International Journal of Molecular Sciences

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Open AccessArticle

Piperlongumine Suppresses Proliferation of Human Oral Squamous Cell Carcinoma through Cell Cycle Arrest, Apoptosis and Senescence

by San-Yuan Chen, Geng-Hung Liu, Wen-Ying Chao, Chung-Sheng Shi, Ching-Yen Lin, Yun-Ping Lim, Chieh-Hsiang Lu, Peng-Yeh Lai, Hau-Ren Chen and Ying-Ray Lee

Int. J. Mol. Sci. 2016, 17(4), 616; https://doi.org/10.3390/ijms17040616 - 23 Apr 2016

Cited by 33 | Viewed by 6634

Abstract

Oral squamous cell carcinoma (OSCC), an aggressive cancer originating in the oral cavity, is one of the leading causes of cancer deaths in males worldwide. This study investigated the antitumor activity and mechanisms of piperlongumine (PL), a natural compound isolated from Piper longum [...] Read more.

Oral squamous cell carcinoma (OSCC), an aggressive cancer originating in the oral cavity, is one of the leading causes of cancer deaths in males worldwide. This study investigated the antitumor activity and mechanisms of piperlongumine (PL), a natural compound isolated from Piper longum L., in human OSCC cells. The effects of PL on cell proliferation, the cell cycle, apoptosis, senescence and reactive oxygen species (ROS) levels in human OSCC cells were investigated. PL effectively inhibited cell growth, caused cell cycle arrest and induced apoptosis and senescence in OSCC cells. Moreover, PL-mediated anti-human OSCC behavior was inhibited by an ROS scavenger N-acetyl-l-cysteine (NAC) treatment, suggesting that regulation of ROS was involved in the mechanism of the anticancer activity of PL. These findings suggest that PL suppresses tumor growth by regulating the cell cycle and inducing apoptosis and senescence and is a potential chemotherapy agent for human OSCC cells. Full article

(This article belongs to the Special Issue Translational Molecular Medicine & Molecular Drug Discovery)

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Open AccessArticle

Epigenetic Modulation of Human Induced Pluripotent Stem Cell Differentiation to Oligodendrocytes

by Panagiotis Douvaras, Tomasz Rusielewicz, Kwi Hye Kim, Jeffery D. Haines, Patrizia Casaccia and Valentina Fossati

Int. J. Mol. Sci. 2016, 17(4), 614; https://doi.org/10.3390/ijms17040614 - 22 Apr 2016

Cited by 24 | Viewed by 8930

Abstract

Pluripotent stem cells provide an invaluable tool for generating human, disease-relevant cells. Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system, characterized by myelin damage. Oligodendrocytes are the myelinating cells of the central nervous system (CNS); they differentiate from progenitor [...] Read more.

Pluripotent stem cells provide an invaluable tool for generating human, disease-relevant cells. Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system, characterized by myelin damage. Oligodendrocytes are the myelinating cells of the central nervous system (CNS); they differentiate from progenitor cells, and their membranes ensheath axons, providing trophic support and allowing fast conduction velocity. The current understanding of oligodendrocyte biology was founded by rodent studies, where the establishment of repressive epigenetic marks on histone proteins, followed by activation of myelin genes, leads to lineage progression. To assess whether this epigenetic regulation is conserved across species, we differentiated human embryonic and induced pluripotent stem cells to oligodendrocytes and asked whether similar histone marks and relative enzymatic activities could be detected. The transcriptional levels of enzymes responsible for methylation and acetylation of histone marks were analyzed during oligodendrocyte differentiation, and the post-translational modifications on histones were detected using immunofluorescence. These studies showed that also in human cells, differentiation along the oligodendrocyte lineage is characterized by the acquisition of multiple repressive histone marks, including deacetylation of lysine residues on histone H3 and trimethylation of residues K9 and K27. These data suggest that the epigenetic modulation of oligodendrocyte identity is highly conserved across species. Full article

(This article belongs to the Special Issue Pluripotent Stem Cell Technology for Disease Modeling, Drug Discovery and Regenerative Medicine)

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Open AccessArticle

Unfractionated Heparin Promotes Osteoclast Formation in Vitro by Inhibiting Osteoprotegerin Activity

by Binghan Li, Dan Lu, Yuqing Chen, Minghui Zhao and Li Zuo

Int. J. Mol. Sci. 2016, 17(4), 613; https://doi.org/10.3390/ijms17040613 - 22 Apr 2016

Cited by 20 | Viewed by 6202

Abstract

Heparin has been proven to enhance bone resorption and induce bone loss. Since osteoclasts play a pivotal role in bone resorption, the effect of heparin on osteoclastogenesis needs to be clarified. Since osteocytes are the key modulator during osteoclastogenesis, we evaluated heparin’s effect [...] Read more.

Heparin has been proven to enhance bone resorption and induce bone loss. Since osteoclasts play a pivotal role in bone resorption, the effect of heparin on osteoclastogenesis needs to be clarified. Since osteocytes are the key modulator during osteoclastogenesis, we evaluated heparin’s effect on osteoclastogenesis in vitro by co-culturing an osteocyte cell line (MLO-Y4) and pre-osteoclasts (RAW264.7). In this co-culture system, heparin enhanced osteoclastogenesis and osteoclastic bone resorption while having no influence on the production of RANKL (receptor activator of NFκB ligand), M-CSF (macrophage colony-stimulating factor), and OPG (osteoprotegerin), which are three main regulatory factors derived from osteocytes. According to previous studies, heparin could bind specifically to OPG and inhibit its activity, so we hypothesized that this might be a possible mechanism of heparin activity. To test this hypothesis, osteoclastogenesis was induced using recombinant RANKL or MLO-Y4 supernatant. We found that heparin has no effect on RANKL-induced osteoclastogenesis (contains no OPG). However, after incubation with OPG, the capacity of MLO-Y4 supernatant for supporting osteoclast formation was increased. This effect disappeared after OPG was neutralized and reappeared after OPG was replenished. These results strongly suggest that heparin promotes osteocyte-modulated osteoclastogenesis in vitro, at least partially, through inhibiting OPG activity. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

The AaDREB1 Transcription Factor from the Cold-Tolerant Plant Adonis amurensis Enhances Abiotic Stress Tolerance in Transgenic Plant

by Jun-Mei Zong, Xiao-Wei Li, Yuan-Hang Zhou, Fa-Wei Wang, Nan Wang, Yuan-Yuan Dong, Yan-Xi Yuan, Huan Chen, Xiu-Ming Liu, Na Yao and Hai-Yan Li

Int. J. Mol. Sci. 2016, 17(4), 611; https://doi.org/10.3390/ijms17040611 - 22 Apr 2016

Cited by 35 | Viewed by 6302

Abstract

Dehydration-responsive element binding (DREB) transcription factors (TFs) play important roles in the regulation of plant resistance to environmental stresses and can specifically bind to dehydration-responsive element/C-repeat element (DRE/CRT) proteins (G/ACCGAC) and activate expression of many stress-inducible genes. Here, we cloned and characterized a [...] Read more.

Dehydration-responsive element binding (DREB) transcription factors (TFs) play important roles in the regulation of plant resistance to environmental stresses and can specifically bind to dehydration-responsive element/C-repeat element (DRE/CRT) proteins (G/ACCGAC) and activate expression of many stress-inducible genes. Here, we cloned and characterized a novel gene (AaDREB1) encoding the DREB1 transcription factor from the cold-tolerant plant Adonis amurensis. Quantitative real-time (qRT)-PCR results indicated that AaDREB1 expression was induced by salt, drought, cold stress, and abscisic acid application. A yeast one-hybrid assay demonstrated that AaDREB1 encodes a transcription activator and specifically binds to DRE/CRT. Furthermore, transgenic Arabidopsis and rice harboring AaDREB1 showed enhanced tolerance to salt, drought, and low temperature. These results indicated that AaDREB1 might be useful in genetic engineering to improve plant stress tolerance. Full article

(This article belongs to the Special Issue Gene–Environment Interactions)

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Open AccessArticle

Smad3 Sensitizes Hepatocelluar Carcinoma Cells to Cisplatin by Repressing Phosphorylation of AKT

by Hong-Hao Zhou, Lin Chen, Hui-Fang Liang, Guang-Zhen Li, Bi-Xiang Zhang and Xiao-Ping Chen

Int. J. Mol. Sci. 2016, 17(4), 610; https://doi.org/10.3390/ijms17040610 - 22 Apr 2016

Cited by 20 | Viewed by 6034

Abstract

Background: Heptocelluar carcinoma (HCC) is insensitive to chemotherapy due to limited bioavailability and acquired drug resistance. Smad3 plays dual roles by inhibiting cell growth initially and promoting the progression of advanced tumors in HCC. However, the role of smad3 in chemosensitivity of HCC [...] Read more.

Background: Heptocelluar carcinoma (HCC) is insensitive to chemotherapy due to limited bioavailability and acquired drug resistance. Smad3 plays dual roles by inhibiting cell growth initially and promoting the progression of advanced tumors in HCC. However, the role of smad3 in chemosensitivity of HCC remains elusive. Methods: The role of smad3 in chemosensitivity of HCC was measured by cell viability, apoptosis, plate colony formation assays and xenograft tumor models. Non-smad signaling was detected by Western blotting to search for the underlying mechanisms. Results: Smad3 enhanced the chemosensitivity of HCC cells to cisplatin. Smad3 upregulated p21^Waf1/Cip1 and downregulated c-myc and bcl2 with the treatment of cisplatin. Moreover, overexpression of smad3 repressed the phosphorylation of AKT, and vice versa. Inhibition of PI3K/AKT pathway by LY294002 restored chemosensitivity of smad3-deficiency cells to cisplatin in HCC. Conclusion: Smad3 sensitizes HCC cells to the effects of cisplatin by repressing phosphorylation of AKT and combination of inhibitor of AKT pathway and conventional chemotherapy may be a potential way to solve drug resistance in HCC. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Human Liver Diseases)

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Open AccessArticle

Mmu-miR-1894-3p Inhibits Cell Proliferation and Migration of Breast Cancer Cells by Targeting Trim46

by Li Zhang, Xiaoying Li, Wei Dong, Caixian Sun, Deyu Guo and Lianfeng Zhang

Int. J. Mol. Sci. 2016, 17(4), 609; https://doi.org/10.3390/ijms17040609 - 22 Apr 2016

Cited by 26 | Viewed by 11090

Abstract

Breast cancer is the second leading cause of cancer death in women and the presence of metastasis significantly decreases survival. MicroRNAs are involved in tumor progression and the metastatic spreading of breast cancer. Here, we reported that a microRNA, mmu-miR-1894, significantly decreased the [...] Read more.

Breast cancer is the second leading cause of cancer death in women and the presence of metastasis significantly decreases survival. MicroRNAs are involved in tumor progression and the metastatic spreading of breast cancer. Here, we reported that a microRNA, mmu-miR-1894, significantly decreased the lung metastasis of 4TO7 mouse breast cancer cells by 86.7% in mouse models. Mmu-miR-1894-3p was the functional mature form of miR-1894 and significantly decreased the lung metastasis of 4TO7 cells by 90.8% in mouse models. A dual-luciferase reporter assay indicated that mmu-miR-1894-3p directly targeted the tripartite motif containing 46 (Trim46) 3′-untranslated region (UTR) and downregulated the expression of Trim46 in 4TO7 cells. Consistent with the effect of mmu-miR-1894-3p, knockdown of Trim46 inhibited the experimental lung metastasis of 4TO7 cells. Moreover, knockdown of human Trim46 also prohibited the cell proliferation, migration and wound healing of MBA-MD-231 human breast cancer cells. These results suggested that the effect of knockdown of Trim46 alone was sufficient to recapitulate the effect of mmu-miR-1894 on the metastasis of the breast cancer cells in mouse and that Trim46 was involved in the proliferation and migration of mouse and human breast cancer cells. Full article

(This article belongs to the Collection Regulation by Non-coding RNAs)

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Open AccessReview

Amniotic Fluid Stem Cells: A Novel Source for Modeling of Human Genetic Diseases

by Ivana Antonucci, Martina Provenzano, Melissa Rodrigues, Andrea Pantalone, Vincenzo Salini, Patrizia Ballerini, Cesar V. Borlongan and Liborio Stuppia

Int. J. Mol. Sci. 2016, 17(4), 607; https://doi.org/10.3390/ijms17040607 - 22 Apr 2016

Cited by 16 | Viewed by 8870

Abstract

In recent years, great interest has been devoted to the use of Induced Pluripotent Stem cells (iPS) for modeling of human genetic diseases, due to the possibility of reprogramming somatic cells of affected patients into pluripotent cells, enabling differentiation into several cell types, [...] Read more.

In recent years, great interest has been devoted to the use of Induced Pluripotent Stem cells (iPS) for modeling of human genetic diseases, due to the possibility of reprogramming somatic cells of affected patients into pluripotent cells, enabling differentiation into several cell types, and allowing investigations into the molecular mechanisms of the disease. However, the protocol of iPS generation still suffers from technical limitations, showing low efficiency, being expensive and time consuming. Amniotic Fluid Stem cells (AFS) represent a potential alternative novel source of stem cells for modeling of human genetic diseases. In fact, by means of prenatal diagnosis, a number of fetuses affected by chromosomal or Mendelian diseases can be identified, and the amniotic fluid collected for genetic testing can be used, after diagnosis, for the isolation, culture and differentiation of AFS cells. This can provide a useful stem cell model for the investigation of the molecular basis of the diagnosed disease without the necessity of producing iPS, since AFS cells show some features of pluripotency and are able to differentiate in cells derived from all three germ layers “in vitro”. In this article, we describe the potential benefits provided by using AFS cells in the modeling of human genetic diseases. Full article

(This article belongs to the Special Issue Pluripotent Stem Cell Technology for Disease Modeling, Drug Discovery and Regenerative Medicine)

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Open AccessArticle

A Reverse-Genetics Mutational Analysis of the Barley HvDWARF Gene Results in Identification of a Series of Alleles and Mutants with Short Stature of Various Degree and Disturbance in BR Biosynthesis Allowing a New Insight into the Process

by Damian Gruszka, Malgorzata Gorniak, Ewelina Glodowska, Ewa Wierus, Jana Oklestkova, Anna Janeczko, Miroslaw Maluszynski and Iwona Szarejko

Int. J. Mol. Sci. 2016, 17(4), 600; https://doi.org/10.3390/ijms17040600 - 22 Apr 2016

Cited by 19 | Viewed by 6270

Abstract

Brassinosteroids (BRs) are plant steroid hormones, regulating a broad range of physiological processes. The largest amount of data related with BR biosynthesis has been gathered in Arabidopsis thaliana, however understanding of this process is far less elucidated in monocot crops. Up to [...] Read more.

Brassinosteroids (BRs) are plant steroid hormones, regulating a broad range of physiological processes. The largest amount of data related with BR biosynthesis has been gathered in Arabidopsis thaliana, however understanding of this process is far less elucidated in monocot crops. Up to now, only four barley genes implicated in BR biosynthesis have been identified. Two of them, HvDWARF and HvBRD, encode BR-6-oxidases catalyzing biosynthesis of castasterone, but their relation is not yet understood. In the present study, the identification of the HvDWARF genomic sequence, its mutational and functional analysis and characterization of new mutants are reported. Various types of mutations located in different positions within functional domains were identified and characterized. Analysis of their impact on phenotype of the mutants was performed. The identified homozygous mutants show reduced height of various degree and disrupted skotomorphogenesis. Mutational analysis of the HvDWARF gene with the “reverse genetics” approach allowed for its detailed functional analysis at the level of protein functional domains. The HvDWARF gene function and mutants’ phenotypes were also validated by measurement of endogenous BR concentration. These results allowed a new insight into the BR biosynthesis in barley. Full article

(This article belongs to the Section Molecular Plant Sciences)

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Open AccessArticle

Biodiesel Production from Chlorella protothecoides Oil by Microwave-Assisted Transesterification

by Mustafa Ömer Gülyurt, Didem Özçimen and Benan İnan

Int. J. Mol. Sci. 2016, 17(4), 579; https://doi.org/10.3390/ijms17040579 - 22 Apr 2016

Cited by 31 | Viewed by 5979

Abstract

In this study, biodiesel production from microalgal oil by microwave-assisted transesterification was carried out to investigate its efficiency. Transesterification reactions were performed by using Chlorella protothecoides oil as feedstock, methanol, and potassium hydroxide as the catalyst. Methanol:oil ratio, reaction time and catalyst:oil ratio [...] Read more.

In this study, biodiesel production from microalgal oil by microwave-assisted transesterification was carried out to investigate its efficiency. Transesterification reactions were performed by using Chlorella protothecoides oil as feedstock, methanol, and potassium hydroxide as the catalyst. Methanol:oil ratio, reaction time and catalyst:oil ratio were investigated as process parameters affected methyl ester yield. 9:1 methanol/oil molar ratio, 1.5% KOH catalyst/oil ratio and 10 min were optimum values for the highest fatty acid methyl ester yield. Full article

(This article belongs to the Special Issue Algae Based Bio-Renewable Energy for Sustainability)

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Open AccessArticle

The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential

by Kun-Chun Chiang, Ta-Sen Yeh, Shin-Cheh Chen, Jong-Hwei S. Pang, Chun-Nan Yeh, Jun-Te Hsu, Li-Wei Chen, Sheng-Fong Kuo, Masashi Takano, Atsushi Kittaka, Tai C. Chen, Chi-Chin Sun and Horng-Heng Juang

Int. J. Mol. Sci. 2016, 17(4), 606; https://doi.org/10.3390/ijms17040606 - 21 Apr 2016

Cited by 23 | Viewed by 7138

Abstract

Regarding breast cancer treatment, triple negative breast cancer (TNBC) is a difficult issue. Most TNBC patients die of cancer metastasis. Thus, to develop a new regimen to attenuate TNBC metastatic potential is urgently needed. MART-10 (19-nor-2α-(3-hydroxypropyl)-1α,25(OH)₂D₃), the newly-synthesized 1α,25(OH) [...] Read more.

Regarding breast cancer treatment, triple negative breast cancer (TNBC) is a difficult issue. Most TNBC patients die of cancer metastasis. Thus, to develop a new regimen to attenuate TNBC metastatic potential is urgently needed. MART-10 (19-nor-2α-(3-hydroxypropyl)-1α,25(OH)₂D₃), the newly-synthesized 1α,25(OH)₂D₃ analog, has been shown to be much more potent in cancer growth inhibition than 1α,25(OH)₂D₃ and be active in vivo without inducing obvious side effect. In this study, we demonstrated that both 1α,25(OH)₂D₃ and MART-10 could effectively repress TNBC cells migration and invasion with MART-10 more effective. MART-10 and 1α,25(OH)₂D₃ induced cadherin switching (upregulation of E-cadherin and downregulation of N-cadherin) and downregulated P-cadherin expression in MDA-MB-231 cells. The EMT(epithelial mesenchymal transition) process in MDA-MB-231 cells was repressed by MART-10 through inhibiting Zeb1, Zeb2, Slug, and Twist expression. LCN2, one kind of breast cancer metastasis stimulator, was also found for the first time to be repressed by 1α,25(OH)₂D₃ and MART-10 in breast cancer cells. Matrix metalloproteinase-9 (MMP-9) activity was also downregulated by MART-10. Furthermore, F-actin synthesis in MDA-MB-231 cells was attenuated as exposure to 1α,25(OH)₂D₃ and MART-10. Based on our result, we conclude that MART-10 could effectively inhibit TNBC cells metastatic potential and deserves further investigation as a new regimen to treat TNBC. Full article

(This article belongs to the Special Issue Commemorative Issue in Honor of Professor Milan R. Uskokovic: Role of Vitamin D in Cancer Therapeutics)

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Open AccessEditorial

Non-Coding RNAs in Cancer: An Interview with Dr. Martin Pichler

by International Journal of Molecular Sciences Editorial Office

Int. J. Mol. Sci. 2016, 17(4), 605; https://doi.org/10.3390/ijms17040605 - 21 Apr 2016

Viewed by 5497

Abstract

In this issue, we are pleased and honored to have an interview with Professor Martin Pichler, who is the Collection Editor for the International Journal of Molecular Sciences Topical Collection of “Regulation by Non-Coding RNAs” [1].[...] Full article

(This article belongs to the Collection Regulation by Non-coding RNAs)

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Open AccessCorrection

Kai, M. Roles of RNA-Binding Proteins in DNA Damage Response. Int. J. Mol. Sci. 2016, 17, 310

by Mihoko Kai

Int. J. Mol. Sci. 2016, 17(4), 604; https://doi.org/10.3390/ijms17040604 - 21 Apr 2016

Cited by 40 | Viewed by 3938

Abstract

The author would like to insert the citation after the following sentence, “These RBPs are detected on laser trackswithin one minute after laser irradiation, and are excluded from the laser tracks shortly (within 10–15 min, depending on conditions of laser irradiation) [1]”, in [...] Read more.

The author would like to insert the citation after the following sentence, “These RBPs are detected on laser trackswithin one minute after laser irradiation, and are excluded from the laser tracks shortly (within 10–15 min, depending on conditions of laser irradiation) [1]”, in the paper published in the International Journal of Molecular Sciences [2].[...] Full article

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Open AccessArticle

Characterization of Stripe Rust Resistance Genes in the Wheat Cultivar Chuanmai45

by Ennian Yang, Guangrong Li, Liping Li, Zhenyu Zhang, Wuyun Yang, Yunliang Peng, Yongqing Zhu, Zujun Yang and Garry M. Rosewarne

Int. J. Mol. Sci. 2016, 17(4), 601; https://doi.org/10.3390/ijms17040601 - 21 Apr 2016

Cited by 20 | Viewed by 6245

Abstract

The objective of this research was to characterize the high level of resistance to stripe that has been observed in the released wheat cultivar, Chuanmai45. A combination of classic genetic analysis, molecular and cytogenetic methods were used to characterize resistance in an F [...] Read more.

The objective of this research was to characterize the high level of resistance to stripe that has been observed in the released wheat cultivar, Chuanmai45. A combination of classic genetic analysis, molecular and cytogenetic methods were used to characterize resistance in an F₂ population derived from Chuanmai45 and the susceptible Chuanmai42. Inheritance of resistance was shown to be conferred by two genes in Chuanmai45. Fluorescence in situ hybridization (FISH) was used along with segregation studies to show that one gene was located on a 1RS.1BL translocation. Molecular markers were employed to show that the other locus was located on chromosome 4B. The defeated gene, Yr24/26, on chromosome 1BL was present in the susceptible parent and lines that recombined this gene with the 1RS.1BL translocation were identified. The germplasm, loci, and associated markers identified in this study will be useful for application in breeding programs utilizing marker-assisted selection. Full article

(This article belongs to the Special Issue Plant Innate Immunity)

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Open AccessArticle

In Silico Structure and Sequence Analysis of Bacterial Porins and Specific Diffusion Channels for Hydrophilic Molecules: Conservation, Multimericity and Multifunctionality

by Hilde S. Vollan, Tone Tannæs, Gert Vriend and Geir Bukholm

Int. J. Mol. Sci. 2016, 17(4), 599; https://doi.org/10.3390/ijms17040599 - 21 Apr 2016

Cited by 14 | Viewed by 10391

Abstract

Diffusion channels are involved in the selective uptake of nutrients and form the largest outer membrane protein (OMP) family in Gram-negative bacteria. Differences in pore size and amino acid composition contribute to the specificity. Structure-based multiple sequence alignments shed light on the structure-function [...] Read more.

Diffusion channels are involved in the selective uptake of nutrients and form the largest outer membrane protein (OMP) family in Gram-negative bacteria. Differences in pore size and amino acid composition contribute to the specificity. Structure-based multiple sequence alignments shed light on the structure-function relations for all eight subclasses. Entropy-variability analysis results are correlated to known structural and functional aspects, such as structural integrity, multimericity, specificity and biological niche adaptation. The high mutation rate in their surface-exposed loops is likely an important mechanism for host immune system evasion. Multiple sequence alignments for each subclass revealed conserved residue positions that are involved in substrate recognition and specificity. An analysis of monomeric protein channels revealed particular sequence patterns of amino acids that were observed in other classes at multimeric interfaces. This adds to the emerging evidence that all members of the family exist in a multimeric state. Our findings are important for understanding the role of members of this family in a wide range of bacterial processes, including bacterial food uptake, survival and adaptation mechanisms. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Overexpression of the Transcription Factors GmSHN1 and GmSHN9 Differentially Regulates Wax and Cutin Biosynthesis, Alters Cuticle Properties, and Changes Leaf Phenotypes in Arabidopsis

by Yangyang Xu, Hanying Wu, Mingming Zhao, Wang Wu, Yinong Xu and Dan Gu

Int. J. Mol. Sci. 2016, 17(4), 587; https://doi.org/10.3390/ijms17040587 - 21 Apr 2016

Cited by 26 | Viewed by 8133

Abstract

SHINE (SHN/WIN) clade proteins, transcription factors of the plant-specific APETALA 2/ethylene-responsive element binding factor (AP2/ERF) family, have been proven to be involved in wax and cutin biosynthesis. Glycine max is an important economic crop, but its molecular mechanism of wax biosynthesis is rarely [...] Read more.

SHINE (SHN/WIN) clade proteins, transcription factors of the plant-specific APETALA 2/ethylene-responsive element binding factor (AP2/ERF) family, have been proven to be involved in wax and cutin biosynthesis. Glycine max is an important economic crop, but its molecular mechanism of wax biosynthesis is rarely characterized. In this study, 10 homologs of Arabidopsis SHN genes were identified from soybean. These homologs were different in gene structures and organ expression patterns. Constitutive expression of each of the soybean SHN genes in Arabidopsis led to different leaf phenotypes, as well as different levels of glossiness on leaf surfaces. Overexpression of GmSHN1 and GmSHN9 in Arabidopsis exhibited 7.8-fold and 9.9-fold up-regulation of leaf cuticle wax productions, respectively. C31 and C29 alkanes contributed most to the increased wax contents. Total cutin contents of leaves were increased 11.4-fold in GmSHN1 overexpressors and 5.7-fold in GmSHN9 overexpressors, mainly through increasing C16:0 di-OH and dioic acids. GmSHN1 and GmSHN9 also altered leaf cuticle membrane ultrastructure and increased water loss rate in transgenic Arabidopsis plants. Transcript levels of many wax and cutin biosynthesis and leaf development related genes were altered in GmSHN1 and GmSHN9 overexpressors. Overall, these results suggest that GmSHN1 and GmSHN9 may differentially regulate the leaf development process as well as wax and cutin biosynthesis. Full article

(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism 2015)

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Open AccessArticle

Significance of Matrix Metalloproteinase 9 Expression as Supporting Marker to Cytokeratin 19 mRNA in Sentinel Lymph Nodes in Breast Cancer Patients

by Marek Murawski, Marta Woźniak, Kamila Duś-Szachniewicz, Paweł Kołodziej, Marta Rzeszutko and Piotr Ziółkowski

Int. J. Mol. Sci. 2016, 17(4), 571; https://doi.org/10.3390/ijms17040571 - 21 Apr 2016

Cited by 3 | Viewed by 5608

Abstract

One-step nucleic acid amplification (OSNA) detects and quantifies, with the use of a polymerase chain reaction, the presence of cytokeratin 19 mRNA in sentinel lymph nodes. The main advantage of the OSNA assay is the avoidance of second surgery in case of positive [...] Read more.

One-step nucleic acid amplification (OSNA) detects and quantifies, with the use of a polymerase chain reaction, the presence of cytokeratin 19 mRNA in sentinel lymph nodes. The main advantage of the OSNA assay is the avoidance of second surgery in case of positive sentinel lymph node diagnosis. The objective of this study was to evaluate the significance of matrix metalloproteinase 9 expression by immunohistochemistry as supporting marker to cytokeratin 19 mRNA in sentinel lymph nodes in breast cancer patients and to relate this expression with clinicopathological data. This study was conducted on fresh sentinel lymph nodes obtained from 40 patients with tumors classified as carcinoma of no special type. The presence of metastatic cells in the slices of lymph nodes was evaluated by immunohistochemistry using antibodies for CK19 and MMP-9. Expression of CK19 and MMP-9 in lymph nodes was also confirmed by means of Western blot analysis. Results indicated that the strongest correlation with CK19 mRNA was displayed by MMP-9, CK19 (by immunohistochemistry, IHC), and nodal metastases (p < 0.001). Higher histological grading also positively correlated with CK19 mRNA, however that correlation was less significant. Since MMP-9 shows very strong correlation with CK19 mRNA in breast carcinoma of no special type metastases, expression of MMP-9 in sentinel lymph nodes should be considered as useful method whenever OSNA analysis is not available. Full article

(This article belongs to the Special Issue Advances in Molecular Oncology)

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Open AccessArticle

Analysis of Protein Composition and Bioactivity of Neoponera villosa Venom (Hymenoptera: Formicidae)

by Wallace Felipe Blohem Pessoa, Ludimilla Carvalho Cerqueira Silva, Leila De Oliveira Dias, Jacques Hubert Charles Delabie, Helena Costa and Carla Cristina Romano

Int. J. Mol. Sci. 2016, 17(4), 513; https://doi.org/10.3390/ijms17040513 - 21 Apr 2016

Cited by 15 | Viewed by 6007

Abstract

Ants cause a series of accidents involving humans. Such accidents generate different reactions in the body, ranging from a mild irritation at the bite site to anaphylactic shock, and these reactions depend on the mechanism of action of the venom. The study of [...] Read more.

Ants cause a series of accidents involving humans. Such accidents generate different reactions in the body, ranging from a mild irritation at the bite site to anaphylactic shock, and these reactions depend on the mechanism of action of the venom. The study of animal venom is a science known as venomics. Through venomics, the composition of the venom of several ant species has already been characterized and their biological activities described. Thus, the aim of this study was to evaluate the protein composition and biological activities (hemolytic and immunostimulatory) of the venom of Neoponera villosa (N. villosa), an ant widely distributed in South America. The protein composition was evaluated by proteomic techniques, such as two-dimensional electrophoresis. To assess the biological activity, hemolysis assay was carried out and cytokines were quantified after exposure of macrophages to the venom. The venom of N. villosa has a profile composed of 145 proteins, including structural and metabolic components (e.g., tubulin and ATPase), allergenic and immunomodulatory proteins (arginine kinase and heat shock proteins (HSPs)), protective proteins of venom (superoxide dismutase (SOD) and catalase) and tissue degradation proteins (hyaluronidase and phospholipase A2). The venom was able to induce hemolysis in human erythrocytes and also induced release of both pro-inflammatory cytokines, as the anti-inflammatory cytokine release by murine macrophages. These results allow better understanding of the composition and complexity of N. villosa venom in the human body, as well as the possible mechanisms of action after the bite. Full article

(This article belongs to the Section Biochemistry)

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Open AccessCommunication

Active and Repressive Chromatin-Associated Proteome after MPA Treatment and the Role of Midkine in Epithelial Monolayer Permeability

by Niamat Khan, Christof Lenz, Lutz Binder, Dasaradha Venkata Krishna Pantakani and Abdul R. Asif

Int. J. Mol. Sci. 2016, 17(4), 597; https://doi.org/10.3390/ijms17040597 - 20 Apr 2016

Cited by 4 | Viewed by 6687

Abstract

Mycophenolic acid (MPA) is prescribed to maintain allografts in organ-transplanted patients. However, gastrointestinal (GI) complications, particularly diarrhea, are frequently observed as a side effect following MPA therapy. We recently reported that MPA altered the tight junction (TJ)-mediated barrier function in a Caco-2 cell [...] Read more.

Mycophenolic acid (MPA) is prescribed to maintain allografts in organ-transplanted patients. However, gastrointestinal (GI) complications, particularly diarrhea, are frequently observed as a side effect following MPA therapy. We recently reported that MPA altered the tight junction (TJ)-mediated barrier function in a Caco-2 cell monolayer model system. This study investigates whether MPA induces epigenetic changes which lead to GI complications, especially diarrhea. Methods: We employed a Chromatin Immunoprecipitation-O-Proteomics (ChIP-O-Proteomics) approach to identify proteins associated with active (H3K4me3) as well as repressive (H3K27me3) chromatin histone modifications in MPA-treated cells, and further characterized the role of midkine, a H3K4me3-associated protein, in the context of epithelial monolayer permeability. Results: We identified a total of 333 and 306 proteins associated with active and repressive histone modification marks, respectively. Among them, 241 proteins were common both in active and repressive chromatin, 92 proteins were associated exclusively with the active histone modification mark, while 65 proteins remained specific to repressive chromatin. Our results show that 45 proteins which bind to the active and seven proteins which bind to the repressive chromatin region exhibited significantly altered abundance in MPA-treated cells as compared to DMSO control cells. A number of novel proteins whose function is not known in bowel barrier regulation were among the identified proteins, including midkine. Our functional integrity assays on the Caco-2 cell monolayer showed that the inhibition of midkine expression prior to MPA treatment could completely block the MPA-mediated increase in barrier permeability. Conclusions: The ChIP-O-Proteomics approach delivered a number of novel proteins with potential implications in MPA toxicity. Consequently, it can be proposed that midkine inhibition could be a potent therapeutic approach to prevent the MPA-mediated increase in TJ permeability and leak flux diarrhea in organ transplant patients. Full article

(This article belongs to the Special Issue Biomarkers in Drug-Induced Organ Injury)

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Open AccessArticle

Tetrabromidocuprates(II)—Synthesis, Structure and EPR

by André Zabel, Alette Winter, Alexandra Kelling, Uwe Schilde and Peter Strauch

Int. J. Mol. Sci. 2016, 17(4), 596; https://doi.org/10.3390/ijms17040596 - 20 Apr 2016

Cited by 8 | Viewed by 6835

Abstract

Metal-containing ionic liquids (ILs) are of interest for a variety of technical applications, e.g., particle synthesis and materials with magnetic or thermochromic properties. In this paper we report the synthesis of, and two structures for, some new tetrabromidocuprates(II) with several “onium” cations in [...] Read more.

Metal-containing ionic liquids (ILs) are of interest for a variety of technical applications, e.g., particle synthesis and materials with magnetic or thermochromic properties. In this paper we report the synthesis of, and two structures for, some new tetrabromidocuprates(II) with several “onium” cations in comparison to the results of electron paramagnetic resonance (EPR) spectroscopic analyses. The sterically demanding cations were used to separate the paramagnetic Cu(II) ions for EPR measurements. The EPR hyperfine structure in the spectra of these new compounds is not resolved, due to the line broadening resulting from magnetic exchange between the still-incomplete separated paramagnetic Cu(II) centres. For the majority of compounds, the principal g values (g_‖ and g_⊥) of the tensors could be determined and information on the structural changes in the [CuBr₄]²⁻ anions can be obtained. The complexes have high potential, e.g., as ionic liquids, as precursors for the synthesis of copper bromide particles, as catalytically active or paramagnetic ionic liquids. Full article

(This article belongs to the Special Issue Ionic Liquids 2016 and Selected Papers from ILMAT III)

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Development of a Three-Dimensional (3D) Printed Biodegradable Cage to Convert Morselized Corticocancellous Bone Chips into a Structured Cortical Bone Graft

by Ying-Chao Chou, Demei Lee, Tzu-Min Chang, Yung-Heng Hsu, Yi-Hsun Yu, Shih-Jung Liu and Steve Wen-Neng Ueng

Int. J. Mol. Sci. 2016, 17(4), 595; https://doi.org/10.3390/ijms17040595 - 20 Apr 2016

Cited by 20 | Viewed by 7870

Abstract

This study aimed to develop a new biodegradable polymeric cage to convert corticocancellous bone chips into a structured strut graft for treating segmental bone defects. A total of 24 adult New Zealand white rabbits underwent a left femoral segmental bone defect creation. Twelve [...] Read more.

This study aimed to develop a new biodegradable polymeric cage to convert corticocancellous bone chips into a structured strut graft for treating segmental bone defects. A total of 24 adult New Zealand white rabbits underwent a left femoral segmental bone defect creation. Twelve rabbits in group A underwent three-dimensional (3D) printed cage insertion, corticocancellous chips implantation, and Kirschner-wire (K-wire) fixation, while the other 12 rabbits in group B received bone chips implantation and K-wire fixation only. All rabbits received a one-week activity assessment and the initial image study at postoperative 1 week. The final image study was repeated at postoperative 12 or 24 weeks before the rabbit scarification procedure on schedule. After the animals were sacrificed, both femurs of all the rabbits were prepared for leg length ratios and 3-point bending tests. The rabbits in group A showed an increase of activities during the first week postoperatively and decreased anterior cortical disruptions in the postoperative image assessments. Additionally, higher leg length ratios and 3-point bending strengths demonstrated improved final bony ingrowths within the bone defects for rabbits in group A. In conclusion, through this bone graft converting technique, orthopedic surgeons can treat segmental bone defects by using bone chips but with imitate characters of structured cortical bone graft. Full article

(This article belongs to the Special Issue Molecular Research on Dental Materials and Biomaterials)

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Rationale and Methodology of Reprogramming for Generation of Induced Pluripotent Stem Cells and Induced Neural Progenitor Cells

by Zuojun Tian, Fuzheng Guo, Sangita Biswas and Wenbin Deng

Int. J. Mol. Sci. 2016, 17(4), 594; https://doi.org/10.3390/ijms17040594 - 20 Apr 2016

Cited by 7 | Viewed by 9080

Abstract

Great progress has been made regarding the capabilities to modify somatic cell fate ever since the technology for generation of induced pluripotent stem cells (iPSCs) was discovered in 2006. Later, induced neural progenitor cells (iNPCs) were generated from mouse and human cells, bypassing [...] Read more.

Great progress has been made regarding the capabilities to modify somatic cell fate ever since the technology for generation of induced pluripotent stem cells (iPSCs) was discovered in 2006. Later, induced neural progenitor cells (iNPCs) were generated from mouse and human cells, bypassing some of the concerns and risks of using iPSCs in neuroscience applications. To overcome the limitation of viral vector induced reprogramming, bioactive small molecules (SM) have been explored to enhance the efficiency of reprogramming or even replace transcription factors (TFs), making the reprogrammed cells more amenable to clinical application. The chemical induced reprogramming process is a simple process from a technical perspective, but the choice of SM at each step is vital during the procedure. The mechanisms underlying cell transdifferentiation are still poorly understood, although, several experimental data and insights have indicated the rationale of cell reprogramming. The process begins with the forced expression of specific TFs or activation/inhibition of cell signaling pathways by bioactive chemicals in defined culture condition, which initiates the further reactivation of endogenous gene program and an optimal stoichiometric expression of the endogenous pluri- or multi-potency genes, and finally leads to the birth of reprogrammed cells such as iPSCs and iNPCs. In this review, we first outline the rationale and discuss the methodology of iPSCs and iNPCs in a stepwise manner; and then we also discuss the chemical-based reprogramming of iPSCs and iNPCs. Full article

(This article belongs to the Special Issue Pluripotent Stem Cell Technology for Disease Modeling, Drug Discovery and Regenerative Medicine)

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Matrilin-3 Role in Cartilage Development and Osteoarthritis

by Manjunatha S. Muttigi, Inbo Han, Hun-Kuk Park, Hansoo Park and Soo-Hong Lee

Int. J. Mol. Sci. 2016, 17(4), 590; https://doi.org/10.3390/ijms17040590 - 20 Apr 2016

Cited by 26 | Viewed by 7221

Abstract

The extracellular matrix (ECM) of cartilage performs essential functions in differentiation and chondroprogenitor cell maintenance during development and regeneration. Here, we discuss the vital role of matrilin-3, an ECM protein involved in cartilage development and potential osteoarthritis pathomechanisms. As an adaptor protein, matrilin-3 [...] Read more.

The extracellular matrix (ECM) of cartilage performs essential functions in differentiation and chondroprogenitor cell maintenance during development and regeneration. Here, we discuss the vital role of matrilin-3, an ECM protein involved in cartilage development and potential osteoarthritis pathomechanisms. As an adaptor protein, matrilin-3 binds to collagen IX to form a filamentous network around cells. Matrilin-3 is an essential component during cartilage development and ossification. In addition, it interacts directly or indirectly with transforming growth factor β (TGF-β), and bone morphogenetic protein 2 (BMP2) eventually regulates chondrocyte proliferation and hypertrophic differentiation. Interestingly, matrilin-3 increases interleukin receptor antagonists (IL-Ra) in chondrocytes, suggesting its role in the suppression of IL-1β-mediated inflammatory action. Matrilin-3 downregulates the expression of matrix-degrading enzymes, such as a disintegrin metalloproteinase with thrombospondin motifs 4 (ADAMTS4) and ADAMTS5, matrix metalloproteinase 13 (MMP13), and collagen X, a hypertrophy marker during development and inflammatory conditions. Matrilin-3 essentially enhances collagen II and aggrecan expression, which are required to maintain the tensile strength and elasticity of cartilage, respectively. Interestingly, despite these attributes, matrilin-3 induces osteoarthritis-associated markers in chondrocytes in a concentration-dependent manner. Existing data provide insights into the critical role of matrilin-3 in inflammation, matrix degradation, and matrix formation in cartilage development and osteoarthritis. Full article

(This article belongs to the Special Issue Translational Molecular Medicine & Molecular Drug Discovery)

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Exogenous R-Spondin1 Induces Precocious Telogen-to-Anagen Transition in Mouse Hair Follicles

by Na Li, Shu Liu, Hui-Shan Zhang, Zhi-Li Deng, Hua-Shan Zhao, Qian Zhao, Xiao-Hua Lei, Li-Na Ning, Yu-Jing Cao, Hai-Bin Wang, Shuang Liu and En-Kui Duan

Int. J. Mol. Sci. 2016, 17(4), 582; https://doi.org/10.3390/ijms17040582 - 20 Apr 2016

Cited by 24 | Viewed by 8611

Abstract

R-spondin proteins are novel Wnt/β-catenin agonists, which signal through their receptors leucine-rich repeat-containing G-protein coupled receptor (LGR) 4/5/6 and substantially enhance Wnt/β-catenin activity. R-spondins are reported to function in embryonic development. They also play important roles in stem cell functions in adult tissues, [...] Read more.

R-spondin proteins are novel Wnt/β-catenin agonists, which signal through their receptors leucine-rich repeat-containing G-protein coupled receptor (LGR) 4/5/6 and substantially enhance Wnt/β-catenin activity. R-spondins are reported to function in embryonic development. They also play important roles in stem cell functions in adult tissues, such as the intestine and mammary glands, which largely rely on Wnt/β-catenin signaling. However, in the skin epithelium and hair follicles, the information about R-spondins is deficient, although the expressions and functions of their receptors, LGR4/5/6, have already been studied in detail. In the present study, highly-enriched expression of the R-spondin family genes (Rspo1/2/3/4) in the hair follicle dermal papilla is revealed. Expression of Rspo1 in the dermal papilla is specifically and prominently upregulated before anagen entry, and exogenous recombinant R-spondin1 protein injection in mid-telogen leads to precocious anagen entry. Moreover, R-spondin1 activates Wnt/β-catenin signaling in cultured bulge stem cells in vitro, changing their fate determination without altering the cell proliferation. Our pioneering study uncovers a role of R-spondin1 in the activation of cultured hair follicle stem cells and the regulation of hair cycle progression, shedding new light on the governance of Wnt/β-catenin signaling in skin biology and providing helpful clues for future treatment of hair follicle disorders. Full article

(This article belongs to the Section Biochemistry)

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Open AccessReview

Proteomic and Microscopic Strategies towards the Analysis of the Cytoskeletal Networks in Major Neuropsychiatric Disorders

by Joëlle V. F. Coumans, Suresh K. A. Palanisamy, Jim McFarlane and Pierre D. J. Moens

Int. J. Mol. Sci. 2016, 17(4), 581; https://doi.org/10.3390/ijms17040581 - 20 Apr 2016

Cited by 8 | Viewed by 9433

Abstract

Mental health disorders have become worldwide health priorities. It is estimated that in the next 20 years they will account for a 16 trillion United State dollars (US$) loss. Up to now, the underlying pathophysiology of psychiatric disorders remains elusive. Altered cytoskeleton proteins [...] Read more.

Mental health disorders have become worldwide health priorities. It is estimated that in the next 20 years they will account for a 16 trillion United State dollars (US$) loss. Up to now, the underlying pathophysiology of psychiatric disorders remains elusive. Altered cytoskeleton proteins expression that may influence the assembly, organization and maintenance of cytoskeletal integrity has been reported in major depressive disorders, schizophrenia and to some extent bipolar disorders. The use of quantitative proteomics, dynamic microscopy and super-resolution microscopy to investigate disease-specific protein signatures holds great promise to improve our understanding of these disorders. In this review, we present the currently available quantitative proteomic approaches use in neurology, gel-based, stable isotope-labelling and label-free methodologies and evaluate their strengths and limitations. We also reported on enrichment/subfractionation methods that target the cytoskeleton associated proteins and discuss the need of alternative methods for further characterization of the neurocytoskeletal proteome. Finally, we present live cell imaging approaches and emerging dynamic microscopy technology that will provide the tools necessary to investigate protein interactions and their dynamics in the whole cells. While these areas of research are still in their infancy, they offer huge potential towards the understanding of the neuronal network stability and its modification across neuropsychiatric disorders. Full article

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

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The Isolation of DNA by Polycharged Magnetic Particles: An Analysis of the Interaction by Zeta Potential and Particle Size

by Yazan Haddad, Kledi Xhaxhiu, Pavel Kopel, David Hynek, Ondrej Zitka and Vojtech Adam

Int. J. Mol. Sci. 2016, 17(4), 550; https://doi.org/10.3390/ijms17040550 - 20 Apr 2016

Cited by 22 | Viewed by 9663

Abstract

Magnetic isolation of biological targets is in major demand in the biotechnology industry today. This study considers the interaction of four surface-modified magnetic micro- and nanoparticles with selected DNA fragments. Different surface modifications of nanomaghemite precursors were investigated: MAN37 (silica-coated), MAN127 (polyvinylpyrrolidone-coated), MAN158 [...] Read more.

Magnetic isolation of biological targets is in major demand in the biotechnology industry today. This study considers the interaction of four surface-modified magnetic micro- and nanoparticles with selected DNA fragments. Different surface modifications of nanomaghemite precursors were investigated: MAN37 (silica-coated), MAN127 (polyvinylpyrrolidone-coated), MAN158 (phosphate-coated), and MAN164 (tripolyphosphate-coated). All particles were positive polycharged agglomerated monodispersed systems. Mean particle sizes were 0.48, 2.97, 2.93, and 3.67 μm for MAN37, MAN127, MAN164, and MAN158, respectively. DNA fragments exhibited negative zeta potential of −0.22 mV under binding conditions (high ionic strength, low pH, and dehydration). A decrease in zeta potential of particles upon exposure to DNA was observed with exception of MAN158 particles. The measured particle size of MAN164 particles increased by nearly twofold upon exposure to DNA. Quantitative PCR isolation of DNA with a high retrieval rate was observed by magnetic particles MAN127 and MAN164. Interaction between polycharged magnetic particles and DNA is mediated by various binding mechanisms such as hydrophobic and electrostatic interactions. Future development of DNA isolation technology requires an understanding of the physical and biochemical conditions of this process. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Is It Reliable to Use Common Molecular Docking Methods for Comparing the Binding Affinities of Enantiomer Pairs for Their Protein Target?

by David Ramírez and Julio Caballero

Int. J. Mol. Sci. 2016, 17(4), 525; https://doi.org/10.3390/ijms17040525 - 20 Apr 2016

Cited by 120 | Viewed by 9433

Abstract

Molecular docking is a computational chemistry method which has become essential for the rational drug design process. In this context, it has had great impact as a successful tool for the study of ligand–receptor interaction modes, and for the exploration of large chemical [...] Read more.

Molecular docking is a computational chemistry method which has become essential for the rational drug design process. In this context, it has had great impact as a successful tool for the study of ligand–receptor interaction modes, and for the exploration of large chemical datasets through virtual screening experiments. Despite their unquestionable merits, docking methods are not reliable for predicting binding energies due to the simple scoring functions they use. However, comparisons between two or three complexes using the predicted binding energies as a criterion are commonly found in the literature. In the present work we tested how wise is it to trust the docking energies when two complexes between a target protein and enantiomer pairs are compared. For this purpose, a ligand library composed by 141 enantiomeric pairs was used, including compounds with biological activities reported against seven protein targets. Docking results using the software Glide (considering extra precision (XP), standard precision (SP), and high-throughput virtual screening (HTVS) modes) and AutoDock Vina were compared with the reported biological activities using a classification scheme. Our test failed for all modes and targets, demonstrating that an accurate prediction when binding energies of enantiomers are compared using docking may be due to chance. We also compared pairs of compounds with different molecular weights and found the same results. Full article

(This article belongs to the Special Issue Big Data Analysis and QSAR/QSPR Research in Chemistry, Bio-Medical, and Network Sciences)

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NAFLD and Increased Aortic Stiffness: Parallel or Common Physiopathological Mechanisms?

by Cristiane A. Villela-Nogueira, Nathalie C. Leite, Claudia R. L. Cardoso and Gil F. Salles

Int. J. Mol. Sci. 2016, 17(4), 460; https://doi.org/10.3390/ijms17040460 - 20 Apr 2016

Cited by 36 | Viewed by 6442

Abstract

Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver diseases worldwide. Liver inflammation and fibrosis related to NAFLD contribute to disease progression and increasing liver-related mortality and morbidity. Increasing data suggest that NAFLD may be linked to atherosclerotic vascular [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver diseases worldwide. Liver inflammation and fibrosis related to NAFLD contribute to disease progression and increasing liver-related mortality and morbidity. Increasing data suggest that NAFLD may be linked to atherosclerotic vascular disease independent of other established cardiovascular risk factors. Central arterial stiffness has been recognized as a measure of cumulative cardiovascular risk marker load, and the measure of carotid-femoral pulse wave velocity (cf-PWV) is regarded as the gold standard assessment of aortic stiffness. It has been shown that increased aortic stiffness predicts cardiovascular morbidity and mortality in several clinical settings, including type 2 diabetes mellitus, a well-known condition associated with advanced stages of NAFLD. Furthermore, recently-published studies reported a strong association between NAFLD and increased arterial stiffness, suggesting a possible link in the pathogenesis of atherosclerosis and NAFLD. We sought to review the published data on the associations between NAFLD and aortic stiffness, in order to better understand the interplay between these two conditions and identify possible common physiopathological mechanisms. Full article

(This article belongs to the Special Issue Non-Alcoholic Fatty Liver Disease Research 2016)

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Environmental Conditions Influence Induction of Key ABC-Transporter Genes Affecting Glyphosate Resistance Mechanism in Conyza canadensis

by Eleni Tani, Demosthenis Chachalis, Ilias S. Travlos and Dimitrios Bilalis

Int. J. Mol. Sci. 2016, 17(4), 342; https://doi.org/10.3390/ijms17040342 - 20 Apr 2016

Cited by 22 | Viewed by 6209

Abstract

Conyza canadensis has been reported to be the most frequent weed species that evolved resistance to glyphosate in various parts of the world. The objective of the present study was to investigate the effect of environmental conditions (temperature and light) on the expression [...] Read more.

Conyza canadensis has been reported to be the most frequent weed species that evolved resistance to glyphosate in various parts of the world. The objective of the present study was to investigate the effect of environmental conditions (temperature and light) on the expression levels of the EPSPS gene and two major ABC-transporter genes (M10 and M11) on glyphosate susceptible (GS) and glyphosate resistant (GR) horseweed populations, collected from several regions across Greece. Real-time PCR was conducted to determine the expression level of the aforementioned genes when glyphosate was applied at normal (1×; 533 g·a.e.·ha⁻¹) and high rates (4×, 8×), measured at an early one day after treatment (DAT) and a later stage (four DAT) of expression. Plants were exposed to light or dark conditions, at three temperature regimes (8, 25, 35 °C). GR plants were made sensitive when exposed to 8 °C with light; those sensitized plants behaved biochemically (shikimate accumulation) and molecularly (expression of EPSPS and ABC-genes) like the GS plants. Results from the current study show the direct link between the environmental conditions and the induction level of the above key genes that likely affect the efficiency of the proposed mechanism of glyphosate resistance. Full article

(This article belongs to the Special Issue Effects of Herbicides and Heavy Metals to the Structure and Function of Plant Cells)

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Neutralization of Bacterial YoeB_Spn Toxicity and Enhanced Plant Growth in Arabidopsis thaliana via Co-Expression of the Toxin-Antitoxin Genes

by Fauziah Abu Bakar, Chew Chieng Yeo and Jennifer Ann Harikrishna

Int. J. Mol. Sci. 2016, 17(4), 321; https://doi.org/10.3390/ijms17040321 - 20 Apr 2016

Cited by 4 | Viewed by 5537

Abstract

Bacterial toxin-antitoxin (TA) systems have various cellular functions, including as part of the general stress response. The genome of the Gram-positive human pathogen Streptococcus pneumoniae harbors several putative TA systems, including yefM-yoeB_Spn, which is one of four systems that had been [...] Read more.

Bacterial toxin-antitoxin (TA) systems have various cellular functions, including as part of the general stress response. The genome of the Gram-positive human pathogen Streptococcus pneumoniae harbors several putative TA systems, including yefM-yoeB_Spn, which is one of four systems that had been demonstrated to be biologically functional. Overexpression of the yoeB_Spn toxin gene resulted in cell stasis and eventually cell death in its native host, as well as in Escherichia coli. Our previous work showed that induced expression of a yoeB_Spn toxin-Green Fluorescent Protein (GFP) fusion gene apparently triggered apoptosis and was lethal in the model plant, Arabidopsis thaliana. In this study, we investigated the effects of co-expression of the yefM_Spn antitoxin and yoeB_Spn toxin-GFP fusion in transgenic A. thaliana. When co-expressed in Arabidopsis, the YefM_Spn antitoxin was found to neutralize the toxicity of YoeB_Spn-GFP. Interestingly, the inducible expression of both yefM_Spn antitoxin and yoeB_Spn toxin-GFP fusion in transgenic hybrid Arabidopsis resulted in larger rosette leaves and taller plants with a higher number of inflorescence stems and increased silique production. To our knowledge, this is the first demonstration of a prokaryotic antitoxin neutralizing its cognate toxin in plant cells. Full article

(This article belongs to the Section Molecular Toxicology)

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Soluble Epidermal Growth Factor Receptors (sEGFRs) in Cancer: Biological Aspects and Clinical Relevance

by Sally Maramotti, Massimiliano Paci, Gloria Manzotti, Cristian Rapicetta, Mila Gugnoni, Carla Galeone, Alfredo Cesario and Filippo Lococo

Int. J. Mol. Sci. 2016, 17(4), 593; https://doi.org/10.3390/ijms17040593 - 19 Apr 2016

Cited by 37 | Viewed by 7908

Abstract

The identification of molecules that can reliably detect the presence of a tumor or predict its behavior is one of the biggest challenges of research in cancer biology. Biological fluids are intriguing mediums, containing many molecules that express the individual health status and, [...] Read more.

The identification of molecules that can reliably detect the presence of a tumor or predict its behavior is one of the biggest challenges of research in cancer biology. Biological fluids are intriguing mediums, containing many molecules that express the individual health status and, accordingly, may be useful in establishing the potential risk of cancer, defining differential diagnosis and prognosis, predicting the response to treatment, and monitoring the disease progression. The existence of circulating soluble growth factor receptors (sGFRs) deriving from their membrane counterparts has stimulated the interest of researchers to investigate the use of such molecules as potential cancer biomarkers. But what are the origins of circulating sGFRs? Are they naturally occurring molecules or tumor-derived products? Among these, the epidermal growth factor receptor (EGFR) is a cell-surface molecule significantly involved in cancer development and progression; it can be processed into biological active soluble isoforms (sEGFR). We have carried out an extensive review of the currently available literature on the sEGFRs and their mechanisms of regulation and biological function, with the intent to clarify the role of these molecules in cancer (and other pathological conditions) and, on the basis of the retrieved evidences, speculate about their potential use in the clinical setting. Full article

(This article belongs to the Special Issue Molecular Classification of Human Cancer: Diagnosis and Treatment 2016)

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