bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flexible Nanosomes (SECosomes) Enable Efficient siRNA Delivery in Cultured Primary Skin Cells and in the Viable Epidermis of Ex Vivo Human Skin
Authors: Geusens Barbara , Van Gele Mireille , Braat Sien , De Smedt Stefaan C. , Stuart Marc C. A. , Prow Tarl W. , Sanchez Washington , Roberts Michael S. , Sanders Niek N. , Lambert Jo 
Published: September 2010

AbstractThe extent to which nanoscale‐engineered systems cross intact human skin and can exert pharmacological effects in viable epidermis is controversial. This research seeks to develop a new lipid‐based nanosome that enables the effective delivery of siRNA into human skin. The major finding is that an ultraflexible siRNA‐containing nanosome—prepared using DOTAP, cholesterol, sodium cholate, and 30% ethanol—penetrates into the epidermis of freshly excised intact human skin and is able to enter into the keratinocytes. The nanosomes, called surfactant‐ethanol‐cholesterol‐osomes (SECosomes), show excellent size, surface charge, morphology, deformability, transfection efficiency, stability, and skin penetration capacity after complexation with siRNA. Importantly, these nanosomes have ideal characteristics for siRNA encapsulation, in that the siRNA is stable for at least 4 weeks, they enable highly efficient transfection of in vitro cultured cells, and are shown to transport siRNA delivery through intact human skin where changes in the keratinocyte cell state are demonstrated. It is concluded that increasing flexibility in nanosomes greatly enhances their ability to cross the intact human epidermal membrane and to unload their payload into targeted epidermal cells.
Auditory Morphology and Hearing Sensitivity in Fossil New World Monkeys
Authors: Coleman Mark N. , Kay Richard F. , Colbert Matthew W. 
Published: September 2010

AbstractIn recent years it has become possible to investigate the hearing capabilities in fossils by analogy with studies in living taxa that correlate the bony morphology of the auditory system with hearing sensitivity. In this analysis, we used a jack‐knife procedure to test the accuracy of one such study that examined the functional morphology of the primate auditory system and we found that low‐frequency hearing (sound pressure level at 250 Hz) can be predicted with relatively high confidence (±3–8 dB depending on the structure). Based on these functional relationships, we then used high‐resolution computed tomography to examine the auditory region of three fossil New World monkeys (Homunculus, Dolicocebus, and Tremacebus) and compared their morphology and predicted low‐frequency sensitivity with a phylogenetically diverse sample of extant primates. These comparisons reveal that these extinct taxa shared many auditory characteristics with living platyrrhines. However, the fossil with the best preserved auditory region (Homunculus) also displayed a few unique features such as the relative size of the tympanic membrane and stapedial footplate and the degree of trabeculation of the anterior accessory cavity. Still, the majority of evidence suggests that these fossil species likely had similar low‐frequency sensitivity to extant South American monkeys. This research adds to the small but growing body of evidence on the evolution of hearing abilities in extinct taxa and lays the groundwork for predicting hearing sensitivity in additional fossil primate specimens. Anat Rec 293:1711–1721, 2010. © 2010 Wiley‐Liss, Inc.
Antler Transformation is Advanced by Inversion of Antlerogenic Periosteum Implants in Sika Deer (Cervus nippon)
Authors: Gao Xiuhua , Yang Fuhe , Zhao Haiping , Wang Wenying , Li Chunyi 
Published: September 2010

AbstractDeer antlers offer a unique model for the study of tissue‐specific stem cells and organogenesis, as antler stem cells are confined to the antlerogenic periosteum (AP), a tissue that can be readily located (overlying a frontal crest) and experimentally manipulated. AP consists of an upper fibrous layer and a lower cellular layer. Tissue transplantation and membrane insertion experiments demonstrated that antler formation is triggered by the interactions between AP and the overlying skin. Interestingly, fairly normal antlers can be induced to grow by an inverted AP implant (the AP cellular layer facing the skin) at an ectopic site, raising the question whether the initial inductive signal is derived from the fibrous layer or cellular layer or both. To answer this question, in this study we used eight sika deer stag calves and selected one side of future antler growth region for implanting inverted AP and the contralateral side for noninverted AP as the control. The results showed that implantation of the AP discs in an inverted orientation generated pedicles with final height (17 ± 5.1 mm), less than half the height of those formed from the noninverted AP implants (45 ± 11.7 mm). Critically, antler transformation was initiated from a shorter pedicle, which was formed from the region where the AP cellular layer was brought in close proximity to the overlying skin. Therefore, the AP cellular layer, as opposed to the AP fibrous layer, is likely to be the main source of the initial inductive molecules for antlerogenesis. Anat Rec 293:1787–1796, 2010. © 2010 Wiley‐Liss, Inc.
Fiber Type Composition of the Sternomastoid and Diaphragm Muscles of Dystrophin‐Deficient mdx Mice
Authors: Guido Anderson Neri , Campos Gerson Eduardo Rocha , Neto Humberto Santo , Marques Maria Julia , Minatel Elaine 
Published: September 2010

AbstractThe muscle fiber phenotype is mainly determined by motoneuron innervation and changes in neuromuscular interaction alter the muscle fiber type. In dystrophin‐deficient mdx mice, changes in the molecular assembly of the neuromuscular junction and in nerve terminal sprouting occur in the sternomastoid (STN) muscle during early stages of the disease. In this study, we were interested to see whether early changes in neuromuscular assembly are correlated with alterations in fiber type in dystrophic STN at 2 months of age. A predominance of hybrid fast myofibers (about 52% type IIDB) was observed in control (C57Bl/10) STN. In mdx muscle, the lack of dystrophin did not change this profile (about 54% hybrid type IIDB). Pure fast type IID fibers predominated in normal and dystrophic diaphragm (DIA; about 39% in control and 30% in mdx muscle) and a population of slow Type I fibers was also present (about 10% in control and 13% in mdx muscle). In conclusion, early changes in neuromuscular assembly do not affect the fiber type composition of dystrophic STN. In contrast to the pure fast fibers of the more affected DIA, the hybrid phenotype of the STN may permit dynamic adaptations during progression of the disease. Anat Rec 293:1722–1728, 2010. © 2010 Wiley‐Liss, Inc.
First Evidence of a Leptin‐Like Peptide in a Cartilaginous Fish
Authors: Gambardella Chiara , Gallus Lorenzo , Ravera Silvia , Fasulo Salvatore , Vacchi Marino , Ferrando Sara 
Published: September 2010

AbstractLeptin is a hormone involved in food intake. Although leptin is evolutionarily conserved, no studies have investigated its presence in cartilaginous fish. Here, we report the presence of leptin‐like immunoreactivity in the gastro‐intestinal tract and liver of the cartilaginous fish Scyliorhinus canicula using western blot and immunohistochemical analyses. A leptin‐like immunoreactive band of 16 kDa was detected in the homogenate of the stomach, whereas no immunoreactivity was observed in the intestine or the liver. Immunohistochemistry of the gastric mucosa revealed leptin‐like staining localized to mucous‐secreting cells and endocrine cells. This is the first report of a leptin‐like peptide in a cartilaginous fish. Anat Rec 293:1692–1697, 2010. © 2010 Wiley‐Liss, Inc.
Ground‐penetrating radar assessment of the medieval arch bridge of San Antón, Galicia, Spain
Authors: Solla M. , Lorenzo H. , Novo A. , Rial F.I. 
Published: September 2010

AbstractSeveral arched masonry bridges are listed historical monuments in Spain, which are valued tourist attractions or local landmarks. They are maintained by several organizations dedicated to the cultural heritage such as the International Council on Monuments and Sites (ICOMOS). Many of these important structures are the oldest constructions still in use within the transportation infrastructure and as a result of the increase in traffic loads and their age they have undergone some structural decay. Ground‐penetrating radar (GPR) has been shown to be valuable in evaluating the state of conservation of the San Antón medieval bridge in order to help preserve its historical character. This bridge was surveyed by using the 200, 250 and 500 MHz antennas. Interpretation and analysis of GPR reflection data were supported by finite‐difference time domain numerical modelling, based on the accurate external geometry obtained with three‐dimensional laser scanning methods. Results show that GPR mapping provides valuable information for detecting an internal structural element used for reinforcement as well as a possible interior hidden arch that remains from ancient times. This information is noteworthy for archaeologists and civil engineers as it can be used to make decisions about stability and for future strengthening measures. Copyright © 2010 John Wiley & Sons, Ltd.
Cucurbit[7]uril as a Tool in the Green Synthesis of Gold Nanoparticles
Authors: Premkumar Thathan , Geckeler Kurt E. 
Published: September 2010

AbstractA simple, green, one‐pot synthesis of gold nanoparticles was achieved through the reaction of an aqueous mixture of potassium tetrachloroaurate(III) and the macrocycle cucurbit[7]uril in the presence of sodium hydroxide at room temperature without introducing any kind of traditional reducing agents and/or external energy. The as‐prepared gold nanoparticles showed catalytic activity for the reduction reaction of 4‐nitrophenol in the presence of NaBH4, which has been established by visual inspection and UV/Vis spectroscopy. This report is the first for the preparation of gold nanoparticles using cucurbit[7]uril in aqueous media through chemical reduction without employing conventional reducing agents and/or external energy.
Formulation and evaluation of chitosan microspheres of aceclofenac for colon‐targeted drug delivery
Authors: Umadevi S. K. , Thiruganesh R. , Suresh S. , Reddy K. Bhaskar 
Published: September 2010

AbstractThe objective of this investigation was to develop novel colon specific drug delivery. Aceclofenac, a NSAID, was successfully encapsulated into chitosan microspheres. Various formulations were prepared by varying the ratio of chitosan, span‐85 and stirring speed and the amount of glutaraldehyde. The SEM study showed that microspheres have smooth surfaces. Microspheres were characterised by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) to confirm the absence of chemical interactions between drug and polymer and to know the formation of microspheres structure. The microspheres were evaluated for particle size, encapsulation efficiency, drug loading capacity, mucoadhesion studies, stability studies,in vitroandin vivodrug release studies. Particle sizes, as measured by the laser light scattering technique, were of an average size in the range 41–80 µm. The swelling index was in the range 0.37–0.82 and the entrapment efficiency range was 51–75% for all the formulations. The optimised batch ACM13released 83.6% at 8 h and 104% at 24 h in SCF containing rat caecal content. Eudragit coated chitosan microspheres prevented the release of the aceclofenac in the physiological environment of the stomach and small intestine and released 95.9±0.34% in the colon. With regard to release kinetics, the data were best fitted with the Higuchi model and showed zero order release with non‐Fickian diffusion mechanism. Thein vivofindings suggest that aceclofenac microspheres exhibit a prolonged effect of aceclofenac in rats and produce a significant anti‐inflammatory effect. The findings of the present study conclusively state that chitosan microspheres are promising for colon targeting of aceclofenac to synchronise with chronobiological symptoms of rheumatoid arthritis. Copyright © 2010 John Wiley & Sons, Ltd.
Altered electrolyte handling of the choroid plexus in rats with glycerol‐induced acute renal failure
Authors: Ishikawa Atsuko , Kono Kentaro , Sakae Rie , Aiba Tetsuya , Kawasaki Hiromu , Kurosaki Yuji 
Published: September 2010

AbstractThe altered electrolyte handling of the choroid plexus was investigated in rats with acute renal failure (ARF) using lithium and rubidium as surrogate markers for sodium and potassium, respectively. Firstly, the transport of these two markers from the plasma to cerebrospinal fluid (CSF) was evaluated after they were concurrently injected into the femoral vein. As a result, their disposition from the plasma to CSF was shown to decrease in ARF rats, but the relationship profile between those two markers was not different from that observed in normal rats, indicating that the decreased disposition of lithium and rubidium occurs without affecting the stoichiometric balance. To clarify the mechanisms accounting for the decreased disposition, an inhibition study was then performed. When bumetanide, an inhibitor of the Na+/K+/2Cl−co‐transporter, was directly introduced into the cerebroventricle prior to lithium and rubidium being intravenously administered, a marked increase in the markers' disposition was observed. However, such an increased disposition did not occur when bumetanide was injected into the femoral vein. Other inhibitors, such as amiloride for the Na+/H+exchanger and ouabain for Na+/K+‐ATPase, did not show any effects on marker disposition regardless of the inhibitor being administered into either the cerebroventricle or femoral vein. These findings suggest that the decreased marker disposition in ARF rats is due to an increased efflux process of the choroid plexus mediated by the Na+/K+/2Cl−co‐transporter. That is, electrolyte efflux from the CSF to plasma increases, and thereby the electrolyte influx from the plasma to CSF is counteracted. Copyright © 2010 John Wiley & Sons, Ltd.
Zebrafish: A tool for chemical screens
Authors: Tsang Michael 
Published: September 2010

AbstractThe zebrafish has proven to be an invaluable vertebrate animal model for developmental biology. Recent technological advances have added an arsenal of tools to expand its use into the realm of drug discovery. This includes methodology to generate transgenic reporter lines that allow for the direct visualization of fluorescent markers in live embryos. With the addition of automated imaging and analysis of embryos treated with small molecules, these innovations have expanded its utility into high throughput chemical screens. This review will highlight some of these advances that have propelled zebrafish as a tool for drug discovery. Birth Defects Research (Part C) 90:185–192, 2010. © 2010 Wiley‐Liss, Inc.
Mechanobiology of embryonic skeletal development: Insights from animal models
Authors: Nowlan Niamh C. , Sharpe James , Roddy Karen A. , Prendergast Patrick J. , Murphy Paula 
Published: September 2010

AbstractA range of clinical conditions in which fetal movement is reduced or prevented can have a severe effect on skeletal development. Animal models have been instrumental to our understanding of the interplay between mechanical forces and skeletal development, particularly the mouse and the chick model systems. In the chick, the most commonly used means of altering the mechanical environment is by pharmaceutical agents which induce paralysis, whereas genetically modified mice with nonfunctional or absent skeletal muscle offer a valuable tool for examining the interplay between muscle forces and skeletogenesis in mammals. This article reviews the body of research on animal models of bone or joint formation in vivo in the presence of an altered or abnormal mechanical environment. In both immobilized chicks and “muscleless limb” mice, a range of effects are seen, such as shorter rudiments with less bone formation, changes in rudiment and joint shape, and abnormal joint cavitation. However, although all bones and synovial joints are affected in immobilized chicks, some rudiments and joints are unaffected in muscleless mice. We propose that extrinsic mechanical forces from movements of the mother or littermates impact on skeletogenesis in mammals, whereas the chick embryo is reliant on intrinsic movement for mechanical stimulation. The insights gained from animal models into the mechanobiology of embryonic skeletal development could provide valuable cues to prospective tissue engineers of cartilage and bone and contribute to new or improved treatments to minimize the impact on skeletal development of reduced movement in utero. Birth Defects Research (Part C) 90:203–213, 2010. © 2010 Wiley‐Liss, Inc.
Therapeutic potential of activators and inhibitors of sirtuins
Authors: Balcerczyk Aneta , Pirola Luciano 
Published: September 2010

AbstractSirtuins are evolutionary conserved NAD+‐dependent acetyl‐lysine deacetylases and ADP ribosyltransferases dual‐function enzymes involved in the regulation of metabolism and lifespan. Sirtuins are also implicated in determining the balance between apoptosis, cell survival, and cell proliferation. In humans, seven sirtuins isoforms (SIRT1–7) have been identified that localize either in the nucleus, cytoplasm, or mitochondria. The genetic demonstration that increasing gene dosage of sirtuin orthologs in eukaryotes, including yeast and multicellular Caenorhabditis elegans and Drosophila melanogaster, leads to prolonged lifespan induced considerable interest toward the discovery of sirtuin‐activating molecules, on the ground that the phenomenon of sirtuin‐induced lifespan prolongation—which is consequential to improved metabolic control—can be exploited therapeutically to counteract insulin resistance and diabetes. Conversely, ample evidence that either pharmacological inhibition or activation of sirtuin isoforms is potentially beneficial in study models of cancer and neurodegenerative diseases have been obtained. Here, we (i) survey the key roles of sirtuin isoforms and discuss the evidence in favor of activatory versus inhibitory targeting of sirtuins, (ii) discuss some of the inhibitors and activators of the sirtuin family members that have been described in the literature, (iii) review model systems in which these molecules have proved to exert therapeutic effects, and (iv) discuss the outcome of pharmacokinetic studies and phase I and II clinical trials employing sirtuin modulators. © 2010 International Union of Biochemistry and Molecular Biology, Inc.
Neuroprotective properties of resveratrol in different neurodegenerative disorders
Authors: Albani Diego , Polito Letizia , Signorini Alessandra , Forloni Gianluigi 
Published: September 2010

AbstractThe natural phytocompound resveratrol has been considered for many years a potential anticancer drug, but recently it has come to the attention of neuroscientist too, as it displays neuroprotective actions and activates the sirtuins' family member SIRT1. Sirtuins are enzymes with preferential deacetylase activity. Human sirtuins are coded by seven genes (SIRT1‐7). The most investigated sirtuin is SIRT1, which is involved in several physiologic and pathologic processes including apoptosis, autophagy, diabetes, cancer, cardiovascular disorders, and neurodegeneration. Resveratrol has neuroprotective features both in vitro and in vivo in models of Alzheimer's disease (AD), but it has proved to be beneficial also in ischemic stroke, Parkinson's disease, Huntington's disease, and epilepsy. Here, we summarize the in vitro and in vivo experimental results highlighting the possible role of resveratrol as neuroprotective biofactor with a particular focus on AD.
Pineapple bromelain induces autophagy, facilitating apoptotic response in mammary carcinoma cells
Authors: Bhui Kulpreet , Tyagi Shilpa , Prakash Bharti , Shukla Yogeshwer 
Published: September 2010

AbstractBromelain, from pineapple, possesses potent anticancer effects. We investigated autophagic phenomenon in mammary carcinoma cells (estrogen receptor positive and negative) under bromelain treatment and also illustrated the relationship between autophagy and apoptosis in MCF‐7 cells. MCF‐7 cells exposed to bromelain showed delayed growth inhibitory response and induction of autophagy, identified by monodansylcadaverine localization. It was succeeded by apoptotic cell death, evident by sub‐G1 cell fraction and apoptotic features like chromatin condensation and nuclear cleavage. 3‐Methyladenine (MA, autophagy inhibitor) pretreatment reduced the bromelain‐induced autophagic level, also leading to decline in apoptotic population, indicating that here autophagy facilitates apoptosis. However, addition of caspase‐9 inhibitor Z‐LEHD‐FMK augmented the autophagy levels, inhibited morphological apoptosis but did not prevent cell death. Next, we found that bromelain downregulated the phosphorylation of extracellular signal‐regulated kinase ½ (ERK½), whereas that of c‐jun N‐terminal kinase (JNK) and p38 kinase were upregulated. Also, MA had no influence on bromelain‐suppressed ERK½ activation, yet, it downregulated JNK and p38 activation. Also, addition of mitogen‐activated protein kinase (MAPK) inhibitors enhanced the autophagic ratios, which suggested the role of MAP kinases in bromelain‐induced autophagy. All three MAPKs were seen to be constantly activated over the time. Bromelain was seen to induce the expressions of autophagy‐related proteins, light chain 3 protein B II (LC3BII), and beclin‐1. Using ERK½ inhibitor, expressions of LC3BII and beclin‐1 increased, whereas p38 and JNK inhibitors decreased this protein expression, indicating that bromelain‐induced autophagy was positively regulated by p38 and JNK but negatively regulated by ERK½. Autophagy‐inducing property of bromelain can be further exploited in breast cancer therapy.
Bioactive Triterpenoids from Kadsura heteroclita
Authors: Xu Li‐Jia , Peng Zong‐Gen , Chen Hong‐Shan , Wang Jie , Xiao Pei‐Gen 
Published: September 2010

AbstractA phytochemical study of Kadsura heteroclita led to the isolation of eight triterpenoids, including two new compounds, named kadheterilactone A (1) and kadheterilactone B (2), as well as six known compounds, longipedlactone H (3), longipedlactone A (4), longipedlactone F (5), kadsuranic acid A (6), nigranoic acid (7), and schisandronic acid (8). Their structures were elucidated on the basis of spectroscopic methods, including 2D NMR techniques. The cytotoxic activities of 1–8 were tested against several tumor cell lines by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium hydrobromide (MTT) assay in vitro. As a result, 4 and 5 turned out to be significantly cytotoxic against Hep‐G2 and Bel‐7402 tumor cell lines. All compounds were also tested for inhibition on HIV‐1 protease (PR) and reverse transcriptase (RT). Compounds 6 and 7 showed strong inhibition on HIV‐1 PR, while 8 exhibited moderate activity, others were only weakly active. No compounds were active against HIV‐1 RT.
Regulation of the 5‐HT3A Receptor‐Mediated Current by Alkyl 4‐Hydroxybenzoates Isolated from the Seeds ofNelumbo nucifera
Authors: Joung Youn Ui , Lee Jun‐Ho , Lee Yoo Jin , Nam Joo Won , Bae Hyunsu , Seo Eun‐Kyoung 
Published: September 2010

AbstractFour known alkyl 4‐hydroxybenzoates,i.e., methyl 4‐hydroxybenzoate (1), ethyl 4‐hydroxybenzoate (2), propyl 4‐hydroxybenzoate (3), and butyl 4‐hydroxybenzoate (4), were isolated from the seeds ofNelumbo nuciferaGaertner(Nymphaeaceae) for the first time. The structures of the isolates were identified by 1D‐ and 2D‐NMR spectroscopy and comparison with published values. The compounds were evaluated for their effects on the 5‐HT‐stimulated inward current (I5‐HT) mediated by the human 5‐HT3A receptors expressed inXenopusoocytes. Compounds1and2enhanced theI5‐HT, but4reduced it. These results indicate that4is an inhibitor of the 5‐HT3A receptors expressed inXenopusoocytes.