bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation
Authors: Vinci Maria , Gowan Sharon , Boxall Frances , Patterson Lisa , Zimmermann Miriam , Court William , Lomas Cara , Mendiola Marta , Hardisson David , Eccles Suzanne A 
Published: March 2012

Abstract

Background
There is overwhelming evidence that in vitro three-dimensional tumor cell cultures more accurately reflect the complex in vivo microenvironment than simple two-dimensional cell monolayers, not least with respect to gene expression profiles, signaling pathway activity and drug sensitivity. However, most currently available three-dimensional techniques are time consuming and/or lack reproducibility; thus standardized and rapid protocols are urgently needed.

Results
To address this requirement, we have developed a versatile toolkit of reproducible three-dimensional tumor spheroid models for dynamic, automated, quantitative imaging and analysis that are compatible with routine high-throughput preclinical studies. Not only do these microplate methods measure three-dimensional tumor growth, but they have also been significantly enhanced to facilitate a range of functional assays exemplifying additional key hallmarks of cancer, namely cell motility and matrix invasion. Moreover, mutual tissue invasion and angiogenesis is accommodated by coculturing tumor spheroids with murine embryoid bodies within which angiogenic differentiation occurs. Highly malignant human tumor cells were selected to exemplify therapeutic effects of three specific molecularly-targeted agents: PI-103 (phosphatidylinositol-3-kinase (PI3K)-mammalian target of rapamycin (mTOR) inhibitor), 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) (heat shock protein 90 (HSP90) inhibitor) and CCT130234 (in-house phospholipase C (PLC)γ inhibitor). Fully automated analysis using a Celigo cytometer was validated for tumor spheroid growth and invasion against standard image analysis techniques, with excellent reproducibility and significantly increased throughput. In addition, we discovered key differential sensitivities to targeted agents between two-dimensional and three-dimensional cultures, and also demonstrated enhanced potency of some agents against cell migration/invasion compared with proliferation, suggesting their preferential utility in metastatic disease.

Conclusions
We have established and validated a suite of highly reproducible tumor microplate three-dimensional functional assays to enhance the biological relevance of early preclinical cancer studies. We believe these assays will increase the translational predictive value of in vitro drug evaluation studies and reduce the need for in vivo studies by more effective triaging of compounds.
Acute Morphine Activates Satellite Glial Cells and Up-Regulates IL-1β in Dorsal Root Ganglia in Mice via Matrix Metalloprotease-9
Authors: Berta Temugin , Liu Tong , Liu Yen-Chin , Xu Zhen-Zhong , Ji Ru-Rong 
Published: March 2012

Background: Activation of spinal cord glial cells such as microglia and astrocytes has been shown to regulate chronic opioid-induced antinociceptive tolerance and hyperalgesia, due to spinal up-regulation of the proinflammatory cytokines such as interleukin-1 beta (IL-1β). Matrix metalloprotease-9 (MMP-9) has been implicated in IL-1β activation in neuropathic pain. However, it is unclear whether acute opioid treatment can activate glial cells in the peripheral nervous system. We examined acute morphine-induced activation of satellite glial cells (SGCs) and up-regulation of IL-1β in dorsal root ganglia (DRGs), and further investigated the involvement of MMP-9 in these opioid-induced peripheral changes. Results: Subcutaneous morphine injection (10 mg/kg) induced robust peripheral glial responses, as evidenced by increased GFAP expression in DRGs but not in spinal cords. The acute morphine-induced GFAP expression is transient, peaking at 2 h and declining after 3 h. Acute morphine treatment also increased IL-1β immunoreactivity in SGCs and IL-1β activation in DRGs. MMP-9 and GFAP are expressed in DRG neurons and SGCs, respectively. Confocal analysis revealed a close proximity of MMP-9 and GFAP immunostaining. Importantly, morphine-induced DRG up-regulation of GFAP expression and IL-1β activation was abolished after Mmp9 deletion or naloxone pretreatment. Finally, intrathecal injections of IL-1β-selective siRNA not only reduced DRG IL-1β expression but also prolonged acute morphine-induced analgesia. Conclusions: Acute morphine induces opioid receptors- and MMP-9-dependent up-regulation of GFAP expression and IL-1β activation in SGCs of DRGs. MMP-9 could mask and shorten morphine analgesia via peripheral neuronglial interactions. Targeting peripheral glial activation might prolong acute opioid analgesia.
Auditory stimulation of opera music induced prolongation of murine cardiac allograft survival and maintained generation of regulatory CD4+CD25+ cells
Authors: Uchiyama Masateru , Jin Xiangyuan , Zhang Qi , Hirai Toshihito , Amano Atsushi , Bashuda Hisashi , Niimi Masanori 
Published: March 2012

AbstractBackgroundInteractions between the immune response and brain functions such as olfactory, auditory, and visual sensations are likely. This study investigated the effect of sounds on alloimmune responses in a murine model of cardiac allograft transplantation.MethodsNaïve CBA mice (H2k) underwent transplantation of a C57BL/6 (B6, H2b) heart and were exposed to one of three types of music--opera (La Traviata), classical (Mozart), and New Age (Enya)--or one of six different single sound frequencies, for 7 days. Additionally, we prepared two groups of CBA recipients with tympanic membrane perforation exposed to opera for 7 days and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment). An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Immunohistochemical, cell-proliferation, cytokine, and flow cytometry assessments were also performed.ResultsCBA recipients of a B6 cardiac graft that were exposed to opera music and Mozart had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to a single sound frequency (100, 500, 1000, 5000, 10,000, or 20,000 Hz) or Enya did not (MSTs, 7.5, 8, 9, 8, 7.5, 8.5 and 11 days, respectively). Untreated, CBA mice with tympanic membrane perforations and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment) rejected B6 cardiac grafts acutely (MSTs, 7, 8 and 8 days, respectively). Adoptive transfer of whole splenocytes, CD4+cells, or CD4+CD25+cells from opera-exposed primary allograft recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and > 100 days, respectively). Proliferation of splenocytes, interleukin (IL)-2 and interferon (IFN)-γ production was suppressed in opera-exposed mice, and production of IL-4 and IL-10 from opera-exposed transplant recipients increased compared to that from splenocytes of untreated recipients. Flow cytometry studies showed an increased CD4+CD25+Forkhead box P3 (Foxp3)+cell population in splenocytes from those mice.ConclusionOur findings indicate that exposure to opera music, such as La traviata, could affect such aspects of the peripheral immune response as generation of regulatory CD4+CD25+cells and up-regulation of anti-inflammatory cytokines, resulting in prolonged allograft survival.
Cost-effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts: economic evaluation alongside a randomised controlled trial (EVerT trial)
Authors: Stamuli Eugena , Cockayne Sarah , Hewitt Catherine , Hicks Kate , Jayakody Shalmini , Kang'ombe Arthur Ricky , Turner Gwen , Thomas Kim , Curran Mike , Hashmi Farina , McIntosh Caroline , McLarnon Nichola , Torgerson David J , Watt Ian ,   the EVerT team
Published: March 2012

Abstract

Background
Plantar warts (verrucae) are extremely common. Although many will spontaneously disappear without treatment, treatment may be sought for a variety of reasons such as discomfort. There are a number of different treatments for cutaneous warts, with salicylic acid and cryotherapy using liquid nitrogen being two of the most common forms of treatment. To date, no full economic evaluation of either salicylic acid or cryotherapy has been conducted based on the use of primary data in a pragmatic setting. This paper describes the cost-effectiveness analysis which was conducted alongside a pragmatic multicentre, randomised trial evaluating the clinical effectiveness of cryotherapy versus 50% salicylic acid of the treatment of plantar warts.

Methods
A cost-effectiveness analysis was undertaken alongside a pragmatic multicentre, randomised controlled trial assessing the clinical effectiveness of 50% salicylic acid and cryotherapy using liquid nitrogen at 12 weeks after randomisation of patients. Cost-effectiveness outcomes were expressed as the additional cost required to completely cure the plantar warts of one additional patient. A NHS perspective was taken for the analysis.

Results
Cryotherapy costs on average £101.17 (bias corrected and accelerated (BCA) 95% CI: 85.09-117.26) more per participant over the 12 week time-frame, while there is no additional benefit, in terms of proportion of patients healed compared with salicylic acid.

Conclusions
Cryotherapy is more costly and no more effective than salicylic acid.

Trial registration
Current Controlled Trials ISRCTN18994246 [controlled-trials.com] and National Research Register N0484189151.
Struma ovarii associated with Pseudo-Meig's syndrome and high serum level of CA 125; a case report
Authors: Mostaghel Nahid , Enzevaei Anahita , Zare Khandan , Fallahian Masoome 
Published: March 2012

Abstract
Struma ovarii is a rare form of ovarian neoplasm in a form of mature teratoma and is composed predominantly of thyroid tissue. In the literature review, there has only been 10 cases of this tumor, associated with ascites and pleural effusion (Meig's Syndrome) and increased CA125 so far. In such cases, the tumor mimics malignant ovarian tumor. In this article, the case of a 72-year-old symptomatic woman with a pelvic mass, pleural and peritoneal effusion and high level of serum CA125 is presented. Cytological evaluation for the pleural fluid was performed. She underwent hysterectomy and bilateral salpingo-oophorectomy. The result of pathologic diagnosis is presented in this paper. The patient was well in postoperative period and paraclinical tests including CA 125 were normal as well.
Retinoic acid synthesis and functions in early embryonic development
Authors: Kin Ting Kam Richard , Deng Yi , Chen Yonglong , Zhao Hui 
Published: March 2012

Abstract
Retinoic acid (RA) is a morphogen derived from retinol (vitamin A) that plays important roles in cell growth, differentiation, and organogenesis. The production of RA from retinol requires two consecutive enzymatic reactions catalyzed by different sets of dehydrogenases. The retinol is first oxidized into retinal, which is then oxidized into RA. The RA interacts with retinoic acid receptor (RAR) and retinoic acid X receptor (RXR) which then regulate the target gene expression. In this review, we have discussed the metabolism of RA and the important components of RA signaling pathway, and highlighted current understanding of the functions of RA during early embryonic development.
Genome-wide analysis of plant nat-siRNAs reveals insights into their distribution, biogenesis and function
Authors: Zhang Xiaoming , Xia Jing , Lii Yifan E , Barrera-Figueroa Blanca E , Zhou Xuefeng , Gao Shang , Lu Lu , Niu Dongdong , Chen Zheng , Leung Christy , Wong Timothy , Zhang Huiming , Guo Jianhua , Li Yi , Liu Renyi , Liang Wanqi , Zhu Jian-Kang , Zhang Weixiong , Jin Hailing 
Published: March 2012

Abstract
Background
Many eukaryotic genomes encode cis-natural antisense transcripts (cis-NATs). Sense and antisense transcripts may form double-stranded RNAs that are processed by the RNA interference machinery into small interfering RNAs (siRNAs). A few so-called nat-siRNAs have been reported in plants, mammals, Drosophila, and yeasts. However, many questions remain regarding the features and biogenesis of nat-siRNAs.

Results
Through deep sequencing, we identified more than 17,000 unique siRNAs corresponding to cis-NATs from biotic and abiotic stress-challenged Arabidopsis thaliana and 56,000 from abiotic stress-treated rice. These siRNAs were enriched in the overlapping regions of NATs and exhibited either site-specific or distributed patterns, often with strand bias. Out of 1,439 and 767 cis-NAT pairs identified in Arabidopsis and rice, respectively, 84 and 119 could generate at least 10 siRNAs per million reads from the overlapping regions. Among them, 16 cis-NAT pairs from Arabidopsis and 34 from rice gave rise to nat-siRNAs exclusively in the overlap regions. Genetic analysis showed that the overlapping double-stranded RNAs could be processed by Dicer-like 1 (DCL1) and/or DCL3. The DCL3-dependent nat-siRNAs were also dependent on RNA-dependent RNA polymerase 2 (RDR2) and plant-specific RNA polymerase IV (PolIV), whereas only a fraction of DCL1-dependent nat-siRNAs was RDR- and PolIV-dependent. Furthermore, the levels of some nat-siRNAs were regulated by specific biotic or abiotic stress conditions in Arabidopsis and rice.

Conclusions
Our results suggest that nat-siRNAs display distinct distribution patterns and are generated by DCL1 and/or DCL3. Our analysis further supported the existence of nat-siRNAs in plants and advanced our understanding of their characteristics.
Email-based promotion of self-help for subthreshold depression:
Mood Memos randomised controlled trial
Authors: Morgan Amy J. , Jorm Anthony F. , Mackinnon Andrew J. 
Published: March 2012

BackgroundSubthreshold depression is common, impairs functioning and increases the
risk of major depression. Improving self-help coping strategies could
help subthreshold depression and prevent major depression.AimsTo test the effectiveness of an automated email-based campaign promoting
self-help behaviours.MethodA randomised controlled trial was conducted through the website: www.moodmemos.com. Participants received automated emails twice
weekly for 6 weeks containing advice about self-help strategies. Emails
containing general information about depression served as a control. The
principal outcome was depression symptom level on the nine-item Patient
Health Questionnaire (PHQ-9) (trial registration:
ACTRN12609000925246).ResultsThe study recruited 1326 adults with subthreshold depression. There was a
small significant difference in depression symptoms at post-intervention,
favouring the active group (d = 0.17, 95% CI 0.01–0.34).
There was a lower, although non-significant, risk of major depression in
the active group (number needed to treat (NNT) 25, 95% CI 11 to ∞ to
NNT(harm) 57).ConclusionsEmails promoting self-help strategies were beneficial. Internet delivery
of self-help messages affords a low-cost, easily disseminated and highly
automated approach for indicated prevention of depression.
Association of Intact Parathyroid Hormone Levels with Subsequent Hip BMD Loss: The Osteoporotic Fractures in Men (MrOS) Study
Authors: Curtis Jeffrey R. , Ewing Susan K. , Bauer Douglas C. , Cauley Jane A. , Cawthon Peggy M. , Barrett-Connor Elizabeth , Haney Elizabeth M. , Ishani Areef , Cremers Serge , Orwoll Eric 
Published: March 2012

Introduction:There is little information on the association between intact PTH (iPTH) and longitudinal changes in bone mineral density (BMD) in older men. This association was evaluated in relation to conditions related to higher iPTH [e.g. decreased renal function, low serum 25-hydroxyvitamin D (25[OH]D)].Methods:Eligible men were part of a random sample of 1593 community-dwelling individuals aged 65 yr or older participating in the Osteoporotic Fractures in Men study with baseline iPTH data. Of these, 1227 had at least two BMD measurements at the total hip and femoral neck over a mean follow-up of 4.5 yr. Annualized BMD change across iPTH quartiles was estimated using mixed-effects regression models, adjusting for age, serum calcium, serum 25(OH)D, estimated glomerular filtration rate, and other factors. Splines were used to identify more optimal iPTH thresholds associated with less BMD loss.Results:Among the cohort of 1138 eligible men, men in the highest quartile of iPTH (≥38 pg/ml) lost 0.46% per year at the total hip compared with men in the lowest iPTH quartile who lost 0.22% per year (P = 0.0004). Results were similar at the femoral neck. The association between iPTH and BMD loss was not modified by baseline estimated glomerular filtration rate or 25(OH)D status. Spline results suggested that iPTH levels below 30 pg/ml were more physiologically optimal than higher iPTH values in reducing BMD loss, although an exact threshold for optimal iPTH was not identified.Conclusion:Older men with higher iPTH levels had approximately a 2-fold greater rate of BMD loss compared with men with lower iPTH levels, irrespective of estimated glomerular filtration rate and 25(OH)D.
The influence of pH on the sorption and diffusion of99TcO4−in Beishan granite
Authors: Li Chun , Liu X.Y. , Chen Tao , Tian W. Y. , Zheng Z. , Wang L. H. , Liu C. L. 
Published: March 2012

AbstractIn order to deal with the potential highly increasing amount of high-level radioactive wastes and spent nuclear fuels along with the ambitious development of nuclear power plants, China needs to construct a geologic repository in the middle of the 21stcentury. After about 15 years of basic research, including site survey, radionuclide migration, Beishan area in Northwest China's Gansu Province has been considered as the most promising candidate place. The Beishan granite has been highly considered as one of the potential host rocks, and some geochemical and hydrogeologic work has been carried out with the granite.In terms of pre-safety assessment of a potential site, the sorption, diffusion and migration of important radionuclides which tend to be released from the potential repository in the rock/water system play an important role and must be thoroughly investigated with the site specific rock/water characteristics. Due to the potential mobility of technetium under repository conditions, the investigation of the diffusion of technetium in different potential rocks has been studied, while few work focused on the rock surface characteristics. Since the diffusion/migration of radionuclides in the potential host rocks of geologic repositories is mainly through the pores/fractures of the host rocks, the surface characteristics of the rocks should play non-negligible role. In this paper, the influence of pH in the rock/water system on the diffusion of99TcO4−in Beishan granite is investigated with through-diffusion experiments and batch sorption experiments. Experimental results indicate that the effective diffusion coefficients (De) of99Tc in Beishan granite varied from 9.7 × 10−13to 1.3 × 10−12 m2/s, and the distribution coefficients (Kd) of99Tc in Beishan granite decreased when the pH of the rock/water system increased which may due to the decreasing of the density of positively charged sites on the granite surface.
Subacute Pulmonary Toxicity of Copper Indium Gallium Diselenide Following Intratracheal Instillations into the Lungs of Rats
Authors: Tanaka Akiyo , Hirata Miyuki , Shiratani Masaharu , Koga Kazunori , Kiyohara Yutaka 
Published: March 2012

Subacute Pulmonary Toxicity of Copper Indium Gallium Diselenide Following Intratracheal Instillations into the Lungs of Rats: Akiyo TANAKA, et al. Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University—ObjectivesThe aim of this study was to clarify the pulmonary toxicity of copper indium gallium diselenide (CIGS) solar cells on 62 8‐wk‐old rats.MethodsMale Wistar rats were given 0.5, 5 or 50 mg/kg of CIGS particles, intratracheally, 3 times for a week. Control rats were given vehicle, distilled water, only. These rats were euthanized 0, 1 or 3 wk after the final instillation serially, and toxicological effects were determined.ResultsNone of the CIGS‐treated groups exhibited suppression of body weight gain compared with the control group. The relative lung weight in the CIGS 5 mg/kg‐treated and 50 mg/kg‐treated groups were significantly increased compared with that in the control group throughout the observation period. Although serum copper (Cu) and selenium (Se) concentrations were not affected by instillations of CIGS particles, the indium (In) levels increased with the passage of time in the CIGS 5 mg/kg‐treated and 50 mg/kg‐treated groups. However, the serum gallium (Ga) levels decreased in the CIGS 50 mg/kg‐treated group from 0 to 3 wk. The content of each metal in the lung increased depending on the dose instilled and was constant during observation periods. Histopathologically, foci of slight to severe pulmonary inflammatory response and exudation were present among all the CIGS‐treated groups, and the severity of these lesions worsened with the passage of time.ConclusionThe present results clearly demonstrate that CIGS particles caused subacute pulmonary toxicity and that dissolution of CIGS particles in the lung was considerably slow when repeated intratracheal instillations were given to rats.
Effect of Six Months Lifestyle Intervention in Japanese Men with Metabolic Syndrome: Randomized Controlled Trial
Authors: Nanri Akiko , Tomita Kentaro , Matsushita Yumi , Ichikawa Fumiko , Yamamoto Miki , Nagafuchi Yoshihiro , Kakumoto Yoichiro , Mizoue Tetsuya 
Published: March 2012

Effect of Six Months Lifestyle Intervention in Japanese Men with Metabolic Syndrome: Randomized Controlled Trial: Akiko NANRI, et al. Department of Epidemiology and Prevention, International Clinical Research Center, National Center for Global Health and Medicine—ObjectivesThe prevalence of metabolic syndrome (MS) has been remarkably increasing worldwide. However, few studies have examined the effect of lifestyle intervention among subjects with MS. We investigated the effect of a six month lifestyle modification program on the prevalence of MS and its associated biomarkers among Japanese men with MS.MethodsSubjects were randomly assigned to either the intervention (n=53) or control (n=54) group. Subjects in the intervention group Received a lifestyle modification program focused on exercise and diet behavior from a trained occupational health nurse at the baseline and at one and three months. The effect of intervention was assessed by differences in changes in the prevalence of MS, its components and associated biomarkers between the two groups.ResultsOf the 107 participants, 102 completed the survey at the end of six months (intervention group, n=49; control group, n=53). During the study period, the prevalence of MS decreased to 65.3% and 62.3% in the intervention group and control group, respectively. However, the difference between the two groups was not statistically significant (p=0.75). A significant reduction in body weight, waist circumference and glycated hemoglobin was observed in the intervention group compared with the control group. In the intervention group, time spent on physical activity was increased by nearly one hour per week, and the intakes of cereals and sugar and sweeteners were significantly decreased.ConclusionsAlthough the tailor‐made lifestyle modification program among men with MS did not provide an additional benefit in decreasing the prevalence of MS, it may help weight control and improve glucose metabolism.