bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constitutive STAT3 activation in epidermal keratinocytes enhances cell clonogenicity and favours spontaneous immortalization by opposing differentiation and senescence checkpoints
Authors: Orecchia Valeria , Regis Gabriella , Tassone Beatrice , Valenti Chiara , Avalle Lidia , Saoncella Stefania , Calautti Enzo , Poli Valeria 
Published: November 2014

AbstractSTAT3, a pleiotropic transcription factor acting downstream of cytokines and growth factors, is known to enhance proliferation, migration, invasion and aerobic glycolysis in tumors upon aberrant activation. In the murine epidermis, STAT3 is necessary for experimentally induced carcinogenesis. Skin tumorigenesis is conversely enhanced by overexpression in keratinocytes of the constitutively active STAT3C mutant, which also induces robust, psoriasis‐like epidermal hyperplasia. We show here that STAT3C expression at physiological levels in knock‐in mice leads to mild epidermal hyperplasia and attenuated expression of terminal differentiation markers. Altered differentiation is confirmed in isolated primary epidermal keratinocytes in vitro, correlating with enhanced proliferative and clonogenic potential, attenuated senescence and, strikingly, high‐frequency spontaneous immortalization. These results suggest that moderate levels of continuous STAT3 activation, which closely resemble those triggered by chronic inflammation or persistent growth factor stimulation, may establish a preneoplastic state in part by promoting the escape of epidermal progenitor cells from differentiation and senescence checkpoints.
Ginsenoside F1 attenuates hyperpigmentation in B16F10 melanoma cells by inducing dendrite retraction and activating Rho signalling
Authors: Kim Ji Hye , Baek Eun Ji , Lee Eun Ju , Yeom Myung Hun , Park Jun Seong , Lee Ki Won , Kang Nam Joo 
Published: November 2014

AbstractGinsenoside F1 (GF1) is a metabolite produced by hydrolysis of the ginsenoside Re and Rg1 in Panax ginseng. According to various studies, high amounts of ginseng components are absorbed in the metabolized form, which are key constituents responsible for the biological effects of P. ginseng. Recently, GF1 was reported to have beneficial effects on skin. However, there has not been a sound understanding of its antimelanogenic effect and underlying molecular mechanisms. In this study, GF1 reduced α‐melanocyte‐stimulating hormone‐induced melanin secretion in B16F10 cell culture media by 60%. However, it did not suppress intracellular melanin levels, tyrosinase activity and expression. Immunofluorescence assay showed that GF1 had no effect on melanosome transport, but significantly induced dendrite retraction. Pull‐down assay demonstrated that GF1 primarily modulates the Rho family GTPases resulting in dendrite retraction. Collectively, these data suggest that GF1 could act as a potent skin‐whitening agent.
Repeated administration of IL‐31 upregulates IL‐31 receptor A (IL‐31RA) in dorsal root ganglia and causes severe itch‐associated scratching behaviour in mice
Authors: Arai Iwao , Tsuji Minoru , Miyagawa Kazuya , Takeda Hiroshi , Akiyama Nobutake , Saito Saburo 
Published: November 2014

AbstractWe investigated the effects of repeated administration of interleukin‐31 (IL‐31) on itch‐associated scratching counts (long‐lasting scratching, LLS) and IL‐31‐related receptor mRNA expression in mice. Intra‐dermal (i.d.) injection of IL‐31 (100 and 300 ng/site) every 12 h for 3 days significantly increased LLS. Repeated administration of IL‐31 also increased the expression of IL‐31 receptor A (IL‐31RA) and oncostatin M receptor beta (OSMRβ) in dorsal root ganglia (DRG). After the repeated administration of IL‐31 was discontinued, IL‐31RA expression decreased and reached the baseline level 2 days after the last dose of IL‐31. LLS changed along with DRG IL‐31RA expression. Moreover, IL‐31‐induced IL‐31RA protein expression was confirmed by Western blotting analysis. These data suggest that IL‐31 upregulates IL‐31RA expression in DRG neuron cell bodies, and cutaneous‐injected IL‐31‐induced itching is enhanced by DRG IL‐31RA expression in mice.
Licochalcone A activates Nrf2 in vitro and contributes to licorice extract‐induced lowered cutaneous oxidative stress in vivo
Authors: Kühnl Jochen , Roggenkamp Dennis , Gehrke Sandra A. , Stäb Franz , Wenck Horst , Kolbe Ludger , Neufang Gitta 
Published: November 2014

AbstractThe retrochalcone licochalcone A (LicA) has previously been shown to possess antimicrobial and anti‐inflammatory properties. In this study, we focused on pathways responsible for the antioxidative properties of LicA. In vitro, LicA protected from oxidative stress mediated by reactive oxygen species (ROS) by activating the expression of cytoprotective phase II enzymes. LicA induced nuclear translocation of NF‐E2‐related factor 2 (Nrf2) in primary human fibroblasts and elevated the expression of the cytoprotective and anti‐inflammatory enzymes heme oxygenase 1 and glutamate–cysteine ligase modifier subunit. LicA‐treated cells displayed a higher ratio of reduced to oxidized glutathione and decreased concentrations of ROS in UVA‐irradiated human dermal fibroblasts, as well as in activated neutrophils. In vivo, ultraweak photon emission analysis of skin treated with LicA‐rich licorice extract revealed a significantly lowered UVA‐induced luminescence, indicative for a decrease in oxidative processes. We conclude from these data that topical application of licorice extract is a promising approach to induce Nrf2‐dependent cytoprotection in human skin.
Hair follicle targeting, penetration enhancement and Langerhans cell activation make cyanoacrylate skin surface stripping a promising delivery technique for transcutaneous immunization with large molecules and particle‐based vaccines
Authors: Vogt Annika , Hadam Sabrina , Deckert Iliane , Schmidt Julia , Stroux Andrea , Afraz Zahra , Rancan Fiorenza , Lademann Jürgen , Combadiere Behazine , Blume‐Peytavi Ulrike 
Published: November 2014

AbstractTranscutaneous immunization (TCI) requires targeting of a maximum number of skin antigen‐presenting cells as non‐invasive as possible on small skin areas. In two clinical trials, we introduced cyanoacrylate skin surface stripping (CSSS) as a safe method for TCI. Here, using ex vivo human skin, we demonstrate that one CSSS procedure removed only 30% of stratum corneum, but significantly increased the penetration of 200 nm polystyrene particles deep into vellus and intermediate hair follicles from where they could not been retrieved by conventional tape stripping. Two subsequent CSSS had no striking additional effect. CSSS increased particle penetration in superficial stratum corneum and induced Langerhans cell activation. Formulation in amphiphilic ointment or massage did not substantially influences the interfollicular penetration profiles. Hair follicle (HF) targeting by CSSS could become a highly effective tool for TCI when combined with carrier‐based delivery and is gaining new attention as our understanding on the HF immune system increases.
Unraveling the interactive effects of climate change and oil contamination on laboratory‐simulated estuarine benthic communities
Authors: Coelho Francisco J. R. C. , Cleary Daniel F. R. , Rocha Rui J. M. , Calado Ricardo , Castanheira José M. , Rocha Sílvia M. , Silva Artur M. S. , Simões Mário M. Q. , Oliveira Vanessa , Lillebø Ana I. , Almeida Adelaide , Cunha Ângela , Lopes Isabel , Ribeiro Rui , Moreira‐Santos Matilde , Marques Catarina R. , Costa Rodrigo , Pereira Ruth , Gomes Newton C. M. 
Published: November 2014

AbstractThere is growing concern that modifications to the global environment such as ocean acidification and increased ultraviolet radiation may interact with anthropogenic pollutants to adversely affect the future marine environment. Despite this, little is known about the nature of the potential risks posed by such interactions. Here, we performed a multifactorial microcosm experiment to assess the impact of ocean acidification, ultraviolet B (UV‐B) radiation and oil hydrocarbon contamination on sediment chemistry, the microbial community (composition and function) and biochemical marker response of selected indicator species. We found that increased ocean acidification and oil contamination in the absence of UV‐B will significantly alter bacterial composition by, among other things, greatly reducing the relative abundance of Desulfobacterales, known to be important oil hydrocarbon degraders. Along with changes in bacterial composition, we identified concomitant shifts in the composition of oil hydrocarbons in the sediment and an increase in oxidative stress effects on our indicator species. Interestingly, our study identifies UV‐B as a critical component in the interaction between these factors, as its presence alleviates harmful effects caused by the combination of reduced pH and oil pollution. The model system used here shows that the interactive effect of reduced pH and oil contamination can adversely affect the structure and functioning of sediment benthic communities, with the potential to exacerbate the toxicity of oil hydrocarbons in marine ecosystems.
Changes in isotopic signatures of soil carbon and CO2 respiration immediately and one year after Miscanthus removal
Authors: Drewer Julia , Dufossé Karine , Skiba Ute M. , Gabrielle Benoît 
Published: November 2014

AbstractThe removal of perennial bioenergy crops, such as Miscanthus, has rarely been studied although it is an important form of land use change. Miscanthus is a C4 plant, and the carbon (C) it deposits during its growth has a different isotopic signature (12/13C) compared to a C3 plant. Identifying the proportion of C stored and released to the atmosphere is important information for ecosystem models and life cycle analyses. During a removal experiment in June 2011 of a 20‐year old Miscanthus field (Grignon, France), vegetation was removed mechanically and chemically. Two replicate plots were converted into a rotation of annual crops, two plots had Miscanthus removed with no soil disturbance, followed by bare soil (set‐aside), one control plot was left with continued Miscanthus cultivation, and an adjacent field was used as annual arable crops control. There was a significant difference in the isotopic composition of the total soil C under Miscanthus compared with adjacent annual arable crops in all three measured soil layers (0–5, 5–10 and 10–20 cm). Before Miscanthus removal, total C in the soil under Miscanthus ranged from 4.9% in the top layer to 3.9% in the lower layers with δ13C values of −16.3 to −17.8 while soil C under the adjacent arable crop was significantly lower and ranged from 1.6 to 2% with δ13C values of −23.2. This did not change much in 2012, suggesting the accumulation of soil C under Miscanthus persists for at least the first year. In contrast, the isotopic signals of soil respiration 1 year after Miscanthus removal from recultivated and set‐aside plots were similar to that of the annual arable control, while just after removal the signals were similar to that of the Miscanthus control. This suggests a rapid change in the form of soil C pools that are respired.
Fluid environment for preservation of pore spaces in a deep dolomite reservoir
Authors: Zhu D. , Meng Q. , Jin Z. , Hu W. 
Published: November 2014

AbstractWell TS1 reveals many uncemented pores and vugs at depths of more than 8000 m in a deep Cambrian dolomite reservoir in the Tarim Basin, northwestern China. The fluid environment and mechanism required for the preservation of reservoir spaces have yet not been well constrained. Carbon, oxygen, and strontium isotope compositions and fluid inclusion data suggest two types of fluids, meteoric water and hydrothermal fluid, affecting the Lower Paleozoic carbonate reservoirs in the Tarim Basin. Based on simulation using a thermodynamic model for H2O‐CO2‐NaCl‐CaCO3 system, meteoric water has the ability to continuously dissolve carbonate minerals during downward migration from the surface to deep strata until it reaches a transition depth, below which it will begin to precipitate carbonate minerals to fill preexisting pore spaces. In contrast, hydrothermal fluid has the ability to dissolve carbonate in deep strata and precipitate carbonate in shallow strata during upward migration. Based on the dissolution–precipitation characteristics of the two types of fluids, the ideal fluid environment for the preservation of preexisting reservoir spaces occurs when carbonate reservoir is neither in the CaCO3 precipitation domain of meteoric water nor in the CaCO3 precipitation domain of hydrothermal fluid. Taking the Lower Paleozoic carbonate reservoirs in the north uplift area as an example, the spaces in the deep Cambrian dolomite reservoir near well TS1 were seldom filled because thick Ordovician deposits blocked meteoric water from migrating downward into the Cambrian dolomite reservoir and because the Cambrian dolomite reservoir has been in the domain of hydrothermal dissolution since the Permian. The deep carbonate layers in basins elsewhere with a similar fluid environment may have high uncemented porosity and consequently have good hydrocarbon exploration potential.
The incidence of factor VIII inhibitors in severe haemophilia A following a major switch from full‐length to B‐domain‐deleted factor VIII: a prospective cohort comparison
Authors: Hay C. R. M. , Palmer B. P. , Chalmers E. A. , Hart D. P. , Liesner R. , Rangarajan S. , Talks K. , Williams M. , Collins P. W. 
Published: November 2014

SummaryAlthough it has been suggested that switching of factor VIII (FVIII) products may increase inhibitor formation this is disputed. Half of UK patients changed rFVIII brands because of national contracting in 2010, presenting an opportunity to compare inhibitor incidence of switchers with non‐switchers. Centres were requested to test all the patients for inhibitors prior to the switching date and 6‐monthly thereafter. Positive and negative inhibitor test data were also collected to analyse for testing bias. A total of 1198 patients with severe haemophilia A and treated with Advate, Kogenate/Helixate or Refacto AF preswitch were included in the analysis, of whom 516 switched to Refacto‐AF and 682 did not switch products. Five new inhibitors were reported amongst previously treated patients (>50 exposure days) with a median titre at the time of detection of 1.25 BU mL−1 (IQR 0.7–23.05). One inhibitor occurred in a non‐switcher using Kogenate, an incidence of 1.5 per 1000 treatment‐years (95% CI 0.2–10.5). Four inhibitors arose in patients who had switched from Kogenate (two) or Advate (two) to ReFacto‐AF, an incidence of 7.8 per 1000 treatment‐years (95% CI 2.9–20.8). These incidence rates did not differ significantly from one another (incidence rate ratio 5.3 (95% CI 0.5–260.3) or from the historical rate of 6.05 inhibitors/1000 treatment‐years (95% CI 5.18–7.06). Only one inhibitor (non‐switcher) persisted. Non‐switchers were significantly older (P = 0.03), and used significantly less FVIII per year (P = 0.005) prior to switching. Following switching, factor usage increased similarly (P = 0.53) in both groups. Switching from FLRFVIII to Refacto‐AF (BDDRFVIII) was not associated with an increased inhibitor development.
Hepatitis B vaccination is effective by subcutaneous route in children with bleeding disorders: a universal data collection database analysis
Authors: Carpenter S. L. , Soucie J. M. , Presley R. J. , Ragni M. V. , Wicklund B. M. , Silvey M. , Davidson H. ,   the Hemophilia Treatment Center Network Investigators
Published: November 2014

SummarySubcutaneous (SQ) vs. intramuscular (IM) vaccination may cause fewer injection site complications in children with bleeding disorders, but little is known about comparative immunogenicity. To compare immunogenicity of hepatitis B virus (HBV) vaccination administered SQ or IM to individuals <2 years old with bleeding disorders, we performed a retrospective analysis of HBV surface antibody titres among patients enrolled in the universal data collection database who had received three doses of HBV vaccine solely by one route (SQ or IM). Data reviewed were from an initial visit before 24 months of age, until time of hepatitis antibody titre testing. The SQ and IM study groups did not differ in demographics, haemophilia type or severity or bleeding history. The mean age at the time of HBV surface antibody (anti‐HBs) testing was 56.9 ± 20.3 months. Eighty‐five of 92 subjects (92.4%) who received vaccine SQ developed a positive antibody titre (>12 IU/L), compared to 101/114 (88.6%) who received IM (P = 0.30). There was no statistically significant difference in distribution of titre values. The average age of the subjects at time of testing was 53 ± 20 months in the SQ group vs. 60 ± 20 months in the IM group (P = 0.02). The average time between the last dose of vaccine and anti‐HBs testing was 47.6 ± 18.5 months among SQ vaccinated subjects vs. 51.6 ± 20.5 months in the IM group (P = 0.2). Immunogenicity to hepatitis B vaccination by the SQ and IM routes is similar.
The natural history of occult or angiodysplastic gastrointestinal bleeding in von Willebrand disease
Authors: Makris M. , Federici A. B. , Mannucci P. M. , Bolton‐Maggs P. H. B. , Yee T. T. , Abshire T. , Berntorp E. 
Published: November 2014

SummaryRecurrent gastrointestinal bleeding is one of the most challenging complications encountered in the management of patients with von Willebrand disease (VWD). The commonest cause is angiodysplasia, but often no cause is identified due to the difficulty in making the diagnosis. The optimal treatment to prevent recurrences remains unknown. We performed a retrospective study of VWD patients with occult or angiodysplastic bleeding within the setting of the von Willebrand Disease Prophylaxis Network (VWD PN) to describe diagnostic and treatment strategies. Centres participating in the VWD PN recruited subjects under their care with a history of congenital VWD and gastrointestinal (GI) bleeding due to angiodysplasia, or cases in which the cause was not identified despite investigation. Patients with acquired von Willebrand syndrome or those for whom the GI bleeding was due to another cause were excluded. Forty‐eight patients from 18 centres in 10 countries were recruited. Seven individuals had a family history of GI bleeding and all VWD types except 2N were represented. Angiodysplasia was confirmed in 38%, with video capsule endoscopy and GI tract endoscopies being the most common methods of making the diagnosis. Recurrent GI bleeding in VWD is associated with significant morbidity and required hospital admission on up to 30 occasions. Patients were treated with multiple pharmacological agents with prophylactic von Willebrand factor concentrate being the most efficient in preventing recurrence of the GI bleeding. The diagnosis and treatment of recurrent GI bleeding in congenital VWD remains challenging and is associated with significant morbidity. Prophylactic treatment with von Willebrand factor concentrate was the most effective method of preventing recurrent bleeding but its efficacy remains to be confirmed in a prospective study.
Review: Clinical Management of Helicobacter pylori Infection in China
Authors: Xie Chuan , Lu Nong‐Hua 
Published: November 2014

AbstractHelicobacter pylori (H. pylori) infection has been associated with gastric disorders. The situation of H. pylori infection in China—where a high prevalence of H. pylori infection, a high incidence of gastric cancer, and widespread resistance to clarithromycin, metronidazole, and levofloxacin exist—is quite different from that in Western countries. In order for Chinese clinicians to better manage H. pylori infection, a Chinese Study Group on H. pylori published four consensus reports regarding the management of H. pylori infection in China between 1999 and 2012. The eradication rate with standard triple therapy was <80% in most areas of China. Bismuth is available in China, and bismuth‐containing quadruple therapy has been shown to produce a high eradication rate; thus, bismuth quadruple therapy could be recommended both as an initial and as a rescue therapy in China. There is no advantage of sequential therapy over triple therapy in Chinese patients, but the efficacy of concomitant therapy must be studied further. This review introduces the epidemiology, diagnosis, indicators, and therapies for the eradication of H. pylori in China in recent years.
Helicobacter cinaedi Induced Typhlocolitis in Rag‐2‐Deficient Mice
Authors: Shen Zeli , Feng Yan , Rickman Barry , Fox James G. 
Published: November 2014

AbstractBackgroundHelicobacter cinaedi, an enterohepatic helicobacter species (EHS), is an important human pathogen and is associated with a wide range of diseases, especially in immunocompromised patients. It has been convincingly demonstrated that innate immune response to certain pathogenic enteric bacteria is sufficient to initiate colitis and colon carcinogenesis in recombinase‐activating gene (Rag)‐2‐deficient mice model. To better understand the mechanisms of human IBD and its association with development of colon cancer, we investigated whether H. cinaedi could induce pathological changes noted with murine enterohepatic helicobacter infections in the Rag2−/− mouse model.Materials and MethodsSixty 129SvEv Rag2−/− mice mouse were experimentally or sham infected orally with H. cinaedi strain CCUG 18818. Gastrointestinal pathology and immune responses in infected and control mice were analyzed at 3, 6 and 9 months postinfection (MPI). H. cinaedi colonized the cecum, colon, and stomach in infected mice.ResultsH. cinaedi induced typhlocolitis in Rag2−/− mice by 3 MPI and intestinal lesions became more severe by 9 MPI. H. cinaedi was also associated with the elevation of proinflammatory cytokines, interferon‐γ, tumor‐necrosis factor‐α, IL‐1β, IL‐10; iNOS mRNA levels were also upregulated in the cecum of infected mice. However, changes in IL‐4, IL‐6, Cox‐2, and c‐myc mRNA expressions were not detected.ConclusionsOur results indicated that the Rag2−/− mouse model will be useful to continue investigating the pathogenicity of H. cinaedi, and to study the association of host immune responses in IBD caused by EHS.
Low Prevalence and Incidence of Helicobacter pylori Infection in Children: A Population‐Based Study in Japan
Authors: Okuda Masumi , Osaki Takako , Lin Yingsong , Yonezawa Hideo , Maekawa Kohei , Kamiya Shigeru , Fukuda Yoshihiro , Kikuchi Shogo 
Published: November 2014

AbstractBackgroundInfection of Helicobacter pylori mainly occurs in childhood. In Japan, incidence of gastric cancer is still high in the senior citizen population, but little is known about the current H. pylori infection status among children or their family members.MethodsAs a population‐based study, the prevalence of H. pylori infection and change in infection status over a 1‐year interval in children were determined. Family members of some participants were also invited to participate in the study to determine their infection status. All children of specific ages attending 16 schools in Sasayama, Hyogo Prefecture, were invited to participate. H. pylori infection was determined by the stool antigen test and diagnosis confirmed by polymerase chain reaction and the urea breath test.ResultsHelicobacter pylori prevalence was 1.9% among 689 children aged 0–8 years in 2010 and 1.8% among 835 children aged 0–11 in 2011. No feco‐conversion was observed in 430 children aged 0–8 years (170 were aged 0–4 years) who provided follow‐up stool samples after 1 year. The prevalence of infection was 6% (2 of 33) and 38% (6 of 16) in mothers of negative and positive probands (p = .04), respectively, and 12% (3 of 25) and 50% (8 of 16) (p = .01), respectively, in fathers.ConclusionHelicobacter pylori prevalence in Japanese children is approximately 1.8%, which is much lower than that reported in Japanese adults. New infection may be rare. Parent‐to‐child infection is thought to be the main infection route of the infrequent infection for children in Japan.