International Journal of Molecular Sciences

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Open AccessArticle

Crosslinking Liposomes/Cells Using Cholesteryl Group-Modified Tilapia Gelatin

by Tetsushi Taguchi and Yoshiaki Endo

Int. J. Mol. Sci. 2014, 15(7), 13123-13134; https://doi.org/10.3390/ijms150713123 - 23 Jul 2014

Cited by 11 | Viewed by 6654

Cholesteryl group-modified tilapia gelatins (Chol-T-Gltns) with various Chol contents from 3 to 69 mol % per amino group of Gltn were prepared for the assembly of liposomes and cells. Liposomes were physically crosslinked by anchoring Chol groups of Chol-T-Gltns into lipid membranes. The [...] Read more.

Cholesteryl group-modified tilapia gelatins (Chol-T-Gltns) with various Chol contents from 3 to 69 mol % per amino group of Gltn were prepared for the assembly of liposomes and cells. Liposomes were physically crosslinked by anchoring Chol groups of Chol-T-Gltns into lipid membranes. The resulting liposome gels were enzymatically degraded by addition of collagenase. Liposome gels prepared using Chol-T-Gltn with high Chol content (69Chol-T-Gltn) showed slower enzymatic degradation when compared with gels prepared using Chol-T-Gltn with low Chol content (3Chol-T-Gltn). The hepatocyte cell line HepG2 showed good assembly properties and no cytotoxic effects after addition of 69Chol-T-Gltns. In addition, the number of HepG2 cells increased with concentration of 69Chol-T-Gltns. Therefore, Chol-T-Gltn, particularly, 69Chol-T-Gltn, can be used as an assembling material for liposomes and various cell types. The resulting organization can be applied to various biomedical fields, such as drug delivery systems, tissue engineering and regenerative medicine. Full article

(This article belongs to the Special Issue Biodegradable Materials)

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Open AccessCommunication

DNA Break Mapping Reveals Topoisomerase II Activity Genome-Wide

by Laura Baranello, Fedor Kouzine, Damian Wojtowicz, Kairong Cui, Teresa M. Przytycka, Keji Zhao and David Levens

Int. J. Mol. Sci. 2014, 15(7), 13111-13122; https://doi.org/10.3390/ijms150713111 - 23 Jul 2014

Cited by 66 | Viewed by 10460

Abstract

Genomic DNA is under constant assault by endogenous and exogenous DNA damaging agents. DNA breakage can represent a major threat to genome integrity but can also be necessary for genome function. Here we present approaches to map DNA double-strand breaks (DSBs) and single-strand [...] Read more.

Genomic DNA is under constant assault by endogenous and exogenous DNA damaging agents. DNA breakage can represent a major threat to genome integrity but can also be necessary for genome function. Here we present approaches to map DNA double-strand breaks (DSBs) and single-strand breaks (SSBs) at the genome-wide scale by two methods called DSB- and SSB-Seq, respectively. We tested these methods in human colon cancer cells and validated the results using the Topoisomerase II (Top2)-poisoning agent etoposide (ETO). Our results show that the combination of ETO treatment with break-mapping techniques is a powerful method to elaborate the pattern of Top2 enzymatic activity across the genome. Full article

(This article belongs to the Special Issue Identification and Roles of the Structure of DNA)

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Open AccessArticle

Effects of the Novel Compound DK223 ([1E,2E-1,2-Bis(6-methoxy-2H-chromen-3-yl)methylene]hydrazine) on Migration and Proliferation of Human Keratinocytes and Primary Dermal Fibroblasts

by Manh Tin Ho, Hyun Sik Kang, Jung Sik Huh, Young Mee Kim, Yoongho Lim and Moonjae Cho

Int. J. Mol. Sci. 2014, 15(7), 13091-13110; https://doi.org/10.3390/ijms150713091 - 23 Jul 2014

Cited by 10 | Viewed by 7598

Abstract

Wound healing plays an important role in protecting the human body from external infection. Cell migration and proliferation of keratinocytes and dermal fibroblasts are essential for proper wound healing. Recently, several studies have demonstrated that secondary compounds produced in plants could affect skin [...] Read more.

Wound healing plays an important role in protecting the human body from external infection. Cell migration and proliferation of keratinocytes and dermal fibroblasts are essential for proper wound healing. Recently, several studies have demonstrated that secondary compounds produced in plants could affect skin cells migration and proliferation. In this study, we identified a novel compound DK223 ([1E,2E-1,2-bis(6-methoxy-2H-chromen-3-yl)methylene]hydrazine) that concomitantly induced human keratinocyte migration and dermal fibroblast proliferation. We evaluated the regulation of epithelial and mesenchymal protein markers, such as E-cadherin and Vimentin, in human keratinocytes, as well as extracellular matrix (ECM) secretion and metalloproteinase families in dermal fibroblasts. DK223 upregulated keratinocyte migration and significantly increased the epithelial marker E-cadherin in a time-dependent manner. We also found that reactive oxygen species (ROS) increased significantly in keratinocytes after 2 h of DK223 exposure, returning to normal levels after 24 h, which indicated that DK223 had an early shock effect on ROS production. DK223 also stimulated fibroblast proliferation, and induced significant secretion of ECM proteins, such as collagen I, III, and fibronectin. In dermal fibroblasts, DK223 treatment induced TGF-β1, which is involved in a signaling pathway that mediates proliferation. In conclusion, DK223 simultaneously induced both keratinocyte migration via ROS production and fibroblast proliferation via TGF-β1 induction. Full article

(This article belongs to the Special Issue Molecular Science for Drug Development and Biomedicine)

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Open AccessArticle

Antioxidant Capacities and Total Phenolic Contents Enhancement with Acute Gamma Irradiation in Curcuma alismatifolia (Zingiberaceae) Leaves

by Sima Taheri, Thohirah Lee Abdullah, Ehsan Karimi, Ehsan Oskoueian and Mahdi Ebrahimi

Int. J. Mol. Sci. 2014, 15(7), 13077-13090; https://doi.org/10.3390/ijms150713077 - 23 Jul 2014

Cited by 49 | Viewed by 8532

Abstract

The present study was conducted in order to assess the effect of various doses of acute gamma irradiation (0, 10, 15, and 20 Gy) on the improvement of bioactive compounds and their antioxidant properties of Curcuma alismatifolia var. Sweet pink. The high [...] Read more.

The present study was conducted in order to assess the effect of various doses of acute gamma irradiation (0, 10, 15, and 20 Gy) on the improvement of bioactive compounds and their antioxidant properties of Curcuma alismatifolia var. Sweet pink. The high performance liquid chromatography (HPLC) and gas chromatography (GC) analysis uncovered that various types of phenolic, flavonoid compounds, and fatty acids gradually altered in response to radiation doses. On the other hand, antioxidant activities determined by 1,1-Diphenyl-2-picryl-hydrazyl (DPPH), ferric reduction, antioxidant power (FRAP), and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assay showed a higher irradiation level significantly increased the antioxidant properties. This study revealed an efficient effect of varying levels of gamma radiation, based on the pharmaceutical demand to enhance the accumulation and distribution of bioactive compounds such as phenolic and flavonoid compounds, fatty acids, as well as their antioxidant activities in the leaves of C. alismatifolia var. Sweet pink. Full article

(This article belongs to the Special Issue Bioactive Phenolics and Polyphenols)

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Open AccessReview

Possible Prognostic and Therapeutic Significance of c-Kit Expression, Mast Cell Count and Microvessel Density in Renal Cell Carcinoma

by Ilaria Marech, Cosmo Damiano Gadaleta and Girolamo Ranieri

Int. J. Mol. Sci. 2014, 15(7), 13060-13076; https://doi.org/10.3390/ijms150713060 - 23 Jul 2014

Cited by 33 | Viewed by 12763

Abstract

Renal cell carcinoma (RCC) is the most frequent renal tumor and its incidence is increasing worldwide. Tumor angiogenesis is known to play a crucial role in the etiopathogenesis of RCC and over the last few years an even deeper knowledge of its contribution [...] Read more.

Renal cell carcinoma (RCC) is the most frequent renal tumor and its incidence is increasing worldwide. Tumor angiogenesis is known to play a crucial role in the etiopathogenesis of RCC and over the last few years an even deeper knowledge of its contribution in metastatic RCC development has led to the development of numerous molecular targeting agents (such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib). The above agents are principally directed against vascular endothelial growth factor receptor (VEGFR) members and also against c-Kit receptor (c-KitR). The role of c-kitR inhibition on clear cell RCC (ccRCC), the main RCC subtype, is less well established. Whether c-kitR activation through its ligand, stem cell factor (SCF) contributes significantly to the effects of tyrosine kinase inhibitors (TKIs) treatment remains to be established. It is important to underscore that the c-KitR is expressed on mast cells (MCs) and cancer cells. After an examination of the c-KitR/SCF pathway, we review here the principal studies that have evaluated c-Kit expression in RCC. Moreover, we summarize some investigations that have observed the distribution of MCs in primary renal cancer and in adjacent normal tissue with appropriate histological immunohistochemical techniques. We also focus on few studies that have evaluated the correlation between RCC proliferation, MC count and microvessel density (MVD), as hallmarks of tumor angiogenesis. Thus, the aim of this review of the literature is to clarify if c-KitR expression, MC count and MVD could have prognostic significance and the possible predictive therapeutic implications in RCC. Full article

(This article belongs to the Special Issue Molecular Research in Urology 2014)

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Open AccessArticle

BRCA1 Exon 11, a CERES (Composite Regulatory Element of Splicing) Element Involved in Splice Regulation

by Claudia Tammaro, Michela Raponi, David I. Wilson and Diana Baralle

Int. J. Mol. Sci. 2014, 15(7), 13045-13059; https://doi.org/10.3390/ijms150713045 - 23 Jul 2014

Cited by 13 | Viewed by 7203

Abstract

Unclassified variants (UV) of BRCA1 can affect normal pre-mRNA splicing. Here, we investigate the UV c.693G>A, a “silent” change in BRCA1 exon 11, which we have found induces aberrant splicing in patient carriers and in vitro. Using a minigene assay, we show [...] Read more.

Unclassified variants (UV) of BRCA1 can affect normal pre-mRNA splicing. Here, we investigate the UV c.693G>A, a “silent” change in BRCA1 exon 11, which we have found induces aberrant splicing in patient carriers and in vitro. Using a minigene assay, we show that the UV c.693G>A has a strong effect on the splicing isoform ratio of BRCA1. Systematic site-directed mutagenesis of the area surrounding the nucleotide position c.693G>A induced variable changes in the level of exon 11 inclusion/exclusion in the mRNA, pointing to the presence of a complex regulatory element with overlapping enhancer and silencer functions. Accordingly, protein binding analysis in the region detected several splicing regulatory factors involved, including SRSF1, SRSF6 and SRSF9, suggesting that this sequence represents a composite regulatory element of splicing (CERES). Full article

(This article belongs to the Special Issue Pre-mRNA Splicing)

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Open AccessArticle

Calcium and Zinc Containing Bactericidal Glass Coatings for Biomedical Metallic Substrates

by Leticia Esteban-Tejeda, Luis A. Díaz, Catuxa Prado, Belén Cabal, Ramón Torrecillas and José S. Moya

Int. J. Mol. Sci. 2014, 15(7), 13030-13044; https://doi.org/10.3390/ijms150713030 - 23 Jul 2014

Cited by 19 | Viewed by 6716

Abstract

The present work presents new bactericidal coatings, based on two families of non-toxic, antimicrobial glasses belonging to B₂O₃–SiO₂–Na₂O–ZnO and SiO₂–Na₂O–Al₂O₃–CaO–B₂O₃ systems.Free of cracking, [...] Read more.

The present work presents new bactericidal coatings, based on two families of non-toxic, antimicrobial glasses belonging to B₂O₃–SiO₂–Na₂O–ZnO and SiO₂–Na₂O–Al₂O₃–CaO–B₂O₃ systems.Free of cracking, single layer direct coatings on different biomedical metallic substrates (titanium alloy, Nb, Ta, and stainless steel) have been developed. Thermal expansion mismatch was adjusted by changing glass composition of the glass type, as well as the firing atmosphere (air or Ar) according to the biomedical metallic substrates. Formation of bubbles in some of the glassy coatings has been rationalized considering the reactions that take place at the different metal/coating interfaces. All the obtained coatings were proven to be strongly antibacterial versus Escherichia coli (>4 log). Full article

(This article belongs to the Special Issue Biologic Coatings for Orthopaedic Implant)

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Open AccessArticle

Arginine Enhances Osteoblastogenesis and Inhibits Adipogenesis through the Regulation of Wnt and NFATc Signaling in Human Mesenchymal Stem Cells

by Jeong-Eun Huh, Jun-Young Choi, Ye-Ok Shin, Dong-Suk Park, Jung Won Kang, Dongwoo Nam, Do-Young Choi and Jae-Dong Lee

Int. J. Mol. Sci. 2014, 15(7), 13010-13029; https://doi.org/10.3390/ijms150713010 - 22 Jul 2014

Cited by 30 | Viewed by 8623

Abstract

Arginine, an α-amino acid, has been reported to exert beneficial effects that ameliorate health problems and prevent excessive fat deposition. In this study, we investigated whether the activation of cell signaling by arginine can induce osteogenic differentiation and modulate excessive adipogenic differentiation in [...] Read more.

Arginine, an α-amino acid, has been reported to exert beneficial effects that ameliorate health problems and prevent excessive fat deposition. In this study, we investigated whether the activation of cell signaling by arginine can induce osteogenic differentiation and modulate excessive adipogenic differentiation in human mesenchymal stem cells (MSCs). Arginine potently induced the expression of type Iα1 collagen, osteocalcin, and ALP in a dose-dependent manner without causing cytotoxicity. Arginine significantly increased the mRNA expression of the osteogenic transcription factors runt-related transcription factor 2 (Runx2), DIx5, and osterix. Furthermore, arginine demonstrated its antiadipogenicity by decreasing adipocyte formation and triglyceride (TG) content in MSCs and inhibiting the mRNA expression of the adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and fatty acid binding protein 4 (Fabp4). This effect was associated with increased expression of Wnt5a, and nuclear factor of activated T-cells (NFATc), and was abrogated by antagonists of Wnt and NFATc, which indicated a role of Wnt and NFATc signaling in the switch from adipogenesis to osteoblastogenesis induced by arginine. In conclusion, this is the first report of the dual action of arginine in promoting osteogenesis and inhibiting adipocyte formation through involving Wnt5a and NFATc signaling pathway. Full article

(This article belongs to the Special Issue Bioactive Proteins and Peptides Derived from Food)

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Open AccessArticle

Improved Fibroblast Functionalities by Microporous Pattern Fabricated by Microelectromechanical Systems

by Hongbo Wei, Lingzhou Zhao, Bangdao Chen, Shizhu Bai and Yimin Zhao

Int. J. Mol. Sci. 2014, 15(7), 12998-13009; https://doi.org/10.3390/ijms150712998 - 22 Jul 2014

Cited by 2 | Viewed by 6095

Abstract

Fibroblasts, which play an important role in biological seal formation and maintenance, determine the long-term success of percutaneous implants. In this study, well-defined microporous structures with micropore diameters of 10–60 µm were fabricated by microelectromechanical systems and their influence on the fibroblast functionalities [...] Read more.

Fibroblasts, which play an important role in biological seal formation and maintenance, determine the long-term success of percutaneous implants. In this study, well-defined microporous structures with micropore diameters of 10–60 µm were fabricated by microelectromechanical systems and their influence on the fibroblast functionalities was observed. The results show that the microporous structures with micropore diameters of 10–60 µm did not influence the initial adherent fibroblast number; however, those with diameters of 40 and 50 µm improved the spread, actin stress fiber organization, proliferation and fibronectin secretion of the fibroblasts. The microporous structures with micropore diameters of 40–50 µm may be promising for application in the percutaneous part of an implant. Full article

(This article belongs to the Special Issue Biologic Coatings for Orthopaedic Implant)

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Open AccessReview

Molecular and Cellular Mechanisms of Sperm-Oocyte Interactions Opinions Relative to in Vitro Fertilization (IVF)

by George Anifandis, Christina Messini, Konstantinos Dafopoulos, Sotiris Sotiriou and Ioannis Messinis

Int. J. Mol. Sci. 2014, 15(7), 12972-12997; https://doi.org/10.3390/ijms150712972 - 22 Jul 2014

Cited by 47 | Viewed by 14134

Abstract

One of the biggest prerequisites for pregnancy is the fertilization step, where a human haploid spermatozoon interacts and penetrates one haploid oocyte in order to produce the diploid zygote. Although fertilization is defined by the presence of two pronuclei and the extraction of [...] Read more.

One of the biggest prerequisites for pregnancy is the fertilization step, where a human haploid spermatozoon interacts and penetrates one haploid oocyte in order to produce the diploid zygote. Although fertilization is defined by the presence of two pronuclei and the extraction of the second polar body the process itself requires preparation of both gametes for fertilization to take place at a specific time. These preparations include a number of consecutive biochemical and molecular events with the help of specific molecules and with the consequential interaction between the two gametes. These events take place at three different levels and in a precise order, where the moving spermatozoon penetrates (a) the outer vestments of the oocyte, known as the cumulus cell layer; (b) the zona pellucida (ZP); where exocytosis of the acrosome contents take place and (c) direct interaction of the spermatozoon with the plasma membrane of the oocyte, which involves a firm adhesion of the head of the spermatozoon with the oocyte plasma membrane that culminates with the fusion of both sperm and oocyte membranes (Part I). After the above interactions, a cascade of molecular signal transductions is initiated which results in oocyte activation. Soon after the entry of the first spermatozoon into the oocyte and oocyte activation, the oocyte’s coat (the ZP) and the oocyte’s plasma membrane seem to change quickly in order to initiate a fast block to a second spermatozoon (Part II). Sometimes, two spermatozoa fuse with one oocyte, an incidence of 1%–2%, resulting in polyploid fetuses that account for up to 10%–20% of spontaneously aborted human conceptuses. The present review aims to focus on the first part of the human sperm and oocyte interactions, emphasizing the latest molecular and cellular mechanisms controlling this process. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Sperm-Egg Interaction)

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Open AccessArticle

Astragalus membranaceus Inhibits Peritoneal Fibrosis via Monocyte Chemoattractant Protein (MCP)-1 and the Transforming Growth Factor-β1 (TGF-β1) Pathway in Rats Submitted to Peritoneal Dialysis

by Zhenghong Li, Lu Zhang, Weiming He, Changle Zhu, Jinsong Yang and Meixiao Sheng

Int. J. Mol. Sci. 2014, 15(7), 12959-12971; https://doi.org/10.3390/ijms150712959 - 22 Jul 2014

Cited by 37 | Viewed by 7460

Abstract

Inflammation and transforming growth factor-β1 (TGF-β1) contribute to the development of peritoneal fibrosis (PF), which is associated with peritoneal dialysis (PD). Astragalus membranaceus (Astragalus) has anti-inflammatory and anti-fibrotic effects in many diseases. The goal of this study was to determine the [...] Read more.

Inflammation and transforming growth factor-β1 (TGF-β1) contribute to the development of peritoneal fibrosis (PF), which is associated with peritoneal dialysis (PD). Astragalus membranaceus (Astragalus) has anti-inflammatory and anti-fibrotic effects in many diseases. The goal of this study was to determine the anti-fibrotic effects of Astragalus on the PF response to PD. A rat model of PD was induced using standard PD fluid, and PF was verified by HE and Masson’s staining, as well as through the expression of fibroblast surface protein (FSP) and collagen III. The expression levels of monocyte chemoattractant protein (MCP)-1, F4/80 (macrophage/monocyte marker in rat), TGF-β1 and the downstream proteins phospho-SMAD 2/3 in dialyzed peritoneal tissue treated with or without Astragalus was evaluated using immunohistochemistry analysis. Overall correlations between MCP-1 and TGF-β1 staining were analyzed using both the Spearman and Pearson methods. The results showed that Astragalus could inhibit the recruitment and activation of monocytes/macrophages, thereby reducing the production of TGF-β1 in the dialyzed peritoneal membrane. PF was also significantly decreased following treatment with Astragalus. MCP-1 expression had a strong positive correlation with TGF-β1 sensitivity, suggesting that the anti-fibrotic function of Astragalus was mediated by MCP-1 and the TGF-β1 pathway. Our results indicate that Astragalus could be a useful agent against PD-induced PF. Full article

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Open AccessArticle

Molecular Method for Sex Identification of Half-Smooth Tongue Sole (Cynoglossus semilaevis) Using a Novel Sex-Linked Microsatellite Marker

by Xiaolin Liao, Genbo Xu and Song-Lin Chen

Int. J. Mol. Sci. 2014, 15(7), 12952-12958; https://doi.org/10.3390/ijms150712952 - 22 Jul 2014

Cited by 33 | Viewed by 7392

Abstract

Half-smooth tongue sole (Cynoglossus semilaevis) is one of the most important flatfish species for aquaculture in China. To produce a monosex population, we attempted to develop a marker-assisted sex control technique in this sexually size dimorphic fish. In this study, we [...] Read more.

Half-smooth tongue sole (Cynoglossus semilaevis) is one of the most important flatfish species for aquaculture in China. To produce a monosex population, we attempted to develop a marker-assisted sex control technique in this sexually size dimorphic fish. In this study, we identified a co-dominant sex-linked marker (i.e., CyseSLM) by screening genomic microsatellites and further developed a novel molecular method for sex identification in the tongue sole. CyseSLM has a sequence similarity of 73%–75% with stickleback, medaka, Fugu and Tetraodon. At this locus, two alleles (i.e., A244 and A234) were amplified from 119 tongue sole individuals with primer pairs CyseSLM-F1 and CyseSLM-R. Allele A244 was present in all individuals, while allele A234 (female-associated allele, FAA) was mostly present in females with exceptions in four male individuals. Compared with the sequence of A244, A234 has a 10-bp deletion and 28 SNPs. A specific primer (CyseSLM-F2) was then designed based on the A234 sequence, which amplified a 204 bp fragment in all females and four males with primer CyseSLM-R. A time-efficient multiplex PCR program was developed using primers CyseSLM-F2, CyseSLM-R and the newly designed primer CyseSLM-F3. The multiplex PCR products with co-dominant pattern could be detected by agarose gel electrophoresis, which accurately identified the genetic sex of the tongue sole. Therefore, we have developed a rapid and reliable method for sex identification in tongue sole with a newly identified sex-linked microsatellite marker. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Identifying the Subfamilies of Voltage-Gated Potassium Channels Using Feature Selection Technique

by Wei-Xin Liu, En-Ze Deng, Wei Chen and Hao Lin

Int. J. Mol. Sci. 2014, 15(7), 12940-12951; https://doi.org/10.3390/ijms150712940 - 22 Jul 2014

Cited by 33 | Viewed by 7484

Abstract

Voltage-gated K⁺ channel (VKC) plays important roles in biology procession, especially in nervous system. Different subfamilies of VKCs have different biological functions. Thus, knowing VKCs’ subfamilies has become a meaningful job because it can guide the direction for the disease diagnosis and [...] Read more.

Voltage-gated K⁺ channel (VKC) plays important roles in biology procession, especially in nervous system. Different subfamilies of VKCs have different biological functions. Thus, knowing VKCs’ subfamilies has become a meaningful job because it can guide the direction for the disease diagnosis and drug design. However, the traditional wet-experimental methods were costly and time-consuming. It is highly desirable to develop an effective and powerful computational tool for identifying different subfamilies of VKCs. In this study, a predictor, called iVKC-OTC, has been developed by incorporating the optimized tripeptide composition (OTC) generated by feature selection technique into the general form of pseudo-amino acid composition to identify six subfamilies of VKCs. One of the remarkable advantages of introducing the optimized tripeptide composition is being able to avoid the notorious dimension disaster or over fitting problems in statistical predictions. It was observed on a benchmark dataset, by using a jackknife test, that the overall accuracy achieved by iVKC-OTC reaches to 96.77% in identifying the six subfamilies of VKCs, indicating that the new predictor is promising or at least may become a complementary tool to the existing methods in this area. It has not escaped our notice that the optimized tripeptide composition can also be used to investigate other protein classification problems. Full article

(This article belongs to the Special Issue Advances in Proteomic Research)

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Open AccessArticle

WNT16B from Ovarian Fibroblasts Induces Differentiation of Regulatory T Cells through β-Catenin Signal in Dendritic Cells

by Cong-Cong Shen, Yu-Huan Kang, Ming Zhao, Yi He, Dan-Dan Cui, Yu-Yin Fu, Ling-Lin Yang and Lan-Tu Gou

Int. J. Mol. Sci. 2014, 15(7), 12928-12939; https://doi.org/10.3390/ijms150712928 - 21 Jul 2014

Cited by 20 | Viewed by 6081

Abstract

Treatment for cancer can induce a series of secreted factors into the tumor microenvironment, which can affect cancer progression. Wingless-type MMTV (mouse mammary tumor virus) integration site 16B (WNT16B) is a new member of the WNT family and has been reported to play [...] Read more.

Treatment for cancer can induce a series of secreted factors into the tumor microenvironment, which can affect cancer progression. Wingless-type MMTV (mouse mammary tumor virus) integration site 16B (WNT16B) is a new member of the WNT family and has been reported to play growth-related roles in previous studies. In this study, we found WNT16B could be expressed and secreted into the microenvironment by human ovarian fibroblasts after DNA damage-associated treatment, including chemotherapy drugs and radiation. We also demonstrated that fibroblast-derived WNT16B could result in accumulation of β-catenin in dendritic cells and secretion of interleukin-10 (IL-10) and transforming growth factor beta (TGF-β), which contributed to the differentiation of regulatory T cells in a co-culture environment. These results shed light on the roles of WNT16B in immune regulation, especially in regard to cancer treatment. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Rapid Adsorption of Heavy Metals by Fe₃O₄/Talc Nanocomposite and Optimization Study Using Response Surface Methodology

by Katayoon Kalantari, Mansor B. Ahmad, Hamid Reza Fard Masoumi, Kamyar Shameli, Mahiran Basri and Roshanak Khandanlou

Int. J. Mol. Sci. 2014, 15(7), 12913-12927; https://doi.org/10.3390/ijms150712913 - 21 Jul 2014

Cited by 114 | Viewed by 8413

Abstract

Fe₃O₄/talc nanocomposite was used for removal of Cu(II), Ni(II), and Pb(II) ions from aqueous solutions. Experiments were designed by response surface methodology (RSM) and a quadratic model was used to predict the variables. The adsorption parameters such as adsorbent [...] Read more.

Fe₃O₄/talc nanocomposite was used for removal of Cu(II), Ni(II), and Pb(II) ions from aqueous solutions. Experiments were designed by response surface methodology (RSM) and a quadratic model was used to predict the variables. The adsorption parameters such as adsorbent dosage, removal time, and initial ion concentration were used as the independent variables and their effects on heavy metal ion removal were investigated. Analysis of variance was incorporated to judge the adequacy of the models. Optimal conditions with initial heavy metal ion concentration of 100, 92 and 270 mg/L, 120 s of removal time and 0.12 g of adsorbent amount resulted in 72.15%, 50.23%, and 91.35% removal efficiency for Cu(II), Ni(II), and Pb(II), respectively. The predictions of the model were in good agreement with experimental results and the Fe₃O₄/talc nanocomposite was successfully used to remove heavy metals from aqueous solutions. Full article

(This article belongs to the Section Materials Science)

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Open AccessReview

Iodine Excess as an Environmental Risk Factor for Autoimmune Thyroid Disease

by Yuqian Luo, Akira Kawashima, Yuko Ishido, Aya Yoshihara, Kenzaburo Oda, Naoki Hiroi, Tetsuhide Ito, Norihisa Ishii and Koichi Suzuki

Int. J. Mol. Sci. 2014, 15(7), 12895-12912; https://doi.org/10.3390/ijms150712895 - 21 Jul 2014

Cited by 131 | Viewed by 15616

Abstract

The global effort to prevent iodine deficiency disorders through iodine supplementation, such as universal salt iodization, has achieved impressive progress during the last few decades. However, iodine excess, due to extensive environmental iodine exposure in addition to poor monitoring, is currently a more [...] Read more.

The global effort to prevent iodine deficiency disorders through iodine supplementation, such as universal salt iodization, has achieved impressive progress during the last few decades. However, iodine excess, due to extensive environmental iodine exposure in addition to poor monitoring, is currently a more frequent occurrence than iodine deficiency. Iodine excess is a precipitating environmental factor in the development of autoimmune thyroid disease. Excessive amounts of iodide have been linked to the development of autoimmune thyroiditis in humans and animals, while intrathyroidal depletion of iodine prevents disease in animal strains susceptible to severe thyroiditis. Although the mechanisms by which iodide induces thyroiditis are still unclear, several mechanisms have been proposed: (1) excess iodine induces the production of cytokines and chemokines that can recruit immunocompetent cells to the thyroid; (2) processing excess iodine in thyroid epithelial cells may result in elevated levels of oxidative stress, leading to harmful lipid oxidation and thyroid tissue injuries; and (3) iodine incorporation in the protein chain of thyroglobulin may augment the antigenicity of this molecule. This review will summarize the current knowledge regarding excess iodide as an environmental toxicant and relate it to the development of autoimmune thyroid disease. Full article

(This article belongs to the Special Issue Environmental Toxicants and Autoimmune Disease)

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Open AccessArticle

Effects of β2-Adrenergic Receptor Gene Polymorphisms on Ritodrine Therapy in Pregnant Women with Preterm Labor: Prospective Follow-Up Study

by Jin Young Park, Na Ra Lee, Kyung Eun Lee, Sunny Park, Young Ju Kim and Hye Sun Gwak

Int. J. Mol. Sci. 2014, 15(7), 12885-12894; https://doi.org/10.3390/ijms150712885 - 21 Jul 2014

Cited by 13 | Viewed by 6068

Abstract

This study aimed to evaluate the effects of β2-adrenergic receptor (ADRB2) gene polymorphisms on ritodrine therapy outcomes in patients with preterm labor. Genotyping analysis of ADRB2 gene (rs1042713, rs1042714, rs1042717, rs1042718, and rs1042719) was performed on 137 patients with preterm [...] Read more.

This study aimed to evaluate the effects of β2-adrenergic receptor (ADRB2) gene polymorphisms on ritodrine therapy outcomes in patients with preterm labor. Genotyping analysis of ADRB2 gene (rs1042713, rs1042714, rs1042717, rs1042718, and rs1042719) was performed on 137 patients with preterm labor. Survival analysis was conducted for the effects of SNPs on the median time to delivery as a primary outcome. The median time to delivery in the study patients was 349.3 h. Gestational age at admission and modified Bishop scores revealed significant effects on time to delivery (p < 0.001). Among studied SNPs, rs1042717 and rs1042718 showed linkage disequilibrium in this population, and their effects on time to delivery were marginally significant (p < 0.1). Patients with variant-homozygotes in the rs1042713 showed considerably shortened time to delivery compared to wild-allele carriers. The rs1042719 polymorphism significantly affected time to delivery in both univariate and multivariate analysis; the GC and CC carriers showed 64% decrease in time to delivery compared to the wild-type homozygote carriers. Based on the results, it was concluded that the gene polymorphisms of ADRB2 could affect ritodrine therapy in patients with preterm labor. However, given the single-center and the relatively small sample size, our hypothesis requires further independent validation using multi-center and large sample size. Full article

(This article belongs to the Special Issue Human Single Nucleotide Polymorphisms and Disease Diagnostics)

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4-Hydroxyphenylacetic Acid Attenuated Inflammation and Edema via Suppressing HIF-1α in Seawater Aspiration-Induced Lung Injury in Rats

by Zhongyang Liu, Ronggang Xi, Zhiran Zhang, Wangping Li, Yan Liu, Faguang Jin and Xiaobo Wang

Int. J. Mol. Sci. 2014, 15(7), 12861-12884; https://doi.org/10.3390/ijms150712861 - 21 Jul 2014

Cited by 62 | Viewed by 7486

Abstract

4-Hydroxyphenylacetic acid (4-HPA) is an active component of Chinese herb Aster tataricus which had been widely used in China for the treatment of pulmonary diseases. The aim of this study is to investigate the effect of 4-HPA on seawater aspiration-induced lung injury. Pulmonary [...] Read more.

4-Hydroxyphenylacetic acid (4-HPA) is an active component of Chinese herb Aster tataricus which had been widely used in China for the treatment of pulmonary diseases. The aim of this study is to investigate the effect of 4-HPA on seawater aspiration-induced lung injury. Pulmonary inflammation and edema were assessed by enzyme-linked immunosorbent assay (ELISA), bronchoalveolar lavage fluid (BALF) white cell count, Evans blue dye analysis, wet to dry weight ratios, and histology study. Hypoxia-inducible factor-1α (HIF-1α) siRNA and permeability assay were used to study the effect of 4-HPA on the production of inflammatory cytokines and monolayer permeability in vitro. The results showed that 4-HPA reduced seawater instillation-induced mortality in rats. In lung tissues, 4-HPA attenuated hypoxia, inflammation, vascular leak, and edema, and decreased HIF-1α protein level. In primary rat alveolar epithelial cells (AEC), 4-HPA decreased hypertonicity- and hypoxia-induced HIF-1α protein levels through inhibiting the activations of protein translational regulators and via promoting HIF-1α protein degradation. In addition, 4-HPA lowered inflammatory cytokines levels through suppressing hypertonicity- and hypoxia-induced HIF-1α in NR8383 macrophages. Moreover, 4-HPA decreased monolayer permeability through suppressing hypertonicity and hypoxia-induced HIF-1α, which was mediated by inhibiting vascular endothelial growth factor (VEGF) in rat lung microvascular endothelial cell line (RLMVEC). In conclusion, 4-HPA attenuated inflammation and edema through suppressing hypertonic and hypoxic induction of HIF-1α in seawater aspiration-induced lung injury in rats. Full article

(This article belongs to the Special Issue Molecular Science for Drug Development and Biomedicine)

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Open AccessArticle

Coexpression and Secretion of Endoglucanase and Phytase Genes in Lactobacillus reuteri

by Lei Wang, Yuxin Yang, Bei Cai, Pinghua Cao, Mingming Yang and Yulin Chen

Int. J. Mol. Sci. 2014, 15(7), 12842-12860; https://doi.org/10.3390/ijms150712842 - 21 Jul 2014

Cited by 23 | Viewed by 8235

Abstract

A multifunctional transgenic Lactobacillus with probiotic characteristics and an ability to degrade β-glucan and phytic acid (phytate) was engineered to improve nutrient utilization, increase production performance and decrease digestive diseases in broiler chickens. The Bacillus subtilis WL001 endoglucanase gene (celW) and [...] Read more.

A multifunctional transgenic Lactobacillus with probiotic characteristics and an ability to degrade β-glucan and phytic acid (phytate) was engineered to improve nutrient utilization, increase production performance and decrease digestive diseases in broiler chickens. The Bacillus subtilis WL001 endoglucanase gene (celW) and Aspergillus fumigatus WL002 phytase gene (phyW) mature peptide (phyWM) were cloned into an expression vector with the lactate dehydrogenase promoter of Lactobacillus casei and the secretion signal peptide of the Lactococcus lactis usp45 gene. This construct was then transformed into Lactobacillus reuteri XC1 that had been isolated from the gastrointestinal tract of broilers. Heterologous enzyme production and feed effectiveness of this genetically modified L. reuteri strain were investigated and evaluated. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis showed that the molecular mass of phyWM and celW was approximately 48.2 and 55 kDa, respectively, consistent with their predicted molecular weights. Endoglucanase and phytase activities in the extracellular fraction of the transformed L. reuteri culture were 0.68 and 0.42 U/mL, respectively. Transformed L. reuteri improved the feed conversion ratio of broilers from 21 to 42 days of age and over the whole feeding period. However, there was no effect on body weight gain and feed intake of chicks. Transformed L. reuteri supplementation improved levels of ash, calcium and phosphorus in tibiae at day 21 and of phosphorus at day 42. In addition, populations of Escherichia coli, Veillonella spp. and Bacteroides vulgatus were decreased, while populations of Bifidobacterium genus and Lactobacillus spp. were increased in the cecum at day 21. Full article

(This article belongs to the Section Biochemistry)

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Open AccessReview

Modified Low Density Lipoprotein and Lipoprotein-Containing Circulating Immune Complexes as Diagnostic and Prognostic Biomarkers of Atherosclerosis and Type 1 Diabetes Macrovascular Disease

by Alexander N. Orekhov, Yuri V. Bobryshev, Igor A. Sobenin, Alexandra A. Melnichenko and Dimitry A. Chistiakov

Int. J. Mol. Sci. 2014, 15(7), 12807-12841; https://doi.org/10.3390/ijms150712807 - 21 Jul 2014

Cited by 88 | Viewed by 9388

Abstract

In atherosclerosis; blood low-density lipoproteins (LDL) are subjected to multiple enzymatic and non-enzymatic modifications that increase their atherogenicity and induce immunogenicity. Modified LDL are capable of inducing vascular inflammation through activation of innate immunity; thus, contributing to the progression of atherogenesis. The immunogenicity [...] Read more.

In atherosclerosis; blood low-density lipoproteins (LDL) are subjected to multiple enzymatic and non-enzymatic modifications that increase their atherogenicity and induce immunogenicity. Modified LDL are capable of inducing vascular inflammation through activation of innate immunity; thus, contributing to the progression of atherogenesis. The immunogenicity of modified LDL results in induction of self-antibodies specific to a certain type of modified LDL. The antibodies react with modified LDL forming circulating immune complexes. Circulating immune complexes exhibit prominent immunomodulatory properties that influence atherosclerotic inflammation. Compared to freely circulating modified LDL; modified LDL associated with the immune complexes have a more robust atherogenic and proinflammatory potential. Various lipid components of the immune complexes may serve not only as diagnostic but also as essential predictive markers of cardiovascular events in atherosclerosis. Accumulating evidence indicates that LDL-containing immune complexes can also serve as biomarker for macrovascular disease in type 1 diabetes. Full article

(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

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Open AccessArticle

Antibacterial Effect of Dental Adhesive Containing Dimethylaminododecyl Methacrylate on the Development of Streptococcus mutans Biofilm

by Suping Wang, Keke Zhang, Xuedong Zhou, Ning Xu, Hockin H. K. Xu, Michael D. Weir, Yang Ge, Shida Wang, Mingyun Li, Yuqing Li, Xin Xu and Lei Cheng

Int. J. Mol. Sci. 2014, 15(7), 12791-12806; https://doi.org/10.3390/ijms150712791 - 18 Jul 2014

Cited by 55 | Viewed by 9452

Abstract

Antibacterial bonding agents and composites containing dimethylaminododecyl methacrylate (DMADDM) have been recently developed. The objectives of this study were to investigate the antibacterial effect of novel adhesives containing different mass fractions of DMADDM on Streptococcus mutans (S. mutans) biofilm at different [...] Read more.

Antibacterial bonding agents and composites containing dimethylaminododecyl methacrylate (DMADDM) have been recently developed. The objectives of this study were to investigate the antibacterial effect of novel adhesives containing different mass fractions of DMADDM on Streptococcus mutans (S. mutans) biofilm at different developmental stages. Different mass fractions of DMADDM were incorporated into adhesives and S. mutans biofilm at different developmetal stages were analyzed by MTT assays, lactic acid measurement, confocal laser scanning microscopy and scanning electron microscopy observations. Exopolysaccharides (EPS) staining was used to analyze the inhibitory effect of DMADDM on the biofilm extracellular matrix. Dentin microtensile strengths were also measured. Cured adhesives containing DMADDM could greatly reduce metabolic activity and lactic acid production during the development of S. mutans biofilms (p < 0.05). In earlier stages of biofilm development, there were no significant differences of inhibitory effects between the 2.5% DMADDM and 5% DMADDM group. However, after 72 h, the anti-biofilm effects of adhesives containing 5% DMADDM were significantly stronger than any other group. Incorporation of DMADDM into adhesive did not adversely affect dentin bond strength. In conclusion, adhesives containing DMADDM inhibited the growth, lactic acid production and EPS metabolism of S. mutans biofilm at different stages, with no adverse effect on its dentin adhesive bond strength. The bonding agents have the potential to control dental biofilms and combat tooth decay, and DMADDM is promising for use in a wide range of dental adhesive systems and restoratives. Full article

(This article belongs to the Special Issue Antimicrobial Polymers)

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Open AccessArticle

Cordycepin Down-Regulates Multiple Drug Resistant (MDR)/HIF-1α through Regulating AMPK/mTORC1 Signaling in GBC-SD Gallbladder Cancer Cells

by Wei-Ding Wu, Zhi-Ming Hu, Min-Jie Shang, Da-Jian Zhao, Cheng-Wu Zhang, De-Fei Hong and Dong-Sheng Huang

Int. J. Mol. Sci. 2014, 15(7), 12778-12790; https://doi.org/10.3390/ijms150712778 - 18 Jul 2014

Cited by 59 | Viewed by 7994

Abstract

Gallbladder cancer is the most common malignancy of the bile duct, with low 5-year survival rate and poor prognosis. Novel effective treatments are urgently needed for the therapy of this disease. Here, we showed that cordycepin, the bioactive compound in genus Cordyceps, induced [...] Read more.

Gallbladder cancer is the most common malignancy of the bile duct, with low 5-year survival rate and poor prognosis. Novel effective treatments are urgently needed for the therapy of this disease. Here, we showed that cordycepin, the bioactive compound in genus Cordyceps, induced growth inhibition and apoptosis in cultured gallbladder cancer cells (Mz-ChA-1, QBC939 and GBC-SD lines). We found that cordycepin inhibited mTOR complex 1 (mTORC1) activation and down-regulated multiple drug resistant (MDR)/hypoxia-inducible factor 1α (HIF-1α) expression through activating of AMP-activated protein kinase (AMPK) signaling in gallbladder cancer GBC-SD cells. Contrarily, AMPKα1-shRNA depletion dramatically inhibited cordycepin-induced molecular changes as well as GBC-SD cell apoptosis. Further, our results showed that co-treatment with a low concentration cordycepin could remarkably enhance the chemosensitivity of GBC-SD cells to gemcitabine and 5-fluorouracil (5-FU), and the mechanism may be attributed to AMPK activation and MDR degradation. In summary, cordycepin induces growth inhibition and apoptosis in gallbladder cancer cells via activating AMPK signaling. Cordycepin could be a promising new drug or chemo-adjuvant for gallbladder cancer. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Clinical Significance of POU5F1P1 rs10505477 Polymorphism in Chinese Gastric Cancer Patients Receving Cisplatin-Based Chemotherapy after Surgical Resection

by Lili Shen, Mulong Du, Chun Wang, Dongying Gu, Meilin Wang, Qi Zhang, Tingting Zhao, Xunlei Zhang, Yongfei Tan, Xinying Huo, Weida Gong, Zhi Xu, Jinfei Chen and Zhengdong Zhang

Int. J. Mol. Sci. 2014, 15(7), 12764-12777; https://doi.org/10.3390/ijms150712764 - 18 Jul 2014

Cited by 16 | Viewed by 6763

Abstract

This study aimed to investigate the association between POU class5 homeobox 1 pseudogene 1 gene (POU5F1P1) rs10505477 polymorphism and the prognosis of Chinese gastric cancer patients, who received cisplatin-based chemotherapy after surgical resection. POU5F1P1 rs10505477 was genotyped using the SNaPshot method [...] Read more.

This study aimed to investigate the association between POU class5 homeobox 1 pseudogene 1 gene (POU5F1P1) rs10505477 polymorphism and the prognosis of Chinese gastric cancer patients, who received cisplatin-based chemotherapy after surgical resection. POU5F1P1 rs10505477 was genotyped using the SNaPshot method in 944 gastric cancer patients who received gastrectomy. The association of rs10505477 G > A polymorphism with the progression and prognosis in gastric cancer patients was statistically analyzed using the SPSS version 18.0 for Windows. The results reveal that rs10505477 polymorphism has a negatively effect on the overall survival of gastric cancer patients in cisplatin-based chemotherapy subgroup (HR = 1.764, 95% CI = 1.069–2.911, p = 0.023). Our preliminary study indicates for the first time that POU5F1P1 rs10505477 is correlated with survival of gastric cancer patients who receving cisplatin-based chemotherapy after gastrectomy. Further studies are warranted to investigate the mechanism and to verify our results in different populations. Full article

(This article belongs to the Special Issue Molecular Classification of Human Cancer and Its Role in Tailored Cancer Therapy)

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Open AccessArticle

S-(−)-10,11-Dihydroxyfarnesoic Acid Methyl Ester Inhibits Melanin Synthesis in Murine Melanocyte Cells

by Seung-Hwa Baek, Jun-Won Ahn, Sung-Hee Nam, Cheol-Sik Yoon, Jae-Cheon Shin and Sang-Han Lee

Int. J. Mol. Sci. 2014, 15(7), 12750-12763; https://doi.org/10.3390/ijms150712750 - 18 Jul 2014

Cited by 10 | Viewed by 7385

Abstract

The development of antimelanogenic agents is important for the prevention of serious aesthetic problems such as melasmas, freckles, age spots, and chloasmas. In the course of screening for melanin synthesis inhibitors, we found that the culture broth from an insect morphopathogenic fungus, Beauveria [...] Read more.

The development of antimelanogenic agents is important for the prevention of serious aesthetic problems such as melasmas, freckles, age spots, and chloasmas. In the course of screening for melanin synthesis inhibitors, we found that the culture broth from an insect morphopathogenic fungus, Beauveria bassiana CS1029, exhibits potent antimelanogenic activity. We isolated and purified an active metabolite and identified it as S-(−)-10,11-dihydroxyfarnesoic acid methyl ester (dhFAME), an insect juvenile hormone. To address whether dhFAME inhibits melanin synthesis, we first measured the size of the melanin biosynthesis inhibition zone caused by dhFAME. dhFAME also showed inhibitory activity against mushroom tyrosinase in Melan-a cells. Intracellular, dose-dependent tyrosinase inhibition activity was also confirmed by zymography. In addition, we showed that dhFAME strongly inhibits melanin synthesis in Melan-a cells. Furthermore, we compared levels of TYR, TRP-1, TRP-2, MITF, and MC1R mRNA expression by reverse-transcription polymerase chain reaction and showed that treatment of Melan-a cells with 35 μM dhFAME led to an 11-fold decrease in TYR expression, a 6-fold decrease in TRP-2 expression, and a 5-fold decrease in MITF expression. Together, these results indicate that dhFAME is a potent inhibitor of melanin synthesis that can potentially be used for cosmetic biomaterial(s). Full article

(This article belongs to the Special Issue Inhibitors of Melanogenesis Related Processes: Application to Food, Agricultural and Cosmetic Industry-2014)

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Open AccessArticle

A Novel Feature Extraction Scheme with Ensemble Coding for Protein–Protein Interaction Prediction

by Xiuquan Du, Jiaxing Cheng, Tingting Zheng, Zheng Duan and Fulan Qian

Int. J. Mol. Sci. 2014, 15(7), 12731-12749; https://doi.org/10.3390/ijms150712731 - 18 Jul 2014

Cited by 27 | Viewed by 7217

Abstract

Protein–protein interactions (PPIs) play key roles in most cellular processes, such as cell metabolism, immune response, endocrine function, DNA replication, and transcription regulation. PPI prediction is one of the most challenging problems in functional genomics. Although PPI data have been increasing because of [...] Read more.

Protein–protein interactions (PPIs) play key roles in most cellular processes, such as cell metabolism, immune response, endocrine function, DNA replication, and transcription regulation. PPI prediction is one of the most challenging problems in functional genomics. Although PPI data have been increasing because of the development of high-throughput technologies and computational methods, many problems are still far from being solved. In this study, a novel predictor was designed by using the Random Forest (RF) algorithm with the ensemble coding (EC) method. To reduce computational time, a feature selection method (DX) was adopted to rank the features and search the optimal feature combination. The DXEC method integrates many features and physicochemical/biochemical properties to predict PPIs. On the Gold Yeast dataset, the DXEC method achieves 67.2% overall precision, 80.74% recall, and 70.67% accuracy. On the Silver Yeast dataset, the DXEC method achieves 76.93% precision, 77.98% recall, and 77.27% accuracy. On the human dataset, the prediction accuracy reaches 80% for the DXEC-RF method. We extended the experiment to a bigger and more realistic dataset that maintains 50% recall on the Yeast All dataset and 80% recall on the Human All dataset. These results show that the DXEC method is suitable for performing PPI prediction. The prediction service of the DXEC-RF classifier is available at http://ailab.ahu.edu.cn:8087/ DXECPPI/index.jsp. Full article

(This article belongs to the Special Issue Proteins and Protein-Ligand Interactions)

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Study on the Characteristics of Gas Molecular Mean Free Pathin Nanopores by Molecular Dynamics Simulations

by Qixin Liu and Zhiyong Cai

Int. J. Mol. Sci. 2014, 15(7), 12714-12730; https://doi.org/10.3390/ijms150712714 - 18 Jul 2014

Cited by 23 | Viewed by 5949

Abstract

This paper presents studies on the characteristics of gas molecular mean freepath in nanopores by molecular dynamics simulation. Our study results indicate that themean free path of all molecules in nanopores depend on both the radius of the nanoporeand the gas-solid interaction strength. [...] Read more.

This paper presents studies on the characteristics of gas molecular mean freepath in nanopores by molecular dynamics simulation. Our study results indicate that themean free path of all molecules in nanopores depend on both the radius of the nanoporeand the gas-solid interaction strength. Besides mean free path of all molecules in thenanopore, this paper highlights the gas molecular mean free path at different positions ofthe nanopore and the anisotropy of the gas molecular mean free path at nanopores. Themolecular mean free path varies with the molecule’s distance from the center of thenanopore. The least value of the mean free path occurs at the wall surface of the nanopore.The present paper found that the gas molecular mean free path is anisotropic when gas isconfined in nanopores. The radial gas molecular mean free path is much smaller than themean free path including all molecular collisions occuring in three directions. Our studyresults also indicate that when gas is confined in nanopores the gas molecule number densitydoes not affect the gas molecular mean free path in the same way as it does for the gas inunbounded space. These study results may bring new insights into understanding the gasflow’s characteristic at nanoscale. Full article

(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)

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Carnosic Acid Inhibits the Epithelial-Mesenchymal Transition in B16F10 Melanoma Cells: A Possible Mechanism for the Inhibition of Cell Migration

by So Young Park, Hyerim Song, Mi-Kyung Sung, Young-Hee Kang, Ki Won Lee and Jung Han Yoon Park

Int. J. Mol. Sci. 2014, 15(7), 12698-12713; https://doi.org/10.3390/ijms150712698 - 17 Jul 2014

Cited by 40 | Viewed by 7454

Abstract

Carnosic acid is a natural benzenediol abietane diterpene found in rosemary and exhibits anti-inflammatory, antioxidant, and anti-carcinogenic activities. In this study, we evaluated the effects of carnosic acid on the metastatic characteristics of B16F10 melanoma cells. When B16F10 cells were cultured in an [...] Read more.

Carnosic acid is a natural benzenediol abietane diterpene found in rosemary and exhibits anti-inflammatory, antioxidant, and anti-carcinogenic activities. In this study, we evaluated the effects of carnosic acid on the metastatic characteristics of B16F10 melanoma cells. When B16F10 cells were cultured in an in vitro Transwell system, carnosic acid inhibited cell migration in a dose-dependent manner. Carnosic acid suppressed the adhesion of B16F10 cells, as well as the secretion of matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1, urokinase plasminogen activator (uPA), and vascular cell adhesion molecule (VCAM)-1. Interestingly, secretion of TIMP-2 increased significantly in B16F10 cells treated with 10 μmol/L carnosic acid. Additionally, carnosic acid suppressed the mesenchymal markers snail, slug, vimentin, and N-cadherin and induced epithelial marker E-cadherin. Furthermore, carnosic acid suppressed phosphorylation of Src, FAK, and AKT. These results indicate that inhibition of the epithelial-mesenchymal transition may be important for the carnosic acid-induced inhibition of B16F10 cell migration. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Role of EZH2 Polymorphisms in Esophageal Squamous Cell Carcinoma Risk in Han Chinese Population

by Zhen-Bin Ma, Guang-Hong Guo, Qiong Niu and Ning Shi

Int. J. Mol. Sci. 2014, 15(7), 12688-12697; https://doi.org/10.3390/ijms150712688 - 17 Jul 2014

Cited by 10 | Viewed by 5455

Abstract

Gene single nucleotide polymorphisms play a critical role in the development of esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the associations between EZH2 gene polymorphisms and ESCC risk. We undertook a case-control study to analyze three EZH2 [...] Read more.

Gene single nucleotide polymorphisms play a critical role in the development of esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the associations between EZH2 gene polymorphisms and ESCC risk. We undertook a case-control study to analyze three EZH2 polymorphisms (148505302C > T, 2110 + 6A > C and 626 − 394T > C) in an Han Chinese population, by extraction of genomic DNA from the peripheral blood of 476 patients with ESCC and 492 control participants, and performed EZH2 genotyping using DNA sequencing. The obtained results indicated that overall, no statistically significant association was observed in 148505302C > T and 2110 + 6A > C. However, 626 − 394T > C genotype was at increased risk of ESCCs (p = 0.006; odds ratio (OR) = 1.131, CI 95%: 1.034–1.236). Moreover, 626 − 394C/C genotype ESCCs were more significantly common in patients with tumor size of >5 cm than T allele ESCC and in cases of poor differentiation and lower advanced pathological stage. In conclusion, polymorphism in 626 − 394T > C was observed to be associated with susceptibility of ESCC. Nevertheless, further investigation with a larger sample size is needed to support our results. Full article

(This article belongs to the Special Issue Human Single Nucleotide Polymorphisms and Disease Diagnostics)

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Novel and Functional DNA Sequence Variants within the GATA6 Gene Promoter in Ventricular Septal Defects

by Chunyu Li, Xianke Li, Shuchao Pang, Wei Chen, Xianyun Qin, Wenhui Huang, Changqing Zeng and Bo Yan

Int. J. Mol. Sci. 2014, 15(7), 12677-12687; https://doi.org/10.3390/ijms150712677 - 17 Jul 2014

Cited by 15 | Viewed by 6641

Abstract

Congenital heart disease (CHD) is the most common birth defect in humans. Genetic causes and underlying molecular mechanisms for isolated CHD remain largely unknown. Studies have demonstrated that GATA transcription factor 6 (GATA6) plays an essential role in the heart development. [...] Read more.

Congenital heart disease (CHD) is the most common birth defect in humans. Genetic causes and underlying molecular mechanisms for isolated CHD remain largely unknown. Studies have demonstrated that GATA transcription factor 6 (GATA6) plays an essential role in the heart development. Mutations in GATA6 gene have been associated with diverse types of CHD. As GATA6 functions in a dosage-dependent manner, we speculated that changed GATA6 levels, resulting from DNA sequence variants (DSVs) within the gene regulatory regions, may mediate the CHD development. In the present study, GATA6 gene promoter was genetically and functionally analyzed in large groups of patients with ventricular septal defect (VSD) (n = 359) and ethnic-matched healthy controls (n = 365). In total, 11 DSVs, including four SNPs, were identified in VSD patients and controls. Two novel and heterozygous DSVs, g.22169190A>T and g.22169311C>G, were identified in two VSD patients, but in none of controls. In cultured cardiomyocytes, the activities of the GATA6 gene promoter were significantly reduced by the DSVs g.22169190A>T and g.22169311C>G. Therefore, our findings suggested that the DSVs within the GATA6 gene promoter identified in VSD patients may change GATA6 levels, contributing to the VSD development as a risk factor. Full article

(This article belongs to the Special Issue Human Single Nucleotide Polymorphisms and Disease Diagnostics)

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Transforming Growth Factor-β1 (TGF-β1) Induces Mouse Precartilaginous Stem Cell Proliferation through TGF-β Receptor II (TGFRII)-Akt-β-Catenin Signaling

by Li Cheng, Chengyu Zhang, Ding Li, Jian Zou and Junfang Wang

Int. J. Mol. Sci. 2014, 15(7), 12665-12676; https://doi.org/10.3390/ijms150712665 - 17 Jul 2014

Cited by 16 | Viewed by 6627

Abstract

Precartilaginous stem cells (PSCs) could self-renew or differentiate into chondrocytes to promote bone growth. In the current study, we aim to understand the role of transforming growth factor-β1 (TGF-β1) in precartilaginous stem cell (PSC) proliferation, and to study the underlying mechanisms. We successfully [...] Read more.

Precartilaginous stem cells (PSCs) could self-renew or differentiate into chondrocytes to promote bone growth. In the current study, we aim to understand the role of transforming growth factor-β1 (TGF-β1) in precartilaginous stem cell (PSC) proliferation, and to study the underlying mechanisms. We successfully purified and primary-cultured PSCs from the neonate mice’ perichondrial mesenchyme, and their phenotype was confirmed by the PSC marker fibroblast growth factor receptor-3 (FGFR-3) overexpression. We found that TGF-β1 induced Akt-glycogen synthase kinase-3β (GSK3β) phosphorylation and β-catenin nuclear translocation in the mouse PSCs, which was almost blocked by TGF-β receptor-II (TGFRII) shRNA knockdown. Further, perifosine and MK-2206, two Akt-specific inhibitors, suppressed TGF-β1-induced GSK3β phosphorylation and β-catenin nuclear translocation. Akt inhibitors, as well as β-catenin shRNA knockdown largely inhibited TGF-β1-stimulated cyclin D1/c-myc gene transcription and mouse PSC proliferation. Based on these results, we suggest that TGF-β1 induces Akt activation to promote β-catenin nuclear accumulation, which then regulates cyclin D1/c-myc gene transcription to eventually promote mouse PSC proliferation. Full article

(This article belongs to the Section Biochemistry)

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Int. J. Mol. Sci., Volume 15, Issue 7 (July 2014) – 119 articles , Pages 11204-13134

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