International Journal of Molecular Sciences

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Open AccessEditorial

International Journal of Molecular Science Best Paper Award 2013

by Ophelia Han

Int. J. Mol. Sci. 2013, 14(2), 4372-4374; https://doi.org/10.3390/ijms14024372 - 22 Feb 2013

Cited by 6 | Viewed by 8950

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

by Hongjiang Ruan, Shen Liu, Fengfeng Li, Xujun Li and Cunyi Fan

Int. J. Mol. Sci. 2013, 14(2), 4361-4371; https://doi.org/10.3390/ijms14024361 - 21 Feb 2013

Cited by 27 | Viewed by 9308

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

by Jin-Young Kim, Ramamourthy Gopal, Sang Young Kim, Chang Ho Seo, Hyang Burm Lee, Hyeonsook Cheong and Yoonkyung Park

Int. J. Mol. Sci. 2013, 14(2), 4349-4360; https://doi.org/10.3390/ijms14024349 - 21 Feb 2013

Cited by 15 | Viewed by 8776

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)

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Open AccessArticle

Cyclic Stretch Induces Inducible Nitric Oxide Synthase and Soluble Guanylate Cyclase in Pulmonary Artery Smooth Muscle Cells

by Monica R. Shah, Stephen Wedgwood, Lyubov Czech, Gina A. Kim, Satyan Lakshminrusimha, Paul T. Schumacker, Robin H. Steinhorn and Kathryn N. Farrow

Int. J. Mol. Sci. 2013, 14(2), 4334-4348; https://doi.org/10.3390/ijms14024334 - 21 Feb 2013

Cited by 17 | Viewed by 7576

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)

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Open AccessArticle

Molecular Typing of Mastitis-Causing Staphylococcus aureus Isolated from Heifers and Cows

by Lívia Castelani, Aline Franciele Silva Santos, Mariana Dos Santos Miranda, Luiz Francisco Zafalon, Claudia Rodrigues Pozzi and Juliana Rodrigues Pozzi Arcaro

Int. J. Mol. Sci. 2013, 14(2), 4326-4333; https://doi.org/10.3390/ijms14024326 - 21 Feb 2013

Cited by 20 | Viewed by 6698

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

by Ching-Chyuan Su, Bing-Sang Wong, Chuen Chin, Yu-Jen Wu and Jui-Hsin Su

Int. J. Mol. Sci. 2013, 14(2), 4317-4325; https://doi.org/10.3390/ijms14024317 - 21 Feb 2013

Cited by 23 | Viewed by 6813

Abstract

Chemical examination of the Taiwanese soft coral Sinularia flexibilis led to the isolation of five cembrane-based diterpenoids 1–5, 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 1–5, 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

by Imad Matouk, Eli Raveh, Patricia Ohana, Rasha Abu Lail, Eitan Gershtain, Michal Gilon, Nathan De Groot, Abraham Czerniak and Abraham Hochberg

Int. J. Mol. Sci. 2013, 14(2), 4298-4316; https://doi.org/10.3390/ijms14024298 - 21 Feb 2013

Cited by 89 | Viewed by 10657

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)

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Open AccessArticle

Effect of Nanoencapsulated Vitamin B1 Derivative on Inhibition of Both Mycelial Growth and Spore Germination of Fusarium oxysporum f. sp. raphani

by Jeong Sub Cho, Yong Chang Seo, Tae Bin Yim and Hyeon Yong Lee

Int. J. Mol. Sci. 2013, 14(2), 4283-4297; https://doi.org/10.3390/ijms14024283 - 21 Feb 2013

Cited by 20 | Viewed by 8593

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

by Samaneh Mashaghi, Tayebeh Jadidi, Gijsje Koenderink and Alireza Mashaghi

Int. J. Mol. Sci. 2013, 14(2), 4242-4282; https://doi.org/10.3390/ijms14024242 - 21 Feb 2013

Cited by 181 | Viewed by 41149

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

by Ahmad Shakerardekani, Roselina Karim, Hasanah Mohd Ghazali and Nyuk Ling Chin

Int. J. Mol. Sci. 2013, 14(2), 4223-4241; https://doi.org/10.3390/ijms14024223 - 20 Feb 2013

Cited by 87 | Viewed by 19219

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

by Lina García-Mier, Ramón G. Guevara-González, Víctor M. Mondragón-Olguín, Beatriz Del Rocío Verduzco-Cuellar and Irineo Torres-Pacheco

Int. J. Mol. Sci. 2013, 14(2), 4203-4222; https://doi.org/10.3390/ijms14024203 - 20 Feb 2013

Cited by 49 | Viewed by 10272

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

by Angela L. Davis, Christopher M. Cabello, Shuxi Qiao, Sara Azimian and Georg T. Wondrak

Int. J. Mol. Sci. 2013, 14(2), 4185-4202; https://doi.org/10.3390/ijms14024185 - 19 Feb 2013

Cited by 12 | Viewed by 7774

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

by Yi Tao, Hong-Liang Zhang, Yin-Ming Hu, Shuo Wan and Zheng-Quan Su

Int. J. Mol. Sci. 2013, 14(2), 4174-4184; https://doi.org/10.3390/ijms14024174 - 19 Feb 2013

Cited by 52 | Viewed by 10132

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

by Johannes Lemke, Jan Scheele, Thomas Kapapa, Christian Rainer Wirtz, Doris Henne-Bruns and Marko Kornmann

Int. J. Mol. Sci. 2013, 14(2), 4163-4173; https://doi.org/10.3390/ijms14024163 - 19 Feb 2013

Cited by 33 | Viewed by 10283

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)

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Open AccessArticle

The Environmental Pollutant Cadmium Promotes Influenza Virus Replication in MDCK Cells by Altering Their Redox State

by Paola Checconi, Rossella Sgarbanti, Ignacio Celestino, Dolores Limongi, Donatella Amatore, Alessandra Iuvara, Alessandro Alimonti, Enrico Garaci, Anna Teresa Palamara and Lucia Nencioni

Int. J. Mol. Sci. 2013, 14(2), 4148-4162; https://doi.org/10.3390/ijms14024148 - 19 Feb 2013

Cited by 34 | Viewed by 9694

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)

by Elva I. Cortés-Gutiérrez, Brenda L. Ortíz-Hernández, Martha I. Dávila-Rodríguez, Ricardo M. Cerda-Flores, José Luis Fernández, Carmen López-Fernández and Jaime Gosálvez

Int. J. Mol. Sci. 2013, 14(2), 4135-4147; https://doi.org/10.3390/ijms14024135 - 19 Feb 2013

Cited by 12 | Viewed by 7769

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

by Ming-Yii Huang, Jaw-Yuan Wang, Meng-Lin Huang, Hui-Jen Chang and Shiu-Ru Lin

Int. J. Mol. Sci. 2013, 14(2), 4121-4134; https://doi.org/10.3390/ijms14024121 - 19 Feb 2013

Cited by 10 | Viewed by 6026

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)

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Anti-Proliferative Activities and Apoptosis Induction by Triterpenes Derived from Eriobotrya japonica in Human Leukemia Cell Lines

by Takuhiro Uto, Ayana Sakamoto, Nguyen Huu Tung, Tsukasa Fujiki, Kenji Kishihara, Shigeru Oiso, Hiroko Kariyazono, Osamu Morinaga and Yukihiro Shoyama

Int. J. Mol. Sci. 2013, 14(2), 4106-4120; https://doi.org/10.3390/ijms14024106 - 18 Feb 2013

Cited by 50 | Viewed by 8608

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 (∆ψ_m) 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

by Yingjun Cui and Qingzhang Li

Int. J. Mol. Sci. 2013, 14(2), 4094-4105; https://doi.org/10.3390/ijms14024094 - 18 Feb 2013

Cited by 10 | Viewed by 6078

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

by Angel Ramon Hernández-Martínez, Miriam Estévez, Susana Vargas and Rogelio Rodríguez

Int. J. Mol. Sci. 2013, 14(2), 4081-4093; https://doi.org/10.3390/ijms14024081 - 18 Feb 2013

Cited by 37 | Viewed by 8486

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

by Dorothee Wasserberg, Dana A. Uhlenheuer, Pauline Neirynck, Jordi Cabanas-Danés, Jan Hendrik Schenkel, Bart Jan Ravoo, Qi An, Jurriaan Huskens, Lech-Gustav Milroy, Luc Brunsveld and Pascal Jonkheijm

Int. J. Mol. Sci. 2013, 14(2), 4066-4080; https://doi.org/10.3390/ijms14024066 - 18 Feb 2013

Cited by 18 | Viewed by 8444

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

by Imrich Barák and Katarína Muchová

Int. J. Mol. Sci. 2013, 14(2), 4050-4065; https://doi.org/10.3390/ijms14024050 - 18 Feb 2013

Cited by 103 | Viewed by 13085

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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The Role of F-Box Proteins during Viral Infection

by Régis Lopes Correa, Fernanda Prieto Bruckner, Renan De Souza Cascardo and Poliane Alfenas-Zerbini

Int. J. Mol. Sci. 2013, 14(2), 4030-4049; https://doi.org/10.3390/ijms14024030 - 18 Feb 2013

Cited by 19 | Viewed by 7657

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)

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Theoretical and Experimental Spectroscopic Analysis of Cyano-Substituted Styrylpyridine Compounds

by Maria Eugenia Castro, Maria Judith Percino, Victor M. Chapela, Margarita Ceron, Guillermo Soriano-Moro, Jorge Lopez-Cruz and Francisco J. Melendez

Int. J. Mol. Sci. 2013, 14(2), 4005-4029; https://doi.org/10.3390/ijms14024005 - 18 Feb 2013

Cited by 29 | Viewed by 7264

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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Synthesis and Characterization of Molecularly Imprinted Polymer Membrane for the Removal of 2,4-Dinitrophenol

by Nor Azah Yusof, Nor Dyana Zakaria, Nor Amirah Mohd Maamor, Abdul Halim Abdullah and Md. Jelas Haron

Int. J. Mol. Sci. 2013, 14(2), 3993-4004; https://doi.org/10.3390/ijms14023993 - 18 Feb 2013

Cited by 40 | Viewed by 10043

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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Optical Methods to Study Protein-DNA Interactions in Vitro and in Living Cells at the Single-Molecule Level

by Carina Monico, Marco Capitanio, Gionata Belcastro, Francesco Vanzi and Francesco S. Pavone

Int. J. Mol. Sci. 2013, 14(2), 3961-3992; https://doi.org/10.3390/ijms14023961 - 18 Feb 2013

Cited by 59 | Viewed by 11046

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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Evidence for the Involvement of RhoA Signaling in the Ethanol-Induced Increase in Intestinal Epithelial Barrier Permeability

by Jing Tong, Ying Wang, Bing Chang, Dai Zhang and Bingyuan Wang

Int. J. Mol. Sci. 2013, 14(2), 3946-3960; https://doi.org/10.3390/ijms14023946 - 18 Feb 2013

Cited by 23 | Viewed by 7795

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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Proteome Analysis of Rice (Oryza sativa L.) Mutants Reveals Differentially Induced Proteins during Brown Planthopper (Nilaparvata lugens) Infestation

by Jatinder Singh Sangha, Yolanda H. Chen, Jatinder Kaur, Wajahatullah Khan, Zainularifeen Abduljaleel, Mohammed S. Alanazi, Aaron Mills, Candida B. Adalla, John Bennett, Balakrishnan Prithiviraj, Gary C. Jahn and Hei Leung

Int. J. Mol. Sci. 2013, 14(2), 3921-3945; https://doi.org/10.3390/ijms14023921 - 15 Feb 2013

Cited by 31 | Viewed by 16738

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)

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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

by Maria Angeles Bonmati-Carrion, Nuria Álvarez-Sánchez, Rüdiger Hardeland, Juan Antonio Madrid and Maria Angeles Rol

Int. J. Mol. Sci. 2013, 14(2), 3901-3920; https://doi.org/10.3390/ijms14023901 - 14 Feb 2013

Cited by 21 | Viewed by 9292

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)

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Chemical Inhibitors and microRNAs (miRNA) Targeting the Mammalian Target of Rapamycin (mTOR) Pathway: Potential for Novel Anticancer Therapeutics

by Naif AlQurashi, Saeed M. Hashimi and Ming Q. Wei

Int. J. Mol. Sci. 2013, 14(2), 3874-3900; https://doi.org/10.3390/ijms14023874 - 13 Feb 2013

Cited by 37 | Viewed by 11591

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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Int. J. Mol. Sci., Volume 14, Issue 2 (February 2013) – 121 articles , Pages 2230-4374

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