bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thymoquinone-induced reactive oxygen species causes apoptosis of chondrocytes via PI3K/Akt and p38kinase pathway
Authors: Yu Seon-Mi , Kim Song-Ja 
Published: June 2013

Thymoquinone (TQ), a bioactive ingredient of the volatile oil of black seed ( Nigella sativa), has been shown to possess anti-neoplastic and anti-inflammatory effects on a variety of tumours. However, the precise mechanism of action is not clear in normal cells such as primary chondrocytes. So, we have investigated the effects of TQ on the apoptosis of chondrocytes with a focus on reactive oxygen species (ROS) production. In in vitro experiments, chondrocytes were cultured with increasing concentrations of TQ for 24 h or with 20 µmol/L TQ for the indicated time periods, and various experiments were performed to detect the apoptotic effects caused by TQ. The results showed that TQ significantly increases apoptosis. Apoptosis was dose- and time-dependently expressed, and the generation of ROS also dramatically increased in a dose-dependent manner. Pretreatment of N-acetyl-l-cysteine (NAC), an inhibitor of ROS, inhibited both TQ-induced apoptosis and ROS generation. Also, TQ up-regulated phosphorylation of phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and mitogen-activated protein kinases ([MAPKs] p38kinase, ERK-1/-2, and JNKinase), and these effects were prevented by pretreatment of NAC. However, pretreatment with inhibitors of PI3K/Akt and MAPKs did not inhibit TQ-caused ROS generation. Among the inhibitors of PI3K/Akt, p38kinase, ERK-1/-2, and JNKinase, pretreatment with LY294002 and SB203580 abolished TQ-induced apoptosis, but PD98059 and SP600125 did not have any effect on TQ-caused apoptosis. These findings suggest that TQ-induced ROS generation regulates apoptosis by modulating PI3K/Akt and p38kinase pathways.
Identification and real-time expression analysis of selected Toxoplasma gondii in-vivoinduced antigens recognized by IgG and IgM in sera of acute toxoplasmosis patients
Authors: Amerizadeh Atefeh , Khoo Boon Yin , Teh Ai Ying , Golkar Majid , Abdul Karim Izzati Zahidah , Osman Sabariah , Yunus Muhammad Hafiznur , Noordin Rahmah 
Published: June 2013

Abstract

Background

Toxoplasma gondii is an obligate intracellular zoonotic parasite of the phylum Apicomplexa which infects a wide range of warm-blooded animals, including humans. In this study in-vivo induced antigens of this parasite was investigated using in-vivo induced antigen technology (IVIAT) and pooled sera from patients with serological evidence of acute infection.

Methods
The pooled sera was first pre-absorbed against three different preparations of antigens from in-vitro-grown cells of each T. gondii and E. coli XL1-Blue MRF’, subsequently it was used to screen T. gondii cDNA phage expression library. Positive clones from each group were subjected to quantitative real-time PCR expression analysis on mRNA of in-vivo and in-vitro grown parasites.

Results
A total of 29 reactive clones from each IgM and IgG immunoscreenings were found to have high homology to T. gondii genes. Quantitative real-time PCR expression analysis showed that 20 IgM-detected genes and 11 IgG-detected genes were up-regulated in-vivo relative to their expression levels in-vitro. These included genes encoding micronemes, sterol-regulatory element binding protein site, SRS34A, MIC2-associated protein M2AP, nucleoredoxin, protein phosphatase 2C and several hypothetical proteins. A hypothetical protein (GenBank accession no. 7899266) detected by IgG had the highest in-vivo over in-vitro fold change of 499.86; while another up-regulated hypothetical protein (GenBank accession no. 7898829) recognized by IgM showed high sensitivity (90%) and moderate specificity (70%) in detecting T. gondii antibodies when tested with 20 individual serum samples.

Conclusion
The highly up-regulated genes and the corresponding proteins, in particular the hypothetical proteins, may be useful in further studies on understanding the disease pathogenesis and as potential vaccine candidates.
The diagnostic value of ultrasonography in carpal tunnel syndrome: a comparison between diabetic and non-diabetic patients
Authors: Tsai Nai-Wen , Lee Lian-Hui , Huang Chi-Ren , Chang Wen-Neng , Wang Hung-Chen , Lin Yu-Jun , Lin Wei-Che , Lin Tsu-Kung , Cheng Ben-Chung , Su Yu-Jih , Kung Chia-Te , Chen Shu-Fang , Lu Cheng-Hsien 
Published: June 2013

AbstractBackgroundTo compare the value of ultrasonography for diagnosing carpal tunnel syndrome (CTS) in patients with and without diabetes mellitus (DM).MethodsEighty non-DM and 40 DM patients with electromyography-confirmed CTS were assessed and underwent high-resolution ultrasonography of the wrists. Cross-sectional area (CSA) and flattening ratio (FR) of the median nerve were measured at the carpal tunnel outlet (D) and wrist crease (W).ResultsThe 80 non-DM and 40 DM patients had 81 and 59 CTS-hands, respectively. The CSA_D and CSA_W were significantly larger in the CTS-hands and DM-CTS-hands compared to the normal control (p < 0.001). However, there is no difference of CSA_D and CSA_W between DM and non-DM CTS patients. Receiver operating characteristics [ROC] curve analysis revealed that CSA_W ≥13 mm2was the most powerful predictor of CTS in DM (area under curve [AUC] = 0.72; sensitivity 72.9%, specificity 61.9%) and non-DM (AUC = 0.72; sensitivity 78.5%, specificity 53.2%) patients. The CSA positively correlated with the distal motor latency of the median compound motor action potential (CMAP), distal sensory latency of the median sensory nerve action potential (SNAP), and latency of the median F wave, but negatively correlated with the amplitude of the median CMAP, amplitude of the median SNAP, and sensory NCV of the median nerve. Stepwise logistic regression revealed that CSA_W (OR 1.21, 95% CI 1.07-1.38;p = 0.003) was independently associated with CTS in DM patients and any 1 mm2increase in CSA_W increased the rate of CTS by 28%.ConclusionsThe CSA of the median nerve at the outlet and wrist crease are significantly larger in CTS hands in both DM and non-DM patients compared to normal hands. The CSA of the median nerve by ultrasonography may be a diagnostic tool for evaluating CTS in DM and non-DM patients.
Improved accessibility of emergency obstetrics and newborn care(EmONC) services for maternal and newborn health: a community based project
Authors: Turab Ali , Ariff Shabina , Habib Muhammad A , Ahmed Imran , Hussain Masawar , Rashid Akhtar , Memon Zahid , Khan Mohammad I , Soofi Sajid , Bhutta Zulfiqar A 
Published: June 2013

AbstractBackgroundEvery year an estimated three million neonates die globally and two hundred thousand of these deaths occur in Pakistan. Majority of these neonates die in rural areas of underdeveloped countries from preventable causes (infections, complications related to low birth weight and prematurity). Similarly about three hundred thousand mother died in 2010 and Pakistan is among ten countries where sixty percent burden of these deaths is concentrated. Maternal and neonatal mortality remain to be unacceptably high in Pakistan especially in rural areas where more than half of births occur.Method/DesignThis community based cluster randomized controlled trial will evaluate the impact of an Emergency Obstetric and Newborn Care (EmONC) package in the intervention arm compared to standard of care in control arm. Perinatal and neonatal mortality are primary outcome measure for this trial. The trial will be implemented in 20 clusters (Union councils) of District Rahimyar Khan, Pakistan. The EmONC package consists of provision of maternal and neonatal health pack (clean delivery kit, emollient, chlorhexidine) for safe motherhood and newborn wellbeing and training of community level and facility based health care providers with emphasis on referral of complicated cases to nearest public health facilities and community mobilization.DiscussionEven though there is substantial evidence in support of effectiveness of various health interventions for improving maternal, neonatal and child health. Reduction in perinatal and neonatal mortality remains a big challenge in resource constrained and diverse countries like Pakistan and achieving MDG 4 and 5 appears to be a distant reality. A comprehensive package of community based low cost interventions along the continuum of care tailored according to the socio cultural environment coupled with existing health force capacity building may result in improving the maternal and neonatal outcomes.The findings of this proposed community based trial will provide sufficient evidence on feasibility, acceptability and effectiveness to the policy makers for replicating and scaling up the interventions within the health systemTrial registrationClinicalTrial.govNCT01751945
Connexin-43 can delay early recurrence and metastasis in patients with hepatitis B-related hepatocellular carcinoma and low serum alpha-fetoprotein after radical hepatectomy
Authors: Wang Zu-Sen , Wu Li-Qun , Yi Xin , Geng Chao , Li Yu-Jun , Yao Ru-Yong 
Published: June 2013

Abstract

Background
We studied the relationships among Cx43, CD105, and VEGF in specimens of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different serum AFP levels with respect to recurrence and metastasis.

Methods
Expressions of Cx43, CD105, and VEGF in 234 HCC tissue specimens were examined using tissue microarray and immunohistochemistry. Cx43 mRNA expression was examined in 38 frozen HCC specimens using RT-PCR. Correlations between these expressions and tumor recurrence, metastasis, and prognosis were analyzed using Kaplan–Meier and Cox regression analyses.

Results
Cx43 expression correlated with early tumor recurrence (P = 0.001), disease-free survival (P = 0.026), and overall survival (P = 0.000) in patients with serum AFP < 400 ng/ml, but not in those with serum AFP ≥ 400 μg/L. Cx43 expression is an independent predictor of later recurrence and longer overall survival and is inversely correlated with expression of CD105 and VEGF (P = 0.018 and 0.023, respectively), histological differentiation (P = 0.002), vessel tumor embolism (P = 0.029), and focal number (P = 0.017). Immunohistochemistry showed that Cx43 expression in patients with low AFP was lower in patients with distant metastases than in those with no metastasis or those with liver metastasis. Patients with early recurrence expressed less Cx43 mRNA than did those with no recurrence (χ2 = 9.827, P = 0.002).

Conclusions
Cx43 expression can delay early HCC recurrence, metastasis, and poor prognosis after radical hepatectomy in patients with HBV-related HCC and low AFP.
Rhaphidophora korthalsii modulates peripheral blood natural killer cell proliferation, cytokine secretion and cytotoxicity
Authors: Yeap Swee Keong , Omar Abdul Rahman , Ho Wan Yong , Beh Boon Kee , Ali Abdul Manaf , Alitheen Noorjahan Banu 
Published: June 2013

Abstract

Background

Rhaphidophora korthalsii (Araceae) is a root-climber plant which has been widely used in Chinese traditional medicine for cancer and skin disease treatment. Previous reports have recorded its immunomodulatory effects on mice splenocyte and human peripheral blood. This study investigated the potential immunostimulatory effect of Rhaphidophora korthalsii on human PBMC enriched NK cell.

Methods
PBMC was exposed to various concentrations of R. korthalsii extract and the T and NK cell population in the control and extract treated PBMC were identified by immunophenotyping. Intracellular perforin and granzyme B expressions were detected by flow cytometry and extra-cellular Granzyme B, IFN-γ and TNF-α production in the isolated NK cells were determined by ELISA. The cytotoxicity of effector NK cell towards target K562 cell was assessed by CytoTox 96 assay.

Results

Rhaphidophora korthalsii methanol extract significantly increased PBMC NK cell population and intracellular perforin and granzyme B expressions. Moreover, the extract also enhanced the secretion of IFN-γ and TNF-α which subsequently enhanced the cytotoxicity of NK cell against the NK sensitive target K562 cell line. NK cell enriched with extract treated PBMC showed better activation than NK cell directly treated with the extract.

Conclusion
Our findings indicated a potential IL-2 free immunotherapy through direct and indirect R. korthalsii stimulation on NK cell activation.
Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA
Authors: Michailidis Eleftherios , Ryan Emily M , Hachiya Atsuko , Kirby Karen A , Marchand Bruno , Leslie Maxwell D , Huber Andrew D , Ong Yee T , Jackson Jacob C , Singh Kamalendra , Kodama Eiichi N , Mitsuya Hiroaki , Parniak Michael A , Sarafianos Stefan G 
Published: June 2013

AbstractBackgroundThe K65R substitution in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is the major resistance mutation selected in patients treated with first-line antiretroviral tenofovir disoproxil fumarate (TDF). 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA), is the most potent nucleoside analog RT inhibitor (NRTI) that unlike all approved NRTIs retains a 3'-hydroxyl group and has remarkable potency against wild-type (WT) and drug-resistant HIVs. EFdA acts primarily as a chain terminator by blocking translocation following its incorporation into the nascent DNA chain. EFdA is in preclinical development and its effect on clinically relevant drug resistant HIV strains is critically important for the design of optimal regimens prior to initiation of clinical trials.ResultsHere we report that the K65R RT mutation causes hypersusceptibility to EFdA. Specifically, in single replication cycle experiments we found that EFdA blocks WT HIV ten times more efficiently than TDF. Under the same conditions K65R HIV was inhibited over 70 times more efficiently by EFdA than TDF. We determined the molecular mechanism of this hypersensitivity using enzymatic studies with WT and K65R RT. This substitution causes minor changes in the efficiency of EFdA incorporation with respect to the natural dATP substrate and also in the efficiency of RT translocation following incorporation of the inhibitor into the nascent DNA. However, a significant decrease in the excision efficiency of EFdA-MP from the 3’ primer terminus appears to be the primary cause of increased susceptibility to the inhibitor. Notably, the effects of the mutation are DNA-sequence dependent.ConclusionWe have elucidated the mechanism of K65R HIV hypersusceptibility to EFdA. Our findings highlight the potential of EFdA to improve combination strategies against TDF-resistant HIV-1 strains.
Vaccination induced antibodies to recombinant avian influenza A virus M2 protein or synthetic M2e peptide do not bind to the M2 protein on the virus or virus infected cells
Authors: Swinkels Willem J C , Hoeboer Jeroen , Sikkema Reina , Vervelde Lonneke , Koets Ad P 
Published: June 2013

Abstract

Background
Influenza viruses are characterized by their highly variable surface proteins HA and NA. The third surface protein M2 is a nearly invariant protein in all Influenza A strains. Despite extensive studies in other animal models, this study is the first to describe the use of recombinant M2 protein and a peptide coding for the extracellular part of the M2 protein (M2e) to vaccinate poultry.

Methods
Four groups of layer chickens received a prime-boost vaccination with recombinant M2 protein, M2e, a tetrameric construct from M2e peptide bound to streptavidin and a control tetrameric construct formulated with Stimune adjuvant.

Results
We determined the M2-specific antibody (Ab) responses in the serum before vaccination, three weeks after vaccination and two weeks after booster, at days 21, 42 and 56 of age. The group vaccinated with the M2 protein in combination with Stimune adjuvant showed a significant Ab response to the complete M2 protein as compared to the other groups. In addition an increased Ab response to M2e peptide was found in the group vaccinated with the M2e tetrameric construct. None of the vaccinated animals showed seroconversion to AI in a commercial ELISA. Finally no Ab’s were found that bound to M2 expressed on in vitro AI infected MDCK cells.

Conclusion
Although Ab’s are formed against the M2 protein and to Streptavidin bound M2e peptide in a tetrameric conformation these Ab’s do not recognize of M2 on the virus or on infected cells.
A case of adenocarcinoma of the rete testis accompanied by focal adenomatous hyperplasia
Authors: Lin Xu-Yong , Yu Juan-Han , Xu Hong-Tao , Wang Liang , Fan Chui-Feng , Liu Yang , Wang En-Hua 
Published: June 2013

Abstract

Abstract
Adenocarcinoma of the rete testis is very rare. There is still little knowledge about its etiology and pathogenesis. Herein, we present a case of rete testis adenocarcinoma in a 36-year-old Chinese male. The tumor was predominantly composed of irregular small tubules and papillary structures with cuboidal or polygonal cells. In peripheral area of the tumor, the remaining normal rete testis and adenomatous hyperplasia of the rete testis could also be seen, indicating the possible relationship between adenomatous hyperplasia and adenocarcinoma. In addition, the patient underwent a left hydrocelectomy because of the existence of hydrocele 3 years ago. But, it is unclear whether hydrocele and hydrocelectomy is its cause or just the early clinical presentation of the adenocarcinoma.

Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6757609119625499
Effect of plate working length on plate stiffness and cyclic fatigue life in a cadaveric femoral fracture gap model stabilized with a 12-hole 2.4 mm locking compression plate
Authors: Chao Peini , Conrad Bryan P , Lewis Daniel D , Horodyski MaryBeth , Pozzi Antonio 
Published: June 2013

AbstractBackgroundThere are several factors that can affect the fatigue life of a bone plate, including the mechanical properties of the plate and the complexity of the fracture. The position of the screws can influence construct stiffness, plate strain and cyclic fatigue of the implants. Studies have not investigated these variables in implants utilized for long bone fracture fixation in dogs and cats. The purpose of the present study was to evaluate the effect of plate working length on construct stiffness, gap motion and resistance to cyclic fatigue of dog femora with a simulated fracture gap stabilized using a 12-hole 2.4 mm locking compression plates (LCP). Femora were plated with 12-hole 2.4 mm LCP using 2 screws per fracture segment (long working length group) or with 12-hole 2.4 mm LCP using 5 screws per fracture segment (a short working length group).ResultsConstruct stiffness did not differ significantly between stabilization techniques. Implant failure did not occur in any of the plated femora during cycling. Mean ± SD yield load at failure in the short plate working length group was significantly higher than in the long plate working length group.ConclusionIn a femoral fracture gap model stabilized with a 2.4 mm LCP applied in contact with the bone, plate working length had no effect on stiffness, gap motion and resistance to fatigue. The short plate working length constructs failed at higher loads; however, yield loads for both the short and long plate working length constructs were within physiologic range.
Parallel-META: efficient metagenomic data analysis based on high-performance computation
Authors: Su Xiaoquan , Xu Jian , Ning Kang 
Published: June 2013

Abstract

Background
Metagenomics method directly sequences and analyses genome information from microbial communities. There are usually more than hundreds of genomes from different microbial species in the same community, and the main computational tasks for metagenomic data analyses include taxonomical and functional component examination of all genomes in the microbial community. Metagenomic data analysis is both data- and computation- intensive, which requires extensive computational power. Most of the current metagenomic data analysis softwares were designed to be used on a single computer or single computer clusters, which could not match with the fast increasing number of large metagenomic projects' computational requirements. Therefore, advanced computational methods and pipelines have to be developed to cope with such need for efficient analyses.

Result
In this paper, we proposed Parallel-META, a GPU- and multi-core-CPU-based open-source pipeline for metagenomic data analysis, which enabled the efficient and parallel analysis of multiple metagenomic datasets and the visualization of the results for multiple samples. In Parallel-META, the similarity-based database search was parallelized based on GPU computing and multi-core CPU computing optimization. Experiments have shown that Parallel-META has at least 15 times speed-up compared to traditional metagenomic data analysis method, with the same accuracy of the results http://www.computationalbioenergy.org/parallel-meta.html.

Conclusion
The parallel processing of current metagenomic data would be very promising: with current speed up of 15 times and above, binning would not be a very time-consuming process any more. Therefore, some deeper analysis of the metagenomic data, such as the comparison of different samples, would be feasible in the pipeline, and some of these functionalities have been included into the Parallel-META pipeline.
A computational procedure for identifying master regulator candidates: a case study on diabetes progression in Goto-Kakizaki rats
Authors: Piao Guanying , Saito Shigeru , Sun Yidan , Liu Zhi-Ping , Wang Yong , Han Xiao , Wu Jiarui , Zhou Huarong , Chen Luonan , Horimoto Katsuhisa 
Published: June 2013

Abstract

Background
We have recently identified a number of active regulatory networks involved in diabetes progression in Goto-Kakizaki (GK) rats by network screening. The networks were quite consistent with the previous knowledge of the regulatory relationships between transcription factors (TFs) and their regulated genes. To study the underlying molecular mechanisms directly related to phenotype changes, such as diseases, we also previously developed a computational procedure for identifying transcriptional master regulators (MRs) in conjunction with network screening and network inference, by effectively perturbing the phenotype states.

Results
In this work, we further improved our previous method for identifying MR candidates, by listing them in a more reliable manner, and applied the method to reveal the MR candidates for diabetes progression in GK rats from the active networks. Specifically, the active TF-gene pairs for different time periods in GK rats were first extracted from the networks by network screening. Another set of active TF-gene pairs was selected by network inference, by considering the gene expression signatures for those periods between GK and Wistar-Kyoto (WKY) rats. The TF-gene pairs extracted by the two methods were then further selected, from the viewpoints of the emergence specificity of TF in GK rats and the regulated-gene coverage of TF in the expression signature. Finally, we narrowed all of the genes down to only 5 TFs (Etv4, Fus, Nr2f1, Sp2, and Tcfap2b) as the candidates of MRs, with 54 regulated genes, by merging the selected TF-gene pairs.

Conclusions
The present method has successfully identified biologically plausible MR candidates, including the TFs related to diabetes in previous reports. Although the experimental verifications of the candidates and the present procedure are beyond the scope of this study, we narrowed down the candidates to 5 TFs, which can be used to perform the verification experiments relatively easily. The numerical results showed that our computational method is an efficient way to detect the key molecules responsible for biological phenomena.