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Int. J. Mol. Sci., Volume 14, Issue 2 (February 2013) , Pages 2230-4374

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Open AccessEditorial
International Journal of Molecular Science Best Paper Award 2013
Int. J. Mol. Sci. 2013, 14(2), 4372-4374; https://doi.org/10.3390/ijms14024372
Received: 7 February 2013 / Accepted: 7 February 2013 / Published: 22 February 2013
Cited by 5 | Viewed by 5283 | PDF Full-text (144 KB) | HTML Full-text | XML Full-text
Abstract
Since 2012, International Journal of Molecular Science has instituted an annual award to recognize outstanding papers in the area of chemistry, molecular physics and molecular biology that meet the aims, scope and high standards of this journal [1]. We are pleased to announce [...] Read more.
Since 2012, International Journal of Molecular Science has instituted an annual award to recognize outstanding papers in the area of chemistry, molecular physics and molecular biology that meet the aims, scope and high standards of this journal [1]. We are pleased to announce the second “International Journal of Molecular Science Best Paper Award” for 2013. Nominations were made by the Section Editor-in-Chiefs of International Journal of Molecular Science, with all papers published in 2009 eligible for consideration. The awards are issued for reviews and articles separately. [...] Full article
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Open AccessArticle
Prevention of Tendon Adhesions by ERK2 Small Interfering RNAs
Int. J. Mol. Sci. 2013, 14(2), 4361-4371; https://doi.org/10.3390/ijms14024361
Received: 21 November 2012 / Revised: 6 January 2013 / Accepted: 7 January 2013 / Published: 21 February 2013
Cited by 12 | Viewed by 3363 | PDF Full-text (1721 KB) | HTML Full-text | XML Full-text
Abstract
Tendon adhesions are one of the most concerning complications after surgical repair of flexor tendon injury. Extracellular signal-regulated kinase (ERK) 2 plays crucial roles in fibroblast proliferation and collagen expression which contributes to the formation of tendon adhesions after flexor tendon surgery. Using [...] Read more.
Tendon adhesions are one of the most concerning complications after surgical repair of flexor tendon injury. Extracellular signal-regulated kinase (ERK) 2 plays crucial roles in fibroblast proliferation and collagen expression which contributes to the formation of tendon adhesions after flexor tendon surgery. Using a chicken model, we have examined the effects of a small interfering RNA (siRNA) targeting ERK2 delivered by a lentiviral system on tendon adhesion formation with an adhesion scoring system, histological assessment, and biomechanical evaluation. It was found that ERK2 siRNA effectively suppressed the increase of fibroblasts and the formation of tendon adhesions (p < 0.05 compared with the control group). Moreover, no statistically significant reduction in breaking force was detected between the ERK2 siRNA group and the control group. These results show that the lentiviral-mediated siRNA system is effective in preventing tendon adhesion formation but not to tendon healing, and may be used for tendon repair after confirmation and improvement by future detailed studies. Full article
(This article belongs to the Special Issue Regulation by non-coding RNAs 2013)
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Open AccessArticle
PG-2, a Potent AMP against Pathogenic Microbial Strains, from Potato (Solanum tuberosum L cv. Gogu Valley) Tubers Not Cytotoxic against Human Cells
Int. J. Mol. Sci. 2013, 14(2), 4349-4360; https://doi.org/10.3390/ijms14024349
Received: 16 December 2012 / Revised: 16 January 2013 / Accepted: 6 February 2013 / Published: 21 February 2013
Cited by 6 | Viewed by 3758 | PDF Full-text (983 KB) | HTML Full-text | XML Full-text
Abstract
In an earlier study, we isolated potamin-1 (PT-1), a 5.6-kDa trypsin-chymotrypsin protease inhibitor, from the tubers of a potato strain (Solanum tuberosum L cv. Gogu Valley). We established that PT-1 strongly inhibits pathogenic microbial strains, but not human bacterial strains, and that [...] Read more.
In an earlier study, we isolated potamin-1 (PT-1), a 5.6-kDa trypsin-chymotrypsin protease inhibitor, from the tubers of a potato strain (Solanum tuberosum L cv. Gogu Valley). We established that PT-1 strongly inhibits pathogenic microbial strains, but not human bacterial strains, and that its sequence shows 62% homology with a serine protease inhibitor. In the present study, we isolated an antifungal and antibacterial peptide with no cytotoxicity from tubers of the same potato strain. The peptide (peptide-G2, PG-2) was isolated using salt-extraction, ultrafiltration and reverse-phase high performance liquid chromatography (RP-HPLC). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) showed the protein to have a molecular mass of 3228.5 Da, while automated Edman degradation showed the N-terminal sequence of PG-2 to be LVKDNPLDISPKQVQALCTDLVIRCMCCC-. PG-2 exhibited antimicrobial activity against Candida albicans, a human pathogenic yeast strain, and Clavibacter michiganensis subsp. michiganensis, a plant late blight strain. PG-2 also showed antibacterial activity against Staphylococcus aureus, but did not lyse human red blood cells and was thermostable. Overall, these results suggest PG-2 may be a good candidate to serve as a natural antimicrobial agent, agricultural pesticide and/or food additive. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessArticle
Cyclic Stretch Induces Inducible Nitric Oxide Synthase and Soluble Guanylate Cyclase in Pulmonary Artery Smooth Muscle Cells
Int. J. Mol. Sci. 2013, 14(2), 4334-4348; https://doi.org/10.3390/ijms14024334
Received: 31 December 2012 / Revised: 12 February 2013 / Accepted: 17 February 2013 / Published: 21 February 2013
Cited by 12 | Viewed by 3004 | PDF Full-text (581 KB) | HTML Full-text | XML Full-text
Abstract
In the pulmonary vasculature, mechanical forces such as cyclic stretch induce changes in vascular signaling, tone and remodeling. Nitric oxide is a potent regulator of soluble guanylate cyclase (sGC), which drives cGMP production, causing vasorelaxation. Pulmonary artery smooth muscle cells (PASMCs) express inducible [...] Read more.
In the pulmonary vasculature, mechanical forces such as cyclic stretch induce changes in vascular signaling, tone and remodeling. Nitric oxide is a potent regulator of soluble guanylate cyclase (sGC), which drives cGMP production, causing vasorelaxation. Pulmonary artery smooth muscle cells (PASMCs) express inducible nitric oxide synthase (iNOS), and while iNOS expression increases during late gestation, little is known about how cyclic stretch impacts this pathway. In this study, PASMC were subjected to cyclic stretch of 20% amplitude and frequency of 1 Hz for 24 h and compared to control cells maintained under static conditions. Cyclic stretch significantly increased cytosolic oxidative stress as compared to static cells (62.9 ± 5.9% vs. 33.3 ± 5.7% maximal oxidation), as measured by the intracellular redox sensor roGFP. Cyclic stretch also increased sGCβ protein expression (2.5 ± 0.9-fold), sGC activity (1.5 ± 0.2-fold) and cGMP levels (1.8 ± 0.2-fold), as well as iNOS mRNA and protein expression (3.0 ± 0.9 and 2.6 ± 0.7-fold, respectively) relative to control cells. An antioxidant, recombinant human superoxide dismutase (rhSOD), significantly decreased stretch-induced cytosolic oxidative stress, but did not block stretch-induced sGC activity. Inhibition of iNOS with 1400 W or an iNOS-specific siRNA inhibited stretch-induced sGC activity by 30% and 68% respectively vs. static controls. In conclusion, cyclic stretch increases sGC expression and activity in an iNOS-dependent manner in PASMC from fetal lambs. The mechanism that produces iNOS and sGC upregulation is not yet known, but we speculate these effects represent an early compensatory mechanism to counteract the effects of stretch-induced oxidative stress. A better understanding of the interplay between these two distinct pathways could provide key insights into future avenues to treat infants with pulmonary hypertension. Full article
(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)
Open AccessArticle
Molecular Typing of Mastitis-Causing Staphylococcus aureus Isolated from Heifers and Cows
Int. J. Mol. Sci. 2013, 14(2), 4326-4333; https://doi.org/10.3390/ijms14024326
Received: 22 November 2012 / Revised: 31 January 2013 / Accepted: 5 February 2013 / Published: 21 February 2013
Cited by 13 | Viewed by 2990 | PDF Full-text (219 KB) | HTML Full-text | XML Full-text
Abstract
Staphylococcus aureus is among the main etiologic agents of bovine mastitis. A total of 83 isolates of S. aureus from mammary glands of primiparous heifers were collected in the prepartum, calving and during lactation. For lactating cows, a total of 27 isolates of [...] Read more.
Staphylococcus aureus is among the main etiologic agents of bovine mastitis. A total of 83 isolates of S. aureus from mammary glands of primiparous heifers were collected in the prepartum, calving and during lactation. For lactating cows, a total of 27 isolates of S. aureus from mammary glands were collected during lactation. The samples were taken in two dairy farms located in Sao Paulo State, Brazil. The highest frequency of S. aureus isolation in heifers was at the end of lactation. Strains were typified through Pulsed-field gel electrophoresis (PFGE) and grouped according to patterns of restriction enzyme SmaI. PFGE generated seven clonal profiles that were grouped into three different lineages, with the LA lineage being predominant and identified in heifers, as well as in the cows from the two regions studied. It was concluded that the cows showed a significant source of dispersion of S. aureus. At the first lactation the heifers were infected by the same clonal profiles of S. aureus which were isolated from multiparous lactating cows. The heifers were infected during milking over the months of lactation. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle
Oxygenated Cembranoids from the Soft Coral Sinularia flexibilis
Int. J. Mol. Sci. 2013, 14(2), 4317-4325; https://doi.org/10.3390/ijms14024317
Received: 9 January 2013 / Revised: 1 February 2013 / Accepted: 4 February 2013 / Published: 21 February 2013
Cited by 14 | Viewed by 3045 | PDF Full-text (440 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chemical examination of the Taiwanese soft coral Sinularia flexibilis led to the isolation of five cembrane-based diterpenoids 15, including two new metabolites, 11-acetylsinuflexolide (1) and 11-acetyldihydrosinuflexolide (2). The structures of the new metabolites were determined based [...] Read more.
Chemical examination of the Taiwanese soft coral Sinularia flexibilis led to the isolation of five cembrane-based diterpenoids 15, including two new metabolites, 11-acetylsinuflexolide (1) and 11-acetyldihydrosinuflexolide (2). The structures of the new metabolites were determined based on extensive spectroscopic analysis, particularly mass spectrometry and 2D NMR (1H–1H COSY, HMQC, HMBC, and NOESY) spectroscopy. Metabolites 1, 3 and 4 exhibited moderate to weak cytotoxicity to human tumor cell lines, HeLa, HEp-2, MCF-7 and MDA-MB-231. Full article
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Open AccessReview
The Increasing Complexity of the Oncofetal H19 Gene Locus: Functional Dissection and Therapeutic Intervention
Int. J. Mol. Sci. 2013, 14(2), 4298-4316; https://doi.org/10.3390/ijms14024298
Received: 3 December 2012 / Revised: 29 January 2013 / Accepted: 6 February 2013 / Published: 21 February 2013
Cited by 59 | Viewed by 4835 | PDF Full-text (601 KB) | HTML Full-text | XML Full-text
Abstract
The field of the long non-coding RNA (lncRNA) is advancing rapidly. Currently, it is one of the most popular fields in the biological and medical sciences. It is becoming increasingly obvious that the majority of the human transcriptome has little or no-protein coding [...] Read more.
The field of the long non-coding RNA (lncRNA) is advancing rapidly. Currently, it is one of the most popular fields in the biological and medical sciences. It is becoming increasingly obvious that the majority of the human transcriptome has little or no-protein coding capacity. Historically, H19 was the first imprinted non-coding RNA (ncRNA) transcript identified, and the H19/IGF2 locus has served as a paradigm for the study of genomic imprinting since its discovery. In recent years, we have extensively investigated the expression of the H19 gene in a number of human cancers and explored the role of H19 RNA in tumor development. Here, we discuss recently published data from our group and others that provide further support for a central role of H19 RNA in the process of tumorigenesis. Furthermore, we focus on major transcriptional modulators of the H19 gene and discuss them in the context of the tumor-promoting activity of the H19 RNA. Based on the pivotal role of the H19 gene in human cancers, we have developed a DNA-based therapeutic approach for the treatment of cancers that have upregulated levels of H19 expression. This approach uses a diphtheria toxin A (DTA) protein expressed under the regulation of the H19 promoter to treat tumors with significant expression of H19 RNA. In this review, we discuss the treatment of four cancer indications in human subjects using this approach, which is currently under development. This represents perhaps one of the very few examples of an existing DNA-based therapy centered on an lncRNA system. Apart from cancer, H19 expression has been reported also in other conditions, syndromes and diseases, where deregulated imprinting at the H19 locus was obvious in some cases and will be summarized below. Moreover, the H19 locus proved to be much more complicated than initially thought. It houses a genomic sequence that can transcribe, yielding various transcriptional outputs, both in sense and antisense directions. The major transcriptional outputs of the H19 locus are presented here. Full article
(This article belongs to the Special Issue Non-Coding RNAs 2012)
Open AccessArticle
Effect of Nanoencapsulated Vitamin B1 Derivative on Inhibition of Both Mycelial Growth and Spore Germination of Fusarium oxysporum f. sp. raphani
Int. J. Mol. Sci. 2013, 14(2), 4283-4297; https://doi.org/10.3390/ijms14024283
Received: 20 December 2012 / Revised: 23 January 2013 / Accepted: 29 January 2013 / Published: 21 February 2013
Cited by 9 | Viewed by 3227 | PDF Full-text (1364 KB) | HTML Full-text | XML Full-text
Abstract
Nanoencapsulation of thiamine dilauryl sulfate (TDS), a vitamin B1 derivative, was proved to effectively inhibit the spore germination of Fusarium oxysporum f. sp. raphani (F. oxysporum), as well as mycelial growth. The average diameter of nanoparticles was measured as 136 [...] Read more.
Nanoencapsulation of thiamine dilauryl sulfate (TDS), a vitamin B1 derivative, was proved to effectively inhibit the spore germination of Fusarium oxysporum f. sp. raphani (F. oxysporum), as well as mycelial growth. The average diameter of nanoparticles was measured as 136 nm by being encapsulated with an edible encapsulant, lecithin, whose encapsulation efficiency was about 55% in containing 200 ppm of TDS concentration: the 100 ppm TDS nanoparticle solution showed a mycelial growth inhibition rate of 59%. These results were about similar or even better than the cases of treating 100 ppm of dazomet, a positive antifungal control (64%). Moreover, kinetic analysis of inhibiting spore germination were estimated as 6.6% reduction of spore germination rates after 24 h treatment, which were 3.3% similar to the case of treating 100 ppm of a positive control (dazomet) for the same treatment time. It was also found that TDS itself could work as an antifungal agent by inhibiting both mycelial growth and spore germination, even though its efficacy was lower than those of nanoparticles. Nanoparticles especially played a more efficient role in limiting the spore germination, due to their easy penetration into hard cell membranes and long resident time on the surface of the spore shell walls. In this work, it was first demonstrated that the nanoparticle of TDS not a harmful chemical can control the growth of F. oxysporum by using a lower dosage than commercial herbicides, as well as the inhibiting mechanism of the TDS. However, field trials of the TDS nanoparticles encapsulated with lecithin should be further studied to be effectively used for field applications. Full article
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Open AccessReview
Lipid Nanotechnology
Int. J. Mol. Sci. 2013, 14(2), 4242-4282; https://doi.org/10.3390/ijms14024242
Received: 17 December 2012 / Revised: 29 January 2013 / Accepted: 30 January 2013 / Published: 21 February 2013
Cited by 96 | Viewed by 17662 | PDF Full-text (2247 KB) | HTML Full-text | XML Full-text
Abstract
Nanotechnology is a multidisciplinary field that covers a vast and diverse array of devices and machines derived from engineering, physics, materials science, chemistry and biology. These devices have found applications in biomedical sciences, such as targeted drug delivery, bio-imaging, sensing and diagnosis of [...] Read more.
Nanotechnology is a multidisciplinary field that covers a vast and diverse array of devices and machines derived from engineering, physics, materials science, chemistry and biology. These devices have found applications in biomedical sciences, such as targeted drug delivery, bio-imaging, sensing and diagnosis of pathologies at early stages. In these applications, nano-devices typically interface with the plasma membrane of cells. On the other hand, naturally occurring nanostructures in biology have been a source of inspiration for new nanotechnological designs and hybrid nanostructures made of biological and non-biological, organic and inorganic building blocks. Lipids, with their amphiphilicity, diversity of head and tail chemistry, and antifouling properties that block nonspecific binding to lipid-coated surfaces, provide a powerful toolbox for nanotechnology. This review discusses the progress in the emerging field of lipid nanotechnology. Full article
(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)
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Open AccessReview
Textural, Rheological and Sensory Properties and Oxidative Stability of Nut Spreads—A Review
Int. J. Mol. Sci. 2013, 14(2), 4223-4241; https://doi.org/10.3390/ijms14024223
Received: 27 November 2012 / Revised: 5 February 2013 / Accepted: 5 February 2013 / Published: 20 February 2013
Cited by 31 | Viewed by 4606 | PDF Full-text (224 KB) | HTML Full-text | XML Full-text
Abstract
Tree nuts are rich in macro and micronutrients, phytochemicals, tocopherols and phenolic compounds. The development of nut spreads would potentially increase the food uses of nuts and introduce consumers with a healthier, non-animal breakfast snack food. Nut spreads are spreadable products made from [...] Read more.
Tree nuts are rich in macro and micronutrients, phytochemicals, tocopherols and phenolic compounds. The development of nut spreads would potentially increase the food uses of nuts and introduce consumers with a healthier, non-animal breakfast snack food. Nut spreads are spreadable products made from nuts that are ground into paste. Roasting and milling (particle size reduction) are two important stages for the production of nut spreads that affected the textural, rheological characteristic and overall quality of the nut spread. Textural, color, and flavor properties of nut spreads play a major role in consumer appeal, buying decisions and eventual consumption. Stability of nut spreads is influenced by its particle size. Proper combination of ingredients (nut paste, sweetener, vegetable oil and protein sources) is also required to ensure a stable nut spread product is produced. Most of the nut spreads behaved like a non-Newtonian pseudo-plastic fluid under yield stress which help the producers how to start pumping and stirring of the nut spreads. Similar to other high oil content products, nut spreads are susceptible to autoxidation. Their oxidation can be controlled by application of antioxidants, using processing techniques that minimize tocopherol and other natural antioxidant losses. Full article
(This article belongs to the Section Biochemistry)
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Open AccessReview
Agriculture and Bioactives: Achieving Both Crop Yield and Phytochemicals
Int. J. Mol. Sci. 2013, 14(2), 4203-4222; https://doi.org/10.3390/ijms14024203
Received: 27 November 2012 / Revised: 8 January 2013 / Accepted: 29 January 2013 / Published: 20 February 2013
Cited by 25 | Viewed by 3678 | PDF Full-text (256 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Plants are fundamental elements of the human diet, either as direct sources of nutrients or indirectly as feed for animals. During the past few years, the main goal of agriculture has been to increase yield in order to provide the food that is [...] Read more.
Plants are fundamental elements of the human diet, either as direct sources of nutrients or indirectly as feed for animals. During the past few years, the main goal of agriculture has been to increase yield in order to provide the food that is needed by a growing world population. As important as yield, but commonly forgotten in conventional agriculture, is to keep and, if it is possible, to increase the phytochemical content due to their health implications. Nowadays, it is necessary to go beyond this, reconciling yield and phytochemicals that, at first glance, might seem in conflict. This can be accomplished through reviewing food requirements, plant consumption with health implications, and farming methods. The aim of this work is to show how both yield and phytochemicals converge into a new vision of agricultural management in a framework of integrated agricultural practices. Full article
(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism)
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Open AccessArticle
Phenotypic Identification of the Redox Dye Methylene Blue as an Antagonist of Heat Shock Response Gene Expression in Metastatic Melanoma Cells
Int. J. Mol. Sci. 2013, 14(2), 4185-4202; https://doi.org/10.3390/ijms14024185
Received: 5 January 2013 / Revised: 24 January 2013 / Accepted: 29 January 2013 / Published: 19 February 2013
Cited by 8 | Viewed by 3173 | PDF Full-text (1647 KB) | HTML Full-text | XML Full-text
Abstract
Repurposing approved and abandoned non-oncological drugs is an alternative developmental strategy for the identification of anticancer therapeutics that has recently attracted considerable attention. Due to the essential role of the cellular heat shock response in cytoprotection through the maintenance of proteostasis and suppression [...] Read more.
Repurposing approved and abandoned non-oncological drugs is an alternative developmental strategy for the identification of anticancer therapeutics that has recently attracted considerable attention. Due to the essential role of the cellular heat shock response in cytoprotection through the maintenance of proteostasis and suppression of apoptosis, small molecule heat shock response antagonists can be harnessed for targeted induction of cytotoxic effects in cancer cells. Guided by gene expression array analysis and a phenotypic screen interrogating a collection of 3,7-diamino-phenothiazinium derivatives, we have identified the redox-drug methylene blue (MB), used clinically for the infusional treatment of methemoglobinemia, as a negative modulator of heat shock response gene expression in human metastatic melanoma cells. MB-treatment blocked thermal (43 °C) and pharmacological (celastrol, geldanamycin) induction of heat shock response gene expression, suppressing Hsp70 (HSPA1A) and Hsp27 (HSPB1) upregulation at the mRNA and protein level. MB sensitized melanoma cells to the apoptogenic activity of geldanamycin, an Hsp90 antagonist known to induce the counter-regulatory upregulation of Hsp70 expression underlying cancer cell resistance to geldanamycin chemotherapy. Similarly, MB-cotreatment sensitized melanoma cells to other chemotherapeutics (etoposide, doxorubicin). Taken together, these data suggest feasibility of repurposing the non-oncological redox drug MB as a therapeutic heat shock response antagonist for cancer cell chemosensitization. Full article
(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)
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Open AccessArticle
Preparation of Chitosan and Water-Soluble Chitosan Microspheres via Spray-Drying Method to Lower Blood Lipids in Rats Fed with High-Fat Diets
Int. J. Mol. Sci. 2013, 14(2), 4174-4184; https://doi.org/10.3390/ijms14024174
Received: 27 November 2012 / Revised: 30 January 2013 / Accepted: 1 February 2013 / Published: 19 February 2013
Cited by 35 | Viewed by 4225 | PDF Full-text (1251 KB) | HTML Full-text | XML Full-text
Abstract
This experiment aimed to investigate the effects of the chitosan (CTS) and water-soluble chitosan (WSC) microspheres on plasma lipids in male Sprague-Dawley rats fed with high-fat diets. CTS microspheres and WSC microspheres were prepared by the spray-drying technique. Scanning electron microscopy (SEM) micrographs [...] Read more.
This experiment aimed to investigate the effects of the chitosan (CTS) and water-soluble chitosan (WSC) microspheres on plasma lipids in male Sprague-Dawley rats fed with high-fat diets. CTS microspheres and WSC microspheres were prepared by the spray-drying technique. Scanning electron microscopy (SEM) micrographs showed that the microspheres were nearly spherical in shape. The mean size of CTS microspheres was 4.07 μm (varying from 1.50 to 7.21 μm) and of WSC microspheres was 2.00 μm (varying from 0.85 to 3.58 μm). The rats were classified into eight groups (n = 8) and were fed with high-fat diets for two weeks to establish the hyperlipidemic condition and were then treated with CTS microspheres and WSC microspheres, CTS and WSC for four weeks. The results showed that CTS and WSC microspheres reduced blood lipids and plasma viscosity and increased the serum superoxide dismutase (SOD) levels significantly. This study is the first report of the lipid-lowering effects of CTS and WSC microspheres. CTS and WSC microspheres were found to be more effective in improving hyperlipidemia in rats than common CTS and WSC. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles 2012)
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Open AccessReview
Brain Metastasis in Pancreatic Cancer
Int. J. Mol. Sci. 2013, 14(2), 4163-4173; https://doi.org/10.3390/ijms14024163
Received: 8 January 2013 / Revised: 3 February 2013 / Accepted: 4 February 2013 / Published: 19 February 2013
Cited by 16 | Viewed by 4762 | PDF Full-text (166 KB) | HTML Full-text | XML Full-text
Abstract
Pancreatic cancer is a fatal disease with a 5-year survival rate below 5%. Most patients are diagnosed at an advanced tumor stage and existence of distant metastases. However, involvement of the central nervous system is rare in pancreatic cancer. We retrospectively analyzed all [...] Read more.
Pancreatic cancer is a fatal disease with a 5-year survival rate below 5%. Most patients are diagnosed at an advanced tumor stage and existence of distant metastases. However, involvement of the central nervous system is rare in pancreatic cancer. We retrospectively analyzed all cases of brain metastases in pancreatic cancer reported to date focusing on patient characteristics, clinical appearance, therapy and survival. Including our own, 12 cases of brain metastases originating from pancreatic cancer were identified. In three patients brain metastases were the first manifestation of pancreatic cancer. All other patients developed brain metastases during their clinical course. In most cases, the disease progressed rapidly and the patients died within weeks or months. However, two patients showed long-term survival. Of note, both patients received resection of the pancreatic cancer as well as curative resection of the metachronous brain metastases. Brain metastases in pancreatic cancer are a rare condition and usually predict a very poor prognosis. However, there is evidence that resection of brain metastases of pancreatic cancer can be immensely beneficial to patient’s survival, even with the chance for cure. Therefore, a surgical approach in metastatic pancreatic cancer should be considered in selective cases. Full article
(This article belongs to the Special Issue Brain Metastasis)
Open AccessArticle
The Environmental Pollutant Cadmium Promotes Influenza Virus Replication in MDCK Cells by Altering Their Redox State
Int. J. Mol. Sci. 2013, 14(2), 4148-4162; https://doi.org/10.3390/ijms14024148
Received: 27 December 2012 / Revised: 4 February 2013 / Accepted: 6 February 2013 / Published: 19 February 2013
Cited by 20 | Viewed by 3633 | PDF Full-text (2561 KB) | HTML Full-text | XML Full-text
Abstract
Cadmium (Cd) is a toxic heavy metal that is considered an environmental contaminant. Several sources of human exposure to Cd, including employment in primary metal industries, production of certain batteries, foods, soil and cigarette smoke, are known. Its inhalation has been related to [...] Read more.
Cadmium (Cd) is a toxic heavy metal that is considered an environmental contaminant. Several sources of human exposure to Cd, including employment in primary metal industries, production of certain batteries, foods, soil and cigarette smoke, are known. Its inhalation has been related to different respiratory diseases and toxic effects, among which alterations of the physiological redox state in individuals exposed to the metal have been described. Host-cell redox changes characteristic of oxidative stress facilitate the progression of viral infection through different mechanisms. In this paper, we have demonstrated that pre-treatment with CdCl2 of MDCK cells increased influenza virus replication in a dose-dependent manner. This phenomenon was related to increased viral protein expression (about 40% compared with untreated cells). The concentration of CdCl2, able to raise the virus titer, also induced oxidative stress. The addition of two antioxidants, a glutathione (GSH) derivative or the GSH precursor, N-acetyl-L-cysteine, to Cd pre-treated and infected cells restored the intracellular redox state and significantly inhibited viral replication. In conclusion, our data demonstrate that Cd-induced oxidative stress directly increases the ability of influenza virus to replicate in the host-cell, thus suggesting that exposure to heavy metals, such as this, could be a risk factor for individuals exposed to a greater extent to the contaminant, resulting in increased severity of virus-induced respiratory diseases. Full article
(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)
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Open AccessArticle
5-bp Classical Satellite DNA Loci from Chromosome-1 Instability in Cervical Neoplasia Detected by DNA Breakage Detection/Fluorescence in Situ Hybridization (DBD-FISH)
Int. J. Mol. Sci. 2013, 14(2), 4135-4147; https://doi.org/10.3390/ijms14024135
Received: 24 December 2012 / Revised: 28 January 2013 / Accepted: 28 January 2013 / Published: 19 February 2013
Cited by 4 | Viewed by 3211 | PDF Full-text (1372 KB) | HTML Full-text | XML Full-text
Abstract
We aimed to evaluate the association between the progressive stages of cervical neoplasia and DNA damage in 5-bp classical satellite DNA sequences from chromosome-1 in cervical epithelium and in peripheral blood lymphocytes using DNA breakage detection/fluorescence in situ hybridization (DBD-FISH). A hospital-based unmatched [...] Read more.
We aimed to evaluate the association between the progressive stages of cervical neoplasia and DNA damage in 5-bp classical satellite DNA sequences from chromosome-1 in cervical epithelium and in peripheral blood lymphocytes using DNA breakage detection/fluorescence in situ hybridization (DBD-FISH). A hospital-based unmatched case-control study was conducted in 2011 with a sample of 30 women grouped according to disease stage and selected according to histological diagnosis; 10 with low-grade squamous intraepithelial lesions (LG-SIL), 10 with high-grade SIL (HG-SIL), and 10 with no cervical lesions, from the Unidad Medica de Alta Especialidad of The Mexican Social Security Institute, IMSS, Mexico. Specific chromosome damage levels in 5-bp classical satellite DNA sequences from chromosome-1 were evaluated in cervical epithelium and peripheral blood lymphocytes using the DBD-FISH technique. Whole-genome DNA hybridization was used as a reference for the level of damage. Results of Kruskal-Wallis test showed a significant increase according to neoplastic development in both tissues. The instability of 5-bp classical satellite DNA sequences from chromosome-1 was evidenced using chromosome-orientation FISH. In conclusion, we suggest that the progression to malignant transformation involves an increase in the instability of 5-bp classical satellite DNA sequences from chromosome-1. Full article
(This article belongs to the Special Issue DNA Damage and Repair in Degenerative Diseases)
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Open AccessArticle
Polymorphisms in XPD and ERCC1 Associated with Colorectal Cancer Outcome
Int. J. Mol. Sci. 2013, 14(2), 4121-4134; https://doi.org/10.3390/ijms14024121
Received: 9 November 2012 / Revised: 9 December 2012 / Accepted: 25 January 2013 / Published: 19 February 2013
Cited by 6 | Viewed by 2814 | PDF Full-text (202 KB) | HTML Full-text | XML Full-text
Abstract
Using the comprehensive approach to selecting polymorphisms to date, we sought to examine whether recurrence in colorectal cancer was associated with inherited variation in three genes involved in DNA repair and cell proliferation. Three polymorphisms, which are excision repair cross-complementation 1 (ERCC1), xeroderma [...] Read more.
Using the comprehensive approach to selecting polymorphisms to date, we sought to examine whether recurrence in colorectal cancer was associated with inherited variation in three genes involved in DNA repair and cell proliferation. Three polymorphisms, which are excision repair cross-complementation 1 (ERCC1), xeroderma pigmentosum group D (XPD) and epidermal growth factor receptor (EGFR), were assessed in 257 postoperative stage II/III CRC patients with 5-fluorouracial chemotherapy in Taiwan. In addition, the correlations between genetic polymorphisms and patients’ clinicopathological features were investigated. Genotypes of XPD codon751 A/A and ERCC1 codon118 T/T were associated with regional recurrence in a statistically significant way (p = 0.018). Patients who carried XPD AA and ERCC1 TT genotypes demonstrated a significantly greater regional recurrence risk (OR = 5.625, 95% CI, 1.557–20.32). Inherited variation in XPD and ERCC1 was associated with outcome in patients with colorectal cancer in Taiwan. As the significant association of single-nucleotide polymorphisms has not been studied previously in colorectal cancer, these findings suggest novel sites of variation, in part explaining the range of treatment responses seen in this disease. Full article
(This article belongs to the Special Issue Pathogenesis and Prevention of Colorectal Cancer)
Open AccessArticle
Anti-Proliferative Activities and Apoptosis Induction by Triterpenes Derived from Eriobotrya japonica in Human Leukemia Cell Lines
Int. J. Mol. Sci. 2013, 14(2), 4106-4120; https://doi.org/10.3390/ijms14024106
Received: 19 December 2012 / Revised: 15 January 2013 / Accepted: 4 February 2013 / Published: 18 February 2013
Cited by 30 | Viewed by 3408 | PDF Full-text (2005 KB) | HTML Full-text | XML Full-text
Abstract
Eriobotrya japonica leaf is a traditional herbal medicine that contains numerous triterpenes, which have various pharmacological properties. In this study, we investigated the anti-proliferative activity of four triterpenes derived from E. japonica, including corosolic acid (CA), ursolic acid (UA), maslinic acid (MA) [...] Read more.
Eriobotrya japonica leaf is a traditional herbal medicine that contains numerous triterpenes, which have various pharmacological properties. In this study, we investigated the anti-proliferative activity of four triterpenes derived from E. japonica, including corosolic acid (CA), ursolic acid (UA), maslinic acid (MA) and oleanolic acid (OA), in human leukemia cell lines. CA showed the strongest anti-proliferative activity in all of the leukemia cell lines tested, but not in normal human skin fibroblast cell lines. To determine the mechanism underlying the anti-proliferative effect of CA, we examined the effect of CA on molecular events known as apoptosis induction. CA induced chromatin condensation, DNA fragmentation, sub-G1 phase DNA, activation of caspase-3, -8 and -9 and the cleavage of PARP in HL-60. CA also activated Bid and Bax, leading to the loss of mitochondrial membrane potential (∆ψm) and cytochrome c release into the cytosol, whereas Bcl-2 and Bcl-xL were unaffected by CA. These results suggest that CA has an anti-proliferative effect on leukemia cells via the induction of apoptosis mediated by mitochondrial dysfunction and caspase activation. CA may be a potential chemotherapeutic agent for the treatment of human leukemia. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle
Expression and Functions of Fibroblast Growth Factor 10 in the Mouse Mammary Gland
Int. J. Mol. Sci. 2013, 14(2), 4094-4105; https://doi.org/10.3390/ijms14024094
Received: 13 December 2012 / Revised: 15 January 2013 / Accepted: 5 February 2013 / Published: 18 February 2013
Cited by 4 | Viewed by 2466 | PDF Full-text (6143 KB) | HTML Full-text | XML Full-text
Abstract
Fibroblast growth factor 10 (FGF10) is important as a mesenchymal mediator of epithelial growth and morphogenesis. In this study, the expression and localization of the FGF10 protein were detected by laser scanning confocal microscopy during mouse postnatal mammary gland development. Mammary explants were [...] Read more.
Fibroblast growth factor 10 (FGF10) is important as a mesenchymal mediator of epithelial growth and morphogenesis. In this study, the expression and localization of the FGF10 protein were detected by laser scanning confocal microscopy during mouse postnatal mammary gland development. Mammary explants were cultured to investigate the functions of FGF10. The results revealed that FGF10 localizes mainly in the mesenchyme near the ductal epithelial cells and the alveolar epithelial cells of the mammary gland. Peak FGF10 expression levels were observed at lactation day 10. FGF10 induced FGFR2-IIIb expression in the mammary epithelium, except in virgin or pregnant mice. FGF10 promoted the proliferation of mammary gland epithelial cells and reduced apoptosis. FGF10 is important during the mouse mammary gland growth, development, and reconstruction, and its effects are mediated by FGFR2-IIIb. Full article
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Open AccessArticle
Stabilized Conversion Efficiency and Dye-Sensitized Solar Cells from Beta vulgaris Pigment
Int. J. Mol. Sci. 2013, 14(2), 4081-4093; https://doi.org/10.3390/ijms14024081
Received: 9 November 2012 / Revised: 11 January 2013 / Accepted: 17 January 2013 / Published: 18 February 2013
Cited by 19 | Viewed by 3446 | PDF Full-text (1218 KB) | HTML Full-text | XML Full-text
Abstract
Dye-Sensitized Solar Cells (DSSCs), based on TiO2 and assembled using a dye from Beta vulgaris extract (BVE) with Tetraethylorthosilicate (TEOS), are reported. The dye BVE/TEOS increased its UV resistance, rendering an increase in the cell lifetime; the performance of these solar cells [...] Read more.
Dye-Sensitized Solar Cells (DSSCs), based on TiO2 and assembled using a dye from Beta vulgaris extract (BVE) with Tetraethylorthosilicate (TEOS), are reported. The dye BVE/TEOS increased its UV resistance, rendering an increase in the cell lifetime; the performance of these solar cells was compared to those prepared with BVE without TEOS. The efficiency η for the solar energy conversion was, for BVE and BVE/TEOS, of 0.89% ± 0.006% and 0.68% ± 0.006% with a current density Jsc of 2.71 ± 0.003 mA/cm2 and 2.08 ± 0.003 mA/cm2, respectively, using in both cases an irradiation of 100 mW/cm2 at 25 °C. The efficiency of the BVE solar cell dropped from 0.9 ± 0.006 to 0.85 ± 0.006 after 72 h of operation, whereas for the BVE/TEOS, the efficiency remained practically constant in the same period of time. Full article
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Open AccessArticle
Immobilization of Ferrocene-Modified SNAP-Fusion Proteins
Int. J. Mol. Sci. 2013, 14(2), 4066-4080; https://doi.org/10.3390/ijms14024066
Received: 30 November 2012 / Revised: 4 February 2013 / Accepted: 4 February 2013 / Published: 18 February 2013
Cited by 14 | Viewed by 3779 | PDF Full-text (606 KB) | HTML Full-text | XML Full-text
Abstract
The supramolecular assembly of proteins on surfaces has been investigated via the site-selective incorporation of a supramolecular moiety on proteins. To this end, fluorescent proteins have been site-selectively labeled with ferrocenes, as supramolecular guest moieties, via SNAP-tag technology. The assembly of guest-functionalized SNAP-fusion [...] Read more.
The supramolecular assembly of proteins on surfaces has been investigated via the site-selective incorporation of a supramolecular moiety on proteins. To this end, fluorescent proteins have been site-selectively labeled with ferrocenes, as supramolecular guest moieties, via SNAP-tag technology. The assembly of guest-functionalized SNAP-fusion proteins on cyclodextrin- and cucurbit[7]uril-coated surfaces yielded stable monolayers. The binding of all ferrocene fusion proteins is specific as determined by surface plasmon resonance. Micropatterns of the fusion proteins, on patterned cyclodextrin and cucurbituril surfaces, have been visualized using fluorescence microscopy. The SNAP-fusion proteins were also immobilized on cyclodextrin vesicles. The supramolecular SNAP-tag labeling of proteins, thus, allows for the assembly of modified proteins via supramolecular host-guest interaction on different surfaces in a controlled manner. These findings extend the toolbox of fabricating supramolecular protein patterns on surfaces taking advantage of the high labeling efficiency of the SNAP-tag with versatile supramolecular moieties. Full article
(This article belongs to the Special Issue Molecular Self-Assembly 2012)
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Open AccessReview
The Role of Lipid Domains in Bacterial Cell Processes
Int. J. Mol. Sci. 2013, 14(2), 4050-4065; https://doi.org/10.3390/ijms14024050
Received: 31 December 2012 / Revised: 25 January 2013 / Accepted: 28 January 2013 / Published: 18 February 2013
Cited by 45 | Viewed by 3693 | PDF Full-text (253 KB) | HTML Full-text | XML Full-text
Abstract
Membranes are vital structures for cellular life forms. As thin, hydrophobic films, they provide a physical barrier separating the aqueous cytoplasm from the outside world or from the interiors of other cellular compartments. They maintain a selective permeability for the import and export [...] Read more.
Membranes are vital structures for cellular life forms. As thin, hydrophobic films, they provide a physical barrier separating the aqueous cytoplasm from the outside world or from the interiors of other cellular compartments. They maintain a selective permeability for the import and export of water-soluble compounds, enabling the living cell to maintain a stable chemical environment for biological processes. Cell membranes are primarily composed of two crucial substances, lipids and proteins. Bacterial membranes can sense environmental changes or communication signals from other cells and they support different cell processes, including cell division, differentiation, protein secretion and supplementary protein functions. The original fluid mosaic model of membrane structure has been recently revised because it has become apparent that domains of different lipid composition are present in both eukaryotic and prokaryotic cell membranes. In this review, we summarize different aspects of phospholipid domain formation in bacterial membranes, mainly in Gram-negative Escherichia coli and Gram-positive Bacillus subtilis. We describe the role of these lipid domains in membrane dynamics and the localization of specific proteins and protein complexes in relation to the regulation of cellular function. Full article
(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)
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Open AccessReview
The Role of F-Box Proteins during Viral Infection
Int. J. Mol. Sci. 2013, 14(2), 4030-4049; https://doi.org/10.3390/ijms14024030
Received: 23 October 2012 / Revised: 14 December 2012 / Accepted: 17 January 2013 / Published: 18 February 2013
Cited by 5 | Viewed by 2936 | PDF Full-text (207 KB) | HTML Full-text | XML Full-text
Abstract
The F-box domain is a protein structural motif of about 50 amino acids that mediates protein–protein interactions. The F-box protein is one of the four components of the SCF (SKp1, Cullin, F-box protein) complex, which mediates ubiquitination of proteins targeted for degradation by [...] Read more.
The F-box domain is a protein structural motif of about 50 amino acids that mediates protein–protein interactions. The F-box protein is one of the four components of the SCF (SKp1, Cullin, F-box protein) complex, which mediates ubiquitination of proteins targeted for degradation by the proteasome, playing an essential role in many cellular processes. Several discoveries have been made on the use of the ubiquitin–proteasome system by viruses of several families to complete their infection cycle. On the other hand, F-box proteins can be used in the defense response by the host. This review describes the role of F-box proteins and the use of the ubiquitin–proteasome system in virus–host interactions. Full article
(This article belongs to the Special Issue Advances in Molecular Plant Biology)
Open AccessArticle
Theoretical and Experimental Spectroscopic Analysis of Cyano-Substituted Styrylpyridine Compounds
Int. J. Mol. Sci. 2013, 14(2), 4005-4029; https://doi.org/10.3390/ijms14024005
Received: 14 November 2012 / Revised: 30 December 2012 / Accepted: 23 January 2013 / Published: 18 February 2013
Cited by 13 | Viewed by 3035 | PDF Full-text (5653 KB) | HTML Full-text | XML Full-text
Abstract
A combined theoretical and experimental study on the structure, infrared, UV-Vis and 1H NMR data of trans-2-(m-cyanostyryl)pyridine, trans-2-[3-methyl-(m-cyanostyryl)]pyridine and trans-4-(m-cyanostyryl)pyridine is presented. The synthesis was carried out with an efficient Knoevenagel condensation using [...] Read more.
A combined theoretical and experimental study on the structure, infrared, UV-Vis and 1H NMR data of trans-2-(m-cyanostyryl)pyridine, trans-2-[3-methyl-(m-cyanostyryl)]pyridine and trans-4-(m-cyanostyryl)pyridine is presented. The synthesis was carried out with an efficient Knoevenagel condensation using green chemistry conditions. Theoretical geometry optimizations and their IR spectra were carried out using the Density Functional Theory (DFT) in both gas and solution phases. For theoretical UV-Vis and 1H NMR spectra, the Time-Dependent DFT (TD-DFT) and the Gauge-Including Atomic Orbital (GIAO) methods were used, respectively. The theoretical characterization matched the experimental measurements, showing a good correlation. The effect of cyano- and methyl- substituents, as well as of the N-atom position in the pyridine ring on the UV-Vis, IR and NMR spectra, was evaluated. The UV-Vis results showed no significant effect due to electron-withdrawing cyano- and electron-donating methyl-substituents. The N-atom position, however, caused a slight change in the maximum absorption wavelengths. The IR normal modes were assigned for the cyano- and methyl-groups. 1H NMR spectra showed the typical doublet signals due to protons in the trans position of a double bond. The theoretical characterization was visibly useful to assign accurately the signals in IR and 1H NMR spectra, as well as to identify the most probable conformation that could be present in the formation of the styrylpyridine-like compounds. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
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Open AccessArticle
Synthesis and Characterization of Molecularly Imprinted Polymer Membrane for the Removal of 2,4-Dinitrophenol
Int. J. Mol. Sci. 2013, 14(2), 3993-4004; https://doi.org/10.3390/ijms14023993
Received: 1 November 2012 / Revised: 4 January 2013 / Accepted: 16 January 2013 / Published: 18 February 2013
Cited by 17 | Viewed by 3864 | PDF Full-text (970 KB) | HTML Full-text | XML Full-text
Abstract
Molecularly imprinted polymers (MIPs) were prepared by bulk polymerization in acetonitrile using 2,4-dinitrophenol, acrylamide, ethylene glycol dimethacrylate, and benzoyl peroxide, as the template, functional monomer, cross-linker, and initiator, respectively. The MIP membrane was prepared by hybridization of MIP particles with cellulose acetate (CA) [...] Read more.
Molecularly imprinted polymers (MIPs) were prepared by bulk polymerization in acetonitrile using 2,4-dinitrophenol, acrylamide, ethylene glycol dimethacrylate, and benzoyl peroxide, as the template, functional monomer, cross-linker, and initiator, respectively. The MIP membrane was prepared by hybridization of MIP particles with cellulose acetate (CA) and polystyrene (PS) after being ground and sieved. The prepared MIP membrane was characterized using Fourier transform infrared spectroscopy and scanning electron microscopy. The parameters studied for the removal of 2,4-dinitrophenol included the effect of pH, sorption kinetics, and the selectivity of the MIP membrane. Maximum sorption of 2,4-nitrophenol by the fabricated CA membrane with MIP (CA-MIP) and the PS membrane with MIP (PS-MIP) was observed at pH 7.0 and pH 5.0, respectively. The sorption of 2,4-dinitrophenol by CA-MIP and PS-MIP followed a pseudo–second-order kinetic model. For a selectivity study, 2,4-dichlorophenol, 3-chlorophenol, and phenol were selected as potential interferences. The sorption capability of CA-MIP and PS-MIP towards 2,4-dinitrophenol was observed to be higher than that of 2,4-dichlorophenol, 3-chlorophenol, or phenol. Full article
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Open AccessReview
Optical Methods to Study Protein-DNA Interactions in Vitro and in Living Cells at the Single-Molecule Level
Int. J. Mol. Sci. 2013, 14(2), 3961-3992; https://doi.org/10.3390/ijms14023961
Received: 15 December 2012 / Revised: 13 January 2013 / Accepted: 4 February 2013 / Published: 18 February 2013
Cited by 44 | Viewed by 4231 | PDF Full-text (1363 KB) | HTML Full-text | XML Full-text
Abstract
The maintenance of intact genetic information, as well as the deployment of transcription for specific sets of genes, critically rely on a family of proteins interacting with DNA and recognizing specific sequences or features. The mechanisms by which these proteins search for target [...] Read more.
The maintenance of intact genetic information, as well as the deployment of transcription for specific sets of genes, critically rely on a family of proteins interacting with DNA and recognizing specific sequences or features. The mechanisms by which these proteins search for target DNA are the subject of intense investigations employing a variety of methods in biology. A large interest in these processes stems from the faster-than-diffusion association rates, explained in current models by a combination of 3D and 1D diffusion. Here, we present a review of the single-molecule approaches at the forefront of the study of protein-DNA interaction dynamics and target search in vitro and in vivo. Flow stretch, optical and magnetic manipulation, single fluorophore detection and localization as well as combinations of different methods are described and the results obtained with these techniques are discussed in the framework of the current facilitated diffusion model. Full article
(This article belongs to the Special Issue Advances in Single Molecule Spectroscopy)
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Open AccessArticle
Evidence for the Involvement of RhoA Signaling in the Ethanol-Induced Increase in Intestinal Epithelial Barrier Permeability
Int. J. Mol. Sci. 2013, 14(2), 3946-3960; https://doi.org/10.3390/ijms14023946
Received: 4 January 2013 / Revised: 19 January 2013 / Accepted: 24 January 2013 / Published: 18 February 2013
Cited by 15 | Viewed by 2921 | PDF Full-text (1161 KB) | HTML Full-text | XML Full-text
Abstract
In this work, we investigated the potential role of the small G protein RhoA in ethanol-induced tight junction (TJ) protein disassembly and increased intestinal epithelial barrier (IEB) permeability. Our study used Caco-2 cells as an in vitro IEB model and RhoA short hairpin [...] Read more.
In this work, we investigated the potential role of the small G protein RhoA in ethanol-induced tight junction (TJ) protein disassembly and increased intestinal epithelial barrier (IEB) permeability. Our study used Caco-2 cells as an in vitro IEB model and RhoA short hairpin RNA (shRNA) interference to establish whether RhoA plays a role in ethanol-induced TJ opening. RhoA shRNA interference partially inhibited epithelial leakage and restored normal transepithelial electrical resistance (TEER) values in the IEB. Moreover, RhoA shRNA interference prevented a shift in occludin distribution from insoluble to soluble fractions. Additionally, RhoA shRNA interference inhibited the ethanol-induced expression of zonula occludens-1 (ZO-1). Finally, RhoA shRNA interference inhibited an ethanol-induced increase in RhoA activity. The contributions of RhoA to an ethanol-induced increase in IEB permeability are associated with TJ disassembly. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
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Open AccessArticle
Proteome Analysis of Rice (Oryza sativa L.) Mutants Reveals Differentially Induced Proteins during Brown Planthopper (Nilaparvata lugens) Infestation
Int. J. Mol. Sci. 2013, 14(2), 3921-3945; https://doi.org/10.3390/ijms14023921
Received: 17 September 2012 / Revised: 20 January 2013 / Accepted: 22 January 2013 / Published: 15 February 2013
Cited by 18 | Viewed by 8017 | PDF Full-text (4056 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Although rice resistance plays an important role in controlling the brown planthopper (BPH), Nilaparvata lugens, not all varieties have the same level of protection against BPH infestation. Understanding the molecular interactions in rice defense response is an important tool to help to [...] Read more.
Although rice resistance plays an important role in controlling the brown planthopper (BPH), Nilaparvata lugens, not all varieties have the same level of protection against BPH infestation. Understanding the molecular interactions in rice defense response is an important tool to help to reveal unexplained processes that underlie rice resistance to BPH. A proteomics approach was used to explore how wild type IR64 and near-isogenic rice mutants with gain and loss of resistance to BPH respond during infestation. A total of 65 proteins were found markedly altered in wild type IR64 during BPH infestation. Fifty-two proteins associated with 11 functional categories were identified using mass spectrometry. Protein abundance was less altered at 2 and 14 days after infestation (DAI) (T1, T2, respectively), whereas higher protein levels were observed at 28 DAI (T3). This trend diminished at 34 DAI (T4). Comparative analysis of IR64 with mutants showed 22 proteins that may be potentially associated with rice resistance to the brown planthopper (BPH). Ten proteins were altered in susceptible mutant (D1131) whereas abundance of 12 proteins including S-like RNase, Glyoxalase I, EFTu1 and Salt stress root protein “RS1” was differentially changed in resistant mutant (D518). S-like RNase was found in greater quantities in D518 after BPH infestation but remained unchanged in IR64 and decreased in D1131. Taken together, this study shows a noticeable level of protein abundance in the resistant mutant D518 compared to the susceptible mutant D1131 that may be involved in rendering enhanced level of resistance against BPH. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessArticle
A Comparison of B16 Melanoma Cells and 3T3 Fibroblasts Concerning Cell Viability and ROS Production in the Presence of Melatonin, Tested Over a Wide Range of Concentrations
Int. J. Mol. Sci. 2013, 14(2), 3901-3920; https://doi.org/10.3390/ijms14023901
Received: 22 January 2013 / Revised: 31 January 2013 / Accepted: 4 February 2013 / Published: 14 February 2013
Cited by 11 | Viewed by 3840 | PDF Full-text (954 KB) | HTML Full-text | XML Full-text
Abstract
Melatonin is a pleiotropic molecule with many cellular and systemic actions, including chronobiotic effects. Beneficial effects are widely documented concerning the treatment of neoplastic diseases in vivo as well as reductions in viability of cultured cells from melanoma, one of the most aggressive [...] Read more.
Melatonin is a pleiotropic molecule with many cellular and systemic actions, including chronobiotic effects. Beneficial effects are widely documented concerning the treatment of neoplastic diseases in vivo as well as reductions in viability of cultured cells from melanoma, one of the most aggressive cancers in humans. However, studies of its effects on non-tumor cells in vitro have not focused on viability, except for experiments aiming to protect against oxidotoxicity or other toxicological insults. Furthermore, there is no agreement on the range of effective melatonin concentrations in vitro, and the mechanisms that reduce cell viability have remained unclear. Tumor cell-specific increases in the production of reactive oxygen and nitrogen species (ROS/RNS) may provide a possible explanation. Our aim was to analyze the potential inhibition of tumor (B16 melanoma 4A5) and non-tumor cell (3T3 Swiss albino) viability using a wide range of melatonin concentrations (10−11–10−2 M), and to determine whether intracellular ROS enhancement was involved in this process. In the absence of fetal bovine serum (FBS), low melatonin concentrations (10−9–10−5 M) reduced the proliferation of melanoma cells with no effect in fibroblasts, whereas, in the presence of FBS, they had no effect or even increased the proliferation of both fibroblast and melanoma cells. Melatonin concentrations in the upper millimolar range increased ROS levels and reduced the viability of both cell types, but more markedly so in non-tumor cells. Thus, low melatonin concentrations reduce proliferation in this specific melanoma cell line, whereas high concentrations affect the viability of both tumor (B16 4A5 melanoma) and non-tumor (3T3 fibroblasts) cells. Increased ROS levels in both lines indicate a role for ROS production in the reduction of cell viability at high—but not low—melatonin concentrations, although the mechanism of action still remains to be elucidated. Full article
(This article belongs to the Special Issue Advances in the Research of Melatonin)
Open AccessReview
Chemical Inhibitors and microRNAs (miRNA) Targeting the Mammalian Target of Rapamycin (mTOR) Pathway: Potential for Novel Anticancer Therapeutics
Int. J. Mol. Sci. 2013, 14(2), 3874-3900; https://doi.org/10.3390/ijms14023874
Received: 13 September 2012 / Revised: 8 January 2013 / Accepted: 10 January 2013 / Published: 13 February 2013
Cited by 25 | Viewed by 4454 | PDF Full-text (856 KB) | HTML Full-text | XML Full-text
Abstract
The mammalian target of rapamycin (mTOR) is a critical regulator of many fundamental features in response to upstream cellular signals, such as growth factors, energy, stress and nutrients, controlling cell growth, proliferation and metabolism through two complexes, mTORC1 and mTORC2. Dysregulation of mTOR [...] Read more.
The mammalian target of rapamycin (mTOR) is a critical regulator of many fundamental features in response to upstream cellular signals, such as growth factors, energy, stress and nutrients, controlling cell growth, proliferation and metabolism through two complexes, mTORC1 and mTORC2. Dysregulation of mTOR signalling often occurs in a variety of human malignant diseases making it a crucial and validated target in the treatment of cancer. Tumour cells have shown high susceptibility to mTOR inhibitors. Rapamycin and its derivatives (rapalogs) have been tested in clinical trials in several tumour types and found to be effective as anticancer agents in patients with advanced cancers. To block mTOR function, they form a complex with FKBP12 and then bind the FRB domain of mTOR. Furthermore, a new generation of mTOR inhibitors targeting ATP-binding in the catalytic site of mTOR showed potent and more selective inhibition. More recently, microRNAs (miRNA) have emerged as modulators of biological pathways that are essential in cancer initiation, development and progression. Evidence collected to date shows that miRNAs may function as tumour suppressors or oncogenes in several human neoplasms. The mTOR pathway is a promising target by miRNAs for anticancer therapy. Extensive studies have indicated that regulation of the mTOR pathway by miRNAs plays a major role in cancer progression, indicating a novel way to investigate the tumorigenesis and therapy of cancer. Here, we summarize current findings of the role of mTOR inhibitors and miRNAs in carcinogenesis through targeting mTOR signalling pathways and determine their potential as novel anti-cancer therapeutics. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))
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