bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of GMP‐1 a molecular chaperone network modulator protecting mitochondrial function and its assessment in fly and mice models of Alzheimer's disease
Authors: Pavlov Pavel F. , Hutter‐Paier Birgit , Havas Daniel , Windisch Manfred , Winblad Bengt 
Published: April 2018

AbstractMitochondrial dysfunction is an early feature of Alzheimer's disease (AD) and may play an important role in the pathogenesis of disease. It has been shown that amyloid beta peptide (Aβ) and amyloid precursor protein (APP) interact with mitochondria contributing to the mitochondrial dysfunction in AD. Prevention of abnormal protein targeting to mitochondria can protect normal mitochondrial function, increase neuronal survival and at the end, ameliorate symptoms of AD and other neurodegenerative disorders. First steps of mitochondrial protein import are coordinated by molecular chaperones Hsp70 and Hsp90 that bind to the newly synthesized mitochondria‐destined proteins and deliver them to the protein import receptors on the surface of organelle. Here, we have described the development of a novel compound named GMP‐1 that disrupts interactions between Hsp70/Hsp90 molecular chaperones and protein import receptor Tom70. GMP‐1 treatment of SH‐SY5Y cells results in decrease in mitochondria‐associated APP and protects SH‐SY5Y cells from toxic effect of Aβ1‐42 exposure. Experiments in drosophila and mice models of AD demonstrated neuroprotective effect of GMP‐1 treatment, improvement in memory and behaviour tests as well as restoration of mitochondrial function.
Tretinoin (0.05% cream vs. 5% peel) for photoaging and field cancerization of the forearms: randomized, evaluator‐blinded, clinical trial
Authors: Sumita J.M. , Miot H.A. , Soares J.L.M. , Raminelli A.C.P. , Pereira S.M. , Ogawa M.M. , Picosse F.R. , Guadanhim L.R.S. , Enokihara M.M.S.S. , Leonardi G.R. , Bagatin E. 
Published: April 2018

AbstractBackgroundTopical tretinoin cream is the gold standard treatment for skin ageing, particularly photoaging. The purpose of tretinoin peel was to obtain similar results, but in a shorter time, however, there have been few controlled trials on its effectiveness.ObjectiveTo compare efficacy and safety of tretinoin 0.05% cream and 5% as a peeling agent on photoaging and field cancerization of the forearms.MethodsClinical trial with therapeutic intervention, prospective, randomized (computer‐generated randomization list), parallel, comparative (intrasubject) and evaluator‐blinded (except for histology and immunohistochemistry), including 24 women (48 forearms) aged over 60 years who have not undergone hormone replacement and categorized as Fitzpatrick skin phototype II or III. The forearms of the participants were randomized for treatment with 0.05% tretinoin cream three nights a week, or 5% tretinoin peel every 2 weeks. The opinion of the participant, severity of photoaging, corneometry, profilometry, high‐frequency ultrasound, histology (haematoxylin–eosin and Verhoeff stainings) and immunohistochemistry (p53, bcl‐2, Ki67 and collagen I) were assessed.ResultsOne participant dropped out. The mean photoaging score reduced 20% and the mean actinic keratosis (AK) count reduced 60% with no difference between treatments. Three efficacy parameters showed opposite effects between the tretinoin treatments (P < 0.05%): (i) thickness of the corneal layer decreased with 0.05% tretinoin and increased by 5%; (ii) dermis echogenicity increased by 0.05% and decreased by 5% and (iii) Ki67 expression increased by 0.05% and decreased by 5%. There was good tolerability for both regimens.ConclusionTretinoin as a cream 0.05% or peeling (5%) is safe and effective for the treatment of moderate photoaging and forearm field cancerization. The cream was superior in improving ultrasonographic parameters of ageing. Peeling was shown a superior performance in the stabilization of field cancerization.
Alitretinoin can be a good treatment option for idiopathic recalcitrant trachyonychia in adults: an open‐label study
Authors: Shin K. , Kim T.‐W. , Park S.‐M. , Lee H.‐J. , Jin H. , You H.‐S. , Shim W.‐H. , Kim G.‐W. , Kim H.‐S. , Ko H.‐C. , Kim B.‐S. , Kim M.‐B. 
Published: April 2018

AbstractBackgroundTrachyonychia can be refractory to conventional treatments including topical, intralesional or systemic corticosteroids, as well as cyclosporine and retinoids. Therefore, new treatment options are needed for recalcitrant trachyonychia.ObjectiveTo evaluate the efficacy and safety of oral alitretinoin for idiopathic recalcitrant trachyonychia.MethodsA total of 21 adult patients with 210 nails affected by idiopathic recalcitrant trachyonychia were evaluated in this open‐label prospective study. All patients took 30 mg of alitretinoin daily for at least 3 months. Clinical outcomes were assessed using the Physician Global Assessment (PGA) scale proposed by Park et al. (degree of roughness: 0, clear; 1, mild; 2, moderate; 3, marked; 4, severe) at baseline and 1, 3 and 6 months after treatment.ResultsAfter 1, 3 and 6 months of treatment, 74.3% (123/210), 98.1% (206/210) and 99.2% (119/120) of nails showed clinical improvement, respectively; 0% (0/210), 22.9% (48/210) and 69.2% (83/120) were completely free from nail abnormalities. The mean PGA score at baseline was 3.4, decreasing significantly to 2.7, 1.3 and 0.7 at 1, 3 and 6 months following treatment, respectively.LimitationsA small number of participants and lack of a control group were limitations.ConclusionsFor the first time, this study evaluated the efficacy and safety of oral alitretinoin for idiopathic recalcitrant trachyonychia in adults. The results suggest that oral alitretinoin can be a good treatment option for adult patients with recalcitrant trachyonychia.
Katharsis of the skin: peeling applications and agents of chemical peelings in Greek medical textbooks of Graeco‐Roman antiquity
Authors: Ursin F. , Steger F. , Borelli C. 
Published: April 2018

AbstractBackgroundRecipes for peelings date back to medical texts of old Egypt. The oldest medical papyri contain recipes for ‘improving beauty of the skin’ and ‘removing wrinkles’ by use of agents such as salt and soda. The Egyptian Queen Cleopatra (69–30 BC) is said to have taken bathes in donkey's milk to improve the beauty of her skin. However, little is known about other agents and peeling applications in later Greek medical textbooks.ObjectiveWe will discover new agents and describe ancient peeling applications. First, we will have to identify ancient Greek medical terms for the modern terms ‘peeling’ and ‘chemical peeling’. Second, on the basis of the identified terms, we will perform a systematic full‐text search for agents in original sources. Third, we will categorize the results into three peeling applications: (i) cleansing, (ii) aesthetical improvement of the skin and (iii) therapy of dermatological diseases.MethodsWe performed a full systematic keyword search with the identified Greek terms in databases of ancient Greek texts. Our keywords for peeling and chemical peeling are ‘smēxis’ and ‘trīpsis’. Our keywords for agents of peeling and chemical peeling are ‘smégmata’, ‘rhýmmata’, ‘kathartiká’ and ‘trímmata’.ResultsDiocles (4th century BC) was the first one who mentioned ‘smēxis’ and ‘trīpsis’ as parts of daily cleansing routine. Criton (2nd century AD) wrote about peeling applications, but any reference to the agents is lost. Antyllus (2nd century AD) composed three lists of peeling applications including their agents.ConclusionGreek medical textbooks of Graeco‐Roman antiquity report several peeling applications such as cleansing, brightening, darkening, softening and aesthetical improvement of the skin by use of peeling and chemical peeling, as well as therapy of dermatological diseases. There are 27 ancient agents for what is contemporarily called peeling and chemical peeling. We discovered more specific agents than hitherto known to research.
Comparison of PCR‐based methods for the diagnosis of cutaneous leishmaniasis in two different epidemiological scenarios: Spain and Morocco
Authors: Merino‐Espinosa G. , Rodríguez‐Granger J. , Morillas‐Márquez F. , Tercedor J. , Corpas‐López V. , Chiheb S. , Alcalde‐Alonso M. , Azaña‐Defez J.M. , Riyad M. , Díaz‐Sáez V. , Martín‐Sánchez J. 
Published: April 2018

AbstractBackgroundCutaneous leishmaniasis (CL) is a disfiguring and stigmatising disease occurring in more than 70 countries across the world including Spain and Morocco. The use of sensitive tests that can differentiate Leishmania species is advised.ObjectiveTo evaluate the influence of the epidemiological scenario on the reliability of the PCR techniques and contribute to the selection of the most efficient one for CL diagnosis.MethodsThe sensitivities of parasitological methods and four PCRs were compared in cutaneous samples from 77 patients from Spanish (PSH) and Moroccan hospitals (PMH). Exudates and fresh or paraffin‐embedded tissue biopsies were used.ResultsNone of the PCRs used in this study allowed the diagnosis of all CL cases, showing also some drawbacks. Lmj4/Uni21‐PCR displayed the best sensitivity with PMH, but it did not provide positive results in PSH with CL confirmed by other PCRs. Conversely, JW13/JW14‐PCR and L. infantum‐PCR‐ELISA displayed good sensitivities with PSH that were not achieved with PMH. Nested‐ITS‐1‐PCR did not show enough sensitivity with paraffin‐embedded tissue biopsies. False‐negative results were obtained in 19% of PSH due to unspecific hybridizations of ITS‐1 primers with human chromosome1.ConclusionsPCR should be routinely used in patients with cutaneous lesions compatible with CL and furthermore, the combination of two PCR techniques is advisable. The selection of these PCRs will be influenced by the epidemiological scenario: In areas where L. infantum is endemic, the use of the PCR‐ELISA joint with JW13/JW14‐PCR seems an appropriate choice, whereas in areas such as Morocco, Lmj4/Uni21 and ITS‐1 provide satisfactory results.
Leaf stage‐associated resistance is correlated with phytohormones in a pathosystem‐dependent manner
Authors: Xu You‐Ping , Lv Lin‐Hui , Xu Ya‐Jing , Yang Juan , Cao Jia‐Yi , Cai Xin‐Zhong 
Published: April 2018

AbstractIt has been reported in several pathosystems that disease resistance can vary in leaves at different stages. However, how general this leaf stage‐associated resistance is, and the molecular mechanism(s) underlying it, remain largely unknown. Here, we investigated the effect of leaf stage on basal resistance, effector‐triggered immunity (ETI) and nonhost resistance, using eight pathosystems involving the hosts Arabidopsis thaliana, Nicotiana tabacum, and N. benthamiana and the pathogens Sclerotinia sclerotiorum, Pseudomonas syringae pv. tabaci, P. syringae pv. tomato DC3000, and Xanthomonas oryzae pv. oryzae (Xoo). We show evidence that leaf stage‐associated resistance exists ubiquitously in plants, but with varying intensity at different stages in diverse pathosystems. Microarray expression profiling assays demonstrated that hundreds of genes involved in defense responses, phytohormone biosynthesis and signaling, and calcium signaling, were differentially expressed between leaves at different stages. The Arabidopsis mutants sid1, sid2‐3, ein2, jar1‐1, aba1 and aao3 lost leaf stage‐associated resistance to S. sclerotiorum, and the mutants aba1 and sid2‐3 were affected in leaf stage‐associated RPS2/AvrRpt2+‐conferred ETI, whereas only the mutant sid2‐3 influenced leaf stage‐associated nonhost resistance to Xoo. Our results reveal that the phytohormones salicylic acid, ethylene, jasmonic acid and abscisic acid likely play an essential, but pathosystem‐dependent, role in leaf stage‐associated resistance.
Calcium/calmodulin‐dependent kinase II and memory destabilization: a new role in memory maintenance
Authors: Vigil Fabio Antonio , Giese Karl Peter 
Published: April 2018

AbstractIn this review, we discuss the poorly explored role of calcium/calmodulin‐dependent protein kinase II (CaMKII) in memory maintenance, and its influence on memory destabilization. After a brief review on CaMKII and memory destabilization, we present critical pieces of evidence suggesting that CaMKII activity increases retrieval‐induced memory destabilization. We then proceed to propose two potential molecular pathways to explain the association between CaMKII activation and increased memory destabilization. This review will pinpoint gaps in our knowledge and discuss some ‘controversial’ observations, establishing the basis for new experiments on the role of CaMKII in memory reconsolidation. The role of CaMKII in memory destabilization is of great clinical relevance. Still, because of the lack of scientific literature on the subject, more basic science research is necessary to pursue this pathway as a clinical tool.
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The role of corticostriatal–hypothalamic neural circuits in feeding behaviour: implications for obesity
Authors: Clarke Rachel E. , Verdejo‐Garcia Antonio , Andrews Zane B. 
Published: April 2018

AbstractEmerging evidence from human imaging studies suggests that obese individuals have altered connectivity between the hypothalamus, the key brain region controlling energy homeostasis, and cortical regions involved in decision‐making and reward processing. Historically, animal studies have demonstrated that the lateral hypothalamus is the key hypothalamic region involved in feeding and reward. The lateral hypothalamus is a heterogeneous structure comprised of several distinct types of neurons which are scattered throughout. In addition, the lateral hypothalamus receives inputs from a number of cortical brain regions suggesting that it is uniquely positioned to be a key integrator of cortical information and metabolic feedback. In this review, we summarize how human brain imaging can inform detailed animal studies to investigate neural pathways connecting cortical regions and the hypothalamus. Here, we discuss key cortical brain regions that are reciprocally connected to the lateral hypothalamus and are implicated in decision‐making processes surrounding food.
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Are reflective models appropriate for very short scales? Proofs of concept of formative models using the Ten‐Item Personality Inventory
Authors: Myszkowski Nils , Storme Martin , Tavani Jean‐Louis 
Published: April 2018

AbstractObjectiveBecause of their length and objective of broad content coverage, very short scales can show limited internal consistency and structural validity. We argue that it is because their objectives may be better aligned with formative investigations than with reflective measurement methods that capitalize on content overlap. As proofs of concept of formative investigations of short scales, we investigate the Ten‐Item Personality Inventory (TIPI).MethodIn Study 1, we administered the TIPI and the Big Five Inventory (BFI) to 938 adults and fitted a formative Multiple Indicators Multiple Causes model, which consisted of the TIPI items forming five latent variables, which in turn predicted the five BFI scores. These results were replicated in Study 2 on a sample of 759 adults, but this time with the Revised NEO Personality Inventory (NEO‐PI‐R) as the external criterion.ResultsThe models fit the data adequately, and moderate to strong significant effects (.37 < |β| < .69, all ps < .001) of all five latent formative variables on their corresponding BFI and NEO‐PI‐R scores were observed.ConclusionsThis study presents a formative approach that we propose to be more consistent with the aims of scales with broad content and short length like the TIPI.
Potential role of periodontal pathogens in compromising epithelial barrier function by inducing epithelial‐mesenchymal transition
Authors: Abdulkareem A. A. , Shelton R. M. , Landini G. , Cooper P. R. , Milward M. R. 
Published: April 2018

Background and ObjectiveEpithelial‐mesenchymal transition (EMT) is a process by which epithelial cells acquire a mesenchymal‐like phenotype and this may be induced by exposure to gram‐negative bacteria. It has been proposed that EMT is responsible for compromising epithelial barrier function in the pathogenesis of several diseases. However, the possible role of EMT in the pathogenesis of periodontitis has not previously been investigated. The aim of this study therefore was to investigate whether gram‐negative, anaerobic periodontal pathogens could trigger EMT in primary oral keratinocytes in vitro.Material and MethodsPrimary oral keratinocytes were harvested from labial mandibular mucosa of Wistar Han rats. Cells were exposed to heat‐killed Fusobacterium nucleatum and Porphyromonas gingivalis (100 bacteria/epithelial cell) and to 20 μg/mL of Escherichia coli lipopolysaccharide over an 8‐day period. Exposure to bacteria did not significantly change epithelial cell number or vitality in comparison with unstimulated controls at the majority of time‐points examined. Expression of EMT marker genes was determined by semiquantitative RT‐PCR at 1, 5, and 8 days following stimulation. The expression of EMT markers was also assessed by immunofluorescence (E‐cadherin and vimentin) and using immunocytochemistry to determine Snail activation. The loss of epithelial monolayer coherence, in response to bacterial challenge, was determined by measuring trans‐epithelial electrical resistance. The induction of a migratory phenotype was investigated using scratch‐wound and transwell migration assays.ResultsExposure of primary epithelial cell cultures to periodontal pathogens was associated with a significant decrease in transcription (~3‐fold) of E‐cadherin and the upregulation of N‐cadherin, vimentin, Snail, matrix metalloproteinase‐2 (~3‐5 fold) and toll‐like receptor 4. Bacterial stimulation (for 8 days) also resulted in an increased percentage of vimentin‐positive cells (an increase of 20% after stimulation with P. gingivalis and an increase of 30% after stimulation with F. nucleatum, compared with controls). Furthermore, periodontal pathogens significantly increased the activation of Snail (60%) and cultures exhibited a decrease in electrical impedance (P < .001) in comparison with unexposed controls. The migratory ability of the cells increased significantly in response to bacterial stimulation, as shown by both the number of migrated cells and scratch‐wound closure rates.ConclusionProlonged exposure of primary rat oral keratinocyte cultures to periodontal pathogens generated EMT‐like features, which introduces the possibility that this process may be involved in loss of epithelial integrity during periodontitis.
Cementum protein 1 transfection does not lead to ultrastructural changes in nucleolar organization of human gingival fibroblasts
Authors: Villegas‐Mercado C. E. , Agredano‐Moreno L. T. , Bermúdez M. , Segura‐Valdez M. L. , Arzate H. , Del Toro‐Rangel E. F. , Jiménez‐García L. F. 
Published: April 2018

Background and ObjectiveTransfection of cementum protein 1 (CEMP1) into human gingival fibroblasts (HGFs) notably increases cell metabolism and results in overexpression of molecules related to biomineralization at transcriptional and protein levels. Therefore, HGF‐CEMP1 cells are considered as putative cementoblasts. This represents a significant advance in periodontal research because cementum neoformation is a key event in periodontal regeneration. In addition, it is well known that important changes in cell metabolism and protein expression are related to nucleolar structure and the function of this organelle, which is implicated in ribosome biogenesis. The aim of this study was to determine the effect of transfecting CEMP1 gene in human HGF on the ultrastructure of the nucleolus.Material and MethodsCells were processed using the conventional technique for transmission electron microscopy, fixed with glutaraldehyde, postfixed with osmium tetraoxide, and embedded in epoxy resin. Semi‐thin sections were stained with Toluidine blue and observed by light microscopy. Thin sections were stained with uranyl acetate and lead citrate. For ribonucleoprotein detection, the staining method based on the regressive effect of EDTA was used. In addition, the osmium ammine technique was used for specific staining of DNA.ResultsThe results obtained in this study suggest that transfection of CEMP1 into HGFs does not produce changes in the general nucleolar ultrastructure because the different components of the organelle are present as fibrillary centers, and dense fibrillar and granular components compared with the control.ConclusionThe transfection of CEMP1 into HGFs allows these cells to perform cementoblast‐like functions without alteration of the ultrastructure of the nucleolus, evaluated by the presence of the different compartments of this organelle involved in ribosomal biogenesis.
MicroRNA‐3064‐3p regulates the differentiation of cementoblasts through targeting DKK1
Authors: Wang C. , Liao H. , Sun H. , Zhang Y. , Cao Z. 
Published: April 2018

Background and ObjectiveMicroRNAs (miRNAs) are short, noncoding RNAs that interfere with translation of target mRNAs and thereby play a pivotal role in a variety of biological processes. Cementoblasts are the cells that build up cementum. They share a similar gene expression pattern with osteoblasts. Recent studies have suggested that miRNAs are able to control osteoblast‐mediated bone formation. However, the effects of miRNA on cementoblast differentiation still remain unsolved. Herein, we wanted to elucidate the role of miR‐3064‐3p in cementoblast differentiation.Material and MethodsA miRNA microarray was operated to explore the miRNA expression patterns during cementoblast differentiation. miR‐3064‐3p agomir/antagomir was used to promote or inhibit, respectively, the expression of miR‐3064‐3p. In order to measure the differentiation level of cementoblasts, quantitative RT‐PCR (qRT‐PCR), Alizarin red staining, and assessment of alkaline phosphatase activity were performed. Luciferase assays, qRT‐PCR, and western blotting were used to identify the target gene of miR‐3064‐3p.ResultsmiR‐3064‐3p showed persistently decreased expression during cementoblast differentiation. Overexpression of miR‐3064‐3p suppressed cementoblast differentiation, while inhibition of miR‐3064‐3p promoted cementoblast differentiation. Target prediction‐analysis tools and dual‐luciferase assay identified Dickkopf WNT signaling pathway inhibitor 1 (DKK1) as a direct target of miR‐3064‐3p. Results from qRT‐PCR and western blotting showed that inhibition of miR‐3064‐3p led to a remarkable increase in DKK1/Dickkopf related protein 1 (Dkk‐1) expression. In addition, pretreatment with recombinant Dickkopf related protein 1 (Dkk‐1) rescued the miR‐3064‐3p‐mediated suppression of cementoblast differentiation.ConclusionThis study demonstrates, for the first time, that miR‐3064‐3p suppresses cementoblast differentiation via the regulation of DKK1.