-9110; doi:10.3390/ijms14059099
Received: 5 March 2013 / Revised: 19 April 2013 / Accepted: 22 April 2013 / Published: 25 April 2013
Cited by 11 | PDF Full-text (368 KB) | HTML Full-text | XML Full-text
Abstract
A wide variety of biological effects are induced in cells that are exposed to ionizing radiation. The expression changes of coding mRNA and non-coding micro-RNA have been implicated in irradiated cells. The involvement of other classes of non-coding RNAs (ncRNA), such as small
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A wide variety of biological effects are induced in cells that are exposed to ionizing radiation. The expression changes of coding mRNA and non-coding micro-RNA have been implicated in irradiated cells. The involvement of other classes of non-coding RNAs (ncRNA), such as small nucleolar RNAs (snoRNAs), long ncRNAs (lncRNAs), and PIWI-interacting RNAs (piRNAs) in cells recovering from radiation-induced damage has not been examined. Thus, we investigated whether these ncRNA were undergoing changes in cells exposed to ionizing radiation. The modulation of ncRNAs expression was determined in human TK6 (p53 positive) and WTK1 (p53 negative) cells. The snoRNA host genes SNHG1, SNHG6, and SNHG11 were induced in TK6 cells. In WTK1 cells, SNHG1 was induced but SNHG6, and SNHG11 were repressed. SNHG7 was repressed in TK6 cells and was upregulated in WTK1 cells. The lncRNA MALAT1 and SOX2OT were induced in both TK6 and WTK1 cells and SRA1 was induced in TK6 cells only. Interestingly, the MIAT and PIWIL1 were not expressed in TK6 cells before or after the ionizing radiation treatment. The MIAT and PIWIL1 were upregulated in WTK1 cells. This data provides evidence that altered ncRNA expression is a part of the complex stress response operating in radiation-treated cells and this response depends on functional p53. Full article
(This article belongs to the collection Radiation Toxicity in Cells)
Open AccessArticle Tumour Cell Labelling by Magnetic Nanoparticles with Determination of Intracellular Iron Content and Spatial Distribution of the Intracellular Iron
Int. J. Mol. Sci. 2013, 14(5), 9111-9125; doi:10.3390/ijms14059111
Received: 1 March 2013 / Revised: 26 March 2013 / Accepted: 2 April 2013 / Published: 26 April 2013
Cited by 18 | PDF Full-text (488 KB) | HTML Full-text | XML Full-text
Abstract
Magnetically labelled cells are used for in vivo cell tracking by MRI, used for the clinical translation of cell-base therapies. Studies involving magnetic labelled cells may include separation of labelled cells, targeted delivery and controlled release of drugs, contrast enhanced MRI and magnetic
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Magnetically labelled cells are used for in vivo cell tracking by MRI, used for the clinical translation of cell-base therapies. Studies involving magnetic labelled cells may include separation of labelled cells, targeted delivery and controlled release of drugs, contrast enhanced MRI and magnetic hyperthermia for the in situ ablation of tumours. Dextran-coated super-paramagnetic iron oxide (SPIO) ferumoxides are used clinically as an MR contrast agents primarily for hepatic imaging. The material is also widely used for in vitro cell labelling, as are other SPIO-based particles. Our results on the uptake by human cancer cell lines of ferumoxides indicate that electroporation in the presence of protamine sulphate (PS) results in rapid high uptake of SPIO nanoparticles (SPIONs) by parenchymal tumour cells without significant impairment of cell viability. Quantitative determination of cellular iron uptake performed by colorimetric assay is in agreement with data from the literature. These results on intracellular iron content together with the intracellular distribution of SPIONs by magnetic force microscopy (MFM) following in vitro uptake by parenchymal tumour cells confirm the potential of this technique for clinical tumour cell detection and destruction. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
Open AccessArticle The Effect of the Aerial Part of Lindera akoensis on Lipopolysaccharides (LPS)-Induced Nitric Oxide Production in RAW264.7 Cells
Int. J. Mol. Sci. 2013, 14(5), 9168-9181; doi:10.3390/ijms14059168
Received: 12 March 2013 / Revised: 12 April 2013 / Accepted: 15 April 2013 / Published: 26 April 2013
Cited by 11 | PDF Full-text (444 KB) | HTML Full-text | XML Full-text
Abstract
Four new secondary metabolites, 3α-((E)-Dodec-1-enyl)-4β-hydroxy-5β-methyldihydrofuran-2-one (1), linderinol (6), 4'-O-methylkaempferol 3-O-α-L-(4''-E-p-coumaroyl)rhamnoside (11) and kaempferol 3-O-α-L-(4''-Z-p-coumaroyl)rhamnoside (12) with eleven known compounds—3-epilistenolide
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Four new secondary metabolites, 3α-((E)-Dodec-1-enyl)-4β-hydroxy-5β-methyldihydrofuran-2-one (1), linderinol (6), 4'-O-methylkaempferol 3-O-α-L-(4''-E-p-coumaroyl)rhamnoside (11) and kaempferol 3-O-α-L-(4''-Z-p-coumaroyl)rhamnoside (12) with eleven known compounds—3-epilistenolide D1 (2), 3-epilistenolide D2 (3), (3Z,4α,5β)-3-(dodec-11-ynylidene)-4-hydroxy-5-methylbutanolide (4), (3E,4β,5β)-3-(dodec-11-ynylidene)-4-hydroxy-5-methylbutanolide (5), matairesinol (7), syringaresinol (8), (+)-pinoresinol (9), salicifoliol (10), 4''-p-coumaroylafzelin (13), catechin (14) and epicatechin (15)—were first isolated from the aerial part of Lindera akoensis. Their structures were determined by detailed analysis of 1D- and 2D-NMR spectroscopic data. All of the compounds isolated from Lindera akoensis showed that in vitro anti-inflammatory activity decreases the LPS-stimulated production of nitric oxide (NO) in RAW 264.7 cell, with IC50 values of 4.1–413.8 µM. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Growth and Potential Damage of Human Bone-Derived Cells on Fresh and Aged Fullerene C60 Films
Int. J. Mol. Sci. 2013, 14(5), 9182-9204; doi:10.3390/ijms14059182
Received: 15 January 2013 / Revised: 10 April 2013 / Accepted: 15 April 2013 / Published: 26 April 2013
Cited by 6 | PDF Full-text (6048 KB) | HTML Full-text | XML Full-text
Abstract
Fullerenes are nanoparticles composed of carbon atoms arranged in a spherical hollow cage-like structure. Numerous studies have evaluated the therapeutic potential of fullerene derivates against oxidative stress-associated conditions, including the prevention or treatment of arthritis. On the other hand, fullerenes are not only
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Fullerenes are nanoparticles composed of carbon atoms arranged in a spherical hollow cage-like structure. Numerous studies have evaluated the therapeutic potential of fullerene derivates against oxidative stress-associated conditions, including the prevention or treatment of arthritis. On the other hand, fullerenes are not only able to quench, but also to generate harmful reactive oxygen species. The reactivity of fullerenes may change in time due to the oxidation and polymerization of fullerenes in an air atmosphere. In this study, we therefore tested the dependence between the age of fullerene films (from one week to one year) and the proliferation, viability and metabolic activity of human osteosarcoma cells (lines MG-63 and U-2 OS). We also monitored potential membrane and DNA damage and morphological changes of the cells. After seven days of cultivation, we did not observe any cytotoxic morphological changes, such as enlarged cells or cytosolic vacuole formation. Furthermore, there was no increased level of DNA damage. The increasing age of the fullerene films did not cause enhancement of cytotoxicity. On the contrary, it resulted in an improvement in the properties of these materials, which are more suitable for cell cultivation. Therefore, fullerene films could be considered as a promising material with potential use as a bioactive coating of cell carriers for bone tissue engineering. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles 2012)
Open AccessArticle Excitation and Adaptation in Bacteria–a Model Signal Transduction System that Controls Taxis and Spatial Pattern Formation
Int. J. Mol. Sci. 2013, 14(5), 9205-9248; doi:10.3390/ijms14059205
Received: 1 February 2013 / Revised: 20 March 2013 / Accepted: 22 March 2013 / Published: 26 April 2013
Cited by 4 | PDF Full-text (1600 KB) | HTML Full-text | XML Full-text
Abstract
The machinery for transduction of chemotactic stimuli in the bacterium E. coli is one of the most completely characterized signal transduction systems, and because of its relative simplicity, quantitative analysis of this system is possible. Here we discuss models which reproduce many of
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The machinery for transduction of chemotactic stimuli in the bacterium E. coli is one of the most completely characterized signal transduction systems, and because of its relative simplicity, quantitative analysis of this system is possible. Here we discuss models which reproduce many of the important behaviors of the system. The important characteristics of the signal transduction system are excitation and adaptation, and the latter implies that the transduction system can function as a “derivative sensor” with respect to the ligand concentration in that the DC component of a signal is ultimately ignored if it is not too large. This temporal sensing mechanism provides the bacterium with a memory of its passage through spatially- or temporally-varying signal fields, and adaptation is essential for successful chemotaxis. We also discuss some of the spatial patterns observed in populations and indicate how cell-level behavior can be embedded in population-level descriptions. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Open AccessArticle Biodegradable Polycaprolactone-Titania Nanocomposites: Preparation, Characterization and Antimicrobial Properties
Int. J. Mol. Sci. 2013, 14(5), 9249-9266; doi:10.3390/ijms14059249
Received: 27 March 2013 / Revised: 11 April 2013 / Accepted: 16 April 2013 / Published: 29 April 2013
Cited by 17 | PDF Full-text (792 KB) | HTML Full-text | XML Full-text
Abstract
Nanocomposites obtained from the incorporation of synthesized TiO2 nanoparticles (≈10 nm average primary particle size) in different amounts, ranging from 0.5 to 5 wt.%, into a biodegradable polycaprolactone matrix are achieved via a straightforward and commercial melting processing. The resulting nanocomposites have
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Nanocomposites obtained from the incorporation of synthesized TiO2 nanoparticles (≈10 nm average primary particle size) in different amounts, ranging from 0.5 to 5 wt.%, into a biodegradable polycaprolactone matrix are achieved via a straightforward and commercial melting processing. The resulting nanocomposites have been structurally and thermally characterized by transmission electron microscopy (TEM), wide/small angle X-ray diffraction (WAXS/SAXS, respectively) and differential scanning calorimetry (DSC). TEM evaluation provides evidence of an excellent nanometric dispersion of the oxide component in the polymeric matrix, with aggregates having an average size well below 100 nm. Presence of these TiO2 nanoparticles induces a nucleant effect during polymer crystallization. Moreover, the antimicrobial activity of nanocomposites has been tested using both UV and visible light against Gram-negative Escherichia coli bacteria and Gram-positive Staphylococcus aureus. The bactericidal behavior has been explained through the analysis of the material optical properties, with a key role played by the creation of new electronic states within the polymer-based nanocomposites. Full article
(This article belongs to the Special Issue Antimicrobial Polymers)
Open AccessArticle Differential Activity of Plasma and Vacuolar Membrane Transporters Contributes to Genotypic Differences in Salinity Tolerance in a Halophyte Species, Chenopodium quinoa
Int. J. Mol. Sci. 2013, 14(5), 9267-9285; doi:10.3390/ijms14059267
Received: 22 February 2013 / Revised: 13 April 2013 / Accepted: 15 April 2013 / Published: 29 April 2013
Cited by 28 | PDF Full-text (2251 KB) | HTML Full-text | XML Full-text
Abstract
Halophytes species can be used as a highly convenient model system to reveal key ionic and molecular mechanisms that confer salinity tolerance in plants. Earlier, we reported that quinoa (Chenopodium quinoa Willd.), a facultative C3 halophyte species, can efficiently control the activity
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Halophytes species can be used as a highly convenient model system to reveal key ionic and molecular mechanisms that confer salinity tolerance in plants. Earlier, we reported that quinoa (Chenopodium quinoa Willd.), a facultative C3 halophyte species, can efficiently control the activity of slow (SV) and fast (FV) tonoplast channels to match specific growth conditions by ensuring that most of accumulated Na+ is safely locked in the vacuole (Bonales-Alatorre et al. (2013) Plant Physiology). This work extends these finding by comparing the properties of tonoplast FV and SV channels in two quinoa genotypes contrasting in their salinity tolerance. The work is complemented by studies of the kinetics of net ion fluxes across the plasma membrane of quinoa leaf mesophyll tissue. Our results suggest that multiple mechanisms contribute towards genotypic differences in salinity tolerance in quinoa. These include: (i) a higher rate of Na+ exclusion from leaf mesophyll; (ii) maintenance of low cytosolic Na+ levels; (iii) better K+ retention in the leaf mesophyll; (iv) a high rate of H+ pumping, which increases the ability of mesophyll cells to restore their membrane potential; and (v) the ability to reduce the activity of SV and FV channels under saline conditions. These mechanisms appear to be highly orchestrated, thus enabling the remarkable overall salinity tolerance of quinoa species. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessArticle Off-Target Effect of Endogenous siRNA Derived from RMRP in Human Cells
Int. J. Mol. Sci. 2013, 14(5), 9305-9318; doi:10.3390/ijms14059305
Received: 28 February 2013 / Revised: 16 April 2013 / Accepted: 17 April 2013 / Published: 29 April 2013
Cited by 3 | PDF Full-text (433 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Endogenous siRNAs (endo-siRNAs) are key regulators of RNA silencing in plants and worms; however, the biogenesis and function of endogenous siRNAs in mammals remain largely unknown. We previously demonstrated that human telomerase reverse transcriptase produces a self-targeting endogenous siRNA from non-coding RMRP RNA
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Endogenous siRNAs (endo-siRNAs) are key regulators of RNA silencing in plants and worms; however, the biogenesis and function of endogenous siRNAs in mammals remain largely unknown. We previously demonstrated that human telomerase reverse transcriptase produces a self-targeting endogenous siRNA from non-coding RMRP RNA via RNA-dependent RNA polymerase (RdRP) activity. Here, we investigated whether the endo-siRNA derived from RMRP targets other genes in addition to RMRP. Four algorithms for microRNA target prediction were used to identify possible targets of the endo-siRNA, and the phytanoyl-CoA hydroxylase-interacting protein-like gene (PHYHIPL) was identified as the most promising candidate. The 3' UTR of PHYHIPL was found to contain three possible target sites with perfect seed pairing; deletion of each of these sites resulted in recovery of upstream luciferase expression. In addition, sequence-specific inhibition of the RMRP-derived endo-siRNA increased expression of PHYHIPL mRNA. The results described here suggest that the endo-siRNA uses silencing mechanisms that are similar to those used by microRNAs for gene silencing. To our knowledge, this study is the first confirmation of the off-target effect of human endogenous siRNA produced by RdRP activity. Full article
(This article belongs to the Special Issue Molecular Cut and Paste)
Open AccessArticle Simple and Rapid Synthesis of Magnetite/Hydroxyapatite Composites for Hyperthermia Treatments via a Mechanochemical Route
Int. J. Mol. Sci. 2013, 14(5), 9365-9378; doi:10.3390/ijms14059365
Received: 22 February 2013 / Revised: 19 April 2013 / Accepted: 22 April 2013 / Published: 29 April 2013
Cited by 18 | PDF Full-text (1897 KB) | HTML Full-text | XML Full-text
Abstract
This paper presents a simple method for the rapid synthesis of magnetite/hydroxyapatite composite particles. In this method, superparamagnetic magnetite nanoparticles are first synthesized by coprecipitation using ferrous chloride and ferric chloride. Immediately following the synthesis, carbonate-substituted (B-type) hydroxyapatite particles are mechanochemically synthesized by
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This paper presents a simple method for the rapid synthesis of magnetite/hydroxyapatite composite particles. In this method, superparamagnetic magnetite nanoparticles are first synthesized by coprecipitation using ferrous chloride and ferric chloride. Immediately following the synthesis, carbonate-substituted (B-type) hydroxyapatite particles are mechanochemically synthesized by wet milling dicalcium phosphate dihydrate and calcium carbonate in a dispersed suspension of magnetite nanoparticles, during which the magnetite nanoparticles are incorporated into the hydroxyapatite matrix. We observed that the resultant magnetite/hydroxyapatite composites possessed a homogeneous dispersion of magnetite nanoparticles, characterized by an absence of large aggregates. When this material was subjected to an alternating magnetic field, the heat generated increased with increasing magnetite concentration. For a magnetite concentration of 30 mass%, a temperature increase greater than 20 K was achieved in less than 50 s. These results suggest that our composites exhibit good hyperthermia properties and are promising candidates for hyperthermia treatments. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
Open AccessArticle Senescence Marker Protein-30 (SMP30) Deficiency Impairs Myocardium-Induced Dilation of Coronary Arterioles Associated with Reactive Oxygen Species
Int. J. Mol. Sci. 2013, 14(5), 9408-9423; doi:10.3390/ijms14059408
Received: 19 March 2013 / Revised: 15 April 2013 / Accepted: 16 April 2013 / Published: 29 April 2013
Cited by 7 | PDF Full-text (466 KB) | HTML Full-text | XML Full-text
Abstract
Senescence marker protein-30 (SMP30) decreases with aging. Mice with SMP30 deficiency, a model of aging, have a short lifespan with increased oxidant stress. To elucidate SMP30’s effect on coronary circulation derived from myocytes, we measured the changes in the diameter of isolated coronary
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Senescence marker protein-30 (SMP30) decreases with aging. Mice with SMP30 deficiency, a model of aging, have a short lifespan with increased oxidant stress. To elucidate SMP30’s effect on coronary circulation derived from myocytes, we measured the changes in the diameter of isolated coronary arterioles in wild-type (WT) mice exposed to supernatant collected from isolated paced cardiac myocytes from SMP30 KO or WT mice. Pacing increased hydrogen peroxide in myocytes, and hydrogen peroxide was greater in SMP30 KO myocytes compared to WT myocytes. Antimycin enhanced and FCCP (oxidative phosphorylation uncoupler in mitochondria) decreased superoxide production in both groups. Addition of supernatant from stimulated myocytes, either SMP30 KO or WT, caused vasodilation. The degree of the vasodilation response to supernatant was smaller in SMP30 KO mice compared to WT mice. Administration of catalase to arterioles eliminated vasodilation in myocyte supernatant of WT mice and converted vasodilation to vasoconstriction in myocyte supernatant of SMP30 KO mice. This vasoconstriction was eliminated by olmesartan, an angiotensin II receptor antagonist. Thus, SMP30 deficiency combined with oxidant stress increases angiotensin and hydrogen peroxide release from cardiac myocytes. SMP30 plays an important role in the regulation of coronary vascular tone by myocardium. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
Open AccessArticle Synthesis, Cytotoxicity, DNA Binding and Apoptosis of Rhein-Phosphonate Derivatives as Antitumor Agents
Int. J. Mol. Sci. 2013, 14(5), 9424-9439; doi:10.3390/ijms14059424
Received: 31 January 2013 / Revised: 12 April 2013 / Accepted: 15 April 2013 / Published: 29 April 2013
Cited by 9 | PDF Full-text (1434 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Several rhein-phosphonate derivatives (5ac) were synthesized and evaluated for in vitro cytotoxicity against HepG-2, CNE, Spca-2, Hela and Hct-116 cell lines. Some compounds showed relatively high cytotoxicity. Especially compounds 5b exhibited the strongest cytotoxicity against HepG-2 and Spca-2 cells
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Several rhein-phosphonate derivatives (5ac) were synthesized and evaluated for in vitro cytotoxicity against HepG-2, CNE, Spca-2, Hela and Hct-116 cell lines. Some compounds showed relatively high cytotoxicity. Especially compounds 5b exhibited the strongest cytotoxicity against HepG-2 and Spca-2 cells (IC50 was 8.82 and 9.01 µM), respectively. All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. Further experiments proved that 5b could disturb the cell cycle in HepG-2 cells and induce apoptosis. In addition, the binding properties of a model conjugate 5b to DNA were investigated by methods (UV-Vis, fluorescence, CD spectroscopy). Results indicated that 5b showed moderate ability to interact ct-DNA. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Characterization of Rice NADPH Oxidase Genes and Their Expression under Various Environmental Conditions
Int. J. Mol. Sci. 2013, 14(5), 9440-9458; doi:10.3390/ijms14059440
Received: 29 January 2013 / Revised: 4 April 2013 / Accepted: 17 April 2013 / Published: 29 April 2013
Cited by 12 | PDF Full-text (2673 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Plasma membrane NADPH oxidases (Noxs) are key producers of reactive oxygen species under both normal and stress conditions in plants. We demonstrate that at least eleven genes in the genome of rice (Oryza sativa L.) were predicted to encode Nox proteins, including
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Plasma membrane NADPH oxidases (Noxs) are key producers of reactive oxygen species under both normal and stress conditions in plants. We demonstrate that at least eleven genes in the genome of rice (Oryza sativa L.) were predicted to encode Nox proteins, including nine genes (OsNox19) that encode typical Noxs and two that encode ancient Nox forms (ferric reduction oxidase 1 and 7, OsFRO1 and OsFRO7). Phylogenetic analysis divided the Noxs from nine plant species into six subfamilies, with rice Nox genes distributed among subfamilies I to V. Gene expression analysis using semi-quantitative RT-PCR and real-time qRT-PCR indicated that the expression of rice Nox genes depends on organs and environmental conditions. Exogenous calcium strongly stimulated the expression of OsNox3, OsNox5, OsNox7, and OsNox8, but depressed the expression of OsFRO1. Drought stress substantially upregulated the expression of OsNox13, OsNox5, OsNox9, and OsFRO1, but downregulated OsNox6. High temperature upregulated OsNox59, but significantly downregulated OsNox13 and OsFRO1. NaCl treatment increased the expression of OsNox2, OsNox8, OsFRO1, and OsFRO7, but decreased that of OsNox1, OsNox3, OsNox5, and OsNox6. These results suggest that the expression profiles of rice Nox genes have unique stress-response characteristics, reflecting their related but distinct functions in response to different environmental stresses. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
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Open AccessArticle Improved Nutritive Quality and Salt Resistance in Transgenic Maize by Simultaneously Overexpression of a Natural Lysine-Rich Protein Gene, SBgLR, and an ERF Transcription Factor Gene, TSRF1
Int. J. Mol. Sci. 2013, 14(5), 9459-9474; doi:10.3390/ijms14059459
Received: 31 December 2012 / Revised: 16 April 2013 / Accepted: 16 April 2013 / Published: 29 April 2013
Cited by 11 | PDF Full-text (3676 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Maize (Zea mays L.), as one of the most important crops in the world, is deficient in lysine and tryptophan. Environmental conditions greatly impact plant growth, development and productivity. In this study, we used particle bombardment mediated co-transformation to obtain marker-free transgenic
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Maize (Zea mays L.), as one of the most important crops in the world, is deficient in lysine and tryptophan. Environmental conditions greatly impact plant growth, development and productivity. In this study, we used particle bombardment mediated co-transformation to obtain marker-free transgenic maize inbred X178 lines harboring a lysine-rich protein gene SBgLR from potato and an ethylene responsive factor (ERF) transcription factor gene, TSRF1, from tomato. Both of the target genes were successfully expressed and showed various expression levels in different transgenic lines. Analysis showed that the protein and lysine content in T1 transgenic maize seeds increased significantly. Compared to non-transformed maize, the protein and lysine content increased by 7.7% to 24.38% and 8.70% to 30.43%, respectively. Moreover, transgenic maize exhibited more tolerance to salt stress. When treated with 200 mM NaCl for 48 h, both non-transformed and transgenic plant leaves displayed wilting and losing green symptoms and dramatic increase of the free proline contents. However, the degree of control seedlings was much more serious than that of transgenic lines and much more increases of the free proline contents in the transgenic lines than that in the control seedlings were observed. Meanwhile, lower extent decreases of the chlorophyll contents were detected in the transgenic seedlings. Quantitative RT-PCR was performed to analyze the expression of ten stress-related genes, including stress responsive transcription factor genes, ZmMYB59 and ZmMYC1, proline synthesis related genes, ZmP5CS1 and ZmP5CS2, photosynthesis-related genes, ZmELIP, ZmPSI-N, ZmOEE, Zmrbcs and ZmPLAS, and one ABA biosynthesis related gene, ZmSDR. The results showed that with the exception of ZmP5CS1 and ZmP5CS2 in line 9–10 and 19–11, ZmMYC1 in line 19–11 and ZmSDR in line 19–11, the expression of other stress-related genes were inhibited in transgenic lines under normal conditions. After salt treatment, the expressions of the ten stress-related genes were significantly induced in both wild-type (WT) and transgenic lines. However, compared to WT, the increases of ZmP5CS1 in all these three transgenic lines and ZmP5CS2 in line 9–10 were less than WT plants. This study provides an effective approach of maize genetic engineering for improved nutritive quality and salt tolerance. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessArticle Oxidative Stress Mediates the Disruption of Airway Epithelial Tight Junctions through a TRPM2-PLCγ1-PKCα Signaling Pathway
Int. J. Mol. Sci. 2013, 14(5), 9475-9486; doi:10.3390/ijms14059475
Received: 24 January 2013 / Revised: 18 March 2013 / Accepted: 16 April 2013 / Published: 29 April 2013
Cited by 7 | PDF Full-text (819 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Oxidative stress has been implicated as an important contributing factor in the pathogenesis of several pulmonary inflammatory diseases. Previous studies have indicated a relationship between oxidative stress and the attenuation of epithelial tight junctions (TJs). In Human Bronchial Epithelial-16 cells (16HBE), we demonstrated
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Oxidative stress has been implicated as an important contributing factor in the pathogenesis of several pulmonary inflammatory diseases. Previous studies have indicated a relationship between oxidative stress and the attenuation of epithelial tight junctions (TJs). In Human Bronchial Epithelial-16 cells (16HBE), we demonstrated the degradation of zonula occludens-1 (ZO-1), and claudin-2 exhibited a great dependence on the activation of the transient receptor potential melastatin (TRPM) 2 channel, phospholipase Cγ1 (PLCγ1) and the protein kinase Cα (PKCα) signaling cascade. Full article
(This article belongs to the Special Issue Oxidative Stress and Ageing)
Open AccessArticle Drought Stress Acclimation Imparts Tolerance to Sclerotinia sclerotiorum and Pseudomonas syringae in Nicotiana benthamiana
Int. J. Mol. Sci. 2013, 14(5), 9497-9513; doi:10.3390/ijms14059497
Received: 12 March 2013 / Revised: 13 April 2013 / Accepted: 22 April 2013 / Published: 2 May 2013
Cited by 16 | PDF Full-text (2845 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Acclimation of plants with an abiotic stress can impart tolerance to some biotic stresses. Such a priming response has not been widely studied. In particular, little is known about enhanced defense capacity of drought stress acclimated plants to fungal and bacterial pathogens. Here
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Acclimation of plants with an abiotic stress can impart tolerance to some biotic stresses. Such a priming response has not been widely studied. In particular, little is known about enhanced defense capacity of drought stress acclimated plants to fungal and bacterial pathogens. Here we show that prior drought acclimation in Nicotiana benthamiana plants imparts tolerance to necrotrophic fungus, Sclerotinia sclerotiorum, and also to hemi-biotrophic bacterial pathogen, Pseudomonas syringae pv. tabaci. S. sclerotiorum inoculation on N. benthamiana plants acclimated with drought stress lead to less disease-induced cell death compared to non-acclimated plants. Furthermore, inoculation of P. syringae pv. tabaci on N. benthamiana plants acclimated to moderate drought stress showed reduced disease symptoms. The levels of reactive oxygen species (ROS) in drought acclimated plants were highly correlated with disease resistance. Further, in planta growth of GFPuv expressing P. syringae pv. tabaci on plants pre-treated with methyl viologen showed complete inhibition of bacterial growth. Taken together, these experimental results suggested a role for ROS generated during drought acclimation in imparting tolerance against S. sclerotiorum and P. syringae pv. tabaci. We speculate that the generation of ROS during drought acclimation primed a defense response in plants that subsequently caused the tolerance against the pathogens tested. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessArticle Antioxidant Systems from Pepper (Capsicum annuum L.): Involvement in the Response to Temperature Changes in Ripe Fruits
Int. J. Mol. Sci. 2013, 14(5), 9556-9580; doi:10.3390/ijms14059556
Received: 21 February 2013 / Revised: 18 April 2013 / Accepted: 23 April 2013 / Published: 2 May 2013
Cited by 7 | PDF Full-text (1162 KB) | HTML Full-text | XML Full-text
Abstract
Sweet pepper is susceptible to changes in the environmental conditions, especially temperatures below 15 °C. In this work, two sets of pepper fruits (Capsicum annuum L.) which underwent distinct temperature profiles in planta were investigated. Accordingly, two harvesting times corresponding to each
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Sweet pepper is susceptible to changes in the environmental conditions, especially temperatures below 15 °C. In this work, two sets of pepper fruits (Capsicum annuum L.) which underwent distinct temperature profiles in planta were investigated. Accordingly, two harvesting times corresponding to each set were established: Harvest 1, whose fruits developed and ripened at 14.9 °C as average temperature; and Harvest 2, with average temperature of 12.4 °C. The oxidative metabolism was analyzed in all fruits. Although total ascorbate content did not vary between Harvests, a shift from the reduced to the oxidized form (dehydroascorbate), accompanied by a higher ascorbate peroxidase activity, was observed in Harvest 2 with respect to Harvest 1. Moreover, a decrease of the ascorbate-generating enzymatic system, the γ-galactono-lactone dehydrogenase, was found at Harvest 2. The activity values of the NADP-dependent dehydrogenases analyzed seem to indicate that a lower NADPH synthesis may occur in fruits which underwent lower temperature conditions. In spite of the important changes observed in the oxidative metabolism in fruits subjected to lower temperature, no oxidative stress appears to occur, as indicated by the lipid peroxidation and protein oxidation profiles. Thus, the antioxidative systems of pepper fruits seem to be involved in the response against temperature changes. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
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Open AccessArticle Isolation of Multipotent Nestin-Expressing Stem Cells Derived from the Epidermis of Elderly Humans and TAT-VHL Peptide-Mediated Neuronal Differentiation of These Cells
Int. J. Mol. Sci. 2013, 14(5), 9604-9617; doi:10.3390/ijms14059604
Received: 7 March 2013 / Revised: 17 April 2013 / Accepted: 23 April 2013 / Published: 3 May 2013
Cited by 3 | PDF Full-text (2693 KB) | HTML Full-text | XML Full-text
Abstract
A specialized population of cells residing in the hair follicle is quiescent but shows pluripotency for differentiating into epithelial-mesenchymal lineage cells. Therefore, such cells are hoped to be useful as implantable donor cells for regenerative therapy. Recently, it was reported that intracellular delivery
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A specialized population of cells residing in the hair follicle is quiescent but shows pluripotency for differentiating into epithelial-mesenchymal lineage cells. Therefore, such cells are hoped to be useful as implantable donor cells for regenerative therapy. Recently, it was reported that intracellular delivery of TAT-VHL peptide induces neuronal differentiation of skin-derived precursors. In the present study, we successfully isolated multipotent stem cells derived from the epidermis of elderly humans, characterized these cells as being capable of sphere formation and strong expression of nestin, fibronectin, and CD34 but not of keratin 15, and identified the niche of these cells as being the outer root sheath of the hair follicles. In addition, we showed that TAT-VHL peptide induced their neuronal differentiation in vitro, and confirmed by fluorescence immunohistochemistry the neuronal differentiation of such peptide-treated cells implanted into rodent brains. These multipotent nestin-expressing stem cells derived from human epidermis are easily accessible and should be useful as donor cells for neuronal regenerative cell therapy. Full article
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells)
Open AccessArticle Chebulagic Acid, a Hydrolyzable Tannin, Exhibited Antiviral Activity in Vitro and in Vivo against Human Enterovirus 71
Int. J. Mol. Sci. 2013, 14(5), 9618-9627; doi:10.3390/ijms14059618
Received: 7 March 2013 / Revised: 12 April 2013 / Accepted: 27 April 2013 / Published: 3 May 2013
Cited by 12 | PDF Full-text (1011 KB) | HTML Full-text | XML Full-text
Abstract
Human enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children under six years of age. Presently, no vaccines or antiviral drugs have been clinically available to employ against EV71. In this study, we demonstrate that
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Human enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children under six years of age. Presently, no vaccines or antiviral drugs have been clinically available to employ against EV71. In this study, we demonstrate that treatment with chebulagic acid reduced the viral cytopathic effect on rhabdomyosarcoma cells with an IC50 of 12.5 μg/mL. The utilization of the chebulagic acid treatment on mice challenged with a lethal dose of enterovirus 71 was able to efficiently reduce mortality and relieve clinical symptoms through the inhibition of viral replication. Chebulagic acid may represent a potential therapeutic agent to control infections to enterovirus 71. Full article
Open AccessArticle Identification and Validation of a New Set of Five Genes for Prediction of Risk in Early Breast Cancer
Int. J. Mol. Sci. 2013, 14(5), 9686-9702; doi:10.3390/ijms14059686
Received: 18 February 2013 / Revised: 21 April 2013 / Accepted: 28 April 2013 / Published: 6 May 2013
Cited by 8 | PDF Full-text (294 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Molecular tests predicting the outcome of breast cancer patients based on gene expression levels can be used to assist in making treatment decisions after consideration of conventional markers. In this study we identified a subset of 20 mRNA differentially regulated in breast cancer
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Molecular tests predicting the outcome of breast cancer patients based on gene expression levels can be used to assist in making treatment decisions after consideration of conventional markers. In this study we identified a subset of 20 mRNA differentially regulated in breast cancer analyzing several publicly available array gene expression data using R/Bioconductor package. Using RTqPCR we evaluate 261 consecutive invasive breast cancer cases not selected for age, adjuvant treatment, nodal and estrogen receptor status from paraffin embedded sections. The biological samples dataset was split into a training (137 cases) and a validation set (124 cases). The gene signature was developed on the training set and a multivariate stepwise Cox analysis selected five genes independently associated with DFS: FGF18 (HR = 1.13, p = 0.05), BCL2 (HR = 0.57, p = 0.001), PRC1 (HR = 1.51, p = 0.001), MMP9 (HR = 1.11, p = 0.08), SERF1a (HR = 0.83, p = 0.007). These five genes were combined into a linear score (signature) weighted according to the coefficients of the Cox model, as: 0.125FGF18 − 0.560BCL2 + 0.409PRC1 + 0.104MMP9 − 0.188SERF1A (HR = 2.7, 95% CI = 1.9–4.0, p < 0.001). The signature was then evaluated on the validation set assessing the discrimination ability by a Kaplan Meier analysis, using the same cut offs classifying patients at low, intermediate or high risk of disease relapse as defined on the training set (p < 0.001). Our signature, after a further clinical validation, could be proposed as prognostic signature for disease free survival in breast cancer patients where the indication for adjuvant chemotherapy added to endocrine treatment is uncertain. Full article
(This article belongs to the Special Issue Advances in Cancer Diagnosis)
Open AccessArticle A Chimeric UDP-Glucose Pyrophosphorylase Produced by Protein Engineering Exhibits Sensitivity to Allosteric Regulators
Int. J. Mol. Sci. 2013, 14(5), 9703-9721; doi:10.3390/ijms14059703
Received: 1 March 2013 / Revised: 10 April 2013 / Accepted: 18 April 2013 / Published: 6 May 2013
Cited by 5 | PDF Full-text (976 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In bacteria, glycogen or oligosaccharide accumulation involves glucose-1-phosphate partitioning into either ADP-glucose (ADP-Glc) or UDP-Glc. Their respective synthesis is catalyzed by allosterically regulated ADP-Glc pyrophosphorylase (EC 2.7.7.27, ADP-Glc PPase) or unregulated UDP-Glc PPase (EC 2.7.7.9). In this work, we characterized the UDP-Glc PPase
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In bacteria, glycogen or oligosaccharide accumulation involves glucose-1-phosphate partitioning into either ADP-glucose (ADP-Glc) or UDP-Glc. Their respective synthesis is catalyzed by allosterically regulated ADP-Glc pyrophosphorylase (EC 2.7.7.27, ADP-Glc PPase) or unregulated UDP-Glc PPase (EC 2.7.7.9). In this work, we characterized the UDP-Glc PPase from Streptococcus mutans. In addition, we constructed a chimeric protein by cutting the C-terminal domain of the ADP-Glc PPase from Escherichia coli and pasting it to the entire S. mutans UDP-Glc PPase. Both proteins were fully active as UDP-Glc PPases and their kinetic parameters were measured. The chimeric enzyme had a slightly higher affinity for substrates than the native S. mutans UDP-Glc PPase, but the maximal activity was four times lower. Interestingly, the chimeric protein was sensitive to regulation by pyruvate, 3-phosphoglyceric acid and fructose-1,6-bis-phosphate, which are known to be effectors of ADP-Glc PPases from different sources. The three compounds activated the chimeric enzyme up to three-fold, and increased the affinity for substrates. This chimeric protein is the first reported UDP-Glc PPase with allosteric regulatory properties. In addition, this is a pioneer work dealing with a chimeric enzyme constructed as a hybrid of two pyrophosphorylases with different specificity toward nucleoside-diphospho-glucose and our results turn to be relevant for a deeper understanding of the evolution of allosterism in this family of enzymes. Full article
(This article belongs to the Special Issue Molecular Cut and Paste)
Open AccessArticle Molecular Interaction of a New Antibacterial Polymer with a Supported Lipid Bilayer Measured by an in situ Label-Free Optical Technique
Int. J. Mol. Sci. 2013, 14(5), 9722-9736; doi:10.3390/ijms14059722
Received: 19 March 2013 / Revised: 21 April 2013 / Accepted: 2 May 2013 / Published: 6 May 2013
Cited by 11 | PDF Full-text (1051 KB) | HTML Full-text | XML Full-text
Abstract
The interaction of the antibacterial polymer–branched poly(ethylene imine) substituted with quaternary ammonium groups, PEO and alkyl chains, PEI25QI5J5A815–with a solid supported lipid bilayer was investigated using surface sensitive optical waveguide spectroscopy. The analysis of the
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The interaction of the antibacterial polymer–branched poly(ethylene imine) substituted with quaternary ammonium groups, PEO and alkyl chains, PEI25QI5J5A815–with a solid supported lipid bilayer was investigated using surface sensitive optical waveguide spectroscopy. The analysis of the optogeometrical parameters was extended developing a new composite layer model in which the structural and optical anisotropy of the molecular layers was taken into consideration. Following in situ the change of optical birefringence we were able to determine the composition of the lipid/polymer surface layer as well as the displacement of lipid bilayer by the antibacterial polymer without using additional labeling. Comparative assessment of the data of layer thickness and optical anisotropy helps to reveal the molecular mechanism of antibacterial effect of the polymer investigated. Full article
(This article belongs to the Special Issue Antimicrobial Polymers)
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Open AccessArticle Ultrasound Targeted Microbubble Destruction Stimulates Cellular Endocytosis in Facilitation of Adeno-Associated Virus Delivery
Int. J. Mol. Sci. 2013, 14(5), 9737-9750; doi:10.3390/ijms14059737
Received: 7 March 2013 / Revised: 24 April 2013 / Accepted: 27 April 2013 / Published: 7 May 2013
Cited by 9 | PDF Full-text (2684 KB) | HTML Full-text | XML Full-text
Abstract
The generally accepted mechanism for ultrasound targeted microbubble destruction (UTMD) to enhance drug and gene delivery is through sonoporation. However, passive uptake of adeno-associated virus (AAV) into cells following sonoporation does not adequately explain observations of enhanced transduction by UTMD. This study investigated
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The generally accepted mechanism for ultrasound targeted microbubble destruction (UTMD) to enhance drug and gene delivery is through sonoporation. However, passive uptake of adeno-associated virus (AAV) into cells following sonoporation does not adequately explain observations of enhanced transduction by UTMD. This study investigated alternative mechanisms of UTMD enhancement in AAV delivery. UTMD significantly enhanced transduction efficiency of AAV in a dose-dependent manner. UTMD stimulated a persistent uptake of AAV into the cytoplasm and nucleus. This phenomenon occurred over several hours, suggesting that some viral particles are endocytosed by cells rather than exclusively passing through pores created by sonoporation. Additionally, UTMD enhanced clathrin expression and accumulation at the plasma membrane suggesting greater clathrin-mediated endocytosis following UTMD. Transmission electron microscopy (TEM) revealed that UTMD stimulated formation of clathrin-coated pits (CPs) and uncoated pits (nCPs). Furthermore, inhibition of clathrin-mediated endocytosis partially blocked the enhancement of AAV uptake following UTMD. The results of this study implicate endocytosis as a mechanism that contributes to UTMD-enhanced AAV delivery. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessArticle Resistin Promotes the Expression of Vascular Endothelial Growth Factor in Ovary Carcinoma Cells
Int. J. Mol. Sci. 2013, 14(5), 9751-9766; doi:10.3390/ijms14059751
Received: 14 February 2013 / Revised: 18 April 2013 / Accepted: 24 April 2013 / Published: 7 May 2013
Cited by 8 | PDF Full-text (1086 KB) | HTML Full-text | XML Full-text
Abstract
Resistin is a novel hormone that is secreted by human adipocytes and mononuclear cells and is associated with obesity, insulin resistance and inflammation. Recently, resistin has been postulated to play a role in angiogenesis. Here, we investigated the hypothesis that resistin regulates ovary
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Resistin is a novel hormone that is secreted by human adipocytes and mononuclear cells and is associated with obesity, insulin resistance and inflammation. Recently, resistin has been postulated to play a role in angiogenesis. Here, we investigated the hypothesis that resistin regulates ovary carcinoma production of vascular endothelial growth factor (VEGF) and the angiogenic processes. We found that in human ovarian epithelial carcinoma cells (HO-8910), resistin (10–150 ng/mL) enhanced both VEGF protein and mRNA expression in a time- and concentration-dependent manner, as well as promoter activity. Furthermore, resistin enhanced DNA-binding activity of Sp1 with VEGF promoter in a PI3K/Akt-dependent manner. PI3K/Akt activated by resistin led to increasing interaction with Sp1, triggering a progressive phosphorylation of Sp1 on Thr453 and Thr739, resulting in the upregulation of VEGF expression. In an in vitro angiogenesis system for endothelial cells (EA.hy926) co-cultured with HO-8910 cells, we observed that the addition of resistin stimulated endothelial cell tube formation, which could be abolished by VEGF neutralizing antibody. Our findings suggest that the PI3K/Akt-Sp1 pathway is involved in resistin-induced VEGF expression in HO-8910 cells and indicates that antiangiogenesis therapy may be beneficial treatment against ovarian epithelial carcinoma, especially in obese patients. Full article
(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)
Open AccessArticle Oenothein B Suppresses Lipopolysaccharide (LPS)-Induced Inflammation in the Mouse Brain
Int. J. Mol. Sci. 2013, 14(5), 9767-9778; doi:10.3390/ijms14059767
Received: 7 April 2013 / Revised: 28 April 2013 / Accepted: 2 May 2013 / Published: 7 May 2013
Cited by 8 | PDF Full-text (1073 KB) | HTML Full-text | XML Full-text
Abstract
Oenothein B has been recently evaluated for its ability to affect inflammatory responses in peripheral tissues. In this study, we examined its effect on the damage to the central nervous system due to systemic inflammation. For this purpose, ICR mice were injected with
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Oenothein B has been recently evaluated for its ability to affect inflammatory responses in peripheral tissues. In this study, we examined its effect on the damage to the central nervous system due to systemic inflammation. For this purpose, ICR mice were injected with an intraperitoneal (i.p.) dose of lipopolysaccharide (LPS; 1 mg/kg mouse). When oenothein B was administered per os (p.o.), it suppressed (1) LPS-induced abnormal behavior in open field; (2) LPS-induced microglial activation in the hippocampus and striatum; and (3) LPS-induced cyclooxygenase (COX)-2 production in the hippocampus and striatum of these mice. These results suggest that oenothein B had the ability to reduce neuroinflammation in the brain during systemic inflammation. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Effects of (−)-Gallocatechin-3-Gallate on Tetrodotoxin-Resistant Voltage-Gated Sodium Channels in Rat Dorsal Root Ganglion Neurons
Int. J. Mol. Sci. 2013, 14(5), 9779-9789; doi:10.3390/ijms14059779
Received: 30 January 2013 / Revised: 10 April 2013 / Accepted: 24 April 2013 / Published: 7 May 2013
Cited by 1 | PDF Full-text (895 KB) | HTML Full-text | XML Full-text
Abstract
The (−)-gallocatechin-3-gallate (GCG) concentration in some tea beverages can account for as much as 50% of the total catechins. It has been shown that catechins have analgesic properties. Voltage-gated sodium channels (Nav) mediate neuronal action potentials. Tetrodotoxin inhibits all Nav isoforms, but Nav1.8
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The (−)-gallocatechin-3-gallate (GCG) concentration in some tea beverages can account for as much as 50% of the total catechins. It has been shown that catechins have analgesic properties. Voltage-gated sodium channels (Nav) mediate neuronal action potentials. Tetrodotoxin inhibits all Nav isoforms, but Nav1.8 and Nav1.9 are relatively tetrodotoxin-resistant compared to other isoforms and functionally linked to nociception. In this study, the effects of GCG on tetrodotoxin-resistant Na+ currents were investigated in rat primary cultures of dorsal root ganglion neurons via the whole-cell patch-clamp technique. We found that 1 μM GCG reduced the amplitudes of peak current density of tetrodotoxin-resistant Na+ currents significantly. Furthermore, the inhibition was accompanied by a depolarizing shift of the activation voltage and a hyperpolarizing shift of steady-state inactivation voltage. The percentage block of GCG (1 μM) on tetrodotoxin-resistant Na+ current was 45.1% ± 1.1% in 10 min. In addition, GCG did not produce frequency-dependent block of tetrodotoxin-resistant Na+ currents at stimulation frequencies of 1 Hz, 2 Hz and 5 Hz. On the basis of these findings, we propose that GCG may be a potential analgesic agent. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
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Open AccessArticle D-pinitol Inhibits Prostate Cancer Metastasis through Inhibition of αVβ3 Integrin by Modulating FAK, c-Src and NF-κB Pathways
Int. J. Mol. Sci. 2013, 14(5), 9790-9802; doi:10.3390/ijms14059790
Received: 29 March 2013 / Revised: 26 April 2013 / Accepted: 2 May 2013 / Published: 8 May 2013
Cited by 14 | PDF Full-text (1118 KB) | HTML Full-text | XML Full-text
Abstract
Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. D-pinitol, a 3-methoxy analogue of d-chiro-inositol, was identified as an active principle in soy foods and legumes, and it has been proven to induce
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Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. D-pinitol, a 3-methoxy analogue of d-chiro-inositol, was identified as an active principle in soy foods and legumes, and it has been proven to induce tumor apoptosis and metastasis of cancer cells. In this study, we investigated the anti-metastasis effects of D-pinitol in human prostate cancer cells. We found that D-pinitol reduced the migration and the invasion of prostate cancer cells (PC3 and DU145) at noncytotoxic concentrations. Integrins are the major adhesive molecules in mammalian cells and have been associated with the metastasis of cancer cells. Treatment of prostate cancer cells with D-pinitol reduced mRNA and cell surface expression of αvβ3 integrin. In addition, D-pinitol exerted its inhibitory effects by reducing focal adhesion kinase (FAK) phosphorylation, c-Src kinase activity and NF-kB activation. Thus, D-pinitol may be a novel anti-metastasis agent for the treatment of prostate cancer metastasis. Full article
(This article belongs to the Special Issue Molecular Research in Urology)
Open AccessArticle Two Volatile Organic Compounds Trigger Plant Self-Defense against a Bacterial Pathogen and a Sucking Insect in Cucumber under Open Field Conditions
Int. J. Mol. Sci. 2013, 14(5), 9803-9819; doi:10.3390/ijms14059803
Received: 13 March 2013 / Revised: 27 April 2013 / Accepted: 3 May 2013 / Published: 8 May 2013
Cited by 24 | PDF Full-text (365 KB) | HTML Full-text | XML Full-text
Abstract
Systemic acquired resistance (SAR) is a plant self-defense mechanism against a broad-range of pathogens and insect pests. Among chemical SAR triggers, plant and bacterial volatiles are promising candidates for use in pest management, as these volatiles are highly effective, inexpensive, and can be
[...] Read more.
Systemic acquired resistance (SAR) is a plant self-defense mechanism against a broad-range of pathogens and insect pests. Among chemical SAR triggers, plant and bacterial volatiles are promising candidates for use in pest management, as these volatiles are highly effective, inexpensive, and can be employed at relatively low concentrations compared with agrochemicals. However, such volatiles have some drawbacks, including the high evaporation rate of these compounds after application in the open field, their negative effects on plant growth, and their inconsistent levels of effectiveness. Here, we demonstrate the effectiveness of volatile organic compound (VOC)-mediated induced resistance against both the bacterial angular leaf spot pathogen, Pseudononas syringae pv. lachrymans, and the sucking insect aphid, Myzus persicae, in the open field. Using the VOCs 3-pentanol and 2-butanone where fruit yields increased gave unexpectedly, a significant increase in the number of ladybird beetles, Coccinella septempunctata, a natural enemy of aphids. The defense-related gene CsLOX was induced by VOC treatment, indicating that triggering the oxylipin pathway in response to the emission of green leaf volatiles can recruit the natural enemy of aphids. These results demonstrate that VOCs may help prevent plant disease and insect damage by eliciting induced resistance, even in open fields. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessArticle Anti-Inflammatory Effect of Ginsenoside Rg5 in Lipopolysaccharide-Stimulated BV2 Microglial Cells
Int. J. Mol. Sci. 2013, 14(5), 9820-9833; doi:10.3390/ijms14059820
Received: 17 February 2013 / Revised: 8 April 2013 / Accepted: 2 May 2013 / Published: 8 May 2013
Cited by 17 | PDF Full-text (391 KB) | HTML Full-text | XML Full-text
Abstract
Microglia are resident immune cells in the central nervous system. They play a role in normal brain development and neuronal recovery. However, overactivation of microglia causes neuronal death, which is associated with neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. Therefore, controlling
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Microglia are resident immune cells in the central nervous system. They play a role in normal brain development and neuronal recovery. However, overactivation of microglia causes neuronal death, which is associated with neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. Therefore, controlling microglial activation has been suggested as an important target for treatment of neurodegenerative diseases. In the present study, we investigated the anti-inflammatory effect of ginsenoside Rg5 in lipopolysaccharide (LPS)-stimulated BV2 microglial cells and rat primary microglia. The data showed that Rg5 suppressed LPS-induced nitric oxide (NO) production and proinflammatory TNF-α secretion. In addition, Rg5 inhibited the mRNA expressions of iNOS, TNF-α, IL-1b, COX-2 and MMP-9 induced by LPS. Further mechanistic studies revealed that Rg5 inhibited the phophorylations of PI3K/Akt and MAPKs and the DNA binding activities of NF-kB and AP-1, which are upstream molecules controlling inflammatory reactions. Moreover, Rg5 suppressed ROS production with upregulation of hemeoxygenase-1 (HO-1) expression in LPS-stimulated BV2 cells. Overall, microglial inactivation by ginsenoside Rg5 may provide a therapeutic potential for various neuroinflammatory disorders. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Effective and Selective Recovery of Precious Metals by Thiourea Modified Magnetic Nanoparticles
Int. J. Mol. Sci. 2013, 14(5), 9834-9847; doi:10.3390/ijms14059834
Received: 1 April 2013 / Revised: 26 April 2013 / Accepted: 3 May 2013 / Published: 8 May 2013
Cited by 6 | PDF Full-text (447 KB) | HTML Full-text | XML Full-text
Abstract
Adsorption of precious metals in acidic aqueous solutions using thiourea modified magnetic magnetite nanoparticle (MNP-Tu) was examined. The MNP-Tu was synthesized, characterized and examined as a reusable adsorbent for the recovery of precious metals. The adsorption kinetics were well fitted with pseudo second-order
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Adsorption of precious metals in acidic aqueous solutions using thiourea modified magnetic magnetite nanoparticle (MNP-Tu) was examined. The MNP-Tu was synthesized, characterized and examined as a reusable adsorbent for the recovery of precious metals. The adsorption kinetics were well fitted with pseudo second-order equation while the adsorption isotherms were fitted with both Langmuir and Freundlich equations. The maximum adsorption capacity of precious metals for MNP-Tu determined by Langmuir model was 43.34, 118.46 and 111.58 mg/g for Pt(IV), Au(III) and Pd(II), respectively at pH 2 and 25 °C. MNP-Tu has high adsorption selectivity towards precious metals even in the presence of competing ions (Cu(II)) at high concentrations. In addition, the MNP-Tu can be regenerated using an aqueous solution containing 0.7 M thiourea and 2% HCl where precious metals can be recovered in a concentrated form. It was found that the MNP-Tu undergoing seven consecutive adsorption-desorption cycles still retained the original adsorption capacity of precious metals. A reductive adsorption resulting in the formation of elemental gold and palladium at the surface of MNP-Tu was observed. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
Open AccessArticle Caffeine Inhibits Acetylcholinesterase, But Not Butyrylcholinesterase
Int. J. Mol. Sci. 2013, 14(5), 9873-9882; doi:10.3390/ijms14059873
Received: 4 April 2013 / Revised: 29 April 2013 / Accepted: 30 April 2013 / Published: 8 May 2013
Cited by 19 | PDF Full-text (327 KB) | HTML Full-text | XML Full-text
Abstract
Caffeine is an alkaloid with a stimulant effect in the body. It can interfere in transmissions based on acetylcholine, epinephrine, norepinephrine, serotonin, dopamine and glutamate. Clinical studies indicate that it can be involved in the slowing of Alzheimer disease pathology and some other
[...] Read more.
Caffeine is an alkaloid with a stimulant effect in the body. It can interfere in transmissions based on acetylcholine, epinephrine, norepinephrine, serotonin, dopamine and glutamate. Clinical studies indicate that it can be involved in the slowing of Alzheimer disease pathology and some other effects. The effects are not well understood. In the present work, we focused on the question whether caffeine can inhibit acetylcholinesterase (AChE) and/or, butyrylcholinesterase (BChE), the two enzymes participating in cholinergic neurotransmission. A standard Ellman test with human AChE and BChE was done for altering concentrations of caffeine. The test was supported by an in silico examination as well. Donepezil and tacrine were used as standards. In compliance with Dixon’s plot, caffeine was proved to be a non-competitive inhibitor of AChE and BChE. However, inhibition of BChE was quite weak, as the inhibition constant, Ki, was 13.9 ± 7.4 mol/L. Inhibition of AChE was more relevant, as Ki was found to be 175 ± 9 µmol/L. The predicted free energy of binding was −6.7 kcal/mol. The proposed binding orientation of caffeine can interact with Trp86, and it can be stabilize by Tyr337 in comparison to the smaller Ala328 in the case of human BChE; thus, it can explain the lower binding affinity of caffeine for BChE with reference to AChE. The biological relevance of the findings is discussed. Full article
(This article belongs to the Section Molecular Toxicology)
Open AccessArticle Combining Coarse-Grained Protein Models with Replica-Exchange All-Atom Molecular Dynamics
Int. J. Mol. Sci. 2013, 14(5), 9893-9905; doi:10.3390/ijms14059893
Received: 7 March 2013 / Revised: 9 April 2013 / Accepted: 24 April 2013 / Published: 10 May 2013
Cited by 9 | PDF Full-text (407 KB) | HTML Full-text | XML Full-text
Abstract
We describe a combination of all-atom simulations with CABS, a well-established coarse-grained protein modeling tool, into a single multiscale protocol. The simulation method has been tested on the C-terminal beta hairpin of protein G, a model system of protein folding. After reconstructing atomistic
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We describe a combination of all-atom simulations with CABS, a well-established coarse-grained protein modeling tool, into a single multiscale protocol. The simulation method has been tested on the C-terminal beta hairpin of protein G, a model system of protein folding. After reconstructing atomistic details, conformations derived from the CABS simulation were subjected to replica-exchange molecular dynamics simulations with OPLS-AA and AMBER99sb force fields in explicit solvent. Such a combination accelerates system convergence several times in comparison with all-atom simulations starting from the extended chain conformation, demonstrated by the analysis of melting curves, the number of native-like conformations as a function of time and secondary structure propagation. The results strongly suggest that the proposed multiscale method could be an efficient and accurate tool for high-resolution studies of protein folding dynamics in larger systems. Full article
(This article belongs to the collection Protein Folding)
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Open AccessArticle Molecular Dynamics Simulation of Tryptophan Hydroxylase-1: Binding Modes and Free Energy Analysis to Phenylalanine Derivative Inhibitors
Int. J. Mol. Sci. 2013, 14(5), 9947-9962; doi:10.3390/ijms14059947
Received: 28 March 2013 / Revised: 27 April 2013 / Accepted: 6 May 2013 / Published: 10 May 2013
Cited by 11 | PDF Full-text (837 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Serotonin is a neurotransmitter that modulates many central and peripheral functions. Tryptophan hydroxylase-1 (TPH1) is a key enzyme of serotonin synthesis. In the current study, the interaction mechanism of phenylalanine derivative TPH1 inhibitors was investigated using molecular dynamics (MD) simulations, free energy calculations,
[...] Read more.
Serotonin is a neurotransmitter that modulates many central and peripheral functions. Tryptophan hydroxylase-1 (TPH1) is a key enzyme of serotonin synthesis. In the current study, the interaction mechanism of phenylalanine derivative TPH1 inhibitors was investigated using molecular dynamics (MD) simulations, free energy calculations, free energy decomposition analysis and computational alanine scanning. The predicted binding free energies of these complexes are consistent with the experimental data. The analysis of the individual energy terms indicates that although the van der Waals and electrostatics interaction contributions are important in distinguishing the binding affinities of these inhibitors, the electrostatic contribution plays a more crucial role in that. Moreover, it is observed that different configurations of the naphthalene substituent could form different binding patterns with protein, yet lead to similar inhibitory potency. The combination of different molecular modeling techniques is an efficient way to interpret the interaction mechanism of inhibitors and our work could provide valuable information for the TPH1 inhibitor design in the future. Full article
Open AccessArticle Microarray Analysis of Transcriptional Responses to Abscisic Acid and Salt Stress in Arabidopsis thaliana
Int. J. Mol. Sci. 2013, 14(5), 9979-9998; doi:10.3390/ijms14059979
Received: 18 January 2013 / Revised: 11 April 2013 / Accepted: 28 April 2013 / Published: 10 May 2013
Cited by 8 | PDF Full-text (1474 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Abscisic acid (ABA) plays a crucial role in plant responses to abiotic stress. To investigate differences in plant responses to salt and ABA stimulus, differences in gene expression in Arabidopsis in response to salt and ABA were compared using an Agilent oligo microarray.
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Abscisic acid (ABA) plays a crucial role in plant responses to abiotic stress. To investigate differences in plant responses to salt and ABA stimulus, differences in gene expression in Arabidopsis in response to salt and ABA were compared using an Agilent oligo microarray. A total of 144 and 139 genes were significantly up- and downregulated, respectively, under NaCl stress, while 406 and 381 genes were significantly up- and downregulated, respectively, under ABA stress conditions. In addition, 31 genes were upregulated by both NaCl and ABA stresses, and 23 genes were downregulated by these stressors, suggesting that these genes may play similar roles in plant responses to salt and ABA stress. Gene ontology (GO) analysis revealed four subgroups of genes, including genes in the GO categories “Molecular transducer activity”, “Growth”, “Biological adhesion” and “Pigmentation”, which were expressed in response to ABA stress but not NaCl stress. In addition, genes that play specific roles during salt or ABA stress were identified. Our results may help elucidate differences in the response of plants to salt and ABA stress. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
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Open AccessArticle A Novel Colorimetric Immunoassay Utilizing the Peroxidase Mimicking Activity of Magnetic Nanoparticles
Int. J. Mol. Sci. 2013, 14(5), 9999-10014; doi:10.3390/ijms14059999
Received: 7 April 2013 / Revised: 28 April 2013 / Accepted: 6 May 2013 / Published: 10 May 2013
Cited by 10 | PDF Full-text (896 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A simple colorimetric immunoassay system, based on the peroxidase mimicking activity of Fe3O4 magnetic nanoparticles (MNPs), has been developed to detect clinically important antigenic molecules. MNPs with ca. 10 nm in diameter were synthesized and conjugated with specific antibodies against
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A simple colorimetric immunoassay system, based on the peroxidase mimicking activity of Fe3O4 magnetic nanoparticles (MNPs), has been developed to detect clinically important antigenic molecules. MNPs with ca. 10 nm in diameter were synthesized and conjugated with specific antibodies against target molecules, such as rotaviruses and breast cancer cells. Conjugation of the MNPs with antibodies (MNP-Abs) enabled specific recognition of the corresponding target antigenic molecules through the generation of color signals arising from the colorimetric reaction between the selected peroxidase substrate, 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2. Based on the MNP-promoted colorimetric reaction, the target molecules were detected and quantified by measuring absorbance intensities corresponding to the oxidized form of TMB. Owing to the higher stabilities and economic feasibilities of MNPs as compared to horseradish peroxidase (HRP), the new colorimetric system employing MNP-Abs has the potential of serving as a potent immunoassay that should substitute for conventional HRP-based immunoassays. The strategy employed to develop the new methodology has the potential of being extended to the construction of simple diagnostic systems for a variety of biomolecules related to human cancers and infectious diseases, particularly in the realm of point-of-care applications. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
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Open AccessArticle Genome-Wide Gene Expression Profiles in Antioxidant Pathways and Their Potential Sex Differences and Connections to Vitamin C in Mice
Int. J. Mol. Sci. 2013, 14(5), 10042-10062; doi:10.3390/ijms140510042
Received: 10 January 2013 / Revised: 7 April 2013 / Accepted: 28 April 2013 / Published: 10 May 2013
Cited by 5 | PDF Full-text (643 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Vitamin C (VC) is well known as an antioxidant in humans, primates and guinea pigs. Studies have suggested gender differences in VC requirements in humans, and gender differences in oxidant injury vulnerability in early life may represent a biological mechanism contributing to gender
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Vitamin C (VC) is well known as an antioxidant in humans, primates and guinea pigs. Studies have suggested gender differences in VC requirements in humans, and gender differences in oxidant injury vulnerability in early life may represent a biological mechanism contributing to gender disparity in later life. Using spontaneous bone fracture (sfx) mice, which lack the gene for L-Gulonolactone oxidase (Gulo), we studied the potential sex difference in expression profiles of oxidative genes at the whole-genome level. Then, we analyzed data of gene expressions in a mouse population of recombinant inbred (RI) strains originally derived by crossing C57BL/6J (B6) and DBA/2J (D2) mice. Our data indicated that there were sex differences in the regulation of pre- and pro-oxidative genes in sfx mice. The associations of expression levels among Gulo, its partner genes and oxidative genes in the BXD (B6 × D2) RI strains showed a sex difference. Transcriptome mapping suggests that Gulo was regulated differently between female and male mice in BXD RI strains. Our study indicates the importance of investigating sex differences in Gulo and its oxidative function by using available mouse models. Full article
Open AccessArticle The Role of E3 Ubiquitin Ligase Cbl Proteins in β-Elemene Reversing Multi-Drug Resistance of Human Gastric Adenocarcinoma Cells
Int. J. Mol. Sci. 2013, 14(5), 10075-10089; doi:10.3390/ijms140510075
Received: 21 March 2013 / Revised: 27 April 2013 / Accepted: 3 May 2013 / Published: 10 May 2013
Cited by 8 | PDF Full-text (1273 KB) | HTML Full-text | XML Full-text
Abstract
Recent studies indicate that β-elemene, a compound isolated from the Chinese herbal medicine Curcuma wenyujin, is capable of reversing tumor MDR, although the mechanism remains elusive. In this study, β-Elemene treatment markedly increased the intracellular accumulation of doxorubicin (DOX) and rhodamine 123 in
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Recent studies indicate that β-elemene, a compound isolated from the Chinese herbal medicine Curcuma wenyujin, is capable of reversing tumor MDR, although the mechanism remains elusive. In this study, β-Elemene treatment markedly increased the intracellular accumulation of doxorubicin (DOX) and rhodamine 123 in both K562/DNR and SGC7901/ADR cells and significantly inhibited the expression of P-gp. Treatment of SGC7901/ADR cells with β-elemene led to downregulation of Akt phosphorylation and significant upregulation of the E3 ubiquitin ligases, c-Cbl and Cbl-b. Importantly, β-elemene significantly enhanced the anti-tumor activity of DOX in nude mice bearing SGC7901/ADR xenografts. Taken together, our results suggest that β-elemene may target P-gp-overexpressing leukemia and gastric cancer cells to enhance the efficacy of DOX treatment. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Vascular Endothelial Growth Factor Induces CXCL1 Chemokine Release via JNK and PI-3K-Dependent Pathways in Human Lung Carcinoma Epithelial Cells
Int. J. Mol. Sci. 2013, 14(5), 10090-10106; doi:10.3390/ijms140510090
Received: 2 February 2013 / Revised: 23 April 2013 / Accepted: 2 May 2013 / Published: 10 May 2013
Cited by 14 | PDF Full-text (2104 KB) | HTML Full-text | XML Full-text
Abstract
Lung cancer cells express different chemokines and chemokine receptors that modulate leukocyte infiltration within tumor microenvironment. In this study we screened several mediators/growth factors on CXCL1 release in human carcinoma epithelial cells. Of the tested mediators, VEGF was found to have a robust
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Lung cancer cells express different chemokines and chemokine receptors that modulate leukocyte infiltration within tumor microenvironment. In this study we screened several mediators/growth factors on CXCL1 release in human carcinoma epithelial cells. Of the tested mediators, VEGF was found to have a robust increase in causing CXCL1 release. VEGF stimulated CXCL1 release and mRNA expression in a time- and concentration-dependent manner. The release was inhibited by the VEGF receptor antagonists and the JNK, PI-3K, tyrosine kinase, and transcription inhibitors. In parallel, VEGF induced JNK, PI3K and Akt activation. Strikingly, among these inhibitors only the JNK inhibitor could reduce VEGF-induced CXCL1 mRNA expression, suggesting that JNK participated in VEGF-induced CXCL1 synthesis, whereas PI-3K was responsible for cellular CXCL1 secretory process. In addition, the steroid dexamethasone and TGF-β suppressed CXCL1 release through a transcriptional regulation. We also showed that cells stimulated with VEGF significantly attracted monocyte migration, which could be abolished by CXCL1 B/N Ab, CXC receptor 2 antagonist, TGF-β, and dexamethasone. In summary, we provide here evidence showing JNK activation for VEGF-induced CXCL1 DNA transcription and PI-3K pathway for extracellular CXCL1 release in human carcinoma epithelial cells. The released CXCL1 was functionally linked to recruiting monocytes into lung cancer cell microenvironment. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Open AccessArticle Native High Density Lipoproteins (HDL) Interfere with Platelet Activation Induced by Oxidized Low Density Lipoproteins (OxLDL)
Int. J. Mol. Sci. 2013, 14(5), 10107-10121; doi:10.3390/ijms140510107
Received: 11 March 2013 / Revised: 16 April 2013 / Accepted: 29 April 2013 / Published: 10 May 2013
Cited by 7 | PDF Full-text (1430 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Platelets and lipoproteins play a crucial role in atherogenesis, in part by their ability to modulate inflammation and oxidative stress. While oxidized low density lipoproteins (OxLDL) play a central role in the development of this disease, high density lipoproteins (HDL) represent an atheroprotective
[...] Read more.
Platelets and lipoproteins play a crucial role in atherogenesis, in part by their ability to modulate inflammation and oxidative stress. While oxidized low density lipoproteins (OxLDL) play a central role in the development of this disease, high density lipoproteins (HDL) represent an atheroprotective factor of utmost importance. As platelet function is remarkably sensitive to the influence of plasma lipoproteins, it was the aim of this study to clarify if HDL are able to counteract the stimulating effects of OxLDL with special emphasis on aspects of platelet function that are relevant to inflammation. Therefore, HDL were tested for their ability to interfere with pro-thrombotic and pro-inflammatory aspects of platelet function. We are able to show that HDL significantly impaired OxLDL-induced platelet aggregation and adhesion. In gel-filtered platelets, HDL decreased both the formation of reactive oxygen species and CD40L expression. Furthermore, HDL strongly interfered with OxLDL-induced formation of platelet-neutrophil aggregates in whole blood, suggesting that platelets represent a relevant and sensitive target for HDL. The finding that HDL effectively competed with the binding of OxLDL to the platelet surface might contribute to their atheroprotective and antithrombotic properties. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
Open AccessArticle Frequency-Dependent Magnetic Susceptibility of Magnetite and Cobalt Ferrite Nanoparticles Embedded in PAA Hydrogel
Int. J. Mol. Sci. 2013, 14(5), 10162-10177; doi:10.3390/ijms140510162
Received: 11 April 2013 / Revised: 29 April 2013 / Accepted: 7 May 2013 / Published: 14 May 2013
Cited by 11 | PDF Full-text (1764 KB) | HTML Full-text | XML Full-text
Abstract
Chemically responsive hydrogels with embedded magnetic nanoparticles are of interest for biosensors that magnetically detect chemical changes. A crucial point is the irreversible linkage of nanoparticles to the hydrogel network, preventing loss of nanoparticles upon repeated swelling and shrinking of the gel. Here,
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Chemically responsive hydrogels with embedded magnetic nanoparticles are of interest for biosensors that magnetically detect chemical changes. A crucial point is the irreversible linkage of nanoparticles to the hydrogel network, preventing loss of nanoparticles upon repeated swelling and shrinking of the gel. Here, acrylic acid monomers are adsorbed onto ferrite nanoparticles, which subsequently participate in polymerization during synthesis of poly(acrylic acid)-based hydrogels (PAA). To demonstrate the fixation of the nanoparticles to the polymer, our original approach is to measure low-field AC magnetic susceptibility spectra in the 0.1 Hz to 1 MHz range. In the hydrogel, the magnetization dynamics of small iron oxide nanoparticles are comparable to those of the particles dispersed in a liquid, due to fast Néel relaxation inside the particles; this renders the ferrogel useful for chemical sensing at frequencies of several kHz. However, ferrogels holding thermally blocked iron oxide or cobalt ferrite nanoparticles show significant decrease of the magnetic susceptibility resulting from a frozen magnetic structure. This confirms that the nanoparticles are unable to rotate thermally inside the hydrogel, in agreement with their irreversible fixation to the polymer network. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
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Open AccessArticle Oxidative and Molecular Responses in Capsicum annuum L. after Hydrogen Peroxide, Salicylic Acid and Chitosan Foliar Applications
Int. J. Mol. Sci. 2013, 14(5), 10178-10196; doi:10.3390/ijms140510178
Received: 16 February 2013 / Revised: 24 April 2013 / Accepted: 2 May 2013 / Published: 15 May 2013
Cited by 16 | PDF Full-text (2706 KB) | HTML Full-text | XML Full-text
Abstract
Hydrogen peroxide (H2O2) is an important ROS molecule (Reactive oxygen species) that serves as a signal of oxidative stress and activation of signaling cascades as a result of the early response of the plant to biotic stress. This response
[...] Read more.
Hydrogen peroxide (H2O2) is an important ROS molecule (Reactive oxygen species) that serves as a signal of oxidative stress and activation of signaling cascades as a result of the early response of the plant to biotic stress. This response can also be generated with the application of elicitors, stable molecules that induce the activation of transduction cascades and hormonal pathways, which trigger induced resistance to environmental stress. In this work, we evaluated the endogenous H2O2 production caused by salicylic acid (SA), chitosan (QN), and H2O2 elicitors in Capsicum annuum L. Hydrogen peroxide production after elicitation, catalase (CAT) and phenylalanine ammonia lyase (PAL) activities, as well as gene expression analysis of cat1, pal, and pathogenesis-related protein 1 (pr1) were determined. Our results displayed that 6.7 and 10 mM SA concentrations, and, 14 and 18 mM H2O2 concentrations, induced an endogenous H2O2 and gene expression. QN treatments induced the same responses in lesser proportion than the other two elicitors. Endogenous H2O2 production monitored during several days, showed results that could be an indicator for determining application opportunity uses in agriculture for maintaining plant alert systems against a stress. Full article
(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism)
Open AccessArticle Molecular Cloning and Characterization of the First Caspase in the Striped Stem Borer, Chilo suppressalis
Int. J. Mol. Sci. 2013, 14(5), 10229-10241; doi:10.3390/ijms140510229
Received: 8 April 2013 / Revised: 17 April 2013 / Accepted: 3 May 2013 / Published: 15 May 2013
Cited by 5 | PDF Full-text (653 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Apoptosis is executed through the activity of the caspases that are aspartyl-specific proteases. In this study, we isolated the caspase gene (Cscaspase-1) of Chilo suppressalis (one of the leading pests responsible for destruction of rice crops). It possesses the open reading
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Apoptosis is executed through the activity of the caspases that are aspartyl-specific proteases. In this study, we isolated the caspase gene (Cscaspase-1) of Chilo suppressalis (one of the leading pests responsible for destruction of rice crops). It possesses the open reading frame (ORF) of 295 amino acids including prodomain, large subunit and small subunits, and two cleavage sites (Asp23 and Asp194) were found to be located among them. In addition to these profiles, Cscaspase-1 contains two active sites (His134 and Cys176). Genomic analysis demonstrated there was no intron in the genome of Cscaspase-1. The Cscaspase-1 transcripts were found in all tissues of the fifth instar larvae, and higher levels were found in the midgut, hindgut and Malpighian tubules. Examination of Cscaspase-1 expression in different developmental stages indicated low constitutive levels in the eggs and early larvae stages, and higher abundances were exhibited in the last larvae and pupae stages. The relative mRNA levels of Cscaspase-1 were induced by heat and cold temperatures. For example, the highest increase of Cscaspase-1 transcription was at −3 °C and 36 °C respectively. In a word, Cscaspase-1 plays a role of effector in the apoptosis of C. suppressalis. It also correlates with development, metamorphosis and thermotolerance of C. suppreassalis. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle An Exonuclease III Protection-Based Electrochemical Method for Estrogen Receptor Assay
Int. J. Mol. Sci. 2013, 14(5), 10298-10306; doi:10.3390/ijms140510298
Received: 6 March 2013 / Revised: 25 April 2013 / Accepted: 10 May 2013 / Published: 16 May 2013
Cited by 7 | PDF Full-text (421 KB) | HTML Full-text | XML Full-text
Abstract
Estrogen receptor (ER), expressed in approximately 80% of primary breast cancer cells, has proven to be a valuable predictive factor of the disease. Herein, by making use of the specific binding of ER to its DNA response elements, we propose an Exonuclease III
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Estrogen receptor (ER), expressed in approximately 80% of primary breast cancer cells, has proven to be a valuable predictive factor of the disease. Herein, by making use of the specific binding of ER to its DNA response elements, we propose an Exonuclease III (Exo III) protection-based electrochemical method for detecting ER proteins. In this assay, the presence of ER can protect the duplex DNA molecules immobilized on an electrode surface from Exo III-catalyzed digestion, resulting in an increased electrochemical signal. Experimental results have revealed that the proposed method can allow the quantification of ER in the range of 0.5 to 100 nM with a satisfactory detection limit of 0.38 nM. Furthermore, since this approach can also be employed to detect ER directly in nuclear extracts, it may be of great use in biomedical applications in the future. Full article
(This article belongs to the Special Issue Molecular Bases of Cancer Research)
Open AccessArticle Peripheral Blood miR-328 Expression as a Potential Biomarker for the Early Diagnosis of NSCLC
Int. J. Mol. Sci. 2013, 14(5), 10332-10342; doi:10.3390/ijms140510332
Received: 3 April 2013 / Revised: 2 May 2013 / Accepted: 6 May 2013 / Published: 16 May 2013
Cited by 33 | PDF Full-text (265 KB) | HTML Full-text | XML Full-text
Abstract
Lung cancer is often diagnosed at an advanced stage, with subsequently poor prognosis. There are no biomarkers available to facilitate early diagnosis or to discriminate between benign and malignant nodules. MicroRNAs (miRNAs) are stable molecules that can be found and measured in peripheral
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Lung cancer is often diagnosed at an advanced stage, with subsequently poor prognosis. There are no biomarkers available to facilitate early diagnosis or to discriminate between benign and malignant nodules. MicroRNAs (miRNAs) are stable molecules that can be found and measured in peripheral blood, thus representing potential diagnostic biomarkers. We evaluated 100 individuals comprising 86 patients with predominantly early-stage non-small cell lung cancer (NSCLC) and 24 healthy donors. RNA was extracted from peripheral blood samples and the expression of a panel of miRNAs was analyzed by Real-Time PCR method. Expression levels of miR-328, miR-18a, miR-339 and miR-140 were significantly higher in NSCLC patients than in healthy donors (p < 0.05). In particular, miR-328 showed good diagnostic accuracy in discriminating between patients with early NSCLC and healthy donors (AUC ROC 0.82, 95% CI 0.72–0.92), with 70% sensitivity and 83% specificity at the best relative expression cut-off of 300. Moreover, miR-339 was a good discriminant between healthy donors and late-stage NSCLC patients (AUC ROC 0.79, 95% CI 0.68–0.91). In conclusion, miR-328 represents a potential diagnostic biomarker of NSCLC, especially for the identification of early-stage tumors. Its role in discriminating between benign and malignant nodules detected by spiral CT warrants further investigation. Full article
(This article belongs to the Special Issue Advances in Cancer Diagnosis)
Open AccessArticle Ischemic Preconditioning Protects against Spinal Cord Ischemia-Reperfusion Injury in Rabbits by Attenuating Blood Spinal Cord Barrier Disruption
Int. J. Mol. Sci. 2013, 14(5), 10343-10354; doi:10.3390/ijms140510343
Received: 25 February 2013 / Revised: 24 April 2013 / Accepted: 2 May 2013 / Published: 17 May 2013
Cited by 17 | PDF Full-text (1992 KB) | HTML Full-text | XML Full-text
Abstract
Ischemic preconditioning has been reported to protect against spinal cord ischemia-reperfusion (I-R) injury, but the underlying mechanisms are not fully understood. To investigate this, Japanese white rabbits underwent I-R (30 min aortic occlusion followed by reperfusion), ischemic preconditioning (three cycles of 5 min
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Ischemic preconditioning has been reported to protect against spinal cord ischemia-reperfusion (I-R) injury, but the underlying mechanisms are not fully understood. To investigate this, Japanese white rabbits underwent I-R (30 min aortic occlusion followed by reperfusion), ischemic preconditioning (three cycles of 5 min aortic occlusion plus 5 min reperfusion) followed by I-R, or sham surgery. At 4 and 24 h following reperfusion, neurological function was assessed using Tarlov scores, blood spinal cord barrier permeability was measured by Evan’s Blue extravasation, spinal cord edema was evaluated using the wet-dry method, and spinal cord expression of zonula occluden-1 (ZO-1), matrix metalloproteinase-9 (MMP-9), and tumor necrosis factor-α (TNF-α) were measured by Western blot and a real-time polymerase chain reaction. ZO-1 was also assessed using immunofluorescence. Spinal cord I-R injury reduced neurologic scores, and ischemic preconditioning treatment ameliorated this effect. Ischemic preconditioning inhibited I-R-induced increases in blood spinal cord barrier permeability and water content, increased ZO-1 mRNA and protein expression, and reduced MMP-9 and TNF-α mRNA and protein expression. These findings suggest that ischemic preconditioning attenuates the increase in blood spinal cord barrier permeability due to spinal cord I-R injury by preservation of tight junction protein ZO-1 and reducing MMP-9 and TNF-α expression. Full article
(This article belongs to the Special Issue Neuroprotective Strategies 2014)
Open AccessArticle Ultraviolet (UV) and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE) Cell Apoptosis
Int. J. Mol. Sci. 2013, 14(5), 10355-10368; doi:10.3390/ijms140510355
Received: 24 November 2012 / Revised: 15 April 2013 / Accepted: 2 May 2013 / Published: 17 May 2013
Cited by 20 | PDF Full-text (1801 KB) | HTML Full-text | XML Full-text
Abstract
Ultraviolet (UV) radiation and reactive oxygen species (ROS) impair the physiological functions of retinal pigment epithelium (RPE) cells by inducing cell apoptosis, which is the main cause of age-related macular degeneration (AMD). The mechanism by which UV/ROS induces RPE cell death is not
[...] Read more.
Ultraviolet (UV) radiation and reactive oxygen species (ROS) impair the physiological functions of retinal pigment epithelium (RPE) cells by inducing cell apoptosis, which is the main cause of age-related macular degeneration (AMD). The mechanism by which UV/ROS induces RPE cell death is not fully addressed. Here, we observed the activation of a ceramide-endoplasmic reticulum (ER) stress-AMP activated protein kinase (AMPK) signaling axis in UV and hydrogen peroxide (H2O2)-treated RPE cells. UV and H2O2 induced an early ceramide production, profound ER stress and AMPK activation. Pharmacological inhibitors against ER stress (salubrinal), ceramide production (fumonisin B1) and AMPK activation (compound C) suppressed UV- and H2O2-induced RPE cell apoptosis. Conversely, cell permeable short-chain C6 ceramide and AMPK activator AICAR (5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide) mimicked UV and H2O2’s effects and promoted RPE cell apoptosis. Together, these results suggest that UV/H2O2 activates the ceramide-ER stress-AMPK signaling axis to promote RPE cell apoptosis. Full article
(This article belongs to the Special Issue UV-Induced Cell Death 2012)
Open AccessArticle The Role of Peritoneal Alternatively Activated Macrophages in the Process of Peritoneal Fibrosis Related to Peritoneal Dialysis
Int. J. Mol. Sci. 2013, 14(5), 10369-10382; doi:10.3390/ijms140510369
Received: 4 March 2013 / Revised: 7 May 2013 / Accepted: 8 May 2013 / Published: 17 May 2013
Cited by 10 | PDF Full-text (1117 KB) | HTML Full-text | XML Full-text
Abstract
It has been confirmed that alternatively activated macrophages (M2) participate in tissue remodeling and fibrosis occurrence, but the effect of M2 on peritoneal fibrosis related to peritoneal dialysis (PD) hasn’t been elucidated. This study was therefore conducted to assess the association between M2
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It has been confirmed that alternatively activated macrophages (M2) participate in tissue remodeling and fibrosis occurrence, but the effect of M2 on peritoneal fibrosis related to peritoneal dialysis (PD) hasn’t been elucidated. This study was therefore conducted to assess the association between M2 and peritoneal fibrosis related to PD. In this study, peritoneal fibrosis was induced by intraperitoneal (i.p.) injection of Lactate-4.25% dialysate (100 mL/kg) to C57BL/6J mice for 28 days, and liposome-encapsulated clodronate (LC, the specific scavenger of macrophages) was used to treat the peritoneal fibrosis mice model by i.p. injection at day 18 and day 21. All animals were sacrificed at day 29. Parietal peritonea were stained with Masson’s trichrome, and the expression of type I collagen (Col-I), fibronectin, mannose receptor (CD206), transforming growth factor beta (TGF-β), chemokine receptor 7 (CCR7), chitinase 3-like 3 (Ym-1) and arginase-1 (Arg-1) was determined by Western blotting, immunofluorescence and quantitative real-time PCR. Our results revealed that peritoneal thickness, Col-I, fibronectin, CD206, TGF-β, Ym-1 and Arg-1 were upregulated in the peritoneal fibrosis mice model, and all of these indexes were downregulated in those treated with LC. Additionally, there was no difference in the level of CCR7 between the model and treatment group. Our study indicated that peritoneal M2 played an important role in the process of peritoneal fibrosis related to PD and might be a potential target for intervention therapy of peritoneal fibrosis. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Influence of Growth Conditions on Magnetite Nanoparticles Electro-Crystallized in the Presence of Organic Molecules
Int. J. Mol. Sci. 2013, 14(5), 10383-10396; doi:10.3390/ijms140510383
Received: 29 March 2013 / Revised: 4 May 2013 / Accepted: 9 May 2013 / Published: 17 May 2013
Cited by 8 | PDF Full-text (1503 KB) | HTML Full-text | XML Full-text
Abstract
Magnetite nanoparticles were synthesized by electrocrystallization in the presence of thiourea or sodium butanoate as an organic stabilizer. The synthesis was performed in a thermostatic electrochemical cell containing two iron electrodes with an aqueous solution of sodium sulfate as electrolyte. The effects of
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Magnetite nanoparticles were synthesized by electrocrystallization in the presence of thiourea or sodium butanoate as an organic stabilizer. The synthesis was performed in a thermostatic electrochemical cell containing two iron electrodes with an aqueous solution of sodium sulfate as electrolyte. The effects of organic concentration, applied potential and growth temperature on particle size, morphology, structure and magnetic properties were investigated. The magnetite nanoparticles were characterized by X-ray diffraction, electron microscopy, magnetometry and Mössbauer spectrometry. When the synthesis is performed in the presence of sodium butanoate at 60 °C, a paramagnetic ferric salt is obtained as a second phase; it is possible to avoid formation of this phase, increase the specific magnetization and improve the structure of the oxide particles by tuning the growth conditions. Room-temperature magnetization values range from 45 to 90 Am2kg−1, depending on the particle size, type of surfactant and synthesis conditions. Mössbauer spectra, which were recorded at 290 K for all the samples, are typical of nonstoichiometric Fe3−δO4, with a small excess of Fe3+, 0.05 ≤ δ ≤ 0.15. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
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Open AccessArticle An Ultrasensitive Electrochemiluminescence Immunoassay for Carbohydrate Antigen 19-9 in Serum Based on Antibody Labeled Fe3O4 Nanoparticles as Capture Probes and Graphene/CdTe Quantum Dot Bionanoconjugates as Signal Amplifiers
Int. J. Mol. Sci. 2013, 14(5), 10397-10411; doi:10.3390/ijms140510397
Received: 1 February 2013 / Revised: 2 May 2013 / Accepted: 6 May 2013 / Published: 17 May 2013
Cited by 7 | PDF Full-text (867 KB) | HTML Full-text | XML Full-text
Abstract
The CdTe quantum dots (QDs), graphene nanocomposite (CdTe-G) and dextran–Fe3O4 magnetic nanoparticles have been synthesized for developing an ultrasensitive electrochemiluminescence (ECL) immunoassay for Carcinoembryonic antigen 19-9 (CA 19-9) in serums. Firstly, the capture probes (CA 19-9 Ab1/Fe3O4
[...] Read more.
The CdTe quantum dots (QDs), graphene nanocomposite (CdTe-G) and dextran–Fe3O4 magnetic nanoparticles have been synthesized for developing an ultrasensitive electrochemiluminescence (ECL) immunoassay for Carcinoembryonic antigen 19-9 (CA 19-9) in serums. Firstly, the capture probes (CA 19-9 Ab1/Fe3O4) for enriching CA 19-9 were synthesized by immobilizing the CA 19-9’s first antibody (CA 19-9 Ab1) on magnetic nanoparticles (dextran-Fe3O4). Secondly, the signal probes (CA 19-9 Ab2/CdTe-G), which can emit an ECL signal, were formed by attaching the secondary CA 19-9 antibody (CA 19-9 Ab2) to the surface of the CdTe-G. Thirdly, the above two probes were used for conjugating with a serial of CA 19-9 concentrations. Graphene can immobilize dozens of CdTe QDs on their surface, which can emit stronger ECL intensity than CdTe QDs. Based on the amplified signal, ultrasensitive antigen detection can be realized. Under the optimal conditions, the ECL signal depended linearly on the logarithm of CA 19-9 concentration from 0.005 to 100 pg/mL, and the detection limit was 0.002 pg/mL. Finally, five samples of human serum were tested, and the results were compared with a time-resolved fluorescence assay (TRFA). The novel immunoassay provides a stable, specific and highly sensitive immunoassay protocol for tumor marker detection at very low levels, which can be applied in early diagnosis of tumor. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles 2013)
Open AccessArticle The Role of Sulfur Dioxide in the Regulation of Mitochondrion-Related Cardiomyocyte Apoptosis in Rats with Isopropylarterenol-Induced Myocardial Injury
Int. J. Mol. Sci. 2013, 14(5), 10465-10482; doi:10.3390/ijms140510465
Received: 5 March 2013 / Revised: 24 April 2013 / Accepted: 9 May 2013 / Published: 21 May 2013
Cited by 16 | PDF Full-text (1774 KB) | HTML Full-text | XML Full-text
Abstract
The authors investigated the regulatory effects of sulfur dioxide (SO2) on myocardial injury induced by isopropylarterenol (ISO) hydrochloride and its mechanisms. Wistar rats were divided into four groups: control group, ISO group, ISO plus SO2 group, and SO2 only
[...] Read more.
The authors investigated the regulatory effects of sulfur dioxide (SO2) on myocardial injury induced by isopropylarterenol (ISO) hydrochloride and its mechanisms. Wistar rats were divided into four groups: control group, ISO group, ISO plus SO2 group, and SO2 only group. Cardiac function was measured and cardiomyocyte apoptosis was detected. Bcl-2, bax and cytochrome c (cytc) expressions, and caspase-9 and caspase-3 activities in the left ventricular tissues were examined in the rats. The opening status of myocardial mitochondrial permeability transition pore (MPTP) and membrane potential were analyzed. The results showed that ISO-treated rats developed heart dysfunction and cardiac injury. Furthermore, cardiomyocyte apoptosis in the left ventricular tissues was augmented, left ventricular tissue bcl-2 expression was down-regulated, bax expression was up-regulated, mitochondrial membrane potential was significantly reduced, MPTP opened, cytc release from mitochondrion into cytoplasm was significantly increased, and both caspase-9 and caspase-3 activities were increased. Administration of an SO2 donor, however, markedly improved heart function and relieved myocardial injury of the ISO-treated rats; it lessened cardiomyocyte apoptosis, up-regulated myocardial bcl-2, down-regulated bax expression, stimulated mitochondrial membrane potential, closed MPTP, and reduced cytc release as well as caspase-9 and caspase-3 activities in the left ventricular tissue. Hence, SO2 attenuated myocardial injury in association with the inhibition of apoptosis in myocardial tissues, and the bcl-2/cytc/caspase-9/caspase-3 pathway was possibly involved in this process. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
Open AccessArticle Inhibition of CCL2 Signaling in Combination with Docetaxel Treatment Has Profound Inhibitory Effects on Prostate Cancer Growth in Bone
Int. J. Mol. Sci. 2013, 14(5), 10483-10496; doi:10.3390/ijms140510483
Received: 16 February 2013 / Revised: 14 March 2013 / Accepted: 6 May 2013 / Published: 21 May 2013
Cited by 7 | PDF Full-text (951 KB) | HTML Full-text | XML Full-text
Abstract
The C-C chemokine ligand 2 (CCL2) stimulates migration, proliferation, and invasion of prostate cancer (PCa) cells, and its signaling also plays a role in the activation of osteoclasts. Therefore targeting CCL2 signaling in regulation of tumor progression in bone metastases is an area
[...] Read more.
The C-C chemokine ligand 2 (CCL2) stimulates migration, proliferation, and invasion of prostate cancer (PCa) cells, and its signaling also plays a role in the activation of osteoclasts. Therefore targeting CCL2 signaling in regulation of tumor progression in bone metastases is an area of intense research. The objective of our study was to investigate the efficacy of CCL2 blockade by neutralizing antibodies to inhibit the growth of PCa in bone. We used a preclinical model of cancer growth in the bone in which PCa C4-2B cells were injected directly into murine tibiae. Animals were treated for ten weeks with neutralizing anti-CCL2 antibodies, docetaxel, or a combination of both, and then followed an additional nine weeks. CCL2 blockade inhibited the growth of PCa in bone, with even more pronounced inhibition in combination with docetaxel. CCL2 blockade also resulted in increases in bone mineral density. Furthermore, our results showed that the tumor inhibition lasted even after discontinuation of the treatment. Our data provide compelling evidence that CCL2 blockade slows PCa growth in bone, both alone and in combination with docetaxel. These results support the continued investigations of CCL2 blockade as a treatment for advanced metastatic PCa. Full article
(This article belongs to the Special Issue Molecular Research in Urology)
Open AccessArticle NS5ATP9 Contributes to Inhibition of Cell Proliferation by Hepatitis C Virus (HCV) Nonstructural Protein 5A (NS5A) via MEK/Extracellular Signal Regulated Kinase (ERK) Pathway
Int. J. Mol. Sci. 2013, 14(5), 10539-10551; doi:10.3390/ijms140510539
Received: 20 February 2013 / Revised: 10 April 2013 / Accepted: 15 April 2013 / Published: 21 May 2013
Cited by 2 | PDF Full-text (1343 KB) | HTML Full-text | XML Full-text
Abstract
Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a remarkable protein as it clearly plays multiple roles in mediating viral replication, host-cell interactions and viral pathogenesis. However, on the impact of cell growth, there have been different study results. NS5ATP9, also known
[...] Read more.
Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a remarkable protein as it clearly plays multiple roles in mediating viral replication, host-cell interactions and viral pathogenesis. However, on the impact of cell growth, there have been different study results. NS5ATP9, also known as KIAA0101, p15PAF, L5, and OEACT-1, was first identified as a proliferating cell nuclear antigen-binding protein. Earlier studies have shown that NS5ATP9 might play an important role in HCV infection. The aim of this study is to investigate the function of NS5ATP9 on hepatocellular carcinoma (HCC) cell lines proliferation under HCV NS5A expression. The results showed that overexpression of NS5ATP9 inhibited the proliferation of Bel7402 cells, whereas knockdown of NS5ATP9 by interfering RNA promoted the growth of HepG2 cells. Under HCV NS5A expression, RNA interference (RNAi) targeting of NS5ATP9 could reverse the inhibition of HepG2 cell proliferation, suggesting that NS5ATP9 might be an anti-proliferation gene that plays an important role in the suppression of cell growth mediated by HCV NS5A via MEK/ERK signaling pathway. These findings might provide new insights into HCV NS5A and NS5ATP9. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Open AccessArticle Analysis of Conformational Motions and Residue Fluctuations for Escherichia coli Ribose-Binding Protein Revealed with Elastic Network Models
Int. J. Mol. Sci. 2013, 14(5), 10552-10569; doi:10.3390/ijms140510552
Received: 18 March 2013 / Revised: 24 April 2013 / Accepted: 25 April 2013 / Published: 21 May 2013
Cited by 2 | PDF Full-text (1491 KB) | HTML Full-text | XML Full-text
Abstract
The ribose-binding protein (RBP) is a sugar-binding bacterial periplasmic protein whose function is associated with a large allosteric conformational change from an open to a closed conformation upon binding to ribose. The open (ligand-free) and closed (ligand-bound) forms of RBP have been found.
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The ribose-binding protein (RBP) is a sugar-binding bacterial periplasmic protein whose function is associated with a large allosteric conformational change from an open to a closed conformation upon binding to ribose. The open (ligand-free) and closed (ligand-bound) forms of RBP have been found. Here we investigate the conformational motions and residue fluctuations of the RBP by analyzing the modes of motion with two coarse-grained elastic network models, the Gaussian Network Model (GNM) and Anisotropic Network Model (ANM). The calculated B-factors in both the calculated models are in good agreement with the experimentally determined B-factors in X-ray crystal structures. The slowest mode analysis by GNM shows that both forms have the same motion hinge axes around residues Ser103, Gln235, Asp264 and the two domains of both structures have similar fluctuation range. The superposition of the first three dominant modes of ANM, consisting of the rotating, bending and twisting motions of the two forms, accounts for large rearrangement of domains from the ligand-free (open) to ligand-bound (closed) conformation and thus constitutes a critical component of the RBP’s functions. By analyzing cross-correlations between residue fluctuation and the difference-distance plot, it is revealed that the conformational change can be described as a rigid rotation of the two domains with respect to each other, whereas the internal structure of the two domains remains largely intact. The results directly indicate that the dominant dynamic characteristics of protein structures can be captured from their static native state using coarse-grained models. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Intra-Species Bacterial Quorum Sensing Studied at Single Cell Level in a Double Droplet Trapping System
Int. J. Mol. Sci. 2013, 14(5), 10570-10581; doi:10.3390/ijms140510570
Received: 19 April 2013 / Revised: 9 May 2013 / Accepted: 10 May 2013 / Published: 21 May 2013
Cited by 9 | PDF Full-text (1464 KB) | HTML Full-text | XML Full-text
Abstract
In this paper, we investigated the intra-species bacterial quorum sensing at the single cell level using a double droplet trapping system. Escherichia coli transformed to express the quorum sensing receptor protein, LasR, were encapsulated in microdroplets that were positioned adjacent to microdroplets containing
[...] Read more.
In this paper, we investigated the intra-species bacterial quorum sensing at the single cell level using a double droplet trapping system. Escherichia coli transformed to express the quorum sensing receptor protein, LasR, were encapsulated in microdroplets that were positioned adjacent to microdroplets containing the autoinducer, N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL). Functional activation of the LasR protein by diffusion of the OdDHL across the droplet interface was measured by monitoring the expression of green fluorescent protein (GFP) from a LasR-dependent promoter. A threshold concentration of OdDHL was found to induce production of quorum-sensing associated GFP by E. coli. Additionally, we demonstrated that LasR-dependent activation of GFP expression was also initiated when the adjacent droplets contained single E. coli transformed with the OdDHL synthase gene, LasI, representing a simple quorum sensing circuit between two droplets. Full article
(This article belongs to the Special Issue Quorum Sensing Research in Microbial Systems)
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Open AccessArticle Bacterial Growth Kinetics under a Novel Flexible Methacrylate Dressing Serving as a Drug Delivery Vehicle for Antiseptics
Int. J. Mol. Sci. 2013, 14(5), 10582-10590; doi:10.3390/ijms140510582
Received: 3 April 2013 / Revised: 26 April 2013 / Accepted: 6 May 2013 / Published: 21 May 2013
Cited by 3 | PDF Full-text (179 KB) | HTML Full-text | XML Full-text
Abstract
A flexible methacrylate powder dressing (Altrazeal®) transforms into a wound contour conforming matrix once in contact with wound exudate. We hypothesised that it may also serve as a drug delivery vehicle for antiseptics. The antimicrobial efficacy and influence on bacterial growth
[...] Read more.
A flexible methacrylate powder dressing (Altrazeal®) transforms into a wound contour conforming matrix once in contact with wound exudate. We hypothesised that it may also serve as a drug delivery vehicle for antiseptics. The antimicrobial efficacy and influence on bacterial growth kinetics in combination with three antiseptics was investigated in an in vitro porcine wound model. Standardized in vitro wounds were contaminated with Staphylococcus aureus (MRSA; ATCC 33591) and divided into six groups: no dressing (negative control), methacrylate dressing alone, and combinations with application of 0.02% Polyhexamethylene Biguanide (PHMB), 0.4% PHMB, 0.1% PHMB + 0.1% betaine, 7.7 mg/mL Povidone-iodine (PVP-iodine), and 0.1% Octenidine-dihydrochloride (OCT) + 2% phenoxyethanol. Bacterial load per gram tissue was measured over five days. The highest reduction was observed with PVP-iodine at 24 h to log10 1.43 cfu/g, followed by OCT at 48 h to log10 2.41 cfu/g. Whilst 0.02% PHMB resulted in a stable bacterial load over 120 h to log10 4.00 cfu/g over 120 h, 0.1% PHMB + 0.1% betaine inhibited growth during the first 48 h, with slightly increasing bacterial numbers up to log10 5.38 cfu/g at 120 h. These results indicate that this flexible methacrylate dressing can be loaded with various antiseptics serving as drug delivery system. Depending on the selected combination, an individually shaped and controlled antibacterial effect may be achieved using the same type of wound dressing. Full article
(This article belongs to the Special Issue Antimicrobial Polymers)
Open AccessArticle Effect of Plant Derived Antimicrobials on Salmonella Enteritidis Adhesion to and Invasion of Primary Chicken Oviduct Epithelial Cells in vitro and Virulence Gene Expression
Int. J. Mol. Sci. 2013, 14(5), 10608-10625; doi:10.3390/ijms140510608
Received: 18 February 2013 / Revised: 23 April 2013 / Accepted: 1 May 2013 / Published: 21 May 2013
Cited by 11 | PDF Full-text (299 KB) | HTML Full-text | XML Full-text
Abstract
Salmonella Enteritidis (SE) is a major foodborne pathogen in the United States and one of the most frequently reported Salmonella serotypes globally. Eggs are the most common food product associated with SE infections in humans. The pathogen colonizes the intestinal tract in layers,
[...] Read more.
Salmonella Enteritidis (SE) is a major foodborne pathogen in the United States and one of the most frequently reported Salmonella serotypes globally. Eggs are the most common food product associated with SE infections in humans. The pathogen colonizes the intestinal tract in layers, and migrates to reproductive organs systemically. Since adhesion to and invasion of chicken oviduct epithelial cells (COEC) is critical for SE colonization in reproductive tract, reducing these virulence factors could potentially decrease egg yolk contamination. This study investigated the efficacy of sub-inhibitory concentrations of three plant-derived antimicrobials (PDAs), namely carvacrol, thymol and eugenol in reducing SE adhesion to and invasion of COEC, and survival in chicken macrophages. In addition, the effect of PDAs on SE genes critical for oviduct colonization and macrophage survival was determined using real-time quantitative PCR (RT-qPCR). All PDAs significantly reduced SE adhesion to and invasion of COEC (p < 0.001). The PDAs, except thymol consistently decreased SE survival in macrophages (p < 0.001). RT-qPCR results revealed down-regulation in the expression of genes involved in SE colonization and macrophage survival (p < 0.001). The results indicate that PDAs could potentially be used to control SE colonization in chicken reproductive tract; however, in vivo studies validating these results are warranted. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Transcriptional Profiling of Swine Lung Tissue after Experimental Infection with Actinobacillus pleuropneumoniae
Int. J. Mol. Sci. 2013, 14(5), 10626-10660; doi:10.3390/ijms140510626
Received: 1 April 2013 / Revised: 9 May 2013 / Accepted: 10 May 2013 / Published: 21 May 2013
Cited by 6 | PDF Full-text (1228 KB) | HTML Full-text | XML Full-text
Abstract
Porcine pleuropneumonia is a highly contagious respiratory disease that causes great economic losses worldwide. In this study, we aimed to explore the underlying relationship between infection and injury by investigation of the whole porcine genome expression profiles of swine lung tissues post-inoculated with
[...] Read more.
Porcine pleuropneumonia is a highly contagious respiratory disease that causes great economic losses worldwide. In this study, we aimed to explore the underlying relationship between infection and injury by investigation of the whole porcine genome expression profiles of swine lung tissues post-inoculated with experimentally Actinobacillus pleuropneumoniae. Expression profiling experiments of the control group and the treatment group were conducted using a commercially available Agilent Porcine Genechip including 43,603 probe sets. Microarray analysis was conducted on profiles of lung from challenged versus non-challenged swine. We found 11,929 transcripts, identified as differentially expressed at the p ≤0.01 level. There were 1188 genes annotated as swine genes in the GenBank Data Base. GO term analysis identified a total of 89 biological process categories, 82 cellular components and 182 molecular functions that were significantly affected, and at least 27 biological process categories that were related to the host immune response. Gene set enrichment analysis identified 13 pathways that were significantly associated with host response. Many proinflammatory-inflammatory cytokines were activated and involved in the regulation of the host defense response at the site of inflammation; while the cytokines involved in regulation of the host immune response were suppressed. All changes of genes and pathways of induced or repressed expression not only led to a decrease in antigenic peptides presented to T lymphocytes by APCs via the MHC and alleviated immune response injury induced by infection, but also stimulated stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocyte, and promote neutrophils and macrophages to phagocytose bacterial and foreign antigen at the site of inflammation. The defense function of swine infection with Actinobacillus pleuropneumoniae was improved, while its immune function was decreased. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Evaluation of the Effect of Different Doses of Low Energy Shock Wave Therapy on the Erectile Function of Streptozotocin (STZ)-Induced Diabetic Rats
Int. J. Mol. Sci. 2013, 14(5), 10661-10673; doi:10.3390/ijms140510661
Received: 14 February 2013 / Revised: 4 May 2013 / Accepted: 8 May 2013 / Published: 21 May 2013
Cited by 16 | PDF Full-text (1994 KB) | HTML Full-text | XML Full-text
Abstract
To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT) on the erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. SD rats (n = 75) were randomly divided into 5 groups (normal control, diabetic control, 3
[...] Read more.
To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT) on the erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. SD rats (n = 75) were randomly divided into 5 groups (normal control, diabetic control, 3 different dose LESWT treated diabetic groups). Diabetic rats were induced by intra-peritoneal injection of STZ (60 mg/kg) and rats with fasting blood glucose ≥ 300 mg/dL were selected as diabetic models. Twelve weeks later, different doses of LESWT (100, 200 and 300 shocks each time) treatment on penises were used to treat ED (7.33 MPa, 2 shocks/s) three times a week for two weeks. The erectile function was evaluated by intracavernous pressure (ICP) after 1 week washout period. Then the penises were harvested for histological study. The results showed LESWT could significantly improve the erectile function of diabetic rats, increase smooth muscle and endothelial contents, up-regulate the expression of α-SMA, vWF, nNOS and VEGF, and down- regulate the expression of RAGE in corpus cavernosum. The therapeutic effect might relate to treatment dose positively, and the maximal therapeutic effect was noted in the LESWT300 group. Consequently, 300 shocks each time might be the ideal LESWT dose for diabetic ED treatment. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)

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Open AccessReview Improving Pharmaceutical Protein Production in Oryza sativa
Int. J. Mol. Sci. 2013, 14(5), 8719-8739; doi:10.3390/ijms14058719
Received: 21 January 2013 / Revised: 14 April 2013 / Accepted: 15 April 2013 / Published: 24 April 2013
Cited by 15 | PDF Full-text (247 KB) | HTML Full-text | XML Full-text
Abstract
Application of plant expression systems in the production of recombinant proteins has several advantages, such as low maintenance cost, absence of human pathogens, and possession of complex post-translational glycosylation capabilities. Plants have been successfully used to produce recombinant cytokines, vaccines, antibodies, and other
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Application of plant expression systems in the production of recombinant proteins has several advantages, such as low maintenance cost, absence of human pathogens, and possession of complex post-translational glycosylation capabilities. Plants have been successfully used to produce recombinant cytokines, vaccines, antibodies, and other proteins, and rice (Oryza sativa) is a potential plant used as recombinant protein expression system. After successful transformation, transgenic rice cells can be either regenerated into whole plants or grown as cell cultures that can be upscaled into bioreactors. This review summarizes recent advances in the production of different recombinant protein produced in rice and describes their production methods as well as methods to improve protein yield and quality. Glycosylation and its impact in plant development and protein production are discussed, and several methods of improving yield and quality that have not been incorporated in rice expression systems are also proposed. Finally, different bioreactor options are explored and their advantages are analyzed. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessReview The Brassinosteroid Signaling Pathway—New Key Players and Interconnections with Other Signaling Networks Crucial for Plant Development and Stress Tolerance
Int. J. Mol. Sci. 2013, 14(5), 8740-8774; doi:10.3390/ijms14058740
Received: 1 February 2013 / Revised: 1 April 2013 / Accepted: 2 April 2013 / Published: 24 April 2013
Cited by 24 | PDF Full-text (1330 KB) | HTML Full-text | XML Full-text
Abstract
Brassinosteroids (BRs) are a class of steroid hormones regulating a wide range of physiological processes during the plant life cycle from seed development to the modulation of flowering and senescence. The last decades, and recent years in particular, have witnessed a significant advance
[...] Read more.
Brassinosteroids (BRs) are a class of steroid hormones regulating a wide range of physiological processes during the plant life cycle from seed development to the modulation of flowering and senescence. The last decades, and recent years in particular, have witnessed a significant advance in the elucidation of the molecular mechanisms of BR signaling from perception by the transmembrane receptor complex to the regulation of transcription factors influencing expression of the target genes. Application of the new approaches shed light on the molecular functions of the key players regulating the BR signaling cascade and allowed identification of new factors. Recent studies clearly indicated that some of the components of BR signaling pathway act as multifunctional proteins involved in other signaling networks regulating diverse physiological processes, such as photomorphogenesis, cell death control, stomatal development, flowering, plant immunity to pathogens and metabolic responses to stress conditions, including salinity. Regulation of some of these processes is mediated through a crosstalk between BR signalosome and the signaling cascades of other hormones, including auxin, abscisic acid, ethylene and salicylic acid. Unravelling the complicated mechanisms of BR signaling and its interconnections with other molecular networks may be of great importance for future practical applications in agriculture. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessReview Bioactive Molecules in Soil Ecosystems: Masters of the Underground
Int. J. Mol. Sci. 2013, 14(5), 8841-8868; doi:10.3390/ijms14058841
Received: 28 February 2013 / Revised: 10 April 2013 / Accepted: 12 April 2013 / Published: 24 April 2013
Cited by 13 | PDF Full-text (377 KB) | HTML Full-text | XML Full-text
Abstract
Complex biological and ecological processes occur in the rhizosphere through ecosystem-level interactions between roots, microorganisms and soil fauna. Over the past decade, studies of the rhizosphere have revealed that when roots, microorganisms and soil fauna physically contact one another, bioactive molecular exchanges often
[...] Read more.
Complex biological and ecological processes occur in the rhizosphere through ecosystem-level interactions between roots, microorganisms and soil fauna. Over the past decade, studies of the rhizosphere have revealed that when roots, microorganisms and soil fauna physically contact one another, bioactive molecular exchanges often mediate these interactions as intercellular signal, which prepare the partners for successful interactions. Despite the importance of bioactive molecules in sustainable agriculture, little is known of their numerous functions, and improving plant health and productivity by altering ecological processes remains difficult. In this review, we describe the major bioactive molecules present in below-ground ecosystems (i.e., flavonoids, exopolysaccharides, antibiotics and quorum-sensing signals), and we discuss how these molecules affect microbial communities, nutrient availability and plant defense responses. Full article
(This article belongs to the Special Issue Quorum Sensing Research in Microbial Systems)
Open AccessReview Endothelial Aging Associated with Oxidative Stress Can Be Modulated by a Healthy Mediterranean Diet
Int. J. Mol. Sci. 2013, 14(5), 8869-8889; doi:10.3390/ijms14058869
Received: 5 March 2013 / Revised: 28 March 2013 / Accepted: 2 April 2013 / Published: 24 April 2013
Cited by 25 | PDF Full-text (310 KB) | HTML Full-text | XML Full-text
Abstract
Aging is a condition which favors the development of atherosclerosis, which has been associated with a breakdown in repair processes that occurs in response to cell damage. The dysregulation of the biological systems associated with aging are produced partly through damage which accumulates
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Aging is a condition which favors the development of atherosclerosis, which has been associated with a breakdown in repair processes that occurs in response to cell damage. The dysregulation of the biological systems associated with aging are produced partly through damage which accumulates over time. One major source of this injury is oxidative stress, which can impair biological structures and the mechanisms by which they are repaired. These mechanisms are based on the pathogenesis of endothelial dysfunction, which in turn is associated with cardiovascular disease, carcinogenesis and aging. The dependent dysfunction of aging has been correlated with a reduction in the number and/or functional activity of endothelial progenitor cells, which could hinder the repair and regeneration of the endothelium. In addition, aging, inflammation and oxidative stress are endogenous factors that cause telomere shortening, which is dependent on oxidative cell damage. Moreover, telomere length correlates with lifestyle and the consumption of a healthy diet. Thus, diseases associated with aging and age may be caused by the long-term effects of oxidative damage, which are modified by genetic and environmental factors. Considering that diet is a very important source of antioxidants, in this review we will analyze the relationship between oxidative stress, aging, and the mechanisms which may be involved in a higher survival rate and a lower incidence of the diseases associated with aging in populations which follow a healthy diet. Full article
(This article belongs to the Special Issue Oxidative Stress and Ageing)
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Open AccessReview Structural Basis of Membrane Trafficking by Rab Family Small G Protein
Int. J. Mol. Sci. 2013, 14(5), 8912-8923; doi:10.3390/ijms14058912
Received: 1 March 2013 / Revised: 1 April 2013 / Accepted: 10 April 2013 / Published: 25 April 2013
Cited by 8 | PDF Full-text (712 KB) | HTML Full-text | XML Full-text
Abstract
The Ras-superfamily of small G proteins is a family of GTP hydrolases that is regulated by GTP/GDP binding states. One member of the Ras-superfamily, Rab, is involved in the regulation of vesicle trafficking, which is critical to endocytosis, biosynthesis, secretion, cell differentiation and
[...] Read more.
The Ras-superfamily of small G proteins is a family of GTP hydrolases that is regulated by GTP/GDP binding states. One member of the Ras-superfamily, Rab, is involved in the regulation of vesicle trafficking, which is critical to endocytosis, biosynthesis, secretion, cell differentiation and cell growth. The active form of the Rab proteins, which contains GTP, can recruit specific binding partners, such as sorting adaptors, tethering factors, kinases, phosphatases and motor proteins, thereby influencing vesicle formation, transport, and tethering. Many Rab proteins share the same interacting partners and perform unique roles in specific locations. Because functional loss of the Rab pathways has been implicated in a variety of diseases, the Rab GTPase family has been extensively investigated. In this review, we summarize Rab GTPase- mediated membrane trafficking while focusing on the structures of Rab protein and Rab-effector complexes. This review provides detailed information that helps explain how the Rab GTPase family is involved in membrane trafficking. Full article
(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications)
Open AccessReview Melatonin-Based Therapeutics for Neuroprotection in Stroke
Int. J. Mol. Sci. 2013, 14(5), 8924-8947; doi:10.3390/ijms14058924
Received: 8 March 2013 / Revised: 10 April 2013 / Accepted: 11 April 2013 / Published: 25 April 2013
Cited by 10 | PDF Full-text (308 KB) | HTML Full-text | XML Full-text
Abstract
The present review paper supports the approach to deliver melatonin and to target melatonin receptors for neuroprotection in stroke. We discuss laboratory evidence demonstrating neuroprotective effects of exogenous melatonin treatment and transplantation of melatonin-secreting cells in stroke. In addition, we describe a novel
[...] Read more.
The present review paper supports the approach to deliver melatonin and to target melatonin receptors for neuroprotection in stroke. We discuss laboratory evidence demonstrating neuroprotective effects of exogenous melatonin treatment and transplantation of melatonin-secreting cells in stroke. In addition, we describe a novel mechanism of action underlying the therapeutic benefits of stem cell therapy in stroke, implicating the role of melatonin receptors. As we envision the clinical entry of melatonin-based therapeutics, we discuss translational experiments that warrant consideration to reveal an optimal melatonin treatment strategy that is safe and effective for human application. Full article
(This article belongs to the Special Issue Advances in the Research of Melatonin)
Open AccessReview Cell Signaling Experiments Driven by Optical Manipulation
Int. J. Mol. Sci. 2013, 14(5), 8963-8984; doi:10.3390/ijms14058963
Received: 12 February 2013 / Revised: 8 April 2013 / Accepted: 14 April 2013 / Published: 25 April 2013
Cited by 10 | PDF Full-text (1299 KB) | HTML Full-text | XML Full-text
Abstract
Cell signaling involves complex transduction mechanisms in which information released by nearby cells or extracellular cues are transmitted to the cell, regulating fundamental cellular activities. Understanding such mechanisms requires cell stimulation with precise control of low numbers of active molecules at high spatial
[...] Read more.
Cell signaling involves complex transduction mechanisms in which information released by nearby cells or extracellular cues are transmitted to the cell, regulating fundamental cellular activities. Understanding such mechanisms requires cell stimulation with precise control of low numbers of active molecules at high spatial and temporal resolution under physiological conditions. Optical manipulation techniques, such as optical tweezing, mechanical stress probing or nano-ablation, allow handling of probes and sub-cellular elements with nanometric and millisecond resolution. PicoNewton forces, such as those involved in cell motility or intracellular activity, can be measured with femtoNewton sensitivity while controlling the biochemical environment. Recent technical achievements in optical manipulation have new potentials, such as exploring the actions of individual molecules within living cells. Here, we review the progress in optical manipulation techniques for single-cell experiments, with a focus on force probing, cell mechanical stimulation and the local delivery of active molecules using optically manipulated micro-vectors and laser dissection. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
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Open AccessReview Ribonucleoprotein Complexes That Control Circadian Clocks
Int. J. Mol. Sci. 2013, 14(5), 9018-9036; doi:10.3390/ijms14059018
Received: 28 January 2013 / Revised: 7 April 2013 / Accepted: 15 April 2013 / Published: 25 April 2013
Cited by 8 | PDF Full-text (398 KB) | HTML Full-text | XML Full-text
Abstract
Circadian clocks are internal molecular time-keeping mechanisms that enable organisms to adjust their physiology and behavior to the daily surroundings. Misalignment of circadian clocks leads to both physiological and health impairment. Post-transcriptional regulation and translational regulation of circadian clocks have been extensively investigated.
[...] Read more.
Circadian clocks are internal molecular time-keeping mechanisms that enable organisms to adjust their physiology and behavior to the daily surroundings. Misalignment of circadian clocks leads to both physiological and health impairment. Post-transcriptional regulation and translational regulation of circadian clocks have been extensively investigated. In addition, accumulating evidence has shed new light on the involvement of ribonucleoprotein complexes (RNPs) in the post-transcriptional regulation of circadian clocks. Numerous RNA-binding proteins (RBPs) and RNPs have been implicated in the post-transcriptional modification of circadian clock proteins in different model organisms. Herein, we summarize the advances in the current knowledge on the role of RNP complexes in circadian clock regulation. Full article
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Open AccessReview Role of Melatonin in Schizophrenia
Int. J. Mol. Sci. 2013, 14(5), 9037-9050; doi:10.3390/ijms14059037
Received: 19 February 2013 / Revised: 9 April 2013 / Accepted: 10 April 2013 / Published: 25 April 2013
Cited by 11 | PDF Full-text (195 KB) | HTML Full-text | XML Full-text
Abstract
Schizophrenia is a chronic mental disease that disturbs several cognitive functions, such as memory, thought, perception and volition. Schizophrenia’s biological etiology is multifactorial and is still under investigation. Melatonin has been involved in schizophrenia since the first decades of the twentieth century. Research
[...] Read more.
Schizophrenia is a chronic mental disease that disturbs several cognitive functions, such as memory, thought, perception and volition. Schizophrenia’s biological etiology is multifactorial and is still under investigation. Melatonin has been involved in schizophrenia since the first decades of the twentieth century. Research into melatonin regarding schizophrenia has followed two different approaches. The first approach is related to the use of melatonin as a biological marker. The second approach deals with the clinical applications of melatonin as a drug treatment. In this paper, both aspects of melatonin application are reviewed. Its clinical use in schizophrenia is emphasized. Full article
(This article belongs to the Special Issue Advances in the Research of Melatonin)
Open AccessReview Targeting the Redox Balance in Inflammatory Skin Conditions
Int. J. Mol. Sci. 2013, 14(5), 9126-9167; doi:10.3390/ijms14059126
Received: 1 March 2013 / Revised: 10 April 2013 / Accepted: 16 April 2013 / Published: 26 April 2013
Cited by 22 | PDF Full-text (359 KB) | HTML Full-text | XML Full-text
Abstract
Reactive oxygen species (ROS) can be both beneficial and deleterious. Under normal physiological conditions, ROS production is tightly regulated, and ROS participate in both pathogen defense and cellular signaling. However, insufficient ROS detoxification or ROS overproduction generates oxidative stress, resulting in cellular damage.
[...] Read more.
Reactive oxygen species (ROS) can be both beneficial and deleterious. Under normal physiological conditions, ROS production is tightly regulated, and ROS participate in both pathogen defense and cellular signaling. However, insufficient ROS detoxification or ROS overproduction generates oxidative stress, resulting in cellular damage. Oxidative stress has been linked to various inflammatory diseases. Inflammation is an essential response in the protection against injurious insults and thus important at the onset of wound healing. However, hampered resolution of inflammation can result in a chronic, exaggerated response with additional tissue damage. In the pathogenesis of several inflammatory skin conditions, e.g., sunburn and psoriasis, inflammatory-mediated tissue damage is central. The prolonged release of excess ROS in the skin can aggravate inflammatory injury and promote chronic inflammation. The cellular redox balance is therefore tightly regulated by several (enzymatic) antioxidants and pro-oxidants; however, in case of chronic inflammation, the antioxidant system may be depleted, and prolonged oxidative stress occurs. Due to the central role of ROS in inflammatory pathologies, restoring the redox balance forms an innovative therapeutic target in the development of new strategies for treating inflammatory skin conditions. Nevertheless, the clinical use of antioxidant-related therapies is still in its infancy. Full article
(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)
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Open AccessReview The Role of Strigolactones in Nutrient-Stress Responses in Plants
Int. J. Mol. Sci. 2013, 14(5), 9286-9304; doi:10.3390/ijms14059286
Received: 12 March 2013 / Revised: 3 April 2013 / Accepted: 17 April 2013 / Published: 29 April 2013
Cited by 10 | PDF Full-text (1050 KB) | HTML Full-text | XML Full-text
Abstract
Strigolactones (SLs) are a new group of plant hormones, which have been intensively investigated during the last few years. The wide spectrum of SLs actions, including the regulation of shoot/root architecture, and the stimulation of the interactions between roots and fungi or bacteria,
[...] Read more.
Strigolactones (SLs) are a new group of plant hormones, which have been intensively investigated during the last few years. The wide spectrum of SLs actions, including the regulation of shoot/root architecture, and the stimulation of the interactions between roots and fungi or bacteria, as well as the stimulation of germination of parasitic plants, indicates that this group of hormones may play an important role in the mechanisms that control soil exploration, and the root-mediated uptake of nutrients. Current studies have shown that SLs might be factors that have an influence on the plant response to a deficiency of macronutrients. Experimental data from the last four years have confirmed that the biosynthesis and exudation of SLs are increased under phosphorus and nitrogen deficiency. All these data suggest that SLs may regulate the complex response to nutrient stress, which include not only the modification of the plant developmental process, but also the cooperation with other organisms in order to minimize the effects of threats. In this paper the results of studies that indicate that SLs play an important role in the response to nutrient stress are reviewed and the consequences of the higher biosynthesis and exudation of SLs in response to phosphorus and nitrogen deficiency are discussed. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessReview Effects of Nanotoxicity on Female Reproductivity and Fetal Development in Animal Models
Int. J. Mol. Sci. 2013, 14(5), 9319-9337; doi:10.3390/ijms14059319
Received: 28 February 2013 / Revised: 17 April 2013 / Accepted: 18 April 2013 / Published: 29 April 2013
Cited by 20 | PDF Full-text (1217 KB) | HTML Full-text | XML Full-text
Abstract
The extensive application of nanomaterials in industry, medicine and consumer products has raised concerns about their potential toxicity. The female population is particularly vulnerable and deserves special attention because toxicity in this group may impact both female reproductivity and fetal development. Mouse and
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The extensive application of nanomaterials in industry, medicine and consumer products has raised concerns about their potential toxicity. The female population is particularly vulnerable and deserves special attention because toxicity in this group may impact both female reproductivity and fetal development. Mouse and zebrafish models each have their own unique features and studies using these models to examine the potential toxicity of various nanoparticles are compared and summarized in this review. Several nanoparticles exhibit detrimental effects on female reproductivity as well as fetal development, and these adverse effects are related to nanoparticle composition, surface modification, dose, exposure route and animal species. Limited studies on the mechanisms of nanotoxicity are also documented and reviewed herein. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles 2013)
Open AccessReview Biomarkers for Anti-Angiogenic Therapy in Cancer
Int. J. Mol. Sci. 2013, 14(5), 9338-9364; doi:10.3390/ijms14059338
Received: 28 February 2013 / Revised: 25 March 2013 / Accepted: 18 April 2013 / Published: 29 April 2013
Cited by 26 | PDF Full-text (557 KB) | HTML Full-text | XML Full-text
Abstract
Angiogenesis, the development of new vessels from existing vasculature, plays a central role in tumor growth, survival, and progression. On the molecular level it is controlled by a number of pro- and anti-angiogenic cytokines, among which the vascular endothelial growth factors (VEGFs), together
[...] Read more.
Angiogenesis, the development of new vessels from existing vasculature, plays a central role in tumor growth, survival, and progression. On the molecular level it is controlled by a number of pro- and anti-angiogenic cytokines, among which the vascular endothelial growth factors (VEGFs), together with their related VEGF-receptors, have an exceptional position. Therefore, the blockade of VEGF signaling in order to inhibit angiogenesis was deemed an attractive approach for cancer therapy and drugs interfering with the VEGF-ligands, the VEGF receptors, and the intracellular VEGF-mediated signal transduction were developed. Although promising in pre-clinical trials, VEGF-inhibition proved to be problematic in the clinical context. One major drawback was the generally high variability in patient response to anti-angiogenic drugs and the rapid development of therapy resistance, so that, in total, only moderate effects on progression-free and overall survival were observed. Biomarkers predicting the response to VEGF-inhibition might attenuate this problem and help to further individualize drug and dosage determination. Although up to now no definitive biomarker has been identified for this purpose, several candidates are currently under investigation. This review aims to give an overview of the recent developments in this field, focusing on the most prevalent tumor species. Full article
(This article belongs to the Special Issue Advances in Cancer Diagnosis)
Open AccessReview Neuroprotective Effect of Melatonin: A Novel Therapy against Perinatal Hypoxia-Ischemia
Int. J. Mol. Sci. 2013, 14(5), 9379-9395; doi:10.3390/ijms14059379
Received: 28 February 2013 / Revised: 15 April 2013 / Accepted: 16 April 2013 / Published: 29 April 2013
Cited by 19 | PDF Full-text (2530 KB) | HTML Full-text | XML Full-text
Abstract
One of the most common causes of mortality and morbidity in children is perinatal hypoxia-ischemia (HI). In spite of the advances in neonatology, its incidence is not diminishing, generating a pediatric population that will require an extended amount of chronic care throughout their
[...] Read more.
One of the most common causes of mortality and morbidity in children is perinatal hypoxia-ischemia (HI). In spite of the advances in neonatology, its incidence is not diminishing, generating a pediatric population that will require an extended amount of chronic care throughout their lifetime. For this reason, new and more effective neuroprotective strategies are urgently required, in order to minimize as much as possible the neurological consequences of this encephalopathy. In this sense, interest has grown in the neuroprotective possibilities of melatonin, as this hormone may help to maintain cell survival through the modulation of a wide range of physiological functions. Although some of the mechanisms by which melatonin is neuroprotective after neonatal asphyxia remain a subject of investigation, this review tries to summarize some of the most recent advances related with its use as a therapeutic drug against perinatal hypoxic-ischemic brain injury, supporting the high interest in this indoleamine as a future feasible strategy for cerebral asphyctic events. Full article
(This article belongs to the Special Issue Advances in the Research of Melatonin)
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Open AccessReview Recent Advances in Understanding the Control of Secretory Proteins by the Unfolded Protein Response in Plants
Int. J. Mol. Sci. 2013, 14(5), 9396-9407; doi:10.3390/ijms14059396
Received: 1 April 2013 / Revised: 17 April 2013 / Accepted: 18 April 2013 / Published: 29 April 2013
Cited by 3 | PDF Full-text (1642 KB) | HTML Full-text | XML Full-text
Abstract
The membrane transport system is built on the proper functioning of the endoplasmic reticulum (ER). The accumulation of unfolded proteins in the ER lumen (ER stress) disrupts ER homeostasis and disturbs the transport system. In response to ER stress, eukaryotic cells activate intracellular
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The membrane transport system is built on the proper functioning of the endoplasmic reticulum (ER). The accumulation of unfolded proteins in the ER lumen (ER stress) disrupts ER homeostasis and disturbs the transport system. In response to ER stress, eukaryotic cells activate intracellular signaling (named the unfolded protein response, UPR), which contributes to the quality control of secretory proteins. On the other hand, the deleterious effects of UPR on plant health and growth characteristics have frequently been overlooked, due to limited information on this mechanism. However, recent studies have shed light on the molecular mechanism of plant UPR, and a number of its unique characteristics have been elucidated. This study briefly reviews the progress of understanding what is happening in plants under ER stress conditions. Full article
(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications)
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Open AccessReview The Role of microRNA in Gastric Malignancy
Int. J. Mol. Sci. 2013, 14(5), 9487-9496; doi:10.3390/ijms14059487
Received: 27 March 2013 / Revised: 19 April 2013 / Accepted: 25 April 2013 / Published: 29 April 2013
Cited by 20 | PDF Full-text (421 KB) | HTML Full-text | XML Full-text
Abstract
Helicobacter pylori (H. pylori) infection is the main cause of gastritis, gastro-duodenal ulcer, and gastric cancer. MicroRNAs (miRNAs) are small noncoding RNAs that function as endogenous silencers of numerous target genes. Many miRNA genes are expressed in a tissue-specific manner and
[...] Read more.
Helicobacter pylori (H. pylori) infection is the main cause of gastritis, gastro-duodenal ulcer, and gastric cancer. MicroRNAs (miRNAs) are small noncoding RNAs that function as endogenous silencers of numerous target genes. Many miRNA genes are expressed in a tissue-specific manner and play important roles in cell proliferation, apoptosis, and differentiation. Recent discoveries have shed new light on the involvement of miRNAs in gastric malignancy. However, at the same time, several miRNAs have been associated with opposing events, leading to reduced inflammation, inhibition of malignancy, and increased apoptosis of transformed cells. The regulation of miRNA expression could be a novel strategy in the chemoprevention of human gastric malignancy. In this article, the biological importance of miRNAs in gastric malignancy is summarized. Full article
(This article belongs to the Special Issue Regulation by non-coding RNAs 2013)
Open AccessReview HDAC6 and Ovarian Cancer
Int. J. Mol. Sci. 2013, 14(5), 9514-9535; doi:10.3390/ijms14059514
Received: 2 April 2013 / Revised: 23 April 2013 / Accepted: 24 April 2013 / Published: 2 May 2013
Cited by 5 | PDF Full-text (291 KB) | HTML Full-text | XML Full-text
Abstract
The special class IIb histone deacetylase, HDAC6, plays a prominent role in many cellular processes related to cancer, including oncogenesis, the cell stress response, motility, and myriad signaling pathways. Many of the lessons learned from other cancers can be applied to ovarian cancer
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The special class IIb histone deacetylase, HDAC6, plays a prominent role in many cellular processes related to cancer, including oncogenesis, the cell stress response, motility, and myriad signaling pathways. Many of the lessons learned from other cancers can be applied to ovarian cancer as well. HDAC6 interacts with diverse proteins such as HSP90, cortactin, tubulin, dynein, p300, Bax, and GRK2 in both the nucleus and cytoplasm to carry out these cancerous functions. Not all pro-cancer interactions of HDAC6 involve deacetylation. The idea of using HDAC6 as a target for cancer treatment continues to expand in recent years, and more potent and specific HDAC6 inhibitors are required to effectively down-regulate the tumor-prone cell signaling pathways responsible for ovarian cancer. Full article
(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)
Open AccessReview Targeting Signaling Pathways in Epithelial Ovarian Cancer
Int. J. Mol. Sci. 2013, 14(5), 9536-9555; doi:10.3390/ijms14059536
Received: 11 March 2013 / Revised: 13 April 2013 / Accepted: 22 April 2013 / Published: 2 May 2013
Cited by 24 | PDF Full-text (6910 KB) | HTML Full-text | XML Full-text
Abstract
Ovarian carcinoma (OC) is the most lethal gynecological malignancy. Response to platinum-based chemotherapy is poor in some patients and, thus, current research is focusing on new therapy options. The various histological types of OC are characterized by distinctive molecular genetic alterations that are
[...] Read more.
Ovarian carcinoma (OC) is the most lethal gynecological malignancy. Response to platinum-based chemotherapy is poor in some patients and, thus, current research is focusing on new therapy options. The various histological types of OC are characterized by distinctive molecular genetic alterations that are relevant for ovarian tumorigenesis. The understanding of these molecular pathways is essential for the development of novel therapeutic strategies. Purpose: We want to give an overview on the molecular genetic changes of the histopathological types of OC and their role as putative therapeutic targets. In Depth Review of Existing Data: In 2012, the vascular endothelial growth factor (VEGF) inhibitor, bevacizumab, was approved for OC treatment. Bevacizumab has shown promising results as single agent and in combination with conventional chemotherapy, but its target is not distinctive when analyzed before treatment. At present, mammalian target of rapamycin (mTOR) inhibitors, poly-ADP-ribose polymerase (PARP) inhibitors and components of the EGFR pathway are in the focus of clinical research. Interestingly, some phytochemical substances show good synergistic effects when used in combination with chemotherapy. Conclusion: Ongoing studies of targeted agents in conjunction with chemotherapy will show whether there are alternative options to bevacizumab available for OC patients. Novel targets which can be assessed before therapy to predict efficacy are needed. The assessment of therapeutic targets is continuously improved by molecular pathological analyses on tumor tissue. A careful selection of patients for personalized treatment will help to reduce putative side effects and toxicity. Full article
(This article belongs to the Special Issue Molecular Bases of Cancer Research)
Open AccessReview Where Do They Come from and Where Do They Go: Candidates for Regulating Extracellular Vesicle Formation in Fungi
Int. J. Mol. Sci. 2013, 14(5), 9581-9603; doi:10.3390/ijms14059581
Received: 29 March 2013 / Revised: 11 April 2013 / Accepted: 17 April 2013 / Published: 2 May 2013
Cited by 15 | PDF Full-text (503 KB) | HTML Full-text | XML Full-text
Abstract
In the past few years, extracellular vesicles (EVs) from at least eight fungal species were characterized. EV proteome in four fungal species indicated putative biogenesis pathways and suggested interesting similarities with mammalian exosomes. Moreover, as observed for mammalian exosomes, fungal EVs were demonstrated
[...] Read more.
In the past few years, extracellular vesicles (EVs) from at least eight fungal species were characterized. EV proteome in four fungal species indicated putative biogenesis pathways and suggested interesting similarities with mammalian exosomes. Moreover, as observed for mammalian exosomes, fungal EVs were demonstrated to be immunologically active. Here we review the seminal and most recent findings related to the production of EVs by fungi. Based on the current literature about secretion of fungal molecules and biogenesis of EVs in eukaryotes, we focus our discussion on a list of cellular proteins with the potential to regulate vesicle biogenesis in the fungi. Full article
(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications)
Open AccessReview Molecular Motors and Apical CFTR Traffic in Epithelia
Int. J. Mol. Sci. 2013, 14(5), 9628-9642; doi:10.3390/ijms14059628
Received: 7 April 2013 / Revised: 19 April 2013 / Accepted: 2 May 2013 / Published: 3 May 2013
Cited by 3 | PDF Full-text (561 KB) | HTML Full-text | XML Full-text
Abstract
Intracellular protein traffic plays an important role in the regulation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) chloride channels. Microtubule and actin-based motor proteins direct CFTR movement along trafficking pathways. As shown for other regulatory proteins such as adaptors, the involvement of protein
[...] Read more.
Intracellular protein traffic plays an important role in the regulation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) chloride channels. Microtubule and actin-based motor proteins direct CFTR movement along trafficking pathways. As shown for other regulatory proteins such as adaptors, the involvement of protein motors in CFTR traffic is cell-type specific. Understanding motor specificity provides insight into the biology of the channel and opens opportunity for discovery of organ-specific drug targets for treating CFTR-mediated diseases. Full article
(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications)
Open AccessReview Physiological, Biochemical, and Molecular Mechanisms of Heat Stress Tolerance in Plants
Int. J. Mol. Sci. 2013, 14(5), 9643-9684; doi:10.3390/ijms14059643
Received: 1 February 2013 / Revised: 16 April 2013 / Accepted: 19 April 2013 / Published: 3 May 2013
Cited by 108 | PDF Full-text (1649 KB) | HTML Full-text | XML Full-text
Abstract
High temperature (HT) stress is a major environmental stress that limits plant growth, metabolism, and productivity worldwide. Plant growth and development involve numerous biochemical reactions that are sensitive to temperature. Plant responses to HT vary with the degree and duration of HT and
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High temperature (HT) stress is a major environmental stress that limits plant growth, metabolism, and productivity worldwide. Plant growth and development involve numerous biochemical reactions that are sensitive to temperature. Plant responses to HT vary with the degree and duration of HT and the plant type. HT is now a major concern for crop production and approaches for sustaining high yields of crop plants under HT stress are important agricultural goals. Plants possess a number of adaptive, avoidance, or acclimation mechanisms to cope with HT situations. In addition, major tolerance mechanisms that employ ion transporters, proteins, osmoprotectants, antioxidants, and other factors involved in signaling cascades and transcriptional control are activated to offset stress-induced biochemical and physiological alterations. Plant survival under HT stress depends on the ability to perceive the HT stimulus, generate and transmit the signal, and initiate appropriate physiological and biochemical changes. HT-induced gene expression and metabolite synthesis also substantially improve tolerance. The physiological and biochemical responses to heat stress are active research areas, and the molecular approaches are being adopted for developing HT tolerance in plants. This article reviews the recent findings on responses, adaptation, and tolerance to HT at the cellular, organellar, and whole plant levels and describes various approaches being taken to enhance thermotolerance in plants. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
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Open AccessReview Calcium in Red Blood Cells—A Perilous Balance
Int. J. Mol. Sci. 2013, 14(5), 9848-9872; doi:10.3390/ijms14059848
Received: 27 February 2013 / Revised: 18 March 2013 / Accepted: 19 March 2013 / Published: 8 May 2013
Cited by 36 | PDF Full-text (448 KB) | HTML Full-text | XML Full-text
Abstract
Ca2+ is a universal signalling molecule involved in regulating cell cycle and fate, metabolism and structural integrity, motility and volume. Like other cells, red blood cells (RBCs) rely on Ca2+ dependent signalling during differentiation from precursor cells. Intracellular Ca2+ levels
[...] Read more.
Ca2+ is a universal signalling molecule involved in regulating cell cycle and fate, metabolism and structural integrity, motility and volume. Like other cells, red blood cells (RBCs) rely on Ca2+ dependent signalling during differentiation from precursor cells. Intracellular Ca2+ levels in the circulating human RBCs take part not only in controlling biophysical properties such as membrane composition, volume and rheological properties, but also physiological parameters such as metabolic activity, redox state and cell clearance. Extremely low basal permeability of the human RBC membrane to Ca2+ and a powerful Ca2+ pump maintains intracellular free Ca2+ levels between 30 and 60 nM, whereas blood plasma Ca2+ is approximately 1.8 mM. Thus, activation of Ca2+ uptake has an impressive impact on multiple processes in the cells rendering Ca2+ a master regulator in RBCs. Malfunction of Ca2+ transporters in human RBCs leads to excessive accumulation of Ca2+ within the cells. This is associated with a number of pathological states including sickle cell disease, thalassemia, phosphofructokinase deficiency and other forms of hereditary anaemia. Continuous progress in unravelling the molecular nature of Ca2+ transport pathways allows harnessing Ca2+ uptake, avoiding premature RBC clearance and thrombotic complications. This review summarizes our current knowledge of Ca2+ signalling in RBCs emphasizing the importance of this inorganic cation in RBC function and survival. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Open AccessReview Rab27 GTPases Distribute Extracellular Nanomaps for Invasive Growth and Metastasis: Implications for Prognosis and Treatment
Int. J. Mol. Sci. 2013, 14(5), 9883-9892; doi:10.3390/ijms14059883
Received: 13 April 2013 / Revised: 19 April 2013 / Accepted: 3 May 2013 / Published: 10 May 2013
Cited by 4 | PDF Full-text (260 KB) | HTML Full-text | XML Full-text
Abstract
The Rab27 family of small GTPases regulates exocytosis of distinct vesicle types including multivesicular endosomes, which results in the release of exosomes. Exosomes are nanometer-sized membrane vesicles that enclose soluble factors such as proteins and nucleic acids within a lipid bilayer and can
[...] Read more.
The Rab27 family of small GTPases regulates exocytosis of distinct vesicle types including multivesicular endosomes, which results in the release of exosomes. Exosomes are nanometer-sized membrane vesicles that enclose soluble factors such as proteins and nucleic acids within a lipid bilayer and can travel toward distant tissues to influence multiple aspects of cell behavior. In our view that tumors are endocrine organs producing exosomes, Rab27 GTPases and their effector proteins are critical determinants for invasive growth and metastasis. Rab27 proteins and their effectors may serve as prognostic biomarkers or as targets for patient-tailored therapy. Full article
(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications)
Open AccessReview Cationic Antimicrobial Polymers and Their Assemblies
Int. J. Mol. Sci. 2013, 14(5), 9906-9946; doi:10.3390/ijms14059906
Received: 28 February 2013 / Revised: 20 April 2013 / Accepted: 23 April 2013 / Published: 10 May 2013
Cited by 91 | PDF Full-text (938 KB) | HTML Full-text | XML Full-text
Abstract
Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures
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Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures are quaternary ammonium groups, resulting in quaternary ammonium compounds (QACs). The advantage of amphiphilic cationic polymers when compared to small amphiphilic molecules is their enhanced microbicidal activity. Besides, many of these polymeric structures also show low toxicity to human cells; a major requirement for biomedical applications. Determination of the specific elements in polymers, which affect their antimicrobial activity, has been previously difficult due to broad molecular weight distributions and random sequences characteristic of radical polymerization. With the advances in polymerization control, selection of well defined polymers and structures are allowing greater insight into their structure-antimicrobial activity relationship. On the other hand, antimicrobial polymers grafted or self-assembled to inert or non inert vehicles can yield hybrid antimicrobial nanostructures or films, which can act as antimicrobials by themselves or deliver bioactive molecules for a variety of applications, such as wound dressing, photodynamic antimicrobial therapy, food packing and preservation and antifouling applications. Full article
(This article belongs to the Special Issue Antimicrobial Polymers)
Open AccessReview Posttranslational Modifications of GLUT4 Affect Its Subcellular Localization and Translocation
Int. J. Mol. Sci. 2013, 14(5), 9963-9978; doi:10.3390/ijms14059963
Received: 15 April 2013 / Revised: 2 May 2013 / Accepted: 2 May 2013 / Published: 10 May 2013
Cited by 5 | PDF Full-text (239 KB) | HTML Full-text | XML Full-text
Abstract
The facilitative glucose transporter type 4 (GLUT4) is expressed in adipose and muscle and plays a vital role in whole body glucose homeostasis. In the absence of insulin, only ~1% of cellular GLUT4 is present at the plasma membrane, with the vast majority
[...] Read more.
The facilitative glucose transporter type 4 (GLUT4) is expressed in adipose and muscle and plays a vital role in whole body glucose homeostasis. In the absence of insulin, only ~1% of cellular GLUT4 is present at the plasma membrane, with the vast majority localizing to intracellular organelles. GLUT4 is retained intracellularly by continuous trafficking through two inter-related cycles. GLUT4 passes through recycling endosomes, the trans Golgi network and an insulin-sensitive intracellular compartment, termed GLUT4-storage vesicles or GSVs. It is from GSVs that GLUT4 is mobilized to the cell surface in response to insulin, where it increases the rate of glucose uptake into the cell. As with many physiological responses to external stimuli, this regulated trafficking event involves multiple posttranslational modifications. This review outlines the roles of posttranslational modifications of GLUT4 on its function and insulin-regulated trafficking. Full article
(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications)
Open AccessReview Multiple Functions of the RNA-Binding Protein HuR in Cancer Progression, Treatment Responses and Prognosis
Int. J. Mol. Sci. 2013, 14(5), 10015-10041; doi:10.3390/ijms140510015
Received: 14 March 2013 / Revised: 22 April 2013 / Accepted: 25 April 2013 / Published: 10 May 2013
Cited by 37 | PDF Full-text (779 KB) | HTML Full-text | XML Full-text
Abstract
The human embryonic lethal abnormal vision-like protein, HuR, is a member of the Hu family of RNA-binding proteins. Over the past decade, this ubiquitously expressed protein has been extensively investigated in cancer research because it is involved in the regulation of mRNA stability
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The human embryonic lethal abnormal vision-like protein, HuR, is a member of the Hu family of RNA-binding proteins. Over the past decade, this ubiquitously expressed protein has been extensively investigated in cancer research because it is involved in the regulation of mRNA stability and translation in many cell types. HuR activity and function is associated with its subcellular distribution, transcriptional regulation, translational and post-translational modifications. HuR regulation of target mRNAs is based on the interaction between the three specific domains of HuR protein and one or several U- or AU-rich elements (AREs) in the untranslated region of target mRNAs. A number of cancer-related transcripts containing AREs, including mRNAs for proto-oncogenes, cytokines, growth factors, and invasion factors, have been characterized as HuR targets. It has been proposed that HuR has a central tumorigenic activity by enabling multiple cancer phenotypes. In this review, we comprehensively survey the existing evidence with regard to the diverse functions of HuR in caner development and progression. The current data also suggest that HuR might be a novel and promising therapeutic target and a marker for treatment response and prognostic evaluation. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessReview Melatonin Effects on Hard Tissues: Bone and Tooth
Int. J. Mol. Sci. 2013, 14(5), 10063-10074; doi:10.3390/ijms140510063
Received: 22 March 2013 / Revised: 29 April 2013 / Accepted: 2 May 2013 / Published: 10 May 2013
Cited by 16 | PDF Full-text (250 KB) | HTML Full-text | XML Full-text
Abstract
Melatonin is an endogenous hormone rhythmically produced in the pineal gland under the control of the suprachiasmatic nucleus (SCN) and the light/dark cycle. This indole plays an important role in many physiological processes including circadian entrainment, blood pressure regulation, seasonal reproduction, ovarian physiology,
[...] Read more.
Melatonin is an endogenous hormone rhythmically produced in the pineal gland under the control of the suprachiasmatic nucleus (SCN) and the light/dark cycle. This indole plays an important role in many physiological processes including circadian entrainment, blood pressure regulation, seasonal reproduction, ovarian physiology, immune function, etc. Recently, the investigation and applications of melatonin in the hard tissues bone and tooth have received great attention. Melatonin has been investigated relative to bone remolding, osteoporosis, osseointegration of dental implants and dentine formation. In the present review, we discuss the large body of published evidence and review data of melatonin effects on hard tissues, specifically, bone and tooth. Full article
(This article belongs to the Special Issue Advances in the Research of Melatonin)
Open AccessReview TrkB Receptor Signalling: Implications in Neurodegenerative, Psychiatric and Proliferative Disorders
Int. J. Mol. Sci. 2013, 14(5), 10122-10142; doi:10.3390/ijms140510122
Received: 27 March 2013 / Revised: 27 April 2013 / Accepted: 28 April 2013 / Published: 13 May 2013
Cited by 29 | PDF Full-text (452 KB) | HTML Full-text | XML Full-text
Abstract
The Trk family of receptors play a wide variety of roles in physiological and disease processes in both neuronal and non-neuronal tissues. Amongst these the TrkB receptor in particular has attracted major attention due to its critical role in signalling for brain derived
[...] Read more.
The Trk family of receptors play a wide variety of roles in physiological and disease processes in both neuronal and non-neuronal tissues. Amongst these the TrkB receptor in particular has attracted major attention due to its critical role in signalling for brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) and neurotrophin-4 (NT4). TrkB signalling is indispensable for the survival, development and synaptic plasticity of several subtypes of neurons in the nervous system. Substantial evidence has emerged over the last decade about the involvement of aberrant TrkB signalling and its compromise in various neuropsychiatric and degenerative conditions. Unusual changes in TrkB signalling pathway have also been observed and implicated in a range of cancers. Variations in TrkB pathway have been observed in obesity and hyperphagia related disorders as well. Both BDNF and TrkB have been shown to play critical roles in the survival of retinal ganglion cells in the retina. The ability to specifically modulate TrkB signalling can be critical in various pathological scenarios associated with this pathway. In this review, we discuss the mechanisms underlying TrkB signalling, disease implications and explore plausible ameliorative or preventive approaches. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessReview MAPKs and Signal Transduction in the Control of Gastrointestinal Epithelial Cell Proliferation and Differentiation
Int. J. Mol. Sci. 2013, 14(5), 10143-10161; doi:10.3390/ijms140510143
Received: 26 February 2013 / Revised: 19 April 2013 / Accepted: 22 April 2013 / Published: 13 May 2013
Cited by 20 | PDF Full-text (545 KB) | HTML Full-text | XML Full-text
Abstract
Mitogen-activated protein kinase (MAPK) pathways are activated by several stimuli and transduce the signal inside cells, generating diverse responses including cell proliferation, differentiation, migration and apoptosis. Each MAPK cascade comprises a series of molecules, and regulation takes place at different levels. They communicate
[...] Read more.
Mitogen-activated protein kinase (MAPK) pathways are activated by several stimuli and transduce the signal inside cells, generating diverse responses including cell proliferation, differentiation, migration and apoptosis. Each MAPK cascade comprises a series of molecules, and regulation takes place at different levels. They communicate with each other and with additional pathways, creating a signaling network that is important for cell fate determination. In this review, we focus on ERK, JNK, p38 and ERK5, the major MAPKs, and their interactions with PI3K-Akt, TGFβ/Smad and Wnt/β-catenin pathways. More importantly, we describe how MAPKs regulate cell proliferation and differentiation in the rapidly renewing epithelia that lines the gastrointestinal tract and, finally, we highlight the recent findings on nutritional aspects that affect MAPK transduction cascades. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Open AccessReview Bioavailability of Heavy Metals in Soil: Impact on Microbial Biodegradation of Organic Compounds and Possible Improvement Strategies
Int. J. Mol. Sci. 2013, 14(5), 10197-10228; doi:10.3390/ijms140510197
Received: 8 October 2012 / Revised: 10 April 2013 / Accepted: 24 April 2013 / Published: 15 May 2013
Cited by 41 | PDF Full-text (264 KB) | HTML Full-text | XML Full-text
Abstract
Co-contamination of the environment with toxic chlorinated organic and heavy metal pollutants is one of the major problems facing industrialized nations today. Heavy metals may inhibit biodegradation of chlorinated organics by interacting with enzymes directly involved in biodegradation or those involved in general
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Co-contamination of the environment with toxic chlorinated organic and heavy metal pollutants is one of the major problems facing industrialized nations today. Heavy metals may inhibit biodegradation of chlorinated organics by interacting with enzymes directly involved in biodegradation or those involved in general metabolism. Predictions of metal toxicity effects on organic pollutant biodegradation in co-contaminated soil and water environments is difficult since heavy metals may be present in a variety of chemical and physical forms. Recent advances in bioremediation of co-contaminated environments have focussed on the use of metal-resistant bacteria (cell and gene bioaugmentation), treatment amendments, clay minerals and chelating agents to reduce bioavailable heavy metal concentrations. Phytoremediation has also shown promise as an emerging alternative clean-up technology for co-contaminated environments. However, despite various investigations, in both aerobic and anaerobic systems, demonstrating that metal toxicity hampers the biodegradation of the organic component, a paucity of information exists in this area of research. Therefore, in this review, we discuss the problems associated with the degradation of chlorinated organics in co-contaminated environments, owing to metal toxicity and shed light on possible improvement strategies for effective bioremediation of sites co-contaminated with chlorinated organic compounds and heavy metals. Full article
(This article belongs to the Special Issue Green Biocides)
Open AccessReview Plant Defense against Insect Herbivores
Int. J. Mol. Sci. 2013, 14(5), 10242-10297; doi:10.3390/ijms140510242
Received: 2 April 2013 / Revised: 27 April 2013 / Accepted: 2 May 2013 / Published: 16 May 2013
Cited by 70 | PDF Full-text (1044 KB) | HTML Full-text | XML Full-text
Abstract
Plants have been interacting with insects for several hundred million years, leading to complex defense approaches against various insect feeding strategies. Some defenses are constitutive while others are induced, although the insecticidal defense compound or protein classes are often similar. Insect herbivory induce
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Plants have been interacting with insects for several hundred million years, leading to complex defense approaches against various insect feeding strategies. Some defenses are constitutive while others are induced, although the insecticidal defense compound or protein classes are often similar. Insect herbivory induce several internal signals from the wounded tissues, including calcium ion fluxes, phosphorylation cascades and systemic- and jasmonate signaling. These are perceived in undamaged tissues, which thereafter reinforce their defense by producing different, mostly low molecular weight, defense compounds. These bioactive specialized plant defense compounds may repel or intoxicate insects, while defense proteins often interfere with their digestion. Volatiles are released upon herbivory to repel herbivores, attract predators or for communication between leaves or plants, and to induce defense responses. Plants also apply morphological features like waxes, trichomes and latices to make the feeding more difficult for the insects. Extrafloral nectar, food bodies and nesting or refuge sites are produced to accommodate and feed the predators of the herbivores. Meanwhile, herbivorous insects have adapted to resist plant defenses, and in some cases even sequester the compounds and reuse them in their own defense. Both plant defense and insect adaptation involve metabolic costs, so most plant-insect interactions reach a stand-off, where both host and herbivore survive although their development is suboptimal. Full article
(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism)
Open AccessReview Methylated DNA and microRNA in Body Fluids as Biomarkers for Cancer Detection
Int. J. Mol. Sci. 2013, 14(5), 10307-10331; doi:10.3390/ijms140510307
Received: 11 March 2013 / Revised: 1 April 2013 / Accepted: 25 April 2013 / Published: 16 May 2013
Cited by 18 | PDF Full-text (271 KB) | HTML Full-text | XML Full-text
Abstract
Epigenetic alterations including DNA methylation and microRNAs (miRNAs) play important roles in the initiation and progression of human cancers. As the extensively studied epigenetic changes in tumors, DNA methylation and miRNAs are the most potential epigenetic biomarkers for cancer diagnosis. After the identification
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Epigenetic alterations including DNA methylation and microRNAs (miRNAs) play important roles in the initiation and progression of human cancers. As the extensively studied epigenetic changes in tumors, DNA methylation and miRNAs are the most potential epigenetic biomarkers for cancer diagnosis. After the identification of circulating cell-free nuclear acids, increasing evidence demonstrated great potential of cell-free epigenetic biomarkers in the blood or other body fluids for cancer detection. Full article
(This article belongs to the Special Issue Advances in Cancer Diagnosis)
Open AccessReview Claudins Overexpression in Ovarian Cancer: Potential Targets for Clostridium Perfringens Enterotoxin (CPE) Based Diagnosis and Therapy
Int. J. Mol. Sci. 2013, 14(5), 10412-10437; doi:10.3390/ijms140510412
Received: 21 March 2013 / Revised: 26 April 2013 / Accepted: 27 April 2013 / Published: 17 May 2013
Cited by 16 | PDF Full-text (472 KB) | HTML Full-text | XML Full-text
Abstract
Claudins are a family of tight junction proteins regulating paracellular permeability and cell polarity with different patterns of expression in benign and malignant human tissues. There are approximately 27 members of the claudin family identified to date with varying cell and tissue-specific expression.
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Claudins are a family of tight junction proteins regulating paracellular permeability and cell polarity with different patterns of expression in benign and malignant human tissues. There are approximately 27 members of the claudin family identified to date with varying cell and tissue-specific expression. Claudins-3, -4 and -7 represent the most highly differentially expressed claudins in ovarian cancer. While their exact role in ovarian tumors is still being elucidated, these proteins are thought to be critical for ovarian cancer cell invasion/dissemination and resistance to chemotherapy. Claudin-3 and claudin-4 are the natural receptors for the Clostridium perfringens enterotoxin (CPE), a potent cytolytic toxin. These surface proteins may therefore represent attractive targets for the detection and treatment of chemotherapy-resistant ovarian cancer and other aggressive solid tumors overexpressing claudin-3 and -4 using CPE-based theranostic agents. Full article
(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)
Open AccessReview Human Prostatic Acid Phosphatase: Structure, Function and Regulation
Int. J. Mol. Sci. 2013, 14(5), 10438-10464; doi:10.3390/ijms140510438
Received: 15 April 2013 / Revised: 8 May 2013 / Accepted: 8 May 2013 / Published: 21 May 2013
Cited by 18 | PDF Full-text (582 KB) | HTML Full-text | XML Full-text
Abstract
Human prostatic acid phosphatase (PAcP) is a 100 kDa glycoprotein composed of two subunits. Recent advances demonstrate that cellular PAcP (cPAcP) functions as a protein tyrosine phosphatase by dephosphorylating ErbB-2/Neu/HER-2 at the phosphotyrosine residues in prostate cancer (PCa) cells, which results in reduced
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Human prostatic acid phosphatase (PAcP) is a 100 kDa glycoprotein composed of two subunits. Recent advances demonstrate that cellular PAcP (cPAcP) functions as a protein tyrosine phosphatase by dephosphorylating ErbB-2/Neu/HER-2 at the phosphotyrosine residues in prostate cancer (PCa) cells, which results in reduced tumorigenicity. Further, the interaction of cPAcP and ErbB-2 regulates androgen sensitivity of PCa cells. Knockdown of cPAcP expression allows androgen-sensitive PCa cells to develop the castration-resistant phenotype, where cells proliferate under an androgen-reduced condition. Thus, cPAcP has a significant influence on PCa cell growth. Interestingly, promoter analysis suggests that PAcP expression can be regulated by NF-κB, via a novel binding sequence in an androgen-independent manner. Further understanding of PAcP function and regulation of expression will have a significant impact on understanding PCa progression and therapy. Full article
(This article belongs to the Special Issue Molecular Research in Urology)
Open AccessReview Obesity-Associated Oxidative Stress: Strategies Finalized to Improve Redox State
Int. J. Mol. Sci. 2013, 14(5), 10497-10538; doi:10.3390/ijms140510497
Received: 16 February 2013 / Revised: 18 April 2013 / Accepted: 6 May 2013 / Published: 21 May 2013
Cited by 63 | PDF Full-text (631 KB) | HTML Full-text | XML Full-text
Abstract
Obesity represents a major risk factor for a plethora of severe diseases, including diabetes, cardiovascular disease, non-alcoholic fatty liver disease, and cancer. It is often accompanied by an increased risk of mortality and, in the case of non-fatal health problems, the quality of
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Obesity represents a major risk factor for a plethora of severe diseases, including diabetes, cardiovascular disease, non-alcoholic fatty liver disease, and cancer. It is often accompanied by an increased risk of mortality and, in the case of non-fatal health problems, the quality of life is impaired because of associated conditions, including sleep apnea, respiratory problems, osteoarthritis, and infertility. Recent evidence suggests that oxidative stress may be the mechanistic link between obesity and related complications. In obese patients, antioxidant defenses are lower than normal weight counterparts and their levels inversely correlate with central adiposity; obesity is also characterized by enhanced levels of reactive oxygen or nitrogen species. Inadequacy of antioxidant defenses probably relies on different factors: obese individuals may have a lower intake of antioxidant- and phytochemical-rich foods, such as fruits, vegetables, and legumes; otherwise, consumption of antioxidant nutrients is normal, but obese individuals may have an increased utilization of these molecules, likewise to that reported in diabetic patients and smokers. Also inadequate physical activity may account for a decreased antioxidant state. In this review, we describe current concepts in the meaning of obesity as a state of chronic oxidative stress and the potential interventions to improve redox balance. Full article
(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)
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Open AccessReview Nanoparticle-Based Systems for T1-Weighted Magnetic Resonance Imaging Contrast Agents
Int. J. Mol. Sci. 2013, 14(5), 10591-10607; doi:10.3390/ijms140510591
Received: 18 March 2013 / Revised: 9 May 2013 / Accepted: 13 May 2013 / Published: 21 May 2013
Cited by 28 | PDF Full-text (1565 KB) | HTML Full-text | XML Full-text
Abstract
Because magnetic resonance imaging (MRI) contrast agents play a vital role in diagnosing diseases, demand for new MRI contrast agents, with an enhanced sensitivity and advanced functionalities, is very high. During the past decade, various inorganic nanoparticles have been used as MRI contrast
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Because magnetic resonance imaging (MRI) contrast agents play a vital role in diagnosing diseases, demand for new MRI contrast agents, with an enhanced sensitivity and advanced functionalities, is very high. During the past decade, various inorganic nanoparticles have been used as MRI contrast agents due to their unique properties, such as large surface area, easy surface functionalization, excellent contrasting effect, and other size-dependent properties. This review provides an overview of recent progress in the development of nanoparticle-based T1-weighted MRI contrast agents. The chemical synthesis of the nanoparticle-based contrast agents and their potential applications were discussed and summarized. In addition, the recent development in nanoparticle-based multimodal contrast agents including T1-weighted MRI/computed X-ray tomography (CT) and T1-weighted MRI/optical were also described, since nanoparticles may curtail the shortcomings of single mode contrast agents in diagnostic and clinical settings by synergistically incorporating functionality. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
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Open AccessReview New Advances in Urea Transporter UT-A1 Membrane Trafficking
Int. J. Mol. Sci. 2013, 14(5), 10674-10682; doi:10.3390/ijms140510674
Received: 22 April 2013 / Revised: 9 May 2013 / Accepted: 9 May 2013 / Published: 21 May 2013
Cited by 3 | PDF Full-text (632 KB) | HTML Full-text | XML Full-text
Abstract
The vasopressin-regulated urea transporter UT-A1, expressed in kidney inner medullary collecting duct (IMCD) epithelial cells, plays a critical role in the urinary concentrating mechanisms. As a membrane protein, the function of UT-A1 transport activity relies on its presence in the plasma membrane. Therefore,
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The vasopressin-regulated urea transporter UT-A1, expressed in kidney inner medullary collecting duct (IMCD) epithelial cells, plays a critical role in the urinary concentrating mechanisms. As a membrane protein, the function of UT-A1 transport activity relies on its presence in the plasma membrane. Therefore, UT-A1 successfully trafficking to the apical membrane of the polarized epithelial cells is crucial for the regulation of urea transport. This review summarizes the research progress of UT-A1 regulation over the past few years, specifically on the regulation of UT-A1 membrane trafficking by lipid rafts, N-linked glycosylation and a group of accessory proteins. Full article
(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications)

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Open AccessCorrection Correction: Wiedmann, M., et al. Exploration of the Role of the Non-Coding RNA SbrE in L. monocytogenes Stress Response. Int. J. Mol. Sci. 2013, 14, 378-393
Int. J. Mol. Sci. 2013, 14(5), 9685; doi:10.3390/ijms14059685
Received: 18 March 2013 / Revised: 16 April 2013 / Accepted: 16 April 2013 / Published: 3 May 2013
Cited by 1 | PDF Full-text (127 KB) | HTML Full-text | XML Full-text
Abstract
The original version of the paper in Section 3.8 reports that The peptide mass tolerance and fragment mass tolerance values were 10 ppm and 30 mDa, respectively [1] (p. 387). To help others who may want to use the same methods
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The original version of the paper in Section 3.8 reports that The peptide mass tolerance and fragment mass tolerance values were 10 ppm and 30 mDa, respectively [1] (p. 387). To help others who may want to use the same methods in the future, the authors would like to correct the wording to: “The peptide mass tolerance and fragment mass tolerance values were 30 ppm and 0.15 Da, respectively. In order to decrease the probability of false peptide identification, only peptides with significance scores above the identity threshold (at the 95% confidence interval), defined by Mascot probability analysis (www.matrixscience.com/help/scoring_help.html#PBM), were considered to be confidently identified and used for protein identification.  Furthermore, only proteins identified in all four iTRAQ samples through at least two peptides with a p-value of <0.05 (expectation value) were further analyzed”. The authors would like to apologize for any inconvenience this may have caused to the readers of this journal. [...] Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)

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