International Journal of Molecular Sciences

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Open AccessArticle

Henrin A: A New Anti-HIV Ent-Kaurane Diterpene from Pteris henryi

by Wan-Fei Li, Juan Wang, Jing-Jie Zhang, Xun Song, Chuen-Fai Ku, Juan Zou, Ji-Xin Li, Li-Jun Rong, Lu-Tai Pan and Hong-Jie Zhang

Int. J. Mol. Sci. 2015, 16(11), 27978-27987; https://doi.org/10.3390/ijms161126071 - 24 Nov 2015

Cited by 18 | Viewed by 6772

Abstract

Henrin A (1), a new ent-kaurane diterpene, was isolated from the leaves of Pteris henryi. The chemical structure was elucidated by analysis of the spectroscopic data including one-dimensional (1D) and two-dimensional (2D) NMR spectra, and was further confirmed by [...] Read more.

Henrin A (1), a new ent-kaurane diterpene, was isolated from the leaves of Pteris henryi. The chemical structure was elucidated by analysis of the spectroscopic data including one-dimensional (1D) and two-dimensional (2D) NMR spectra, and was further confirmed by X-ray crystallographic analysis. The compound was evaluated for its biological activities against a panel of cancer cell lines, dental bacterial biofilm formation, and HIV. It displayed anti-HIV potential with an IC₅₀ value of 9.1 µM (SI = 12.2). Full article

(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)

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Open AccessArticle

Effects of Monotypic and Binary Mixtures of Metal Oxide Nanoparticles on Microbial Growth in Sandy Soil Collected from Artificial Recharge Sites

by Kyung-Seok Ko, Kyoochul Ha and In Chul Kong

Int. J. Mol. Sci. 2015, 16(11), 27967-27977; https://doi.org/10.3390/ijms161126066 - 24 Nov 2015

Cited by 7 | Viewed by 5641

Abstract

The potential effects of monotypic and binary metal oxide nanoparticles (NPs, ZnO, NiO, Co₃O₄ and TiO₂) on microbial growth were evaluated in sandy soil collected from artificial recharge sites. Microbial growth was assessed based on adenosine triphosphate (ATP) [...] Read more.

The potential effects of monotypic and binary metal oxide nanoparticles (NPs, ZnO, NiO, Co₃O₄ and TiO₂) on microbial growth were evaluated in sandy soil collected from artificial recharge sites. Microbial growth was assessed based on adenosine triphosphate (ATP) content, dehydrogenase activity (DHA), and viable cell counts (VCC). Microbial growth based on ATP content and VCC showed considerable differences depending on NP type and concentration, whereas DHA did not significantly change. In general, ZnO NPs showed the strongest effect on microbial growth in all measurements, showing an EC₅₀ value of 10.9 mg/L for ATP content. The ranking (EC₅₀) of NPs based on their effect on microbial growth assessed by ATP content and VCC was ZnO > Co₃O₄ > NiO > TiO₂. Upon exposure to binary NP mixtures, synergistic and additive modes of action were observed for ATP content and VCC, respectively. The ranges of observed (P(O)) and expected (P(E)) activity were 83%–92% and 78%–82% of the control (p-value 0.0010) based on ATP content and 78%–95% and 72%–94% of the control (p-value 0.8813) based on VCC under the tested conditions, respectively. The results indicate that the effects of NP mixtures on microbial growth in the sandy soil matrix were as great, or greater, than those of single NPs. Therefore, understanding the effects of single NPs and NP mixtures is essential for proper ecological risk assessment. Additionally, these findings demonstrate that the evaluation of NP effects may be profoundly influenced by the method of microbial growth measurement. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Open AccessArticle

The Deubiquitinase USP17 Regulates the Stability and Nuclear Function of IL-33

by Yingmeng Ni, Lianqin Tao, Chen Chen, Huihui Song, Zhiyuan Li, Yayi Gao, Jia Nie, Miranda Piccioni, Guochao Shi and Bin Li

Int. J. Mol. Sci. 2015, 16(11), 27956-27966; https://doi.org/10.3390/ijms161126063 - 24 Nov 2015

Cited by 39 | Viewed by 6199

Abstract

IL-33 is a new member of the IL-1 family cytokines, which is expressed by different types of immune cells and non-immune cells. IL-33 is constitutively expressed in the nucleus, where it can act as a transcriptional regulator. So far, no direct target for [...] Read more.

IL-33 is a new member of the IL-1 family cytokines, which is expressed by different types of immune cells and non-immune cells. IL-33 is constitutively expressed in the nucleus, where it can act as a transcriptional regulator. So far, no direct target for nuclear IL-33 has been identified, and the regulation of IL-33 nuclear function remains largely unclear. Here, we report that the transcription of type 2 inflammatory cytokine IL-13 is positively regulated by nuclear IL-33. IL-33 can directly bind to the conserved non-coding sequence (CNS) before the translation initiation site in the IL13 gene locus. Moreover, IL-33 nuclear function and stability are regulated by the enzyme ubiquitin-specific protease 17 (USP17) through deubiquitination of IL-33 both at the K48 and at the K63 sites. Our data suggest that IL13 gene transcription can be directly activated by nuclear IL-33, which is negatively regulated by the deubiquitinase USP17. Full article

(This article belongs to the Section Biochemistry)

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MiR542-3p Regulates the Epithelial-Mesenchymal Transition by Directly Targeting BMP7 in NRK52e

by Zhicheng Liu, Yuru Zhou, Yue Yuan, Fang Nie, Rui Peng, Qianyin Li, Zhongshi Lyu, Zhaomin Mao, Liyuan Huang, Li Zhou, Yiman Li, Jing Hao, Dongsheng Ni, Qianni Jin, Yaoshui Long, Pan Ju, Wen Yu, Jianing Liu, Yanxia Hu and Qin Zhou

Int. J. Mol. Sci. 2015, 16(11), 27945-27955; https://doi.org/10.3390/ijms161126075 - 24 Nov 2015

Cited by 9 | Viewed by 6391

Abstract

Accumulating evidence demonstrated that miRNAs are highly involved in kidney fibrosis and Epithelial-Eesenchymal Transition (EMT), however, the mechanisms of miRNAs in kidney fibrosis are poorly understood. In this work, we identified that miR542-3p could promote EMT through down-regulating bone morphogenetic protein 7 (BMP7) [...] Read more.

Accumulating evidence demonstrated that miRNAs are highly involved in kidney fibrosis and Epithelial-Eesenchymal Transition (EMT), however, the mechanisms of miRNAs in kidney fibrosis are poorly understood. In this work, we identified that miR542-3p could promote EMT through down-regulating bone morphogenetic protein 7 (BMP7) expression by targeting BMP7 3′UTR. Firstly, real-time PCR results showed that miR542-3p was significantly up-regulated in kidney fibrosis in vitro and in vivo. Moreover, Western blot results demonstrated that miR542-3p may promote EMT in the NRK52e cell line. In addition, we confirmed that BMP7, which played a crucial role in anti-kidney fibrosis and suppressed the progression of EMT, was a target of miR542-3p through Dual-Luciferase reporter assay, as did Western blot analysis. The effects of miR542-3p on regulating EMT could also be suppressed by transiently overexpressing BMP7 in NRK52e cells. Taken together, miR542-3p may be a critical mediator of the induction of EMT via directly targeting BMP7. Full article

(This article belongs to the Special Issue MicroRNA Regulation)

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Open AccessArticle

Molecular Cloning, Promoter Analysis and Expression Profiles of the sox3 Gene in Japanese Flounder, Paralichthys olivaceus

by Jinning Gao, Peizhen Li, Wei Zhang, Zhigang Wang, Xubo Wang and Quanqi Zhang

Int. J. Mol. Sci. 2015, 16(11), 27931-27944; https://doi.org/10.3390/ijms161126079 - 24 Nov 2015

Cited by 18 | Viewed by 7795

Abstract

Sox3, which belongs to the SoxB1 subgroup, plays major roles in neural and gonadal development. In the present study, Japanese flounder Paralichthys olivaceus sox3 gene (Posox3) and its promoter sequence were isolated and characterized. The deduced PoSox3 protein contained 298 amino [...] Read more.

Sox3, which belongs to the SoxB1 subgroup, plays major roles in neural and gonadal development. In the present study, Japanese flounder Paralichthys olivaceus sox3 gene (Posox3) and its promoter sequence were isolated and characterized. The deduced PoSox3 protein contained 298 amino acids with a characteristic HMG-box domain. Alignment and phylogenetic analyses indicated that PoSox3 shares highly identical sequence with Sox3 homologues from different species. The promoter region of Posox3 has many potential transcription factor (TF) binding sites. The expression profiles of Posox3 in different developmental stages and diverse adult tissues were analyzed by quantitative real-time RT-PCR (qRT-PCR). Posox3 mRNA was maternally inherited, and maintained at a considerably high expression level between the blastula stage and the hatching stage during embryonic development. Posox3 was abundantly expressed in the adult brain and showed sexually dimorphic expression pattern. In situ hybridization (ISH) was carried out to investigate the cellular distribution of Posox3 in the ovary, and results showed the uniform distribution of Posox3 throughout the cytoplasm of oogonia and stage I–III oocytes. These results indicate that Posox3 has potentially vital roles in embryonic and neural development and may be involved in the oogenesis process. Our work provides a fundamental understanding of the structure and potential functions of Sox3 in Paralichthys olivaceus. Full article

(This article belongs to the Special Issue Fish Molecular Biology)

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CREB Negatively Regulates IGF2R Gene Expression and Downstream Pathways to Inhibit Hypoxia-Induced H9c2 Cardiomyoblast Cell Death

by Wei-Kung Chen, Wei-Wen Kuo, Dennis Jine-Yuan Hsieh, Hsin-Nung Chang, Pei-Ying Pai, Kuan-Ho Lin, Lung-Fa Pan, Tsung-Jung Ho, Vijaya Padma Viswanadha and Chih-Yang Huang

Int. J. Mol. Sci. 2015, 16(11), 27921-27930; https://doi.org/10.3390/ijms161126067 - 24 Nov 2015

Cited by 15 | Viewed by 9076

Abstract

During hypoxia, gene expression is altered by various transcription factors. Insulin-like growth factor-II (IGF2) is known to be induced by hypoxia, which binds to IGF2 receptor IGF2R that acts like a G protein-coupled receptor, might cause pathological hypertrophy or activation of the mitochondria-mediated [...] Read more.

During hypoxia, gene expression is altered by various transcription factors. Insulin-like growth factor-II (IGF2) is known to be induced by hypoxia, which binds to IGF2 receptor IGF2R that acts like a G protein-coupled receptor, might cause pathological hypertrophy or activation of the mitochondria-mediated apoptosis pathway. Cyclic adenosine monophosphate (cAMP) responsive element-binding protein (CREB) is central to second messenger-regulated transcription and plays a critical role in the cardiomyocyte survival pathway. In this study, we found that IGF2R level was enhanced in H9c2 cardiomyoblasts exposed to hypoxia in a time-dependent manner but was down-regulated by CREB expression. The over-expression of CREB in H9c2 cardiomyoblasts suppressed the induction of hypoxia-induced IGF2R expression levels and reduced cell apoptosis. Gel shift assay results further indicated that CREB binds to the promoter sequence of IGF2R. With a luciferase assay method, we further observed that CREB represses IGF2R promoter activity. These results suggest that CREB plays an important role in the inhibition of IGF2R expression by binding to the IGF2R promoter and further suppresses H9c2 cardiomyoblast cell apoptosis induced by IGF2R signaling under hypoxic conditions. Full article

(This article belongs to the Special Issue Improvement of Cardiac Function in Heart Failure)

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Open AccessArticle

The kin17 Protein in Murine Melanoma Cells

by Anelise C. Ramos, Vanessa P. Gaspar, Sabrina M. G. Kelmer, Tarciso A. Sellani, Ana G. U. Batista, Quirino A. De Lima Neto, Elaine G. Rodrigues and Maria A. Fernandez

Int. J. Mol. Sci. 2015, 16(11), 27912-27920; https://doi.org/10.3390/ijms161126072 - 24 Nov 2015

Cited by 7 | Viewed by 5226

Abstract

kin17 has been described as a protein involved in the processes of DNA replication initiation, DNA recombination, and DNA repair. kin17 has been studied as a potential molecular marker of breast cancer. This work reports the detection and localization of this protein in [...] Read more.

kin17 has been described as a protein involved in the processes of DNA replication initiation, DNA recombination, and DNA repair. kin17 has been studied as a potential molecular marker of breast cancer. This work reports the detection and localization of this protein in the murine melanoma cell line B16F10-Nex2 and in two derived subclones with different metastatic potential, B16-8HR and B16-10CR. Nuclear and chromatin-associated protein fractions were analyzed, and kin17 was detected in all fractions, with an elevated concentration observed in the chromatin-associated fraction of the clone with low metastatic potential, suggesting that the kin17 expression level could be a marker of melanoma. Full article

(This article belongs to the Section Biochemistry)

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Nucleotide-Induced Conformational Changes in Escherichia coli DnaA Protein Are Required for Bacterial ORC to Pre-RC Conversion at the Chromosomal Origin

by Rahul Saxena, Sona Vasudevan, Digvijay Patil, Norah Ashoura, Julia E. Grimwade and Elliott Crooke

Int. J. Mol. Sci. 2015, 16(11), 27897-27911; https://doi.org/10.3390/ijms161126064 - 24 Nov 2015

Cited by 12 | Viewed by 6275

Abstract

DnaA oligomerizes when bound to origins of chromosomal replication. Structural analysis of a truncated form of DnaA from Aquifex aeolicus has provided insight into crucial conformational differences within the AAA+ domain that are specific to the ATP- versus ADP- bound form of DnaA. [...] Read more.

DnaA oligomerizes when bound to origins of chromosomal replication. Structural analysis of a truncated form of DnaA from Aquifex aeolicus has provided insight into crucial conformational differences within the AAA+ domain that are specific to the ATP- versus ADP- bound form of DnaA. In this study molecular docking of ATP and ADP onto Escherichia coli DnaA, modeled on the crystal structure of Aquifex aeolicus DnaA, reveals changes in the orientation of amino acid residues within or near the vicinity of the nucleotide-binding pocket. Upon limited proteolysis with trypsin or chymotrypsin ADP-DnaA, but not ATP-DnaA generated relatively stable proteolytic fragments of various sizes. Examined sites of limited protease susceptibility that differ between ATP-DnaA and ADP-DnaA largely reside in the amino terminal half of DnaA. The concentration of adenine nucleotide needed to induce conformational changes, as detected by these protease susceptibilities of DnaA, coincides with the conversion of an inactive bacterial origin recognition complex (bORC) to a replication efficient pre-replication complex (pre-RC) at the E. coli chromosomal origin of replication (oriC). Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Gap Junctional Blockade Stochastically Induces Different Species-Specific Head Anatomies in Genetically Wild-Type Girardia dorotocephala Flatworms

by Maya Emmons-Bell, Fallon Durant, Jennifer Hammelman, Nicholas Bessonov, Vitaly Volpert, Junji Morokuma, Kaylinnette Pinet, Dany S. Adams, Alexis Pietak, Daniel Lobo and Michael Levin

Int. J. Mol. Sci. 2015, 16(11), 27865-27896; https://doi.org/10.3390/ijms161126065 - 24 Nov 2015

Cited by 81 | Viewed by 32138

Abstract

The shape of an animal body plan is constructed from protein components encoded by the genome. However, bioelectric networks composed of many cell types have their own intrinsic dynamics, and can drive distinct morphological outcomes during embryogenesis and regeneration. Planarian flatworms are a [...] Read more.

The shape of an animal body plan is constructed from protein components encoded by the genome. However, bioelectric networks composed of many cell types have their own intrinsic dynamics, and can drive distinct morphological outcomes during embryogenesis and regeneration. Planarian flatworms are a popular system for exploring body plan patterning due to their regenerative capacity, but despite considerable molecular information regarding stem cell differentiation and basic axial patterning, very little is known about how distinct head shapes are produced. Here, we show that after decapitation in G. dorotocephala, a transient perturbation of physiological connectivity among cells (using the gap junction blocker octanol) can result in regenerated heads with quite different shapes, stochastically matching other known species of planaria (S. mediterranea, D. japonica, and P. felina). We use morphometric analysis to quantify the ability of physiological network perturbations to induce different species-specific head shapes from the same genome. Moreover, we present a computational agent-based model of cell and physical dynamics during regeneration that quantitatively reproduces the observed shape changes. Morphological alterations induced in a genomically wild-type G. dorotocephala during regeneration include not only the shape of the head but also the morphology of the brain, the characteristic distribution of adult stem cells (neoblasts), and the bioelectric gradients of resting potential within the anterior tissues. Interestingly, the shape change is not permanent; after regeneration is complete, intact animals remodel back to G. dorotocephala-appropriate head shape within several weeks in a secondary phase of remodeling following initial complete regeneration. We present a conceptual model to guide future work to delineate the molecular mechanisms by which bioelectric networks stochastically select among a small set of discrete head morphologies. Taken together, these data and analyses shed light on important physiological modifiers of morphological information in dictating species-specific shape, and reveal them to be a novel instructive input into head patterning in regenerating planaria. Full article

(This article belongs to the Special Issue Molecular and Cellular Basis of Regeneration and Tissue Repair)

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Open AccessArticle

Establishment and Comparison of Two Different Diagnostic Platforms for Detection of DENV1 NS1 Protein

by Yin-Liang Tang, Chien-Yu Chiu, Chun-Yu Lin, Chung-Hao Huang, Yen-Hsu Chen, Raul V. Destura, Day-Yu Chao and Han-Chung Wu

Int. J. Mol. Sci. 2015, 16(11), 27850-27864; https://doi.org/10.3390/ijms161126069 - 24 Nov 2015

Cited by 2 | Viewed by 5716

Abstract

Dengue virus (DENV) infection is currently at pandemic levels, with populations in tropical and subtropical regions at greatest risk of infection. Early diagnosis and management remain the cornerstone for good clinical outcomes, thus efficient and accurate diagnostic technology in the early stage of [...] Read more.

Dengue virus (DENV) infection is currently at pandemic levels, with populations in tropical and subtropical regions at greatest risk of infection. Early diagnosis and management remain the cornerstone for good clinical outcomes, thus efficient and accurate diagnostic technology in the early stage of the disease is urgently needed. Serotype-specific monoclonal antibodies (mAbs) against the DENV1 nonstructural protein 1 (NS1), DA12-4, DA13-2, and DA15-3, which were recently generated using the hybridoma technique, are suitable for use in diagnostic platforms. Immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA) and Western blot analysis further confirmed the serotype specificity of these three monoclonal antibodies. The ELISA-based diagnostic platform was established using the combination of two highly sensitive mAbs (DA15-3 and DB20-6). The same combination was also used for the flow cytometry-based diagnostic platform. We report here the detection limits of flow cytometry-based and ELISA-based diagnostic platforms using these mAbs to be 0.1 and 1 ng/mL, respectively. The collected clinical patient serum samples were also assayed by these two serotyping diagnostic platforms. The sensitivity and specificity for detecting NS1 protein of DENV1 are 90% and 96%, respectively. The accuracy of our platform for testing clinical samples is more advanced than that of the two commercial NS1 diagnostic platforms. In conclusion, our platforms are suitable for the early detection of NS1 protein in DENV1 infected patients. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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Open AccessArticle

Tuning the Phosphoryl Donor Specificity of Dihydroxyacetone Kinase from ATP to Inorganic Polyphosphate. An Insight from Computational Studies

by Israel Sánchez-Moreno, Isabel Bordes, Raquel Castillo, José Javier Ruiz-Pernía, Vicent Moliner and Eduardo García-Junceda

Int. J. Mol. Sci. 2015, 16(11), 27835-27849; https://doi.org/10.3390/ijms161126073 - 24 Nov 2015

Cited by 12 | Viewed by 6994

Abstract

Dihydroxyacetone (DHA) kinase from Citrobacter freundii provides an easy entry for the preparation of DHA phosphate; a very important C3 building block in nature. To modify the phosphoryl donor specificity of this enzyme from ATP to inorganic polyphosphate (poly-P); a directed evolution program [...] Read more.

Dihydroxyacetone (DHA) kinase from Citrobacter freundii provides an easy entry for the preparation of DHA phosphate; a very important C3 building block in nature. To modify the phosphoryl donor specificity of this enzyme from ATP to inorganic polyphosphate (poly-P); a directed evolution program has been initiated. In the first cycle of evolution, the native enzyme was subjected to one round of error-prone PCR (EP-PCR) followed directly (without selection) by a round of DNA shuffling. Although the wild-type DHAK did not show activity with poly-P, after screening, sixteen mutant clones showed an activity with poly-phosphate as phosphoryl donor statistically significant. The most active mutant presented a single mutation (Glu526Lys) located in a flexible loop near of the active center. Interestingly, our theoretical studies, based on molecular dynamics simulations and hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) optimizations, suggest that this mutation has an effect on the binding of the poly-P favoring a more adequate position in the active center for the reaction to take place. Full article

(This article belongs to the Special Issue Molecular Biocatalysis)

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Open AccessReview

Noncoding RNA Expression Aberration Is Associated with Cancer Progression and Is a Potential Biomarker in Esophageal Squamous Cell Carcinoma

by Hidetaka Sugihara, Takatsugu Ishimoto, Keisuke Miyake, Daisuke Izumi, Yoshifumi Baba, Naoya Yoshida, Masayuki Watanabe and Hideo Baba

Int. J. Mol. Sci. 2015, 16(11), 27824-27834; https://doi.org/10.3390/ijms161126060 - 24 Nov 2015

Cited by 52 | Viewed by 7272

Abstract

Esophageal cancer is one of the most common cancers worldwide. Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancer in Eastern Asian countries. Several types of noncoding RNAs (ncRNAs) function as key epigenetic regulators of gene expression and are [...] Read more.

Esophageal cancer is one of the most common cancers worldwide. Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancer in Eastern Asian countries. Several types of noncoding RNAs (ncRNAs) function as key epigenetic regulators of gene expression and are implicated in various physiological processes. Unambiguous evidence indicates that dysregulation of ncRNAs is deeply implicated in carcinogenesis, cancer progression and metastases of various cancers, including ESCC. The current review summarizes recent findings on the ncRNA-mediated mechanisms underlying the characteristic behaviors of ESCC that will help support the development of biomarkers and the design of novel therapeutic strategies. Full article

(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)

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Production of Two Novel Methoxy-Isoflavones from Biotransformation of 8-Hydroxydaidzein by Recombinant Escherichia coli Expressing O-Methyltransferase SpOMT2884 from Streptomyces peucetius

by Chien-Min Chiang, Hsiou-Yu Ding, Ya-Ting Tsai and Te-Sheng Chang

Int. J. Mol. Sci. 2015, 16(11), 27816-27823; https://doi.org/10.3390/ijms161126070 - 24 Nov 2015

Cited by 15 | Viewed by 5950

Abstract

Biotransformation of 8-hydroxydaidzein by recombinant Escherichia coli expressing O-methyltransferase (OMT) SpOMT2884 from Streptomyces peucetius was investigated. Two metabolites were isolated and identified as 7,4′-dihydroxy-8-methoxy-isoflavone (1) and 8,4′-dihydroxy-7-methoxy-isoflavone (2), based on mass, 1H-nuclear magnetic resonance (NMR) and 13C-NMR spectrophotometric [...] Read more.

Biotransformation of 8-hydroxydaidzein by recombinant Escherichia coli expressing O-methyltransferase (OMT) SpOMT2884 from Streptomyces peucetius was investigated. Two metabolites were isolated and identified as 7,4′-dihydroxy-8-methoxy-isoflavone (1) and 8,4′-dihydroxy-7-methoxy-isoflavone (2), based on mass, 1H-nuclear magnetic resonance (NMR) and 13C-NMR spectrophotometric analysis. The maximum production yields of compound (1) and (2) in a 5-L fermenter were 9.3 mg/L and 6.0 mg/L, respectively. The two methoxy-isoflavones showed dose-dependent inhibitory effects on melanogenesis in cultured B16 melanoma cells under non-toxic conditions. Among the effects, compound (1) decreased melanogenesis to 63.5% of the control at 25 μM. This is the first report on the 8-O-methylation activity of OMT toward isoflavones. In addition, the present study also first identified compound (1) with potent melanogenesis inhibitory activity. Full article

(This article belongs to the Special Issue Bioprocess Engineering)

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Open AccessReview

Molecular, Cellular and Functional Effects of Radiation-Induced Brain Injury: A Review

by Sona Balentova and Marian Adamkov

Int. J. Mol. Sci. 2015, 16(11), 27796-27815; https://doi.org/10.3390/ijms161126068 - 24 Nov 2015

Cited by 128 | Viewed by 8962

Abstract

Radiation therapy is the most effective non-surgical treatment of primary brain tumors and metastases. Preclinical studies have provided valuable insights into pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced brain injury can damage neuronal, glial and vascular compartments of the brain [...] Read more.

Radiation therapy is the most effective non-surgical treatment of primary brain tumors and metastases. Preclinical studies have provided valuable insights into pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced brain injury can damage neuronal, glial and vascular compartments of the brain and may lead to molecular, cellular and functional changes. Given its central role in memory and adult neurogenesis, the majority of studies have focused on the hippocampus. These findings suggested that hippocampal avoidance in cranial radiotherapy prevents radiation-induced cognitive impairment of patients. However, multiple rodent studies have shown that this problem is more complex. As the radiation-induced cognitive impairment reflects hippocampal and non-hippocampal compartments, it is of critical importance to investigate molecular, cellular and functional modifications in various brain regions as well as their integration at clinically relevant doses and schedules. We here provide a literature overview, including our previously published results, in order to support the translation of preclinical findings to clinical practice, and improve the physical and mental status of patients with brain tumors. Full article

(This article belongs to the Collection Radiation Toxicity in Cells)

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Epigenetic Repression of miR-218 Promotes Esophageal Carcinogenesis by Targeting ROBO1

by Miao Yang, Ran Liu, Xiajun Li, Juan Liao, Yuepu Pu, Enchun Pan, Yi Wang and Lihong Yin

Int. J. Mol. Sci. 2015, 16(11), 27781-27795; https://doi.org/10.3390/ijms161126062 - 20 Nov 2015

Cited by 15 | Viewed by 5495

Abstract

miR-218, consisting of miR-218-1 at 4p15.31 and miR-218-2 at 5q35.1, was significantly decreased in esophageal squamous cell carcinoma (ESCC) in our previous study. The aim of this study was to determine whether aberrant methylation is associated with miR-218 repression. Bisulfite sequencing analysis (BSP), [...] Read more.

miR-218, consisting of miR-218-1 at 4p15.31 and miR-218-2 at 5q35.1, was significantly decreased in esophageal squamous cell carcinoma (ESCC) in our previous study. The aim of this study was to determine whether aberrant methylation is associated with miR-218 repression. Bisulfite sequencing analysis (BSP), methylation specific PCR (MSP), and 5-aza-2′-deoxycytidine treatment assay were applied to determine the methyaltion status of miR-218 in cells and clinical samples. In vitro assays were performed to explore the role of miR-218. Results showed that miR-218-1 was significantly CpG hypermethylated in tumor tissues (81%, 34/42) compared with paired non-tumor tissues (33%, 14/42) (p < 0.05). However, no statistical difference was found in miR-218-2. Accordingly, expression of miR-218 was negatively correlated with miR-218-1 methylation status (p < 0.05). After demethylation treatment by 5-aza-2′-deoxycytidine, there was a 2.53- and 2.40-fold increase of miR-218 expression in EC109 and EC9706, respectively. miR-218 suppressed cell proliferation and arrested cells at G1 phase by targeting 3′ untranslated region (3′UTR) of roundabout guidance receptor 1 (ROBO1). A negative correlation was found between miR-218 and ROBO1 mRNA expression in clinical samples. In conclusion, our results support that aberrant CpG hypermethylation at least partly accounts for miR-218 silencing in ESCC, which impairs its tumor-suppressive function. Full article

(This article belongs to the Section Molecular Toxicology)

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Open AccessReview

Redox Roles of Reactive Oxygen Species in Cardiovascular Diseases

by Feng He and Li Zuo

Int. J. Mol. Sci. 2015, 16(11), 27770-27780; https://doi.org/10.3390/ijms161126059 - 20 Nov 2015

Cited by 191 | Viewed by 11335

Abstract

Cardiovascular disease (CVD), a major cause of mortality in the world, has been extensively studied over the past decade. However, the exact mechanism underlying its pathogenesis has not been fully elucidated. Reactive oxygen species (ROS) play a pivotal role in the progression of [...] Read more.

Cardiovascular disease (CVD), a major cause of mortality in the world, has been extensively studied over the past decade. However, the exact mechanism underlying its pathogenesis has not been fully elucidated. Reactive oxygen species (ROS) play a pivotal role in the progression of CVD. Particularly, ROS are commonly engaged in developing typical characteristics of atherosclerosis, one of the dominant CVDs. This review will discuss the involvement of ROS in atherosclerosis, specifically their effect on inflammation, disturbed blood flow and arterial wall remodeling. Pharmacological interventions target ROS in order to alleviate oxidative stress and CVD symptoms, yet results are varied due to the paradoxical role of ROS in CVD. Lack of effectiveness in clinical trials suggests that understanding the exact role of ROS in the pathophysiology of CVD and developing novel treatments, such as antioxidant gene therapy and nanotechnology-related antioxidant delivery, could provide a therapeutic advance in treating CVDs. While genetic therapies focusing on specific antioxidant expression seem promising in CVD treatments, multiple technological challenges exist precluding its immediate clinical applications. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)

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Resveratrol Protects against Helicobacter pylori-Associated Gastritis by Combating Oxidative Stress

by Xiaolin Zhang, Anmin Jiang, Banghua Qi, Zhongyou Ma, Youyi Xiong, Jinfeng Dou and Jianfei Wang

Int. J. Mol. Sci. 2015, 16(11), 27757-27769; https://doi.org/10.3390/ijms161126061 - 20 Nov 2015

Cited by 59 | Viewed by 7811

Abstract

Helicobacter pylori (H. pylori)-induced oxidative stress has been shown to play a very important role in the inflammation of the gastric mucosa and increases the risk of developing gastric cancer. Resveratrol has many biological functions and activities, including antioxidant and anti-inflammatory [...] Read more.

Helicobacter pylori (H. pylori)-induced oxidative stress has been shown to play a very important role in the inflammation of the gastric mucosa and increases the risk of developing gastric cancer. Resveratrol has many biological functions and activities, including antioxidant and anti-inflammatory effect. The purpose of this study was to probe whether resveratrol inhibits H. pylori-induced gastric inflammation and to elucidate the underlying mechanisms of any effect in mice. A mouse model of H. pylori infection was established via oral inoculation with H. pylori. After one week, mice were administered resveratrol (100 mg/kg body weight/day) orally for six weeks. The mRNA and protein levels of iNOS and IL-8 were assessed using RT-PCR, Western blot and ELISA. The expression levels of IκBα and phosphorylated IκBα (which embodies the level and activation of NF-κB), Heme Oxygenase-1 (HO-1; a potent antioxidant enzyme) and nuclear factor-erythroid 2 related factor 2 (Nrf2) were determined using Western blot, and lipid peroxide (LPO) level and myeloperoxidase (MPO) activity were examined using an MPO colorimetric activity assay, thiobarbituric acid reaction, and histological-grade using HE staining of the gastric mucosa. The results showed that resveratrol improved the histological infiltration score and decreased LPO level and MPO activity in the gastric mucosa. Resveratrol down-regulated the H. pylori-induced mRNA transcription and protein expression levels of IL-8 and iNOS, suppressed H. pylori-induced phosphorylation of IκBα, and increased the levels of HO-1 and Nrf2. In conclusion, resveratrol treatment exerted significant effects against oxidative stress and inflammation in H. pylori-infected mucosa through the suppression of IL-8, iNOS, and NF-κB, and moreover through the activation of the Nrf2/HO-1 pathway. Full article

(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention)

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Open AccessArticle

Inhibitory Effect of Gardenoside on Free Fatty Acid-Induced Steatosis in HepG2 Hepatocytes

by Huiqing Liang, Limin Zhang, Hongguo Wang, Jinmo Tang, Jiaen Yang, Chuncheng Wu and Shaodong Chen

Int. J. Mol. Sci. 2015, 16(11), 27749-27756; https://doi.org/10.3390/ijms161126058 - 20 Nov 2015

Cited by 38 | Viewed by 7459

Abstract

Gardenoside is one of the most important effective extractions of a herb for its hepatoprotective properties. The aim of this study was to address the mechanism of Gardenoside on HepG2 cellular steatosis induced by free fatty acids (FFAs). The model of HepG2 steatosis [...] Read more.

Gardenoside is one of the most important effective extractions of a herb for its hepatoprotective properties. The aim of this study was to address the mechanism of Gardenoside on HepG2 cellular steatosis induced by free fatty acids (FFAs). The model of HepG2 steatosis was duplicated by oleic and palmitic acid at the proportion of 2:1 (FFAs mixture) for 24 h, then lipid toxicity was induced. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) were used to detect cell viability and Oil Red O staining method was used to judge the lipid accumulation respectively. Inflammatory cytokines TNF-α, IL-1β, IL-6 and intracellular NFκB were measured after 24 h. The steatosis was significantly decreased after Gardenoside treatment without cytotoxicity. TNF-α, IL-1β, IL-6 were modulated to HepG2 cells by treatment of Gardenoside. In the meantime, the activation of NFκB was inhibited by Gardenoside. Gardenoside has a protective effect on FFA-induced cellular steatosis in HepG2 cells which indicates that Gardenoside might be a potential therapeutic herb against NASH by suppressed supernatant inflammatory cytokine production and intracellular NFkB activity. Full article

(This article belongs to the Section Biochemistry)

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Open AccessCommunication

Metabolite Profile of Cervicovaginal Fluids from Early Pregnancy Is Not Predictive of Spontaneous Preterm Birth

by Melinda M. Thomas, Karolina Sulek, Elizabeth J. McKenzie, Beatrix Jones, Ting-Li Han, Silas G. Villas-Boas, Louise C. Kenny, Lesley M. E. McCowan and Philip N. Baker

Int. J. Mol. Sci. 2015, 16(11), 27741-27748; https://doi.org/10.3390/ijms161126052 - 19 Nov 2015

Cited by 17 | Viewed by 6063

Abstract

In our study, we used a mass spectrometry-based metabolomic approach to search for biomarkers that may act as early indicators of spontaneous preterm birth (sPTB). Samples were selected as a nested case-control study from the Screening for Pregnancy Endpoints (SCOPE) biobank in Auckland, [...] Read more.

In our study, we used a mass spectrometry-based metabolomic approach to search for biomarkers that may act as early indicators of spontaneous preterm birth (sPTB). Samples were selected as a nested case-control study from the Screening for Pregnancy Endpoints (SCOPE) biobank in Auckland, New Zealand. Cervicovaginal swabs were collected at 20 weeks from women who were originally assessed as being at low risk of sPTB. Samples were analysed using gas chromatography-mass spectrometry (GC-MS). Despite the low amount of biomass (16–23 mg), 112 compounds were detected. Statistical analysis showed no significant correlations with sPTB. Comparison of reported infection and plasma inflammatory markers from early pregnancy showed two inflammatory markers were correlated with reported infection, but no correlation with any compounds in the metabolite profile was observed. We hypothesise that the lack of biomarkers of sPTB in the cervicovaginal fluid metabolome is simply because it lacks such markers in early pregnancy. We propose alternative biofluids be investigated for markers of sPTB. Our results lead us to call for greater scrutiny of previously published metabolomic data relating to biomarkers of sPTB in cervicovaginal fluids, as the use of small, high risk, or late pregnancy cohorts may identify metabolite biomarkers that are irrelevant for predicting risk in normal populations. Full article

(This article belongs to the Special Issue Prediction, Diagnostics and Prevention of Pregnancy Complications)

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Open AccessArticle

Biodistribution, Stability, and Blood Distribution of the Cell Penetrating Peptide Maurocalcine in Mice

by Pascale Perret, Mitra Ahmadi, Laurent Riou, Sandrine Bacot, Julien Pecher, Cathy Poillot, Alexis Broisat, Catherine Ghezzi and Michel De Waard

Int. J. Mol. Sci. 2015, 16(11), 27730-27740; https://doi.org/10.3390/ijms161126054 - 19 Nov 2015

Cited by 14 | Viewed by 5544

Abstract

Maurocalcine (MCa) is the first natural cell penetrating peptide to be discovered in animal venom. In addition to the fact that it represents a potent vector for the cell penetration of structurally diverse therapeutic compounds, MCa also displays several distinguishing features that make [...] Read more.

Maurocalcine (MCa) is the first natural cell penetrating peptide to be discovered in animal venom. In addition to the fact that it represents a potent vector for the cell penetration of structurally diverse therapeutic compounds, MCa also displays several distinguishing features that make it a potential peptide of choice for clinical and biotechnological applications. The aim of the present study was to gain new information about the properties of MCa in vivo in order to delineate the future potential applications of this vector. For this purpose, two analogues of this peptide with (Tyr-MCa) and without (Lin-Tyr-MCa) disulfide bridges were synthesized, radiolabeled with ¹²⁵I, and their in vitro stabilities were first evaluated in mouse blood. The results indicated that ¹²⁵I-Tyr-MCa was stable in vitro and that the disulfide bridges conferred a competitive advantage for the stability of peptide. Following in vivo injection in mice, ¹²⁵I-Tyr-MCa targeted peripheral organs with interesting quantitative differences and the main route of peptide elimination was renal. Full article

(This article belongs to the Special Issue Cell-Penetrating Peptides)

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Open AccessArticle

Safety Profile of TiO₂-Based Photocatalytic Nanofabrics for Indoor Formaldehyde Degradation

by Guixin Cui, Yan Xin, Xin Jiang, Mengqi Dong, Junling Li, Peng Wang, Shumei Zhai, Yongchun Dong, Jianbo Jia and Bing Yan

Int. J. Mol. Sci. 2015, 16(11), 27721-27729; https://doi.org/10.3390/ijms161126055 - 19 Nov 2015

Cited by 14 | Viewed by 6624

Abstract

Anatase TiO₂ nanoparticles (TNPs) are synthesized using the sol-gel method and loaded onto the surface of polyester-cotton (65/35) fabrics. The nanofabrics degrade formaldehyde at an efficiency of 77% in eight hours with visible light irradiation or 97% with UV light. The loaded [...] Read more.

Anatase TiO₂ nanoparticles (TNPs) are synthesized using the sol-gel method and loaded onto the surface of polyester-cotton (65/35) fabrics. The nanofabrics degrade formaldehyde at an efficiency of 77% in eight hours with visible light irradiation or 97% with UV light. The loaded TNPs display very little release from nanofabrics (~0.0%) during a standard fastness to rubbing test. Assuming TNPs may fall off nanofabrics during their life cycles, we also examine the possible toxicity of TNPs to human cells. We found that up to a concentration of 220 μg/mL, they do not affect viability of human acute monocytic leukemia cell line THP-1 macrophages and human liver and kidney cells. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Open AccessArticle

The Role of Porphyrin-Free-Base in the Electronic Structures and Related Properties of N-Fused Carbazole-Zinc Porphyrin Dye Sensitizers

by Xing-Yu Li, Cai-Rong Zhang, You-Zhi Wu, Hai-Min Zhang, Wei Wang, Li-Hua Yuan, Hua Yang, Zi-Jiang Liu and Hong-Shan Chen

Int. J. Mol. Sci. 2015, 16(11), 27707-27720; https://doi.org/10.3390/ijms161126057 - 19 Nov 2015

Cited by 22 | Viewed by 5457

Abstract

Dye sensitizers can significantly affect power conversion efficiency of dye-sensitized solar cells (DSSCs). Porphyrin-based dyes are promising sensitizers due to their performances in DSSCs. Here, based upon a N-fused carbazole-zinc porphyrin-free-base porphyrin triad containing an ethynyl-linkage (coded as DTBC), the novel porphyrin dyes [...] Read more.

Dye sensitizers can significantly affect power conversion efficiency of dye-sensitized solar cells (DSSCs). Porphyrin-based dyes are promising sensitizers due to their performances in DSSCs. Here, based upon a N-fused carbazole-zinc porphyrin-free-base porphyrin triad containing an ethynyl-linkage (coded as DTBC), the novel porphyrin dyes named DTBC-MP and DTBC-TP were designed by varying the porphyrin-free-base units in the π conjugation of DTBC in order to study the effect of porphyrin-free-base in the modification of electronic structures and related properties. The calculated results indicate that, the extension of the conjugate bridge with the porphyrin-free-base unit results in elevation of the highest occupied molecular orbital (HOMO) energies, decrease of the lowest unoccupied molecular orbital (LUMO) energies, reduction of the HOMO-LUMO gap, red-shift of the absorption bands, and enhancement of the absorbance. The free energy changes demonstrate that introducing more porphyrin-free-base units in the conjugate bridge induces a faster rate of electron injection. The transition properties and molecular orbital characters suggest that the different transition properties might lead to a different electron injection mechanism. In terms of electronic structure, absorption spectra, light harvesting capability, and free energy changes, the designed DTBC-TP is a promising candidate dye sensitizer for DSSCs. Full article

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

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Open AccessReview

Multi-Functional Macromers for Hydrogel Design in Biomedical Engineering and Regenerative Medicine

by Michael C. Hacker and Hafiz Awais Nawaz

Int. J. Mol. Sci. 2015, 16(11), 27677-27706; https://doi.org/10.3390/ijms161126056 - 19 Nov 2015

Cited by 41 | Viewed by 11159

Abstract

Contemporary biomaterials are expected to provide tailored mechanical, biological and structural cues to encapsulated or invading cells in regenerative applications. In addition, the degradative properties of the material also have to be adjustable to the desired application. Oligo- or polymeric building blocks that [...] Read more.

Contemporary biomaterials are expected to provide tailored mechanical, biological and structural cues to encapsulated or invading cells in regenerative applications. In addition, the degradative properties of the material also have to be adjustable to the desired application. Oligo- or polymeric building blocks that can be further cross-linked into hydrogel networks, here addressed as macromers, appear as the prime option to assemble gels with the necessary degrees of freedom in the adjustment of the mentioned key parameters. Recent developments in the design of multi-functional macromers with two or more chemically different types of functionalities are summarized and discussed in this review illustrating recent trends in the development of advanced hydrogel building blocks for regenerative applications. Full article

(This article belongs to the Special Issue Artificial Organs)

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Application of Wnt Pathway Inhibitor Delivering Scaffold for Inhibiting Fibrosis in Urethra Strictures: In Vitro and in Vivo Study

by Kaile Zhang, Xuran Guo, Weixin Zhao, Guoguang Niu, Xiumei Mo and Qiang Fu

Int. J. Mol. Sci. 2015, 16(11), 27659-27676; https://doi.org/10.3390/ijms161126050 - 19 Nov 2015

Cited by 51 | Viewed by 7222

Abstract

Objective: To evaluate the mechanical property and biocompatibility of the Wnt pathway inhibitor (ICG-001) delivering collagen/poly(l-lactide-co-caprolactone) (P(LLA-CL)) scaffold for urethroplasty, and also the feasibility of inhibiting the extracellular matrix (ECM) expression in vitro and in vivo. Methods: ICG-001 (1 mg [...] Read more.

Objective: To evaluate the mechanical property and biocompatibility of the Wnt pathway inhibitor (ICG-001) delivering collagen/poly(l-lactide-co-caprolactone) (P(LLA-CL)) scaffold for urethroplasty, and also the feasibility of inhibiting the extracellular matrix (ECM) expression in vitro and in vivo. Methods: ICG-001 (1 mg (2 mM)) was loaded into a (P(LLA-CL)) scaffold with the co-axial electrospinning technique. The characteristics of the mechanical property and drug release fashion of scaffolds were tested with a mechanical testing machine (Instron) and high-performance liquid chromatography (HPLC). Rabbit bladder epithelial cells and the dermal fibroblasts were isolated by enzymatic digestion method. (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay) and scanning electron microscopy (SEM) were used to evaluate the viability and proliferation of the cells on the scaffolds. Fibrolasts treated with TGF-β1 and ICG-001 released medium from scaffolds were used to evaluate the anti-fibrosis effect through immunofluorescence, real time PCR and western blot. Urethrography and histology were used to evaluate the efficacy of urethral implantation. Results: The scaffold delivering ICG-001 was fabricated, the fiber diameter and mechanical strength of scaffolds with inhibitor were comparable with the non-drug scaffold. The SEM and MTT assay showed no toxic effect of ICG-001 to the proliferation of epithelial cells on the collagen/P(LLA-CL) scaffold with ICG-001. After treatment with culture medium released from the drug-delivering scaffold, the expression of Collagen type 1, 3 and fibronectin of fibroblasts could be inhibited significantly at the mRNA and protein levels. In the results of urethrography, urethral strictures and fistulas were found in the rabbits treated with non-ICG-001 delivering scaffolds, but all the rabbits treated with ICG-001-delivering scaffolds showed wide caliber in urethras. Histology results showed less collagen but more smooth muscle and thicker epithelium in urethras repaired with ICG-001 delivering scaffolds. Conclusion: After loading with the Wnt signal pathway inhibitor ICG-001, the Collagen/P(LLA-CL) scaffold could facilitate a decrease in the ECM deposition of fibroblasts. The ICG-001 delivering Collagen/P(LLA-CL) nanofibrous scaffold seeded with epithelial cells has the potential to be a promising substitute material for urethroplasty. Longer follow-up study in larger animals is needed in the future. Full article

(This article belongs to the Special Issue Biomaterials for Tissue Engineering)

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Leptin Promotes cPLA₂ Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade

by Pei-Sung Hsu, Chi-Sheng Wu, Jia-Feng Chang and Wei-Ning Lin

Int. J. Mol. Sci. 2015, 16(11), 27640-27658; https://doi.org/10.3390/ijms161126045 - 18 Nov 2015

Cited by 17 | Viewed by 6151

Abstract

Hyperplasia or hypertrophy of adipose tissues plays a crucial role in obesity, which is accompanied by the release of leptin. Recently, obesity was determined to be associated with various pulmonary diseases including asthma, acute lung injury, and chronic obstructive pulmonary disease. However, how [...] Read more.

Hyperplasia or hypertrophy of adipose tissues plays a crucial role in obesity, which is accompanied by the release of leptin. Recently, obesity was determined to be associated with various pulmonary diseases including asthma, acute lung injury, and chronic obstructive pulmonary disease. However, how obesity contributes to pulmonary diseases and whether leptin directly regulates lung inflammation remains unclear. We used cell and animal models to study the mechanisms of leptin mediation of pulmonary inflammation. We found that leptin activated de novo synthesis of cytosolic phospholipase A₂-α (cPLA₂-α) in vitro in the lung alveolar type II cells, A549, and in vivo in ICR mice. Upregulated cPLA₂-α protein was attenuated by pretreatment with an OB-R blocking antibody, U0126, SB202190, SP600125, Bay11-7086, garcinol, and p300 siRNA, suggesting roles of p42/p44 MAPK, p38 MAPK, JNK1/2, NF-κB, and p300 in leptin effects. Leptin enhanced the activities of p42/p44 MAPK, p38 MAPK, JNK1/2, and p65 NF-κB in a time-dependent manner. Additional studies have suggested the participation of OB-R, p42/p44 MAPK, and JNK1/2 in leptin-increased p65 phosphorylation. Furthermore, p300 phosphorylation and histone H4 acetylation were reduced by blockage of OB-R, p42/p44 MAPK, p38 MAPK, JNK1/2, and NF-κB in leptin-stimulated cells. Similarly, blockage of the MAPKs/NF-κB/p300 cascade significantly inhibited leptin-mediated cPLA₂-α mRNA expression. Our data as a whole showed that leptin contributed to lung cPLA₂-α expression through OB-R-dependent activation of the MAPKs/NF-κB/p300 cascade. Full article

(This article belongs to the Special Issue Molecular Research on Obesity and Diabetes)

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Gold-Coated Superparamagnetic Nanoparticles for Single Methyl Discrimination in DNA Aptamers

by Maria Tintoré, Stefania Mazzini, Laura Polito, Marcello Marelli, Alfonso Latorre, Álvaro Somoza, Anna Aviñó, Carme Fàbrega and Ramon Eritja

Int. J. Mol. Sci. 2015, 16(11), 27625-27639; https://doi.org/10.3390/ijms161126046 - 18 Nov 2015

Cited by 13 | Viewed by 7348

Abstract

Au- and iron-based magnetic nanoparticles (NPs) are promising NPs for biomedical applications due to their unique properties. The combination of a gold coating over a magnetic core puts together the benefits from adding the magnetic properties to the robust chemistry provided by the [...] Read more.

Au- and iron-based magnetic nanoparticles (NPs) are promising NPs for biomedical applications due to their unique properties. The combination of a gold coating over a magnetic core puts together the benefits from adding the magnetic properties to the robust chemistry provided by the thiol functionalization of gold. Here, the use of Au-coated magnetic NPs for molecular detection of a single methylation in DNA aptamer is described. Binding of α-thrombin to two aptamers conjugated to these NPs causes aggregation, a phenomenon that can be observed by UV, DLS and MRI. These techniques discriminate a single methylation in one of the aptamers, preventing aggregation due to the inability of α-thrombin to recognize it. A parallel study with gold and ferromagnetic NPs is detailed, concluding that the Au coating of Fe_xO_y NP does not affect their performance and that they are suitable as complex biosensors. These results prove the high detection potency of Au-coated SPIONs for biomedical applications especially for DNA repair detection. Full article

(This article belongs to the Special Issue Magnetic Nanoparticles 2015)

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Open AccessArticle

Leptin Genes in Blunt Snout Bream: Cloning, Phylogeny and Expression Correlated to Gonads Development

by Honghao Zhao, Cong Zeng, Shaokui Yi, Shiming Wan, Boxiang Chen and Zexia Gao

Int. J. Mol. Sci. 2015, 16(11), 27609-27624; https://doi.org/10.3390/ijms161126044 - 18 Nov 2015

Cited by 17 | Viewed by 6479

Abstract

To investigate the leptin related genes expression patterns and their possible function during the gonadal development in fish, the cDNA and genomic sequences of leptin, leptin receptor (leptinR), and leptin receptor overlapping transcript like-1 (leprotl1) were cloned and [...] Read more.

To investigate the leptin related genes expression patterns and their possible function during the gonadal development in fish, the cDNA and genomic sequences of leptin, leptin receptor (leptinR), and leptin receptor overlapping transcript like-1 (leprotl1) were cloned and their expression levels were quantified in the different gonadal development stages of Megalobrama amblycephala. The results showed that the full length cDNA sequences of leptin, leptinR and leprotl1 were 953, 3432 and 1676 bp, coding 168, 1082, and 131 amino acid polypeptides, and the genomic sequences were 1836, 28,528 and 5480 bp, which respectively had 3, 15 and 4 exons, respectively. The phylogenetic analysis revealed that three genes were relatively conserved in fish species. Quantitative real-time PCR results showed that the three genes were ubiquitously expressed in all examined tissues during the different gonadal development stages. The leptin and leptinR took part in the onset of puberty, especially in female M. amblycephala, by increasing the expression levels in brain during the stage I to III of ovary. The expression levels of leptin and leptinR had significant differences between male and female in hypothalamic-pituitary-gonadal (HPG) axis tissues (p < 0.05). The leptinR had the same variation tendency with leptin, but the opposite changes of expression levels were found in leprotl1, which may resist the expression of leptinR for inhibiting the function of leptin in target organ. These findings revealed details about the possible role of these genes in regulating gonadal maturation in fish species. Full article

(This article belongs to the Special Issue Fish Molecular Biology)

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Open AccessArticle

A Critical Role for Cysteine 57 in the Biological Functions of Selenium Binding Protein-1

by Qi Ying, Emmanuel Ansong, Alan M. Diamond and Wancai Yang

Int. J. Mol. Sci. 2015, 16(11), 27599-27608; https://doi.org/10.3390/ijms161126043 - 18 Nov 2015

Cited by 9 | Viewed by 5425

Abstract

The concentration of selenium-binding protein1 (SBP1) is often lower in tumors than in the corresponding tissue and lower levels have been associated with poor clinical outcomes. SBP1 binds tightly selenium although what role selenium plays in its biological functions remains unknown. Previous studies [...] Read more.

The concentration of selenium-binding protein1 (SBP1) is often lower in tumors than in the corresponding tissue and lower levels have been associated with poor clinical outcomes. SBP1 binds tightly selenium although what role selenium plays in its biological functions remains unknown. Previous studies indicated that cysteine 57 is the most likely candidate amino acid for selenium binding. In order to investigate the role of cysteine 57 in SBP1, this amino acid was altered to a glycine and the mutated protein was expressed in human cancer cells. The SBP1 half-life, as well as the cellular response to selenite cytotoxicity, was altered by this change. The ectopic expression of SBP1^GLY also caused mitochondrial damage in HCT116 cells. Taken together, these results indicated that cysteine 57 is a critical determinant of SBP1 function and may play a significant role in mitochondrial function. Full article

(This article belongs to the Section Bioinorganic Chemistry)

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Brazilein Suppresses Inflammation through Inactivation of IRAK4-NF-κB Pathway in LPS-Induced Raw264.7 Macrophage Cells

by Kui-Jin Kim, Kye-Yoon Yoon, Hyung-Sun Yoon, Sei-Ryang Oh and Boo-Yong Lee

Int. J. Mol. Sci. 2015, 16(11), 27589-27598; https://doi.org/10.3390/ijms161126048 - 18 Nov 2015

Cited by 25 | Viewed by 7640

Abstract

The medicinal herbal plant has been commonly used for prevention and intervention of disease and health promotions worldwide. Brazilein is a bioactive compound extracted from Caesalpinia sappan Linn. Several studies have showed that brazilein exhibited the immune suppressive effect and anti-oxidative function. However, [...] Read more.

The medicinal herbal plant has been commonly used for prevention and intervention of disease and health promotions worldwide. Brazilein is a bioactive compound extracted from Caesalpinia sappan Linn. Several studies have showed that brazilein exhibited the immune suppressive effect and anti-oxidative function. However, the molecular targets of brazilein for inflammation prevention have remained elusive. Here, we investigated the mechanism underlying the inhibitory effect of brazilein on LPS-induced inflammatory response in Raw264.7 macrophage cells. We demonstrated that brazilein decreased the expression of IRAK4 protein led to the suppression of MAPK signaling and IKKβ, and subsequent inactivation of NF-κB and COX2 thus promoting the expression of the downstream target pro-inflammatory cytokines such as IL-1β, MCP-1, MIP-2, and IL-6 in LPS-induced Raw264.7 macrophage cells. Moreover, we observed that brazilein reduced the production of nitrite compared to the control in LPS-induced Raw264.7. Thus, we suggest that brazilein might be a useful bioactive compound for the prevention of IRAK-NF-κB pathway associated chronic diseases. Full article

(This article belongs to the Special Issue Advances in Molecular Research of Functional and Nutraceutical Food)

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Borneol Depresses P-Glycoprotein Function by a NF-κB Signaling Mediated Mechanism in a Blood Brain Barrier in Vitro Model

by Xiang Fan, Lijuan Chai, Han Zhang, Yuefei Wang, Boli Zhang and Xiumei Gao

Int. J. Mol. Sci. 2015, 16(11), 27576-27588; https://doi.org/10.3390/ijms161126051 - 18 Nov 2015

Cited by 70 | Viewed by 7849

Abstract

P-glycoprotein (P-gp) on brain microvascular endothelial cells (BMECs) that form the blood brain barrier (BBB), influences transportation of substances between blood and brain. The objective of this study was to characterize the effects of borneol on P-gp efflux function on BBB and explore [...] Read more.

P-glycoprotein (P-gp) on brain microvascular endothelial cells (BMECs) that form the blood brain barrier (BBB), influences transportation of substances between blood and brain. The objective of this study was to characterize the effects of borneol on P-gp efflux function on BBB and explore the potential mechanisms. We established an in vitro BBB model comprised of rat BMECs and astrocytes to measure the effects of borneol on the known P-gp substrates transport across BBB, and examined the function and expression of P-gp in BMECs and the signaling pathways regulating P-gp expression. Borneol increased intracellular accumulation of Rhodamine 123, enhanced verapamil and digoxin across the BBB in vitro model, and depressed mdr1a mRNA and P-gp expression. Borneol could activate nuclear factor-κB (NF-κB) and inhibition of NF-κB with MG132 (carbobenzoxy-Leu-Leu-leucinal) and SN50 (an inhibitory peptide) obscuring the P-gp decreases induced by borneol. These data suggested that borneol depresses P-gp function in BMECs by a NF-κB signaling medicated mechanism in a BBB in vitro model. Full article

(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention)

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