bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel anti‐fibrotic modalities for liver fibrosis: Molecular targeting and regenerative medicine in fibrosis therapy
Authors: Inagaki Yutaka , Higashiyama Reiichi , Higashi Kiyoshi 
Published: February 2012

AbstractBased on the cellular and molecular mechanisms underlying hepatic fibrogenesis, several kinds of approaches have been proposed to treat liver fibrosis. Among a number of growth factors and cytokines that regulate collagen metabolism, transforming growth factor (TGF)‐β is the most potent factor to accelerate liver fibrosis by activating hepatic stellate cells, stimulating collagen gene transcription, and suppressing matrix metalloproteinases expression. Thus, TGF‐β as well as its intracellular mediators, Smad proteins, can be potential therapeutic targets for liver fibrosis. Constitutive phosphorylation and nuclear accumulation of Smad3 is the common feature of activated stellate cells. We have synthesized a novel small compound that inhibits Smad3‐dependent collagen gene transcription by promoting nuclear import of a transcriptional repressor, YB‐1. Another insight into anti‐fibrotic strategies is the contribution of bone marrow‐derived cells to the regression of liver fibrosis. Administration of granulocyte‐colony stimulating factor enhanced the migration of bone marrow‐derived cells into fibrotic liver tissue and accelerated the regression of experimental liver fibrosis. We have recently identified novel unknown factors expressed by bone marrow‐derived cells that not only ameliorate liver fibrosis but also accelerate regeneration of fibrotic liver.
Obesity, autophagy and the pathogenesis of liver and pancreatic cancers
Authors: Aghajan Mariam , Li Ning , Karin Michael 
Published: February 2012

AbstractLiver and pancreatic cancers are both highly lethal diseases with limited to no therapeutic options for patients. Recent studies suggest that deregulated autophagy plays a role in the pathogenesis of these diseases by perturbing cellular homeostasis and laying the foundation for disease development. While accumulation of p62 upon impaired autophagy has been implicated in hepatocellular carcinoma, its role in pancreatic ductal adenocarcinoma remains less clear. This review will focus on recent studies illustrating the role of autophagy in liver and pancreatic cancers. The relationships between autophagy, nuclear factor‐κB signaling and obesity in hepatocellular carcinoma will be discussed, as well as the dual role of autophagy in pancreatic ductal adenocarcinoma.
Cancer stem cells generated by alcohol, diabetes, and hepatitis C virus
Authors: Machida Keigo , Chen Chia‐Lin , Liu Jian‐Chang , Kashiwabara Claudine , Feldman Douglas , French Samuel W , Sher Linda , Hyeongnam Jeong Joseph , Tsukamoto Hidekazu 
Published: February 2012

AbstractCancer stem cells (tumor‐initiating stem‐like cells: TISCs) are resistant to chemotherapy and are associated with metastatic hepatocellular carcinoma (HCC), which is commonly observed in hepatitis C virus (HCV)‐infected patients with obesity or alcohol abuse. However, it is unknown whether the TLR4‐NANOG pathway serves as a universal oncogenic signaling in the genesis of TISCs and HCC. We aimed to determine whether Tlr4 is a putative proto‐oncogene for TISCs in liver oncogenesis due to different etiologies and how Tlr4 is regulated at the transcriptional and epigenetic levels. CD133+/CD49f+ TISCs were isolated using FACS from HCC developed in HCV Core Tg mice fed alcohol, diethylnitrosamine‐treated mice, and alcoholic patients with or without HCV infection. CD133+/CD49f+ cells isolated from the animal models and patients are tumorigenic both in vitro and in a xenograft model, and Tlr4 or Nanog silencing with shRNA attenuates their tumor initiating property. Functional oncogene screening of a cDNA library identified the organ size control pathway targets Yap1 and AKT activator Igf2bp3 as NANOG‐dependent genes that inhibit transforming growth factor‐β signaling in TISCs. Tlr4 expression is higher in TISCs compared with CD133‐/CD49f+ cells. Taken together, Tlr4 may be a universal proto‐oncogene responsible for the genesis of TLR4‐NANOG dependent TISCs, and this pathway serves as a novel therapeutic target for HCC.
Bone marrow‐derived proangiogenic cells in pancreatic cancer
Authors: Mizukami Yusuke 
Published: February 2012

AbstractTumor‐derived signals systemically induce an angiogenic switch that allows cancer cells to survive and grow. However, the vascular network in tumors is not well organized and fails to meet metabolic needs to maintain tissue homeostasis, resulting in significant hypoxia. Among various tumors, pancreatic ductal adenocarcinoma (PDAC) typically develops in an unusually disordered microenvironment, which contributes to its highly aggressive behavior. Since anti‐vascular endothelial growth factor (VEGF) (Avastin) has failed to demonstrate a survival benefit in PDAC, we need to re‐visit the basic biology of this disease and understand what makes it so refractory to the anti‐angiogenic approaches that are clinically effective in other neoplasms. To address this issue, we specifically focused on the process of neovascularization where bone marrow‐derived cells (BMDCs) play a role during pancreatic tumorigenesis. We have identified subsets of BMDCs that regulate key processes during development of the neovessels through paracrine Hedgehog signaling. Considering the importance of systemic responses occurring in tumor bearing hosts, we are currently using genetically engineered mice, which spontaneously develop PDAC, Pdx1‐Cre;LSL‐KrasG12D;p53lox/+ strain, to clarify critical events that can trigger aberrant angiogenesis in pancreatic cancer. These studies allow us to provide insights into the cellular and molecular mechanisms of pancreatic tumorigenesis and have an implication for the design of therapies against this difficult disease.
Iron and steatohepatitis
Authors: Corradini Elena , Pietrangelo Antonello 
Published: February 2012

AbstractAs the main iron storage site in the body and the main source of the iron‐regulatory hormone, hepcidin, the liver plays a pivotal role in iron homeostasis. A variable degree of hepatic iron accumulation has long been recognized in a number of chronic liver diseases. Both alcoholic and non‐alcoholic steatohepatitis display increased iron deposits in the liver, with an hepatocellular, mesenchymal, or mixed pattern, and recent reports have documented a concomitant aberrant hepcidin expression that could be linked to different coincidental pathogenic events (e.g. the etiological agent itself, necroinflammation, metabolic derangements, genetic predisposition). The present study reviews the pathogenic mechanisms of iron accumulation in steatohepatitis during alcoholic and non‐alcoholic liver disease and the role of excess iron in chronic disease progression.
Morphogens and hepatic stellate cell fate regulation in chronic liver disease
Authors: Tsukamoto Hidekazu , Zhu Nian‐Ling , Wang Jiaohong , Asahina Kinji , Machida Keigo 
Published: February 2012

AbstractHepatic stellate cells (HSC) are the liver mesenchymal cell type which responds to hepatocellular damage and participates in wound healing. Although HSC myofibroblastic trans‐differentiation (activation) is implicated in excessive extracellular matrix deposition, molecular understanding of this phenotypic switch from the viewpoint of cell fate regulation is limited. Recent studies demonstrate the roles of anti‐adipogenic morphogens (Wnt, Necdin, Shh) in epigenetic repression of the HSC differentiation gene Pparγ as a causal event in HSC activation. These morphogens have positive cross‐interactions which converge to epigenetic repression of Pparγ involving the methyl‐CpG binding protein MeCP2. However, these morphogens expressed by activated HSC may also participate in cross‐talk between HSC and hepatoblasts/hepatocytes to support liver regeneration, and their aberrant regulation may contribute to liver tumorigenesis. Implications of HSC‐derived morphogens in these possibilities are discussed.
Alcohol, insulin resistance and the liver–brain axis
Authors: de la Monte Suzanne , Derdak Zoltan , Wands Jack R 
Published: February 2012

AbstractChronic alcohol exposure inhibits insulin and insulin‐like growth factor signaling in the liver and brain by impairing the signaling cascade at multiple levels. These alterations produced by alcohol cause severe hepatic and central nervous system insulin resistance as the cells fail to adequately transmit signals downstream through Erk/mitogen‐activated protein kinase (MAPK), which is needed for DNA synthesis and liver regeneration, and phosphatidylinositol 3‐kinase (PI3K), which promotes growth, survival, cell motility, glucose utilization, plasticity, and energy metabolism. The robust inhibition of insulin signaling in liver and brain is augmented by additional factors involving the activation of phosphatases such as phosphatase and tensin homologue (PTEN), which further impairs insulin signaling through PI3K/Akt. Thus, intact insulin signaling is important for neuronal survival. Chronic alcohol consumption produces steatohepatitis, which also promotes hepatic insulin resistance, oxidative stress and injury, with the attendant increased generation of “toxic lipids” such as ceramides that increase insulin resistance. The PI3K/Akt signaling cascade is altered by direct interaction with ceramides as well as through PTEN upregulation as a downstream target gene of enhanced p53 transcriptional activity. Cytotoxic ceramides transferred from the liver to the blood can enter the brain due to their lipid‐soluble nature, and thereby exert neurodegenerative effects via a liver–brain axis. We postulate that the neurotoxic and neurodegenerative effects of liver‐derived ceramides activate pro‐inflammatory cytokines and increase lipid adducts and insulin resistance in the brain to impair cognitive and motor function. These observations are discussed in the context of insulin sensitizers as potential cytoprotective agents against liver and brain injury induced by alcohol.
Interactions of alcohol and tobacco in gastrointestinal cancer
Authors: Salaspuro Mikko 
Published: February 2012

AbstractCancer prevention is based on the identification of specific etiologic factors. Acetaldehyde derived from the alcoholic beverage itself and formed from ethanol endogenously has recently been classified by the International Agency for Research on Cancer/World Health Organization as a group 1 carcinogen to humans. This is based on the uniform epidemiological and biochemical evidence derived from individuals carrying alcohol and aldehyde dehydrogenase gene mutations. After drinking alcohol, these mutations are associated with increased exposure of the upper digestive tract to acetaldehyde and as well with a remarkably increased risk for upper gastrointestinal (GI) tract cancers. Acetaldehyde is the key intermediate in alcoholic fermentation and ethanol oxidation. Therefore, it is widely present in our environment. Furthermore, it is the most abundant carcinogenic compound of tobacco smoke. Most of the known risk factors for upper digestive tract cancer appear to be associated with an enhanced exposure of GI mucosa to locally formed acetaldehyde. In these process microbes, salivary glands and even mucosal cells appear to play an essential role. Consequently, in the presence of ethanol mutagenic acetaldehyde concentrations are found in the saliva, achlorhydric stomach and colon. Equal acetaldehyde concentrations are seen in saliva also during active smoking. ALDH2‐deficiency and high active ADH1C result in two‐ to threefold salivary acetaldehyde concentrations after a dose of alcohol and this prevails for as long as ethanol is present in the blood and saliva. Regarding cancer prevention, the good news is that acetaldehyde exposure can be markedly reduced. This can be achieved by giving high priority for regulatory measures and consumer guidance.
Sleep and academic performance in Indigenous Australian children from a remote community: An exploratory study
Authors: Cooper Patrick , Kohler Mark , Blunden Sarah 
Published: February 2012

Aim:  Disruptions to sleep in childhood are associated with poor behaviour and deficits in academic performance and executive function. Although academic performance of indigenous children from remote communities in Australia is documented as well below that of non‐indigenous children, the extent of sleep disruption and its contribution to academic performance among this population has not been assessed. This pilot study aimed to objectively assess the sleep of remote indigenous children and the association between sleep disruption and both academic performance and executive function.Method:  Twenty‐one children from a remote Australian indigenous community aged 6–13 years wore actigraphy for two consecutive nights, reported subjective sleepiness, and were objectively assessed for academic performance (Wechsler Individual Achievement Test, 2nd Edition) and executive function (NEuroloPSYcological Assessment‐II).Results:  Results show marked reduction in sleep time, sleep fragmentation, academic performance and auditory attention compared with non‐indigenous norms. Sleep duration was not associated with performance, possibly because of reduced sleep and performance observed across the entire group. Sleep fragmentation was associated with reduced reading and numerical skills (P < 0.05).Conclusions:  The sleep of indigenous children in remote communities is an important area of future inquiry, and our initial findings of poor sleep and an association between sleep disruption and academic performance may have important implications for intervention strategies aimed at ‘closing the gap’. Further studies should assess a broader range of demographic, social and economic factors to better understand the associations reported here and guide future intervention.
Chromosome microarray in Australia: A guide for paediatricians
Authors: Palmer Elizabeth E , Peters Greg B , Mowat David 
Published: February 2012

AbstractChromosomal microarray or molecular karyotype has become the first‐line genetic investigation for children with intellectual disability, autistic spectrum disorder or multiple congenital anomalies. Chromosomal microarray increases the detection rate of pathogenic chromosome imbalances including submicroscopic deletions or duplications in patients with undiagnosed intellectual disability to approximately 15% compared with 3% with conventional cytogenetics. This review article summarises the diagnostic technique and highlights the advantages and limitations of chromosomal microarray. Our aim is to assist clinicians in providing pretest counselling and with interpretation of the result.
Isolation of functional dendritic cells from murine kidneys for immunological characterization
Authors: TETERIS SIMON ALEXANDER , HOCHHEISER KATHARINA , KURTS CHRISTIAN 
Published: February 2012

ABSTRACTAim:  The kidney is a complex organ, requiring the contributions of multiple cell types to perform its various functions. Within this system the dendritic cell has been demonstrated to play a key role in maintaining the immunological balance of the kidney. In this methods paper we aim to identify the best method for isolating murine renal dendritic cells.Methods:  The efficiency of isolating dendritic cells from enzymatically digested renal parenchyma by density centrifugation, MACS and FACS was compared.Results:  Density centrifugation enriched dendritic cells by only approximately two fold. However, MACS and FACS resulted in a much higher purity (80% versus 95% respectively).Conclusions:  Although FACS gave the highest purity, MACS is the optimal method for isolating dendritic cells given cost and time factors. Isolation of a homogeneous population of renal dendritic cells will enable the molecular and functional dissection of these cells in both homeostasis and disease models.
Maternal childrearing anxiety reflects childrearing burden and quality of life
Authors: Mishina Hiroki , Takayama John Ichiro , Aizawa Shiyu , Tsuchida Nao , Sugama Seiichi 
Published: February 2012

AbstractBackground:  The government of Japan has recently initiated public programs to allay maternal childrearing anxiety. The aim of the present study was to determine the prevalence of childrearing anxiety and describe its relationships with perceived childrearing burden and maternal quality of life (QOL).Methods:  A secondary analysis was done of survey data from 1229 mothers enrolled in the Seiiku Birth Cohort Study at the National Center for Child Health and Development between November 2003 and December 2006. Childrearing anxiety was determined by asking mothers, at infant age 3 months, ‘Regarding childrearing, do you have any anxiety or worry?’. Childrearing burden was assessed in specific categories such as physical fatigue, household expenses, and personal time. The validated Japanese translation of the WHOQOL‐BREF instrument was used to measure Maternal QOL.Results:  Sixty‐four percent of mothers reported some and 9% much childrearing anxiety. In total, 73% percent of mothers reported any childrearing anxiety. As childrearing anxiety increased from ‘none’ to ‘some’ and ‘much’, the proportion of mothers who reported any childrearing burden increased from 75% to 99% (P < 0.001). QOL scores in each of four domains (physical, psychological, social relationships, and environment) decreased with increasing level of anxiety (P < 0.001). Primiparity, pregnant with more than a singleton and admission to the neonatal intensive care unit were associated with greater anxiety.Conclusions:  The strong associations between childrearing anxiety and childrearing burden, and between childrearing anxiety and maternal QOL, suggest that childrearing anxiety is an empirically credible and measurable phenomenon.
Reconstructing normality: Characteristics of staff interactions with forensic mental health inpatients
Authors: Gildberg Frederik A. , Bradley Stephen K. , Fristed Peter , Hounsgaard Lise 
Published: February 2012

ABSTRACTForensic psychiatry is an area of priority for the Danish Government. As the field expands, this calls for increased knowledge about mental health nursing practice, as this is part of the forensic psychiatry treatment offered. However, only sparse research exists in this area. The aim of this study was to investigate the characteristics of forensic mental health nursing staff interaction with forensic mental health inpatients and to explore how staff give meaning to these interactions. The project included 32 forensic mental health staff members, with over 307 hours of participant observations, 48 informal interviews, and seven semistructured interviews. The findings show that staff interaction is typified by the use of trust and relationship‐enabling care, which is characterized by the establishment and maintenance of an informal, trusting relationship through a repeated reconstruction of normality. The intention is to establish a trusting relationship to form behaviour and perceptual‐corrective care, which is characterized by staff's endeavours to change, halt, or support the patient's behaviour or perception in relation to staff's perception of normality. The intention is to support and teach the patient normal behaviour by correcting their behaviour, and at the same time, maintaining control and security by staying abreast of potential conflicts.
Language performance and auditory evoked fields in 2‐ to 5‐year‐old children
Authors: Yoshimura Yuko , Kikuchi Mitsuru , Shitamichi Kiyomi , Ueno Sanae , Remijn Gerard B. , Haruta Yasuhiro , Oi Manabu , Munesue Toshio , Tsubokawa Tsunehisa , Higashida Haruhiro , Minabe Yoshio 
Published: February 2012

AbstractLanguage development progresses at a dramatic rate in preschool children. As rapid temporal processing of speech signals is important in daily colloquial environments, we performed magnetoencephalography (MEG) to investigate the linkage between speech‐evoked responses during rapid‐rate stimulus presentation (interstimulus interval < 1 s) and language performance in 2‐ to 5‐year‐old children (n = 59). Our results indicated that syllables with this short stimulus interval evoked detectable P50m, but not N100m, in most participants, indicating a marked influence of longer neuronal refractory period for stimulation. The results of equivalent dipole estimation showed that the intensity of the P50m component in the left hemisphere was positively correlated with language performance (conceptual inference ability). The observed positive correlations were suggested to reflect the maturation of synaptic organisation or axonal maturation and myelination underlying the acquisition of linguistic abilities. The present study is among the first to use MEG to study brain maturation pertaining to language abilities in preschool children.
Ocean acidification reduces coral recruitment by disrupting intimate larval‐algal settlement interactions
Authors: Doropoulos Christopher , Ward Selina , Diaz‐Pulido Guillermo , Hoegh‐Guldberg Ove , Mumby Peter J. 
Published: February 2012

Ecology Letters (2012) 15: 338–346AbstractSuccessful recruitment in shallow reef ecosystems often involves specific cues that connect planktonic invertebrate larvae with particular crustose coralline algae (CCA) during settlement. While ocean acidification (OA) can reduce larval settlement and the abundance of CCA, the impact of OA on the interactions between planktonic larvae and their preferred settlement substrate are unknown. Here, we demonstrate that CO2 concentrations (800 and 1300 μatm) predicted to occur by the end of this century significantly reduce coral (Acropora millepora) settlement and CCA cover by ≥ 45%. The CCA important for inducing coral settlement (Titanoderma spp., Hydrolithon spp.) were the most deleteriously affected by OA. Surprisingly, the only preferred settlement substrate (Titanoderma) in the experimental controls was avoided by coral larvae as pCO2 increased, and other substrata selected. Our results suggest OA may reduce coral population recovery by reducing coral settlement rates, disrupting larval settlement behaviour, and reducing the availability of the most desirable coralline algal species for successful coral recruitment.
Thrombo‐prophylaxis in colorectal surgery: a National Questionnaire Survey of the members of the Association of Coloproctology of Great Britain and Ireland
Authors: Srinivasaiah N. , Arsalani‐Zadeh R. , Monson J. R. 
Published: February 2012

AbstractAim  Available guidelines from the National Institute for Health and Clinical Excellence (NICE) and the Association of Coloproctology of Great Britain and Ireland (ACPGBI) recommend combined (medical + mechanical) thrombo‐ prophylaxis. A Cochrane Library review recommends self‐administered low‐molecular‐weight heparin (LMWH) for 2–3 weeks following surgery. In the light of the recent guidelines from the ACPGBI and NICE, we undertook a National Questionnaire Survey to assess current thrombo‐prophylaxis practice among colorectal surgeons in the UK.Method  A 10‐item questionnaire was designed to enquire into the current management strategy of postoperative thrombo‐prophylaxis. The postal questionnaire survey was sent to all 490 active consultant members of the ACPGBI.Results  Of the 490 questionnaires sent, 259 (52.8%) were returned fully completed. Among these, all (100%) respondents reported the routine use of thrombo‐prophylaxis, with 243 (93.8%) following departmental guidelines. Combined medical and mechanical prophylaxis was used by 247 (95.40%) respondents. A small number – 12 (4.6%) – used medical prophylaxis only. LMWH was the preferred medical‐prophylactic agent of 243 (93.8%) repondents. The majority, 176 (68%), started thrombo‐prophylaxis on admission and stopped it at discharge. Seventy‐one (27.4%) respondents recommended thrombo‐prophylaxis after hospital discharge for an average duration of 4–6 weeks, preferring graduated compression stockings followed by LMWH.Conclusion  The National Questionnaire Survey on thrombo‐prophylaxis demonstrated a high degree of concordance with the available guidelines, except for thrombo‐prophylaxis to be continued postoperatively for a period of 28 days/4 weeks.