bluuebunny/crossref_metadata_2025_split huggingface dataset:
A strategy of tumor treatment in mice with doxorubicin-cyclophosphamide combination based on dendritic cell activation by human double-stranded DNA preparation
Authors: Alyamkina Ekaterina A , Nikolin Valeriy P , Popova Nelly A , Dolgova Evgenia V , Proskurina Anastasia S , Orishchenko Konstantin E , Efremov Yaroslav R , Chernykh Elena R , Ostanin Alexandr A , Sidorov Sergey V , Ponomarenko Dmitriy M , Zagrebelniy Stanislav N , Bogachev Sergey S , Shurdov Mikhail A 
Published: November 2010

AbstractBackgroundImmunization of mice with tumor homogenate after combined treatment with cyclophosphamide (CP) and double-stranded DNA (dsDNA) preparation is effective at inhibition of growth of tumor challenged after the treatment. It was assumed that this inhibition might be due to activation of the antigen-presenting cells. The purpose was to develop improved antitumor strategy using mice. We studied the combined action of cytostatics doxorubicin (Dox) plus CP with subsequent dsDNA preparation on tumor growth.MethodsThree-month old CBA/Lac mice were used in the experiments. Mice were injected with CP and human dsDNA preparation. The percentage of mature dendritic cells (DCs) was estimated by staining of mononuclear cells isolated from spleen and bone marrow 3, 6, and 9 days later with monoclonal antibodies CD34, CD80, and CD86. In the next set of experiments, mice were given intramuscularly injections of 1-3 × 105tumor cells. Four days later, they were injected intravenously with 6-6.7 mg/kg Dox and intraperitoneally with 100-200 mg/kg CP; 200 mkg human DNA was injected intraperitoneally after CP administration. Differences in tumor size between groups were analyzed for statistical significance by Student's t-test. The MTT-test was done to determine the cytotoxic index of mouse leucocytes from treated groups.ResultsThe conducted experiments showed that combined treatment with CP and dsDNA preparation produce an increase in the total amount of mature DCsin vivo. Treatment of tumor bearers with preparation of fragmented dsDNA on the background of pretreatment with Dox plus CP demonstrated a strong suppression of tumor growth in two models. RLS, a weakly immunogenic, resistant to alkalyting cytostatics tumor, grew 3.4-fold slower when compared with the control (p < 0.001). In experiment with Krebs-2 tumor, only 2 of the 10 mice in the Dox+CP+DNA group had a palpable tumor on day 16. The cytotoxic index of leucocytes was 86.5% in the Dox+CP+DNA group, but it was 0% in the Dox+CP group.ConclusionsThus, the set of experiments we performed showed that exogenous dsDNA, when administered on the background of pretreatment with Dox plus CP, has an antitumor effect possibly due to DC activation.
Predictors of adherence to antiretroviral therapy among people living with HIV/AIDS in resource-limited setting of southwest ethiopia
Authors: Tiyou Ayele , Belachew Tefera , Alemseged Fisehaye , Biadgilign Sibhatu 
Published: November 2010

Abstract

Background
Good adherence to antiretroviral therapy is necessary to achieve the best virological response, lower the risk that drug resistance will develop, and reduce morbidity and mortality. Little is known about the rate and predictors of adherence in Ethiopia. Therefore this study determines the magnitude and predictors of adherence to antiretroviral therapy among people living with HIV/AIDS in Southwest Ethiopia.

Methods
A cross sectional study was carried out from January 1, 2009 to March 3, 2009 among 319 adult PLWHA (≥ 18 years) attending ART clinic at Jimma university Specialized Hospital (JUSH). Multiple Logistic regression models were constructed with adherence and independent variables to identify the predictors.

Results
About 303(95%) of the study subjects were adherent based on self report of missed doses (dose adherence) in a one-week recall before the actual interview. The rate of self reported adherence in the study based on the combined indicator of the dose, time and food adherence measurement was 72.4%. Patients who got family support were 2 times [2.12(1.25-3.59)] more likely to adhere than those who didn't get family support as an independent predictor of overall adherence (dose, time and food). The reasons given for missing drugs were 9(27.3%) running out of medication/drug, 7(21.2%) being away from home and 7(21.2%) being busy with other things.

Conclusion
The adherence rate found in this study is similar to other resource limited setting and higher than the developed country. This study highlights emphasis should be given for income generating activities and social supports that helps to remember the patients for medication taking and management of opportunistic infections during the course of treatment.
All that glitters is not gold - founder effects complicate associations of flu mutations to disease severity
Authors: Lee Raphael TC , Santos Cecília LS , Maria de Paiva Terezinha , Cui Lin , Sirota Fernanda L , Eisenhaber Frank , Maurer-Stroh Sebastian 
Published: November 2010

Abstract

Background
The recent 2009 (H1N1) influenza A pandemic saw a rapid spread of the virus to essentially all parts of the world. In the course of its evolution, the virus acquired many mutations, some of which have been investigated in the context of increased severity due to high occurrences in fatal cases. For example, statements such as: "42.9% of individuals who died from laboratory-confirmed cases of the pandemic (H1N1) were infected with the hemagglutinin (HA) Q310 H mutant virus." give the impression that HA-Q310 H would be highly dangerous or important, while careful consideration of all available data suggests that this is unlikely to be the case.

Results
We compare the mutations HA-Q310 H, PB2-K340N, HA-D239N and HA-D239G using whole genome phylogenetic trees, structural modeling in their 3 D context and complete epidemiological data from sequences to clinical outcomes. HA-Q310 H and PB2-K340N appear as isolated subtrees in the phylogenetic analysis pointing to founder effects which is consistent with their clustered temporal appearance as well as the lack of an immediate structural basis that could explain a change of phenotypes. Considering the prevailing viral genomic background, shared origin of samples (all from the city of Sao Paulo) and narrow temporal window (all death case samples within 1 month), it becomes clear that HA-Q310 H was actually a generally common mutation in the region at that time which could readily explain its increased occurrence among the few analyzed fatal cases without requiring necessarily an association with severity. In further support of this, we highlight 3 mild cases with the HA-Q310 H mutation.

Conclusions
We argue that claims of severity of any current and future flu mutation need to be critically considered in the light of phylogenetic, structural and detailed epidemiological data to distinguish increased occurrence due to possible founder effects rather than real phenotypic changes.
Effect of smoking status on total energy expenditure
Authors: Bradley David P , Johnson Lindsey A , Zhang Zhumin , Subar Amy F , Troiano Richard P , Schatzkin Arthur , Schoeller Dale A 
Published: November 2010

Abstract
Individuals who smoke generally have a lower body mass index (BMI) than nonsmokers. The relative roles of energy expenditure and energy intake in maintaining the lower BMI, however, remain controversial. We tested the hypothesis that current smokers have higher total energy expenditure than never smokers in 308 adults aged 40-69 years old of which 47 were current smokers. Energy expenditure was measured by doubly labeled water during a two week period in which the subjects lived at home and performed their normal activities. Smoking status was determined by questionnaire. There were no significant differences in mean BMI (mean ± SD) between smokers and never smokers for either males (27.8+5.1 kg/m2 vs. 27.5+4.0 kg/m2) or females (26.5+5.3 kg/m2 vs. 28.1+6.6 kg/m2), although the difference in females was of similar magnitude to previous reports. Similarly, total energy expenditure of male smokers (3069+764 kcal/d) was not significantly different from that of never smokers (2854+468 kcal/d), and that of female smokers (2266+387 kcal/d) was not different from that of never smokers (2330+415 kcal/d). These findings did not change after adjustment for age, fat-free mass and self-reported physical activity. Using doubly labeled water, we found no evidence of increased energy expenditure among smokers, however, it should be noted that BMI differences in this cohort also did not differ by smoking status.
Acupuncture Modulates Temporal Neural Responses in Wide Brain Networks: Evidence from fMRI Study
Authors: Bai Lijun , Tian Jie , Zhong Chongguang , Xue Ting , You Youbo , Liu Zhenyu , Chen Peng , Gong Qiyong , Ai Lin , Qin Wei , Dai Jianping , Liu Yijun 
Published: November 2010

Background: Accumulating neuroimaging studies in humans have shown that acupuncture can modulate a widely distributed brain network, large portions of which are overlapped with the pain-related areas. Recently, a striking feature of acupuncture-induced analgesia is found to be associated with its long-last effect, which has a delayed onset and gradually reaches a peak even after acupuncture needling being terminated. Identifying temporal neural responses in these areas that occur at particular time – both acute and sustained effects during acupuncture processes – may therefore shed lights on how such peripheral inputs are conducted and mediated through the CNS. In the present study, we adopted a non-repeated event-related (NRER) fMRI paradigm and control theory based approach namely change-point analysis in order to capture the detailed temporal profile of neural responses induced by acupuncture. Results: Our findings demonstrated that neural activities at the different stages of acupuncture presented distinct temporal patterns, in which consistently positive neural responses were found during the period of acupuncture needling while much more complex and dynamic activities found during a post-acupuncture period. These brain responses had a significant time-dependent effect which showed different onset time and duration of neural activities. The amygdala and perigenual anterior cingulate cortex (pACC), exhibited increased activities during the needling phase while decreased gradually to reach a peak below the baseline. The periaqueductal gray (PAG) and hypothalamus presented saliently intermittent activations across the whole fMRI session. Apart from the time-dependent responses, relatively persistent activities were also identified in the anterior insula and prefrontal cortices. The overall findings indicate that acupuncture may engage differential temporal neural responses as a function of time in a wide range of brain networks. Conclusions: Our study has provided evidence supporting a view that acupuncture intervention involves complex modulations of temporal neural response, and its effect can gradually resolve as a function of time. The functional specificity of acupuncture at ST36 may involve multiple levels of differential activities of a wide range of brain networks, which are gradually enhanced even after acupuncture needle being terminated.
Proteomic changes associated with deletion of the Magnaporthe oryzae conidial morphology-regulating gene COM1
Authors: Bhadauria Vijai , Wang Li-Xia , Peng You-Liang 
Published: November 2010

Abstract

Background
The rice blast disease caused by Magnaporthe oryzae is a major constraint on world rice production. The conidia produced by this fungal pathogen are the main source of disease dissemination. The morphology of conidia may be a critical factor in the spore dispersal and virulence of M. oryzae in the field. Deletion of a conidial morphology regulating gene encoding putative transcriptional regulator COM1 in M. oryzae resulted in aberrant conidial shape, reduced conidiation and attenuated virulence.

Results
In this study, a two-dimensional gel electrophoresis/matrix assisted laser desorption ionization- time of flight mass spectrometry (2-DE/MALDI-TOF MS) based proteomics approach was employed to identify the cellular and molecular components regulated by the COM1 protein (COM1p) that might contribute to the aberrant phenotypes in M. oryzae. By comparing the conidial proteomes of COM1 deletion mutant and its isogenic wild-type strain P131, we identified a potpourri of 31 proteins that exhibited statistically significant alterations in their abundance levels. Of these differentially regulated proteins, the abundance levels of nine proteins were elevated and twelve were reduced in the Δcom1 mutant. Three proteins were detected only in the Δcom1 conidial proteome, whereas seven proteins were apparently undetectable. The data obtained in the study suggest that the COM1p plays a key role in transcriptional reprogramming of genes implicated in melanin biosynthesis, carbon and energy metabolism, structural organization of cell, lipid metabolism, amino acid metabolism, etc. Semi-quantitative RT-PCR analysis revealed the down-regulation of genes encoding enzymes involved in melanin biosynthesis in the COM1 mutant.

Conclusions
Our results suggest that the COM1p may regulate the transcription of genes involved in various cellular processes indispensable for conidial development and appressorial penetration. These functions are likely to contribute to the effects of COM1p upon the aberrant phenotypes of M. oryzae.

Reviewers
This article is reviewed by George V. Shpakovski, Karthikeyan Sivaraman (nominated by M. Madan Babu) and Lakshminarayan M. Iyer.
MicroRNA-17-92 significantly enhances radioresistance in human mantle cell lymphoma cells
Authors: Jiang Ping , Rao En Y , Meng Na , Zhao Yong , Wang Jun J 
Published: November 2010

Abstract
The microRNA-17-92 (miRNA-17-92) cluster, at chromosome 13q31-q32, also known as oncomir-1, consists of seven miRNAs that are transcribed as a polycistronic unit. Over-expression of miRNA-17-92 has been observed in lymphomas and other solid tumors. Whether miRNA-17-92 expression affects the response of tumor cells to radiotherapy is not addressed so far. In the present study, we studied the effects of miRNA-17-92 on the radiosensitivity of human mantle cell lymphoma (MCL) cells Z138c. Over-expression of miRNA-17-92 significantly increased survival cell number, cell proliferation and decreased cell death of human MCL cells after different doses of radiation. Immunoblot analysis showed that phosphatase and tension homolog (PTEN) and PHLPP2 was down-modulated and pAkt activity was enhanced in MCL cells after over-expressing miRNA-17-92 after irradiation. These findings are the first direct evidence that over-expression of miRNA-17-92 cluster significantly increases the radioresistance of human MCL cells, which offers a novel target molecule for improving the radiotherapy of MCL in clinic.
Carbonic anhydrase XII expression is associated with histologic grade of cervical cancer and superior radiotherapy outcome
Authors: Yoo Chong Woo , Nam Byung-Ho , Kim Joo-Young , Shin Hye-Jin , Lim Hyunsun , Lee Sun , Lee Su-Kyoung , Lim Myong-Cheol , Song Yong-Jung 
Published: November 2010

Abstract

Background
To investigate whether expression of carbonic anhydrase XII (CA12) is associated with histologic grade of the tumors and radiotherapy outcomes of the patients with invasive cervical cancer.

Methods
CA12 expression was examined by immunohistochemical stains in cervical cancer tissues from 183 radiotherapy patients. Histological grading was classified as well (WD), moderately (MD) or poorly differentiated (PD). Oligonucleotide microarray experiment was performed using seven cervical cancer samples to examine differentially expressed genes between WD and PD cervical cancers. The association between CA12 and histological grade was analyzed by chi-square test. CA12 and histological grades were analyzed individually and as combined CA12 and histologic grade categories for effects on survival outcome.

Results
Immunohistochemical expression of CA12 was highly associated with the histologic grade of cervical cancer. Lack of CA12 expression was associated with PD histology, with an odds ratio of 3.9 (P = 0.01). Microarray analysis showed a fourfold reduction in CA12 gene expression in PD tumors. CA12 expression was marginally associated with superior disease-free survival. Application of the new combined categories resulted in further discrimination of the prognosis of patients with moderate and poorly differentiated tumor grade.

Conclusions
Our study indicates that CA12 may be used as a novel prognostic marker in combination with histologic grade of the tumors.
Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden
Authors: O'Leary John C , Li Qingyou , Marinec Paul , Blair Laura J , Congdon Erin E , Johnson Amelia G , Jinwal Umesh K , Koren John , Jones Jeffrey R , Kraft Clara , Peters Melinda , Abisambra Jose F , Duff Karen E , Weeber Edwin J , Gestwicki Jason E , Dickey Chad A 
Published: November 2010

Abstract

Background
It has traditionally been thought that the pathological accumulation of tau in Alzheimer's disease and other tauopathies facilitates neurodegeneration, which in turn leads to cognitive impairment. However, recent evidence suggests that tau tangles are not the entity responsible for memory loss, rather it is an intermediate tau species that disrupts neuronal function. Thus, efforts to discover therapeutics for tauopathies emphasize soluble tau reductions as well as neuroprotection.

Results
Here, we found that neuroprotection alone caused by methylene blue (MB), the parent compound of the anti-tau phenothiaziazine drug, Rember™, was insufficient to rescue cognition in a mouse model of the human tauopathy, progressive supranuclear palsy (PSP) and fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP17): Only when levels of soluble tau protein were concomitantly reduced by a very high concentration of MB, was cognitive improvement observed. Thus, neurodegeneration can be decoupled from tau accumulation, but phenotypic improvement is only possible when soluble tau levels are also reduced.

Conclusions
Neuroprotection alone is not sufficient to rescue tau-induced memory loss in a transgenic mouse model. Development of neuroprotective agents is an area of intense investigation in the tauopathy drug discovery field. This may ultimately be an unsuccessful approach if soluble toxic tau intermediates are not also reduced. Thus, MB and related compounds, despite their pleiotropic nature, may be the proverbial "magic bullet" because they not only are neuroprotective, but are also able to facilitate soluble tau clearance. Moreover, this shows that neuroprotection is possible without reducing tau levels. This indicates that there is a definitive molecular link between tau and cell death cascades that can be disrupted.
Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells
Authors: Wu Qiong , Qin Shu-Kui , Teng Feng-Meng , Chen Chang-Jie , Wang Rui 
Published: November 2010

Abstract

Background
Hepatocellular carcinoma (HCC) still is a big burden for China. In recent years, the third-generation platinum compounds have been proposed as potential active agents for HCC. However, more experimental and clinical data are warranted to support the proposal. In the present study, the effect of lobaplatin was assessed in five HCC cell lines and the underlying molecular mechanisms in terms of cell cycle kinetics were explored.

Methods
Cytotoxicity of lobaplatin to human HCC cell lines was examined using MTT cell proliferation assay. Cell cycle distribution was determined by flow cytometry. Expression of cell cycle-regulated genes was examined at both the mRNA (RT-PCR) and protein (Western blot) levels. The phosphorylation status of cyclin-dependent kinases (CDKs) and retinoblastoma (Rb) protein was also examined using Western blot analysis.

Results
Lobaplatin inhibited proliferation of human HCC cells in a dose-dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1), pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27.

Conclusion
Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC.
Campylobacter jejuni induces transcytosis of commensal bacteria across the intestinal epithelium through M-like cells
Authors: Kalischuk Lisa D , Leggett Frances , Inglis G Douglas 
Published: November 2010

Abstract

Background
Recent epidemiological analyses have implicated acute Campylobacter enteritis as a factor that may incite or exacerbate inflammatory bowel disease (IBD) in susceptible individuals. We have demonstrated previously that C. jejuni disrupts the intestinal barrier function by rapidly inducing epithelial translocation of non-invasive commensal bacteria via a transcellular lipid raft-mediated mechanism ('transcytosis'). To further characterize this mechanism, the aim of this current study was to elucidate whether C. jejuni utilizes M cells to facilitate transcytosis of commensal intestinal bacteria.

Results

C. jejuni induced translocation of non-invasive E. coli across confluent Caco-2 epithelial monolayers in the absence of disrupted transepithelial electrical resistance or increased permeability to a 3 kDa dextran probe. C. jejuni-infected monolayers displayed increased numbers of cells expressing the M cell-specific marker, galectin-9, reduced numbers of enterocytes that stained with the absorptive enterocyte marker, Ulex europaeus agglutinin-1, and reduced activities of enzymes typically associated with absorptive enterocytes (namely alkaline phosphatase, lactase, and sucrase). Furthermore, in Campylobacter-infected monolayers, E. coli were observed to be internalized specifically within epithelial cells displaying M-like cell characteristics.

Conclusion
These data indicate that C. jejuni may utilize M cells to promote transcytosis of non-invasive bacteria across the intact intestinal epithelial barrier. This mechanism may contribute to the inflammatory immune responses against commensal intestinal bacteria commonly observed in IBD patients.