International Journal of Molecular Sciences

1133 KiB

Open AccessArticle

Identification of Amplified Fragment Length Polymorphism (AFLP) Markers Tightly Associated with Drought Stress Gene in Male Sterile and Fertile Salvia miltiorrhiza Bunge

by Yuejin Zhang, Lijun Guo, Zhiming Shu, Yiyue Sun, Yuanyuan Chen, Zongsuo Liang and Hongbo Guo

Int. J. Mol. Sci. 2013, 14(3), 6518-6528; https://doi.org/10.3390/ijms14036518 - 22 Mar 2013

Cited by 10 | Viewed by 8318

Abstract

Consistent grain yield in drought environment has attracted wide attention due to global climate change. However, the important drought-related traits/genes in crops have been rarely reported. Many near-isogenic lines (NILs) of male sterile and fertile Salvia miltiorrhiza have been obtained in our previous [...] Read more.

Consistent grain yield in drought environment has attracted wide attention due to global climate change. However, the important drought-related traits/genes in crops have been rarely reported. Many near-isogenic lines (NILs) of male sterile and fertile Salvia miltiorrhiza have been obtained in our previous work through testcross and backcross in continuous field experiments conducted in 2006–2009. Both segregating sterile and fertile populations were subjected to bulked segregant analysis (BSA) and amplified fragment length polymorphism (AFLP) with 384 and 170 primer combinations, respectively. One out of 14 AFLP markers (E9/M3₂₄₆) was identified in treated fertile population as tightly linked to the drought stress gene with a recombination frequency of 6.98% and at a distance of 7.02 cM. One of 15 other markers (E2/M5₃₅₇) was identified in a treated sterile population that is closely associated with the drought stress gene. It had a recombination frequency of 4.65% and at a distance of 4.66 cM. Interestingly, the E9/M3₂₄₆ fragment was found to be identical to another AFLP fragment E11/M4₂₀₈ that was tightly linked to the male sterile gene of S. miltiorrhiza with 95% identity and e-value 4 × 10⁻⁹³. Blastn analysis suggested that the drought stress gene sequence showed higher identity with nucleotides in Arabidopsis chromosome 1–5. Full article

(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)

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19 KiB

Open AccessCorrection

Correction: Liang, J., et al. Antisense Oligonucleotide Against Clusterin Regulates Human Hepatocellular Carcinoma Invasion Through Transcriptional Regulation of Matrix Metalloproteinase-2 and E-Cadherin. Int. J. Mol. Sci. 2012, 13, 10594-10607

by Dong Chen, Yan Wang, Kejun Zhang, Xuelong Jiao, Bomin Yan and Jun Liang

Int. J. Mol. Sci. 2013, 14(3), 6516-6517; https://doi.org/10.3390/ijms14036516 - 22 Mar 2013

Viewed by 5345

Abstract

The original version of the paper reports that “OGX-011 is a second generation 21-mer oligonucleotide with a 20-O-(2-methoxy)-ethyl modification, generously provided by OncoGenex Technologies (OncoGenex, Vancouver, Canada)” [1] (p. 10602). OGX-011 was not provided by OncoGenex Technologies directly. Therefore, we would [...] Read more.

The original version of the paper reports that “OGX-011 is a second generation 21-mer oligonucleotide with a 20-O-(2-methoxy)-ethyl modification, generously provided by OncoGenex Technologies (OncoGenex, Vancouver, Canada)” [1] (p. 10602). OGX-011 was not provided by OncoGenex Technologies directly. Therefore, we would like to correct the wording to: “OGX-011 was obtained without the benefit of an agreement with OncoGenex, or The University British Columbia, or any other party”. The authors would like to apologize for any inconvenience this may have caused to the readers of this journal. [...] Full article

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Open AccessArticle

Preparation of a Paeonol-Containing Temperature-Sensitive In Situ Gel and Its Preliminary Efficacy on Allergic Rhinitis

by Kedan Chu, Lidian Chen, Wei Xu, Huang Li, Yuqin Zhang, Weirong Xie and Jian Zheng

Int. J. Mol. Sci. 2013, 14(3), 6499-6515; https://doi.org/10.3390/ijms14036499 - 22 Mar 2013

Cited by 45 | Viewed by 7321

Abstract

In this paper, the optimal composition of a paeonol temperature-sensitive in situ gel composed of poloxamer 407 (P407) was determined, and a preliminary study of its effect on allergic rhinitis was performed. The optimal composition of the paeonol temperature-sensitive in situ gel included [...] Read more.

In this paper, the optimal composition of a paeonol temperature-sensitive in situ gel composed of poloxamer 407 (P407) was determined, and a preliminary study of its effect on allergic rhinitis was performed. The optimal composition of the paeonol temperature-sensitive in situ gel included 2% paeonol inclusion, 22% P407, 2% poloxamer 188 (P188) and 2% PEG6000, as assessed by thermodynamic and rheological studies. The toad palate model was employed to study the toxicity of the paeonol temperature-sensitive in situ gel on the nasal mucosa. The result of this experiment showed low toxicity to cilia, which allows the gel to be used for nasal administration. The Franz diffusion cell method was used to study the in vitro release of paeonol and suggested that the in vitro release was in line with the Higuchi equation. This result suggests that the paeonol could be absorbed into the body through mucous membranes and had some characteristics of a sustained effect. Finally, the guinea pig model of ovalbumin sensitized allergic rhinitis was used to evaluate the preliminary efficacy of the gel, with the paeonol temperature-sensitive in situ gel showing a significant effect on the guinea pig model of sensitized allergic rhinitis (AR). Full article

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Open AccessReview

RUFY, Rab and Rap Family Proteins Involved in a Regulation of Cell Polarity and Membrane Trafficking

by Yasuko Kitagishi and Satoru Matsuda

Int. J. Mol. Sci. 2013, 14(3), 6487-6498; https://doi.org/10.3390/ijms14036487 - 21 Mar 2013

Cited by 26 | Viewed by 8778

Abstract

Cell survival, homeostasis and cell polarity rely on the control of membrane trafficking pathways. The RUN domain (comprised of the RPIP8, UNC-14, and NESCA proteins) has been suggested to be implicated in small GTPase-mediated membrane trafficking and cell polarity. Accumulating evidence supports the [...] Read more.

Cell survival, homeostasis and cell polarity rely on the control of membrane trafficking pathways. The RUN domain (comprised of the RPIP8, UNC-14, and NESCA proteins) has been suggested to be implicated in small GTPase-mediated membrane trafficking and cell polarity. Accumulating evidence supports the hypothesis that the RUN domain-containing proteins might be responsible for an interaction with a filamentous network linked to actin cytoskeleton and/or microtubules. In addition, several downstream molecules of PI3K are involved in regulation of the membrane trafficking by interacting with vesicle-associated RUN proteins such as RUFY family proteins. In this review, we summarize the background of RUN domain research with an emphasis on the interaction between RUN domain proteins including RUFY proteins (designated as RUN and FYVE domain-containing proteins) and several small GTPases with respect to the regulation of cell polarity and membrane trafficking on filamentous network Full article

(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications)

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Open AccessArticle

Differential Expression of Genes Associated with the Progression of Renal Disease in the Kidneys of Liver-Specific Glucokinase Gene Knockout Mice

by Wei Xu, Hui Li, Rong Wang, Zhen Lei, Yiqing Mao, Xi Wang, Yizhuang Zhang, Tingting Guo, Rongjing Song, Xiaojing Zhang, Ling Jin, Zhixin Li, David M. Irwin, Gang Niu and Huanran Tan

Int. J. Mol. Sci. 2013, 14(3), 6467-6486; https://doi.org/10.3390/ijms14036467 - 21 Mar 2013

Cited by 9 | Viewed by 8291

Abstract

Liver glucokinase (GCK) deficient mice possess mild renal complications associated with diabetes. To investigate the progression of kidney disease and identify candidate genes involved in the pathogenesis of renal damage, we examined changes in tissue structure and gene expression in the kidneys of [...] Read more.

Liver glucokinase (GCK) deficient mice possess mild renal complications associated with diabetes. To investigate the progression of kidney disease and identify candidate genes involved in the pathogenesis of renal damage, we examined changes in tissue structure and gene expression in the kidneys of liver-specific GCK knockout (gck^w/−) mice and age-matched normal wild-type control (gck^w/w) mice as they aged. Suppression subtractive hybridization (SSH) was used to identify candidate genes that showed a pattern of differential expression between kidneys of gck^w/− and gck^w/w mice at 60 weeks of age. Differential expression of the candidate genes was examined by real-time qPCR in liver-specific gck^w/− and gck^w/w mice at 16, 26, 40, 60, and 85 weeks of age. Among the candidate genes, only glutathione peroxidase-3 (GPX3) was confirmed to show differential expression by qPCR in the 60-week old mice, however two others genes, MALAT1 and KEG, showed significant changes at other ages. This study shows that liver-specific glucokinase deficient mice display changes in kidney morphology by 40 weeks of age, and that renal complication may be correlated with a reduction in GPX3 levels. Since decreased GPX3 mRNA expression was observed at 26 weeks, which is younger than the age when pathological changes can be seen in kidney biopsies, GPX3 may serve as an early marker for kidney damage. Full article

(This article belongs to the Special Issue Oxidative Stress and Ageing)

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Open AccessReview

UPR Signal Activation by Luminal Sensor Domains

by Marta Carrara, Filippo Prischi and Maruf M. U. Ali

Int. J. Mol. Sci. 2013, 14(3), 6454-6466; https://doi.org/10.3390/ijms14036454 - 21 Mar 2013

Cited by 38 | Viewed by 10092

Abstract

The unfolded protein response (UPR) is a cell-signaling system that detects the accumulation of unfolded protein within the endoplasmic reticulum (ER) and initiates a number of cellular responses to restore ER homeostasis. The presence of unfolded protein is detected by the ER-luminal sensor [...] Read more.

The unfolded protein response (UPR) is a cell-signaling system that detects the accumulation of unfolded protein within the endoplasmic reticulum (ER) and initiates a number of cellular responses to restore ER homeostasis. The presence of unfolded protein is detected by the ER-luminal sensor domains of the three UPR-transducer proteins IRE1, PERK, and ATF6, which then propagate the signal to the cytosol. In this review, we discuss the various mechanisms of action that have been proposed on how the sensor domains detect the presence of unfolded protein to activate downstream UPR signaling. Full article

(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)

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Open AccessArticle

Thermostable Mismatch-Recognizing Protein MutS Suppresses Nonspecific Amplification during Polymerase Chain Reaction (PCR)

by Kenji Fukui, Yoshitaka Bessho, Atsuhiro Shimada, Shigeyuki Yokoyama and Seiki Kuramitsu

Int. J. Mol. Sci. 2013, 14(3), 6436-6453; https://doi.org/10.3390/ijms14036436 - 21 Mar 2013

Cited by 11 | Viewed by 10462

Abstract

Polymerase chain reaction (PCR)-related technologies are hampered mainly by two types of error: nonspecific amplification and DNA polymerase-generated mutations. Here, we report that both errors can be suppressed by the addition of a DNA mismatch-recognizing protein, MutS, from a thermophilic bacterium. Although it [...] Read more.

Polymerase chain reaction (PCR)-related technologies are hampered mainly by two types of error: nonspecific amplification and DNA polymerase-generated mutations. Here, we report that both errors can be suppressed by the addition of a DNA mismatch-recognizing protein, MutS, from a thermophilic bacterium. Although it had been expected that MutS has a potential to suppress polymerase-generated mutations, we unexpectedly found that it also reduced nonspecific amplification. On the basis of this finding, we propose that MutS binds a mismatched primer-template complex, thereby preventing the approach of DNA polymerase to the 3' end of the primer. Our simple methodology improves the efficiency and accuracy of DNA amplification and should therefore benefit various PCR-based applications, ranging from basic biological research to applied medical science. Full article

(This article belongs to the Special Issue Molecular Cut and Paste)

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Open AccessReview

Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy

by Chih-Hung Lee, Shi-Bei Wu, Chien-Hui Hong, Hsin-Su Yu and Yau-Huei Wei

Int. J. Mol. Sci. 2013, 14(3), 6414-6435; https://doi.org/10.3390/ijms14036414 - 20 Mar 2013

Cited by 202 | Viewed by 26927

Abstract

The human skin is an integral system that acts as a physical and immunological barrier to outside pathogens, toxicants, and harmful irradiations. Environmental ultraviolet rays (UV) from the sun might potentially play a more active role in regulating several important biological responses in [...] Read more.

The human skin is an integral system that acts as a physical and immunological barrier to outside pathogens, toxicants, and harmful irradiations. Environmental ultraviolet rays (UV) from the sun might potentially play a more active role in regulating several important biological responses in the context of global warming. UV rays first encounter the uppermost epidermal keratinocytes causing apoptosis. The molecular mechanisms of UV-induced apoptosis of keratinocytes include direct DNA damage (intrinsic), clustering of death receptors on the cell surface (extrinsic), and generation of ROS. When apoptotic keratinocytes are processed by adjacent immature Langerhans cells (LCs), the inappropriately activated Langerhans cells could result in immunosuppression. Furthermore, UV can deplete LCs in the epidermis and impair their migratory capacity, leading to their accumulation in the dermis. Intriguingly, receptor activator of NF-κB (RANK) activation of LCs by UV can induce the pro-survival and anti-apoptotic signals due to the upregulation of Bcl-xL, leading to the generation of regulatory T cells. Meanwhile, a physiological dosage of UV can also enhance melanocyte survival and melanogenesis. Analogous to its effect in keratinocytes, a therapeutic dosage of UV can induce cell cycle arrest, activate antioxidant and DNA repair enzymes, and induce apoptosis through translocation of the Bcl-2 family proteins in melanocytes to ensure genomic integrity and survival of melanocytes. Furthermore, UV can elicit the synthesis of vitamin D, an important molecule in calcium homeostasis of various types of skin cells contributing to DNA repair and immunomodulation. Taken together, the above-mentioned effects of UV on apoptosis and its related biological effects such as proliferation inhibition, melanin synthesis, and immunomodulations on skin residential cells have provided an integrated biochemical and molecular biological basis for phototherapy that has been widely used in the treatment of many dermatological diseases. Full article

(This article belongs to the Special Issue UV-Induced Cell Death 2012)

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Graphical abstract

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Open AccessReview

The Influence of Metal Stress on the Availability and Redox State of Ascorbate, and Possible Interference with Its Cellular Functions

by An Bielen, Tony Remans, Jaco Vangronsveld and Ann Cuypers

Int. J. Mol. Sci. 2013, 14(3), 6382-6413; https://doi.org/10.3390/ijms14036382 - 20 Mar 2013

Cited by 95 | Viewed by 9189

Abstract

Worldwide, metals have been distributed to excessive levels in the environment due to industrial and agricultural activities. Plants growing on soils contaminated with excess levels of metals experience a disturbance of the cellular redox balance, which leads to an augmentation of reactive oxygen [...] Read more.

Worldwide, metals have been distributed to excessive levels in the environment due to industrial and agricultural activities. Plants growing on soils contaminated with excess levels of metals experience a disturbance of the cellular redox balance, which leads to an augmentation of reactive oxygen species (ROS). Even though the increased ROS levels can cause cellular damage, controlled levels play an important role in modulating signaling networks that control physiological processes and stress responses. Plants control ROS levels using their antioxidative defense system both under non-stress conditions, as well as under stress conditions such as exposure to excess metals. Ascorbate (AsA) is a well-known and important component of the plant’s antioxidative system. As primary antioxidant, it can reduce ROS directly and indirectly via ascorbate peroxidase in the ascorbate–glutathione cycle. Furthermore, AsA fulfills an essential role in physiological processes, some of which are disturbed by excess metals. In this review, known direct effects of excess metals on AsA biosynthesis and functioning will be discussed, as well as the possible interference of metals with the role of AsA in physiological and biochemical processes. Full article

(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)

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Open AccessReview

Ubiquitinations in the Notch Signaling Pathway

by Julien Moretti and Christel Brou

Int. J. Mol. Sci. 2013, 14(3), 6359-6381; https://doi.org/10.3390/ijms14036359 - 19 Mar 2013

Cited by 54 | Viewed by 11592

Abstract

The very conserved Notch pathway is used iteratively during development and adulthood to regulate cell fates. Notch activation relies on interactions between neighboring cells, through the binding of Notch receptors to their ligands, both transmembrane molecules. This inter-cellular contact initiates a cascade of [...] Read more.

The very conserved Notch pathway is used iteratively during development and adulthood to regulate cell fates. Notch activation relies on interactions between neighboring cells, through the binding of Notch receptors to their ligands, both transmembrane molecules. This inter-cellular contact initiates a cascade of events eventually transforming the cell surface receptor into a nuclear factor acting on the transcription of specific target genes. This review highlights how the various processes undergone by Notch receptors and ligands that regulate the pathway are linked to ubiquitination events. Full article

(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)

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Graphical abstract

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Open AccessArticle

Abnormal Skeletal Growth in Adolescent Idiopathic Scoliosis Is Associated with Abnormal Quantitative Expression of Melatonin Receptor, MT2

by Annie Po-yee Yim, Hiu-yan Yeung, Guangquan Sun, Kwong-man Lee, Tzi-bun Ng, Tsz-ping Lam, Bobby Kin-wah Ng, Yong Qiu, Alain Moreau and Jack Chun-yiu Cheng

Int. J. Mol. Sci. 2013, 14(3), 6345-6358; https://doi.org/10.3390/ijms14036345 - 19 Mar 2013

Cited by 21 | Viewed by 7992

Abstract

The defect of the melatonin signaling pathway has been proposed to be one of the key etiopathogenic factors in adolescent idiopathic scoliosis (AIS). A previous report showed that melatonin receptor, MT2, was undetectable in some AIS girls. The present study aimed to investigate [...] Read more.

The defect of the melatonin signaling pathway has been proposed to be one of the key etiopathogenic factors in adolescent idiopathic scoliosis (AIS). A previous report showed that melatonin receptor, MT2, was undetectable in some AIS girls. The present study aimed to investigate whether the abnormal MT2 expression in AIS is quantitative or qualitative. Cultured osteoblasts were obtained from 41 AIS girls and nine normal controls. Semi-quantification of protein expression by Western blot and mRNA expression by TaqMan real-time PCR for both MT1 and MT2 were performed. Anthropometric parameters were also compared and correlated with the protein expression and mRNA expression of the receptors. The results showed significantly lower protein and mRNA expression of MT2 in AIS girls compared with that in normal controls (p = 0.02 and p = 0.019, respectively). No differences were found in the expression of MT1. When dichotomizing the AIS girls according to their MT2 expression, the group with low expression was found to have a significantly longer arm span (p = 0.036). The results of this study showed for the first time a quantitative change of MT2 in AIS that was also correlated with abnormal arm span as part of abnormal systemic skeletal growth. Full article

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

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Open AccessReview

Mitochondria and Reactive Oxygen Species: Physiology and Pathophysiology

by Subhashini Bolisetty and Edgar A. Jaimes

Int. J. Mol. Sci. 2013, 14(3), 6306-6344; https://doi.org/10.3390/ijms14036306 - 19 Mar 2013

Cited by 215 | Viewed by 16488

Abstract

The air that we breathe contains nearly 21% oxygen, most of which is utilized by mitochondria during respiration. While we cannot live without it, it was perceived as a bane to aerobic organisms due to the generation of reactive oxygen and nitrogen metabolites [...] Read more.

The air that we breathe contains nearly 21% oxygen, most of which is utilized by mitochondria during respiration. While we cannot live without it, it was perceived as a bane to aerobic organisms due to the generation of reactive oxygen and nitrogen metabolites by mitochondria and other cellular compartments. However, this dogma was challenged when these species were demonstrated to modulate cellular responses through altering signaling pathways. In fact, since this discovery of a dichotomous role of reactive species in immune function and signal transduction, research in this field grew at an exponential pace and the pursuit for mechanisms involved began. Due to a significant number of review articles present on the reactive species mediated cell death, we have focused on emerging novel pathways such as autophagy, signaling and maintenance of the mitochondrial network. Despite its role in several processes, increased reactive species generation has been associated with the origin and pathogenesis of a plethora of diseases. While it is tempting to speculate that anti-oxidant therapy would protect against these disorders, growing evidence suggests that this may not be true. This further supports our belief that these reactive species play a fundamental role in maintenance of cellular and tissue homeostasis. Full article

(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)

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Open AccessReview

Annexin A2 Heterotetramer: Structure and Function

by Alamelu Bharadwaj, Moamen Bydoun, Ryan Holloway and David Waisman

Int. J. Mol. Sci. 2013, 14(3), 6259-6305; https://doi.org/10.3390/ijms14036259 - 19 Mar 2013

Cited by 233 | Viewed by 27334

Abstract

Annexin A2 is a pleiotropic calcium- and anionic phospholipid-binding protein that exists as a monomer and as a heterotetrameric complex with the plasminogen receptor protein, S100A10. Annexin A2 has been proposed to play a key role in many processes including exocytosis, endocytosis, membrane [...] Read more.

Annexin A2 is a pleiotropic calcium- and anionic phospholipid-binding protein that exists as a monomer and as a heterotetrameric complex with the plasminogen receptor protein, S100A10. Annexin A2 has been proposed to play a key role in many processes including exocytosis, endocytosis, membrane organization, ion channel conductance, and also to link F-actin cytoskeleton to the plasma membrane. Despite an impressive list of potential binding partners and regulatory activities, it was somewhat unexpected that the annexin A2-null mouse should show a relatively benign phenotype. Studies with the annexin A2-null mouse have suggested important functions for annexin A2 and the heterotetramer in fibrinolysis, in the regulation of the LDL receptor and in cellular redox regulation. However, the demonstration that depletion of annexin A2 causes the depletion of several other proteins including S100A10, fascin and affects the expression of at least sixty-one genes has confounded the reports of its function. In this review we will discuss the annexin A2 structure and function and its proposed physiological and pathological roles. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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Graphical abstract

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Open AccessArticle

Adsorption and Orientation of Human Islet Amyloid Polypeptide (hIAPP) Monomer at Anionic Lipid Bilayers: Implications for Membrane-Mediated Aggregation

by Yan Jia, Zhenyu Qian, Yun Zhang and Guanghong Wei

Int. J. Mol. Sci. 2013, 14(3), 6241-6258; https://doi.org/10.3390/ijms14036241 - 19 Mar 2013

Cited by 33 | Viewed by 8941

Abstract

Protein misfolding and aggregation cause serious degenerative diseases, such as Alzheimer’s and type II diabetes. Human islet amyloid polypeptide (hIAPP) is the major component of amyloid deposits found in the pancreas of type II diabetic patients. Increasing evidence suggests that β-cell death is [...] Read more.

Protein misfolding and aggregation cause serious degenerative diseases, such as Alzheimer’s and type II diabetes. Human islet amyloid polypeptide (hIAPP) is the major component of amyloid deposits found in the pancreas of type II diabetic patients. Increasing evidence suggests that β-cell death is related to the interaction of hIAPP with the cellular membrane, which accelerates peptide aggregation. In this study, as a first step towards understanding the membrane-mediated hIAPP aggregation, we investigate the atomic details of the initial step of hIAPP-membrane interaction, including the adsorption orientation and conformation of hIAPP monomer at an anionic POPG lipid bilayer by performing all-atom molecular dynamics simulations. We found that hIAPP monomer is quickly adsorbed to bilayer surface, and the adsorption is initiated from the N-terminal residues driven by strong electrostatic interactions of the positively-charged residues K1 and R11 with negatively-charged lipid headgroups. hIAPP binds parallel to the lipid bilayer surface as a stable helix through residues 7–22, consistent with previous experimental study. Remarkably, different simulations lead to the same binding orientation stabilized by electrostatic and H-bonding interactions, with residues R11, F15 and S19 oriented towards membrane and hydrophobic residues L12, A13, L16 and V17 exposed to solvent. Implications for membrane-mediated hIAPP aggregation are discussed. Full article

(This article belongs to the Special Issue Protein Folding)

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Open AccessArticle

Gold-Coated Iron Composite Nanospheres Targeted the Detection of Escherichia coli

by Ugur Tamer, Demet Cetin, Zekiye Suludere, Ismail Hakkı Boyaci, Havva Tumay Temiz, Hande Yegenoglu, Philippe Daniel, İlker Dinçer and Yalçın Elerman

Int. J. Mol. Sci. 2013, 14(3), 6223-6240; https://doi.org/10.3390/ijms14036223 - 18 Mar 2013

Cited by 50 | Viewed by 13028

Abstract

We report the preparation and characterization of spherical core-shell structured Fe₃O₄–Au magnetic nanoparticles, modified with two component self-assembled monolayers (SAMs) consisting of 3–mercaptophenylboronic acid (3–MBA) and 1–decanethiol (1–DT). The rapid and room temperature synthesis of magnetic nanoparticles was achieved [...] Read more.

We report the preparation and characterization of spherical core-shell structured Fe₃O₄–Au magnetic nanoparticles, modified with two component self-assembled monolayers (SAMs) consisting of 3–mercaptophenylboronic acid (3–MBA) and 1–decanethiol (1–DT). The rapid and room temperature synthesis of magnetic nanoparticles was achieved using the hydroxylamine reduction of HAuCl₄ on the surface of ethylenediaminetetraacetic acid (EDTA)-immobilized iron (magnetite Fe₃O₄) nanoparticles in the presence of an aqueous solution of hexadecyltrimetylammonium bromide (CTAB) as a dispersant. The reduction of gold on the surface of Fe₃O₄ nanoparticles exhibits a uniform, highly stable, and narrow particle size distribution of Fe₃O₄–Au nanoparticles with an average diameter of 9 ± 2 nm. The saturation magnetization value for the resulting nanoparticles was found to be 15 emu/g at 298 K. Subsequent surface modification with SAMs against glucoside moieties on the surface of bacteria provided effective magnetic separation. Comparison of the bacteria capturing efficiency, by means of different molecular recognition agents 3–MBA, 1–DT and the mixed monolayer of 3–MBA and 1–DT was presented. The best capturing efficiency of E. coli was achieved with the mixed monolayer of 3–MBA and 1–DT-modified nanoparticles. Molecular specificity and selectivity were also demonstrated by comparing the surface-enhanced Raman scattering (SERS) spectrum of E. coli-nanoparticle conjugates with bacterial growth media. Full article

(This article belongs to the Special Issue Magnetic Nanoparticles 2013)

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Open AccessArticle

Combinatorial Analysis of Secretory Immunoglobulin A (sIgA) Expression in Plants

by Paloma Juarez, Estefania Huet-Trujillo, Alejandro Sarrion-Perdigones, Erica Elvira Falconi, Antonio Granell and Diego Orzaez

Int. J. Mol. Sci. 2013, 14(3), 6205-6222; https://doi.org/10.3390/ijms14036205 - 18 Mar 2013

Cited by 28 | Viewed by 9151

Abstract

Delivery of secretory immunoglobulin A (sIgA) to mucosal surfaces as a passive immunotherapy agent is a promising strategy to prevent infectious diseases. Recombinant sIgA production in plants requires the co-expression of four transcriptional units encoding the light chain (LC), heavy chain (HC), joining [...] Read more.

Delivery of secretory immunoglobulin A (sIgA) to mucosal surfaces as a passive immunotherapy agent is a promising strategy to prevent infectious diseases. Recombinant sIgA production in plants requires the co-expression of four transcriptional units encoding the light chain (LC), heavy chain (HC), joining chain (JC) and secretory component (SC). As a way to optimize sIgA production in plants, we tested the combinatorial expression of 16 versions of a human sIgA against the VP8* rotavirus antigen in Nicotiana benthamiana, using the recently developed GoldenBraid multigene assembly system. Each sIgA version was obtained by combining one of the two types of HC (α1 and α2) with one of the two LC types (k and λ) and linking or not a KDEL peptide to the HC and/or SC. From the analysis of the anti-VP8* activity, it was concluded that those sIgA versions carrying HCα1 and LCλ provided the highest yields. Moreover, ER retention significantly increased antibody production, particularly when the KDEL signal was linked to the SC. Maximum expression levels of 32.5 μg IgA/g fresh weight (FW) were obtained in the best performing combination, with an estimated 33% of it in the form of a secretory complex. Full article

(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)

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Open AccessArticle

A Novel Moderate Constitutive Promoter Derived from Poplar (Populus tomentosa Carrière)

by Zhong Chen, Jia Wang, Mei-Xia Ye, Hao Li, Le-Xiang Ji, Ying Li, Dong-Qing Cui, Jun-Mei Liu and Xin-Min An

Int. J. Mol. Sci. 2013, 14(3), 6187-6204; https://doi.org/10.3390/ijms14036187 - 18 Mar 2013

Cited by 13 | Viewed by 10291

Abstract

A novel sequence that functions as a promoter element for moderate constitutive expression of transgenes, designated as the PtMCP promoter, was isolated from the woody perennial Populus tomentosa. The PtMCP promoter was fused to the GUS reporter gene to characterize its expression [...] Read more.

A novel sequence that functions as a promoter element for moderate constitutive expression of transgenes, designated as the PtMCP promoter, was isolated from the woody perennial Populus tomentosa. The PtMCP promoter was fused to the GUS reporter gene to characterize its expression pattern in different species. In stable Arabidopsis transformants, transcripts of the GUS reporter gene could be detected by RT-PCR in the root, stem, leaf, flower and silique. Further histochemical and fluorometric GUS activity assays demonstrated that the promoter could direct transgene expression in all tissues and organs, including roots, stems, rosette leaves, cauline leaves and flowers of seedlings and maturing plants. Its constitutive expression pattern was similar to that of the CaMV35S promoter, but the level of GUS activity was significantly lower than in CaMV35S promoter::GUS plants. We also characterized the promoter through transient expression in transgenic tobacco and observed similar expression patterns. Histochemical GUS staining and quantitative analysis detected GUS activity in all tissues and organs of tobacco, including roots, stems, leaves, flower buds and flowers, but GUS activity in PtMCP promoter::GUS plants was significantly lower than in CaMV35S promoter::GUS plants. Our results suggested that the PtMCP promoter from poplar is a constitutive promoter with moderate activity and that its function is presumably conserved in different species. Therefore, the PtMCP promoter may provide a practical choice to direct moderate level constitutive expression of transgenes and could be a valuable new tool in plant genetic engineering. Full article

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Open AccessReview

The Lipid Transfer Protein StarD7: Structure, Function, and Regulation

by Jésica Flores-Martin, Viviana Rena, Sofía Angeletti, Graciela M. Panzetta-Dutari and Susana Genti-Raimondi

Int. J. Mol. Sci. 2013, 14(3), 6170-6186; https://doi.org/10.3390/ijms14036170 - 18 Mar 2013

Cited by 28 | Viewed by 10469

Abstract

The steroidogenic acute regulatory (StAR) protein-related lipid transfer (START) domain proteins constitute a family of evolutionarily conserved and widely expressed proteins that have been implicated in lipid transport, metabolism, and signaling. The 15 well-characterized mammalian START domain-containing proteins are grouped into six subfamilies. [...] Read more.

The steroidogenic acute regulatory (StAR) protein-related lipid transfer (START) domain proteins constitute a family of evolutionarily conserved and widely expressed proteins that have been implicated in lipid transport, metabolism, and signaling. The 15 well-characterized mammalian START domain-containing proteins are grouped into six subfamilies. The START domain containing 7 mRNA encodes StarD7, a member of the StarD2/phosphatidylcholine transfer protein (PCTP) subfamily, which was first identified as a gene overexpressed in a choriocarcinoma cell line. Recent studies show that the StarD7 protein facilitates the delivery of phosphatidylcholine to the mitochondria. This review summarizes the latest advances in StarD7 research, focusing on the structural and biochemical features, protein-lipid interactions, and mechanisms that regulate StarD7 expression. The implications of the role of StarD7 in cell proliferation, migration, and differentiation are also discussed. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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Open AccessArticle

LC-MS/MS Determination of Isoprostanes in Plasma Samples Collected from Mice Exposed to Doxorubicin or Tert-Butyl Hydroperoxide

by Monika Janicka, Agata Kot-Wasik, Jolanta Paradziej-Łukowicz, Grażyna Sularz-Peszyńska, Agnieszka Bartoszek and Jacek Namieśnik

Int. J. Mol. Sci. 2013, 14(3), 6157-6169; https://doi.org/10.3390/ijms14036157 - 18 Mar 2013

Cited by 19 | Viewed by 8574

Abstract

Isoprostanes are stable products of arachidonic acid peroxidation and are regarded as the most reliable markers of oxidative stress in vivo. Here we describe the LC-MS/MS procedure enabling simultaneous determination of four regioisomers (8-iso prostaglandin F_2α, 8-iso-15(R)-prostaglandin [...] Read more.

Isoprostanes are stable products of arachidonic acid peroxidation and are regarded as the most reliable markers of oxidative stress in vivo. Here we describe the LC-MS/MS procedure enabling simultaneous determination of four regioisomers (8-iso prostaglandin F_2α, 8-iso-15(R)-prostaglandin F_2α, 11β-prostaglandin F_2α, 15(R)-prostaglandin F_2α) in plasma samples collected from mice. The four plasma isoprostanes are determined by LC–ESI-MS/MS with deuterated 8-iso-PGF_2α-d₄ as an internal standard (I.S.). For plasma samples spiked with the isoprostanes at a level of 200 pg/mL each, the method imprecision has been below 7.1% and mean inaccuracy equaled 8.7%. The applicability of the proposed approach has been verified by the assessment of changes in isoprostane levels in plasma samples derived from mice exposed to tert-butyl hydroperoxide (TBHP), a model inducer of oxidative stress, or to antitumor drug doxorubicin (DOX) known for potent stimulation of redox cycling. Compared to the control group of mice, both oxidative stress inducers tested increased the levels of three out of four isoprostanes in exposed animals; 11β-prostaglandin F_2α being the exception. The greatest rise was observed in the case of 15(R)-prostaglandin F_2α, by about 50% and 70% in plasma samples derived from mice exposed to DOX and TBHP, respectively. Full article

(This article belongs to the Special Issue Oxidative Stress and Ageing)

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Open AccessLetter

CentroidAlign-Web: A Fast and Accurate Multiple Aligner for Long Non-Coding RNAs

by Haruka Yonemoto, Kiyoshi Asai and Michiaki Hamada

Int. J. Mol. Sci. 2013, 14(3), 6144-6156; https://doi.org/10.3390/ijms14036144 - 18 Mar 2013

Cited by 4 | Viewed by 7453

Abstract

Due to the recent discovery of non-coding RNAs (ncRNAs), multiple sequence alignment (MSA) of those long RNA sequences is becoming increasingly important for classifying and determining the functional motifs in RNAs. However, not only primary (nucleotide) sequences, but also secondary structures of ncRNAs [...] Read more.

Due to the recent discovery of non-coding RNAs (ncRNAs), multiple sequence alignment (MSA) of those long RNA sequences is becoming increasingly important for classifying and determining the functional motifs in RNAs. However, not only primary (nucleotide) sequences, but also secondary structures of ncRNAs are closely related to their function and are conserved evolutionarily. Hence, information about secondary structures should be considered in the sequence alignment of ncRNAs. Yet, in general, a huge computational time is required in order to compute MSAs, taking secondary structure information into account. In this paper, we describe a fast and accurate web server, called CentroidAlign-Web, which can handle long RNA sequences. The web server also appropriately incorporates information about known secondary structures into MSAs. Computational experiments indicate that our web server is fast and accurate enough to handle long RNA sequences. CentroidAlign-Web is freely available from http://centroidalign.ncrna.org/. Full article

(This article belongs to the Special Issue Non-Coding RNAs 2012)

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Open AccessReview

Cadmium-Induced Pathologies: Where Is the Oxidative Balance Lost (or Not)?

by Ambily Ravindran Nair, Olivier DeGheselle, Karen Smeets, Emmy Van Kerkhove and Ann Cuypers

Int. J. Mol. Sci. 2013, 14(3), 6116-6143; https://doi.org/10.3390/ijms14036116 - 18 Mar 2013

Cited by 257 | Viewed by 16956

Abstract

Over the years, anthropogenic factors have led to cadmium (Cd) accumulation in the environment causing various health problems in humans. Although Cd is not a Fenton-like metal, it induces oxidative stress in various animal models via indirect mechanisms. The degree of Cd-induced oxidative [...] Read more.

Over the years, anthropogenic factors have led to cadmium (Cd) accumulation in the environment causing various health problems in humans. Although Cd is not a Fenton-like metal, it induces oxidative stress in various animal models via indirect mechanisms. The degree of Cd-induced oxidative stress depends on the dose, duration and frequency of Cd exposure. Also the presence or absence of serum in experimental conditions, type of cells and their antioxidant capacity, as well as the speciation of Cd are important determinants. At the cellular level, the Cd-induced oxidative stress either leads to oxidative damage or activates signal transduction pathways to initiate defence responses. This balance is important on how different organ systems respond to Cd stress and ultimately define the pathological outcome. In this review, we highlight the Cd-induced oxidant/antioxidant status as well as the damage versus signalling scenario in relation to Cd toxicity. Emphasis is addressed to Cd-induced pathologies of major target organs, including a section on cell proliferation and carcinogenesis. Furthermore, attention is paid to Cd-induced oxidative stress in undifferentiated stem cells, which can provide information for future therapies in preventing Cd-induced pathologies. Full article

(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)

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Open AccessArticle

Comparative Analysis of Serum (Anti)oxidative Status Parаmeters in Healthy Persons

by Eugène HJM Jansen and Tatjana Ruskovska

Int. J. Mol. Sci. 2013, 14(3), 6106-6115; https://doi.org/10.3390/ijms14036106 - 18 Mar 2013

Cited by 74 | Viewed by 8453

Abstract

Five antioxidant and two oxidative stress assays were applied to serum samples of 43 healthy males. The antioxidant tests showed different inter-assay correlations. A very good correlation of 0.807 was observed between the ferric reducing ability of plasma (FRAP) and total antioxidant status [...] Read more.

Five antioxidant and two oxidative stress assays were applied to serum samples of 43 healthy males. The antioxidant tests showed different inter-assay correlations. A very good correlation of 0.807 was observed between the ferric reducing ability of plasma (FRAP) and total antioxidant status (TAS) assay and also a fair correlation of 0.501 between the biological antioxidant potential (BAP) and TAS assay. There was no statistically significant correlation between the BAP and FRAP assay. The anti-oxidant assays have a high correlation with uric acid, especially the TAS (0.922) and FRAP assay (0.869). The BAP assay has a much lower and no statistically significant correlation with uric acid (0.302), which makes BAP more suitable for the antioxidant status. The total thiol assay showed no statistically significant correlation with uric acid (0.114). The total thiol assay, which is based on a completely different principle, showed a good and statistically significant correlation with the BAP assay (0.510) and also to the TAS assay, but to a lower and not significant extent (0.279) and not with the FRAP assay (−0.008). The oxy-adsorbent test (OXY) assay has no correlation with any of the other assays tested. The oxidative stress assays, reactive oxygen metabolites (ROM) and total oxidant status (TOS), based on a different principle, do not show a statistically significant correlation with the serum samples in this study. Both assays showed a negative, but not significant, correlation with the antioxidant assays. In conclusion, the ROM, TOS, BAP and TTP assays are based on different principles and will have an additional value when a combination of these assays will be applied in large-scale population studies. Full article

(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)

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Open AccessArticle

PAX2 Expression in Ovarian Cancer

by Huijuan Song, Suet-Yan Kwan, Daisy I. Izaguirre, Zhifei Zu, Yvonne T. Tsang, Celestine S. Tung, Erin R. King, Samuel C. Mok, David M. Gershenson and Kwong-Kwok Wong

Int. J. Mol. Sci. 2013, 14(3), 6090-6105; https://doi.org/10.3390/ijms14036090 - 15 Mar 2013

Cited by 25 | Viewed by 10539

Abstract

PAX2 is one of nine PAX genes that regulate tissue development and cellular differentiation in embryos. However, the functional role of PAX2 in ovarian cancer is not known. Twenty-six ovarian cancer cell lines with different histology origins were screened for PAX2 expression. Two [...] Read more.

PAX2 is one of nine PAX genes that regulate tissue development and cellular differentiation in embryos. However, the functional role of PAX2 in ovarian cancer is not known. Twenty-six ovarian cancer cell lines with different histology origins were screened for PAX2 expression. Two ovarian cancer cell lines: RMUGL (mucinous) and TOV21G (clear cell), with high PAX2 expression were chosen for further study. Knockdown PAX2 expression in these cell lines was achieved by lentiviral shRNAs targeting the PAX2 gene. PAX2 stable knockdown cells were characterized for cell proliferation, migration, apoptosis, protein profiles, and gene expression profiles. The result indicated that these stable PAX2 knockdown cells had reduced cell proliferation and migration. Microarray analysis indicated that several genes involved in growth inhibition and motility, such as G0S2, GREM1, and WFDC1, were up-regulated in PAX2 knockdown cells. On the other hand, over-expressing PAX2 in PAX2-negative ovarian cell lines suppressed their cell proliferation. In summary, PAX2 could have both oncogenic and tumor suppression functions, which might depend on the genetic content of the ovarian cancer cells. Further investigation of PAX2 in tumor suppression and mortality is warranty. Full article

(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)

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Open AccessArticle

Early Exercise Protects against Cerebral Ischemic Injury through Inhibiting Neuron Apoptosis in Cortex in Rats

by Pengyue Zhang, Yuling Zhang, Jie Zhang, Yi Wu, Jie Jia, Junfa Wu and Yongshan Hu

Int. J. Mol. Sci. 2013, 14(3), 6074-6089; https://doi.org/10.3390/ijms14036074 - 15 Mar 2013

Cited by 49 | Viewed by 10034

Abstract

Early exercise is an effective strategy for stroke treatment, but the underlying mechanism remains poorly understood. Apoptosis plays a critical role after stroke. However, it is unclear whether early exercise inhibits apoptosis after stroke. The present study investigated the effect of early exercise [...] Read more.

Early exercise is an effective strategy for stroke treatment, but the underlying mechanism remains poorly understood. Apoptosis plays a critical role after stroke. However, it is unclear whether early exercise inhibits apoptosis after stroke. The present study investigated the effect of early exercise on apoptosis induced by ischemia. Adult SD rats were subjected to transient focal cerebral ischemia by middle cerebral artery occlusion model (MCAO) and were randomly divided into early exercise group, non-exercise group and sham group. Early exercise group received forced treadmill training initiated at 24 h after operation. Fourteen days later, the cell apoptosis were detected by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) and Fluoro-Jade-B staining (F-J-B). Caspase-3, cleaved caspase-3 and Bcl-2 were determined by western blotting. Cerebral infarct volume and motor function were evaluated by cresyl violet staining and foot fault test respectively. The results showed that early exercise decreased the number of apoptotic cells (118.74 ± 6.15 vs. 169.65 ± 8.47, p < 0.05, n = 5), inhibited the expression of caspase-3 and cleaved caspase-3 (p < 0.05, n = 5), and increased the expression of Bcl-2 (p < 0.05, n = 5). These data were consistent with reduced infarct volume and improved motor function. These results suggested that early exercise could provide neuroprotection through inhibiting neuron apoptosis. Full article

(This article belongs to the Collection Programmed Cell Death and Apoptosis)

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Open AccessCase Report

A Case of Stage III c Ovarian Clear Cell Carcinoma: The Role for Predictive Biomarkers and Targeted Therapies

by Munmun Rahman, Kentaro Nakayama, Tomoka Ishibashi, Masako Ishikawa, Mohammed Tanjimur Rahman, Hiroshi Katagiri, Atsuko Katagiri, Kouji Iida, Yoshihiro Kikuchi and Kohji Miyazaki

Int. J. Mol. Sci. 2013, 14(3), 6067-6073; https://doi.org/10.3390/ijms14036067 - 15 Mar 2013

Cited by 6 | Viewed by 8089

Abstract

Ovarian cancer treatment presently does not reflect molecular differences in histologic subtype. Ovarian clear cell carcinoma (OCCC) exhibits several differences in terms of molecular pathogenesis and tumor behavior from the more common, chemosensitive, serous carcinomas, which makes OCCC a candidate for targeted therapies. [...] Read more.

Ovarian cancer treatment presently does not reflect molecular differences in histologic subtype. Ovarian clear cell carcinoma (OCCC) exhibits several differences in terms of molecular pathogenesis and tumor behavior from the more common, chemosensitive, serous carcinomas, which makes OCCC a candidate for targeted therapies. A 53-year-old Japanese woman was diagnosed with stage IIIc ovarian clear cell adenocarcinoma with marked chemoresistance to conventional regimens. She demonstrated a partial response to a multikinase inhibitor. The tumor was resistant to PI3K/mTOR pathway inhibitors despite harboring a PIK3CA mutation. The present case suggests a role for targeted therapies in the treatment of OCCC and a need for the identification of biomarkers that will predict response to targeted therapies. Full article

(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)

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Open AccessReview

The Role of Metallothionein in Oxidative Stress

by Branislav Ruttkay-Nedecky, Lukas Nejdl, Jaromir Gumulec, Ondrej Zitka, Michal Masarik, Tomas Eckschlager, Marie Stiborova, Vojtech Adam and Rene Kizek

Int. J. Mol. Sci. 2013, 14(3), 6044-6066; https://doi.org/10.3390/ijms14036044 - 15 Mar 2013

Cited by 635 | Viewed by 33501

Abstract

Free radicals are chemical particles containing one or more unpaired electrons, which may be part of the molecule. They cause the molecule to become highly reactive. The free radicals are also known to play a dual role in biological systems, as they can [...] Read more.

Free radicals are chemical particles containing one or more unpaired electrons, which may be part of the molecule. They cause the molecule to become highly reactive. The free radicals are also known to play a dual role in biological systems, as they can be either beneficial or harmful for living systems. It is clear that there are numerous mechanisms participating on the protection of a cell against free radicals. In this review, our attention is paid to metallothioneins (MTs) as small, cysteine-rich and heavy metal-binding proteins, which participate in an array of protective stress responses. The mechanism of the reaction of metallothioneins with oxidants and electrophilic compounds is discussed. Numerous reports indicate that MT protects cells from exposure to oxidants and electrophiles, which react readily with sulfhydryl groups. Moreover, MT plays a key role in regulation of zinc levels and distribution in the intracellular space. The connections between zinc, MT and cancer are highlighted. Full article

(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)

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Open AccessArticle

HE4 (WFDC2) Promotes Tumor Growth in Endometrial Cancer Cell Lines

by Jinping Li, Haibin Chen, Andrea Mariani, Dong Chen, Edward Klatt, Karl Podratz, Ronny Drapkin, Russell Broaddus, Sean Dowdy and Shi-Wen Jiang

Int. J. Mol. Sci. 2013, 14(3), 6026-6043; https://doi.org/10.3390/ijms14036026 - 15 Mar 2013

Cited by 61 | Viewed by 10989

Abstract

HE4, also known as WFDC2, is a useful biomarker for ovarian cancer when either used alone or in combination with CA125. HE4 is also overexpressed in endometrial cancer (EC), but its function in cancer cells is not clear. In this study, we investigate [...] Read more.

HE4, also known as WFDC2, is a useful biomarker for ovarian cancer when either used alone or in combination with CA125. HE4 is also overexpressed in endometrial cancer (EC), but its function in cancer cells is not clear. In this study, we investigate the role of HE4 in EC progression. An HE4-overexpression system was established by cloning the HE4 prototypic mRNA variant (HE4-V0) into a eukaryotic expression vector. Following transfection, stable clones in two EC cell lines were selected. The effects of HE4 overexpression on cell growth and function were measured with the use of cell proliferation assay, matrigel invasion, and soft agar gel colony formation assays. HE4-induced cancer cell proliferation in vivo was examined in a mouse xenograft model. HE4 overexpression significantly enhanced EC cell proliferation, matrigel invasion, and colony formation in soft agar. Moreover, HE4 overexpression promoted tumor growth in the mouse xenograft model. HE4 overexpression enhanced several malignant phenotypes in cell culture and in a mouse model. These results are consistent with our previous observation that high levels of serum HE4 closely correlate with the stage, myometrial invasion and tumor size in patients with EC. This study provides evidence that HE4 overexpression directly impacts tumor progression in endometrial cancer. Full article

(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)

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Open AccessArticle

Inhibitory Effect of Baicalin and Baicalein on Ovarian Cancer Cells

by Jianchu Chen, Zhaoliang Li, Allen Y. Chen, Xingqian Ye, Haitao Luo, Gary O. Rankin and Yi Charlie Chen

Int. J. Mol. Sci. 2013, 14(3), 6012-6025; https://doi.org/10.3390/ijms14036012 - 15 Mar 2013

Cited by 104 | Viewed by 11387

Abstract

Ovarian cancer is one of the primary causes of death for women all through the Western world. Baicalin and baicalein are naturally occurring flavonoids that are found in the roots and leaves of some Chinese medicinal plants and are thought to have antioxidant [...] Read more.

Ovarian cancer is one of the primary causes of death for women all through the Western world. Baicalin and baicalein are naturally occurring flavonoids that are found in the roots and leaves of some Chinese medicinal plants and are thought to have antioxidant activity and possible anti-angiogenic, anti-cancer, anxiolytic, anti-inflammatory and neuroprotective activities. Two kinds of ovarian cancer (OVCAR-3 and CP-70) cell lines and a normal ovarian cell line (IOSE-364) were selected to be investigated in the inhibitory effect of baicalin and baicalein on cancer cells. Largely, baicalin and baicalein inhibited ovarian cancer cell viability in both ovarian cancer cell lines with LD₅₀ values in the range of 45–55 µM for baicalin and 25–40 µM for baicalein. On the other hand, both compounds had fewer inhibitory effects on normal ovarian cells viability with LD₅₀ values of 177 µM for baicalin and 68 µM for baicalein. Baicalin decreased expression of VEGF (20 µM), cMyc (80 µM), and NFkB (20 µM); baicalein decreased expression of VEGF (10 µM), HIF-1α (20 µM), cMyc (20 µM), and NFkB (40 µM). Therefore baicalein is more effective in inhibiting cancer cell viability and expression of VEGF, HIF-1α, cMyc, and NFκB in both ovarian cancer cell lines. It seems that baicalein inhibited cancer cell viability through the inhibition of cancer promoting genes expression including VEGF, HIF-1α, cMyc, and NFκB. Overall, this study showed that baicalein and baicalin significantly inhibited the viability of ovarian cancer cells, while generally exerting less of an effect on normal cells. They have potential for chemoprevention and treatment of ovarian cancers. Full article

(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)

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Open AccessArticle

Alteration of Podocyte Protein Expression and Localization in the Early Stage of Various Hemodynamic Conditions

by Kai Li, Juan Wang, Xiaohui Yin, Xiaoyue Zhai and Zilong Li

Int. J. Mol. Sci. 2013, 14(3), 5998-6011; https://doi.org/10.3390/ijms14035998 - 15 Mar 2013

Cited by 9 | Viewed by 7000

Abstract

Given that podocalyxin (PCX) and nestin play important roles in podocyte morphogenesis and the maintenance of structural integrity, we examined whether the expression and localization of these two podocyte proteins were influenced in the early stage of various hemodynamic conditions. Mice kidney tissues [...] Read more.

Given that podocalyxin (PCX) and nestin play important roles in podocyte morphogenesis and the maintenance of structural integrity, we examined whether the expression and localization of these two podocyte proteins were influenced in the early stage of various hemodynamic conditions. Mice kidney tissues were prepared by in vivo cryotechnique (IVCT). The distribution of glomeruli and podocyte proteins was visualized with DAB staining, confocal laser scanning microscopy and immunoelectron microscopy. The mRNA levels were examined by real-time quantitative PCR. The results showed the following: Under the normal condition, PCX stained intensely along glomerular epithelial cells, whereas nestin was clearly staining in the endothelial cells and appeared only weakly in the podocytes. Under the acute hypertensive and cardiac arrest conditions, PCX and nestin staining was not clear, with a disarranged distribution, but the colocalization of PCX and nestin was apparent under this condition. In addition, under the acute hypertensive and cardiac arrest conditions, the mRNA levels of PCX and nestin were significantly decreased. Collectively, the abnormal redistribution and decreased mRNA expressions of PCX and nestin are important molecular events at the early stage of podocyte injury during hemodynamic disorders. IVCT may have more advantages for morphological analysis when researching renal diseases. Full article

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

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Open AccessReview

Integration of Multiple Signaling Pathways Determines Differences in the Osteogenic Potential and Tissue Regeneration of Neural Crest-Derived and Mesoderm-Derived Calvarial Bones

by Kshemendra Senarath-Yapa, Shuli Li, Nathaniel P. Meyer, Michael T. Longaker and Natalina Quarto

Int. J. Mol. Sci. 2013, 14(3), 5978-5997; https://doi.org/10.3390/ijms14035978 - 15 Mar 2013

Cited by 26 | Viewed by 9635

Abstract

The mammalian skull vault, a product of a unique and tightly regulated evolutionary process, in which components of disparate embryonic origin are integrated, is an elegant model with which to study osteoblast biology. Our laboratory has demonstrated that this distinct embryonic origin of [...] Read more.

The mammalian skull vault, a product of a unique and tightly regulated evolutionary process, in which components of disparate embryonic origin are integrated, is an elegant model with which to study osteoblast biology. Our laboratory has demonstrated that this distinct embryonic origin of frontal and parietal bones confer differences in embryonic and postnatal osteogenic potential and skeletal regenerative capacity, with frontal neural crest derived osteoblasts benefitting from greater osteogenic potential.We outline how this model has been used to elucidate some of the molecular mechanisms which underlie these differences and place these findings into the context of our current understanding of the key, highly conserved, pathways which govern the osteoblast lineage including FGF, BMP, Wnt and TGFβ signaling. Furthermore, we explore recent studies which have provided a tantalizing insight into way these pathways interact, with evidence accumulating for certain transcription factors, such as Runx2, acting as a nexus for cross-talk. Full article

(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)

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Int. J. Mol. Sci., Volume 14, Issue 3 (March 2013) – 115 articles , Pages 4375-6528

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