bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of cyclin B1 and Sec62 as biomarkers for recurrence in patients with HBV-related hepatocellular carcinoma after surgical resection
Authors: Weng Li , Du Juan , Zhou Qinghui , Cheng Binbin , Li Jun , Zhang Denghai , Ling Changquan 
Published: June 2012

AbstractBackgroundHepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Frequent tumor recurrence after surgery is related to its poor prognosis. Although gene expression signatures have been associated with outcome, the molecular basis of HCC recurrence is not fully understood, and there is no method to predict recurrence using peripheral blood mononuclear cells (PBMCs), which can be easily obtained for recurrence prediction in the clinical setting.MethodsAccording to the microarray analysis results, we constructed a co-expression network using the k-core algorithm to determine which genes play pivotal roles in the recurrence of HCC associated with the hepatitis B virus (HBV) infection. Furthermore, we evaluated the mRNA and protein expressions in the PBMCs from 80 patients with or without recurrence and 30 healthy subjects. The stability of the signatures was determined in HCC tissues from the same 80 patients. Data analysis included ROC analysis, correlation analysis, log-lank tests, and Cox modeling to identify independent predictors of tumor recurrence.ResultsThe tumor-associated proteins cyclin B1, Sec62, and Birc3 were highly expressed in a subset of samples of recurrent HCC; cyclin B1, Sec62, and Birc3 positivity was observed in 80%, 65.7%, and 54.2% of the samples, respectively. The Kaplan-Meier analysis revealed that high expression levels of these proteins was associated with significantly reduced recurrence-free survival. Cox proportional hazards model analysis revealed that cyclin B1 (hazard ratio [HR], 4.762;p = 0.002) and Sec62 (HR, 2.674;p = 0.018) were independent predictors of HCC recurrence.ConclusionThese results revealed that cyclin B1 and Sec62 may be candidate biomarkers and potential therapeutic targets for HBV-related HCC recurrence after surgery.
A dynamic plasma membrane proteome analysis of alcohol-induced liver cirrhosis
Authors: Jia Xiaofang , Yin Lin , Feng Yanling , Peng Xia , Ma Fang , Yao Yamin , Liu Xiaoqian , Zhang Zhiyong , Yuan Zhenghong , Zhang Lijun 
Published: June 2012

AbstractAlcohol-induced injury has become one of the major causes for liver cirrhosis. However, the molecular mechanisms of ethanol-induced injury are not fully understood. To this end, we performed a dynamic plasma membrane proteomic research on rat model. A rat model from hepatitis to liver cirrhosis was developed. Plasma membrane from liver tissue with liver fibrosis stage of 2 and 4 (S2 and S4) was purified by sucrose density gradient centrifugation. Its purification was verified by western blotting. Proteins from plasma membrane were separated by two-dimensional electrophoresis (2DE) and differentially expressed proteins were identified by tandem mass spectrometry. 16 consistent differentially expressed proteins from S2 to S4 were identified by mass spectrometry. The expression of differentially expressed proteins annexin A6 and annexin A3 were verified by western blotting, and annexin A3 was futher verified by immunohistochemistry. Our research suggests a possible mechanism by which ethanol alters protein expression to enhance the liver fibrosis progression. These differentially expressed proteins might be new drug targets for treating alcoholic liver cirrhosis.
Apoptotic activity in Libyan breast cancer
Authors: Boder Jamela , Abdalla Fathi , Elfagieh Mohamed , Buhmeida Abdelbaset , Collan Yrjö 
Published: June 2012

Abstract

Background
We evaluated the relationship of the apoptotic activity index (AI) and the standardized mitotic-apoptotic ratio (SMI/AI) with clinicopathological features and prognosis in Libyan female breast cancer (BC) patients. We then compared our results with corresponding results in Finnish and Nigerian female BC patients.

Methods
Histological samples of breast carcinoma from 130 patients were retrospectively studied: an estimation of the apoptotic activity per square millimeter (expressed as apoptotic activity index (AI)), and standardized mitotic-apoptotic ratio (SMI/AI) was made, and the results compared with the clinicopathological features and the patient’s survival.

Results
There was a statistically significant correlation between the AI and most of the clinicopathological features; the strongest association was observed for clinical stage lymph node (LN) status (P = 0.005). There were also correlations between AI and histological grade (P = 0.035), large tumor size (P = 0.011) and the clinical stage (P = 0.009). There were, however, prominent AI differences between Libyan, Nigerian and Finnish populations. The mean values of AI and SMI/AI in Libyan BC patients were 12.8 apoptotic figures per square millimeter and 2.8, respectively. The Libyan AI is slightly higher than in Nigeria, but much higher than in Finland. The differences between countries are seen throughout the samples as well as being present in certain subgroups. The survival analysis indicated that short survival time was associated with high apoptotic indices values and so can identify aggressive tumors and provide significant prognostic support. The cutoff (4 and 18 apoptosis/mm2) of AI might be applied as a quantitative criterion for Libyan BC to separate the patients into good, moderate and bad prognosis groups.

Conclusions
The results indicated that the differences in AI among the three countries may be due to the known variation in the distribution of genetic markers in these populations. Improvement in health care and introduction of screening programs, however, could be very helpful in the Libyan population.
Novel preparation of PLGA/HP55 nanoparticles for oral insulin delivery
Authors: Wu Zhi Min , Ling Li , Zhou Li Ying , Guo Xin Dong , Jiang Wei , Qian Yu , Luo Kathy Qian , Zhang Li Juan 
Published: June 2012

Abstract
The aim of the present study was to develop the PLGA/HP55 nanoparticles with improved hypoglycemic effect for oral insulin delivery. The insulin-loaded PLGA/HP55 nanoparticles were produced by a modified multiple emulsion solvent evaporation method. The physicochemical characteristics, in vitro release of insulin, and in vivo efficacy in diabetic rats of the nanoparticles were evaluated. The insulin encapsulation efficiency was up to 94%, and insulin was released in a pH-dependent manner under simulated gastrointestinal conditions. When administered orally (50 IU/kg) to diabetic rats, the nanoparticles can decrease rapidly the blood glucose level with a maximal effect between 1 and 8 h. The relative bioavailability compared with subcutaneous injection (5 IU/kg) in diabetic rats was 11.3% ± 1.05%. This effect may be explained by the fast release of insulin in the upper intestine, where it is better absorbed by the high gradient concentration of insulin than other regions. These results show that the PLGA/HP55 nanoparticles developed in the study might be employed as a potential method for oral insulin delivery.
The first 100 patients in the SUN(^_^)D trial (strategic use of new generation antidepressants for depression): examination of feasibility and adherence during the pilot phase
Authors: Shimodera Shinji , Kato Tadashi , Sato Hirotoshi , Miki Kazuhira , Shinagawa Yoshihiro , Kondo Masaki , Fujita Hirokazu , Morokuma Ippei , Ikeda Yoshio , Akechi Tatsuo , Watanabe Norio , Yamada Mitsuhiko , Inagaki Masatoshi , Yonemoto Naohiro , Furukawa Toshi A ,   For the SUN(^_^)D Investigators
Published: June 2012

Abstract

Background
Initial glitches and unexpected inconsistencies are unavoidable in the early stage of a large, multi-centre trial. Adaptive modifications of the trial’s protocol and operational procedures to ensure its smooth running are therefore imperative. We started a large pragmatic, multi-centre, assessor-blinded, 25-week trial to investigate the optimal first- and second-line treatments for untreated episodes of nonpsychotic major depression in 2010 [Strategic Use of New generation antidepressants for Depression, abbreviated SUN(^_^)D] and would like to herein report an examination of the trial’s feasibility and adherence among the first 100 participants.

Methods
We examined the participants’ characteristics, the treatments that were allocated and received during each step of the trial, and the quality of the outcome assessments among the first 100 patients enrolled in the SUN(^_^)D trial.

Results
Of the 2,743 first-visit patients who visited the two collaborating centres between December 2010 and July 2011, 382 were judged as potentially eligible, and 100 of these patients provided written informed consent. These patients represented the whole spectrum of mild to very severe depression. Of the 93 patients who had reached Week 3 of the study by the end of July 2011, one withdrew consent for both the treatment and the assessment, and eight withdrew consent for the treatment only. Altogether, the primary outcomes were successfully assessed in 90 (96.8%) of the patients at Week 3. Of the 72 patients who had reached Week 9, three withdrew consent for the treatment, but 70 were successfully interviewed (97.2%). Of the 32 patients who had reached Week 25, 29 (90.5%) were successfully followed up. The inter-rater reliability of the assessments of the primary outcomes was nearly perfect and their successful blinding was confirmed. Minor modifications and clarifications to the protocol were deemed necessary.

Discussion
Given the satisfactory feasibility and adherence to the study protocol and the minor modifications that were necessary, we conclude that the data obtained from the first 100 patients can be safely included in the main study. We now intend to accelerate the study by recruiting more collaborating centres and clinics/hospitals.

Trial registration
ClinicalTrials.gov identifier: NCT01109693
Mapping the stabilome: a novel computational method for classifying metabolic protein stability
Authors: Patrick Ralph , Cao Kim-Anh Lê , Davis Melissa , Kobe Bostjan , Bodén Mikael 
Published: June 2012

Abstract

Background
The half-life of a protein is regulated by a range of system properties, including the abundance of components of the degradative machinery and protein modifiers. It is also influenced by protein-specific properties, such as a protein’s structural make-up and interaction partners. New experimental techniques coupled with powerful data integration methods now enable us to not only investigate what features govern protein stability in general, but also to build models that identify what properties determine each protein’s metabolic stability.

Results
In this work we present five groups of features useful for predicting protein stability: (1) post-translational modifications, (2) domain types, (3) structural disorder, (4) the identity of a protein’s N-terminal residue and (5) amino acid sequence. We incorporate these features into a predictive model with promising accuracy. At a 20% false positive rate, the model exhibits an 80% true positive rate, outperforming the only previously proposed stability predictor. We also investigate the impact of N-terminal protein tagging as used to generate the data set, in particular the impact it may have on the measurements for secreted and transmembrane proteins; we train and test our model on a subset of the data with those proteins removed, and show that the model sustains high accuracy. Finally, we estimate system-wide metabolic stability by surveying the whole human proteome.

Conclusions
We describe a variety of protein features that are significantly over- or under-represented in stable and unstable proteins, including phosphorylation, acetylation and destabilizing N-terminal residues. Bayesian networks are ideal for combining these features into a predictive model with superior accuracy and transparency compared to the only other proposed stability predictor. Furthermore, our stability predictions of the human proteome will find application in the analysis of functionally related proteins, shedding new light on regulation by protein synthesis and degradation.
Biochemical characterization and evaluation of cytotoxicity of antistaphylococcal chimeric protein P128
Authors: George Shilpa E , Chikkamadaiah Ravisha , Durgaiah Murali , Joshi Amruta A , Thankappan Ullas P , Madhusudhana Shampur N , Sriram Bharathi 
Published: June 2012

Abstract

Background
Antibiotic resistant S. aureus infection is a global threat. Newer approaches are required to control this organism in the current scenario. Cell wall degrading enzymes have been proposed as antibacterial agents for human therapy. P128 is a novel antistaphylococcal chimeric protein under development against S. aureus for human use which derives its bacterial cell wall degrading catalytic endopeptidase domain from ORF56, the Phage K tail-structure associated enzyme. Lead therapeutic entities have to be extensively characterized before they are assessed in animals for preclinical safety and toxicity. P128 is effective against antibiotic resistant strains as well as against a panel of isolates of global significance. Its efficacy against S. aureus in vivo has been established in our lab. Against this background, this study describes the characterization of this protein for its biochemical properties and other attributes.

Results
We evaluated the requirement or effect of divalent cations and the metal ion chelator, EDTA upon biological activity of P128. As the protein is intended for therapeutic use, we tested its activity in presence of body fluids and antibodies specific to P128. For the same reason, we used standard human cell lines to evaluate cytotoxic effects, if any.
The divalent cations, calcium and magnesium at upto 25 mM and Zinc upto 2.5 mM neither inhibited nor enhanced P128 activity. Incubation of this protein with EDTA, human serum, plasma and blood also did not alter the antibacterial properties of the molecule. No inhibitory effect was observed in presence of hyper-immune sera raised against the protein. Finally, P128 did not show any cytotoxic effect on HEp2 and Vero cells at the highest concentration (5 mg/mL) tested.

Conclusions
The results presented here throw light on several properties of protein P128. Taken together, these substantiate the potential of P128 for therapeutic use against S. aureus. Further development of the protein and conduct of preclinical safety studies in animals is warranted.
Interrater and intrarater reliability of photoplethysmography for measuring toe blood pressure and toe‐brachial index in people with diabetes mellitus
Authors: Scanlon Christopher , Park Kris , Mapletoft David , Begg Lindy , Burns Joshua 
Published: June 2012

AbstractBackgroundA reliable tool to measure arterial flow to the feet in people with diabetes is required given that they are particularly prone to peripheral arterial disease. Traditionally, the ankle brachial index (ABI) has been used to measure arterial circulation, but its application is limited due to calcification of larger arteries. More recently, toe pressure and the toe brachial index (TBI) has been suggested as superior to ABI measurements because they assess smaller digital arteries less prone to arterial calcification. However, reliability studies for the clinical use of photoplethysmography (PPG) in people with diabetes are lacking.MethodsSixty people with diabetes mellitus (35 males and 25 females, mean age 59.6 yrs) consented to take part in the study. The majority (92%) had type 2 diabetes and 8% had type 1 diabetes. Forty‐three percent were diagnosed as having peripheral neuropathy when tested using a biothesiometer and 15% were current smokers (10 – 40/day). A podiatrist and a diabetes educator measured toe and brachial blood pressure independently and in a random order using PPG. These measurements were repeated again seven days later, and subsequently analysed with intraclass correlation coefficients (ICC), 95% confidence intervals (CI) and standard error of measurement (SEM).ResultsThe intrarater reliability of measuring toe pressures was excellent (ICC3,1 =0.78‐0.79, SEM 8 mmHg) and interrater reliability was also excellent (ICC2,2 = 0.93, SEM 4 mmHg). The intrarater reliability for measuring brachial pressures was generally poor (ICC3,1 = 0.40 – 0.42, SEM 19 mmHg) and interrater reliability was fair‐good (ICC2,2. 0.65, SEM 14 mmHg). The TBI intrarater reliability was fair‐good (ICC3,1 = 0.51‐0.72, SEM 0.08), whilst the interrater reliability of TBI was excellent (ICC2,2 = 0.85, SEM 0.07).ConclusionsBased on these results, interrater and intrarater reliability of PPG is excellent for measuring toe blood pressure, good for TBI and only fair for brachial pressures in people with diabetes mellitus.
Bioinformatics insights into acute lung injury/acute respiratory distress syndrome
Authors: Fang Xiaocong , Bai Chunxue , Wang Xiangdong 
Published: June 2012

AbstractBioinformatics is the application of omics science, information technology, mathematics and statistics in the field of biomarker detection. Clinical bioinformatics can be applied for identification and validation of new biomarkers to improve current methods of monitoring disease activity and identify new therapeutic targets. Acute lung injurt (ALI)/Acute respiratory distress syndrome (ARDS) affects a large number of patients with a poor prognosis. The present review mainly focused on the progress in understanding disease heterogeneity through the use of evolving biological, genomic, and genetic approaches and the role of clinical bioinformatics in the pathogenesis and treatment of ALI/ARDS. The remarkable advances in clinical bioinformatics can be a new way for understanding disease pathogenesis, diagnosis and treatment.
Loss of vascular early response gene reduces edema formation after experimental stroke
Authors: Liu Fudong , Turtzo L Christine , Li Jun , Regard Jean , Worley Paul , Zeevi Neer , McCullough Louise D 
Published: June 2012

Abstract
Vascular Early Response Gene (Verge) is an immediate early gene (IEG) that is up-regulated in endothelial cells in response to a number of stressors, including ischemic stroke. Endothelial cell lines that stably express Verge show enhanced permeability. Increased Verge expression has also been associated with blood brain barrier breakdown. In this study we investigated the role of Verge in ischemic injury induced by middle cerebral artery occlusion (MCAO) in both Verge knockout (KO) and wild type (WT) mice. Verge KO mice had significantly less cerebral edema formation after MCAO compared to WT mice. However, stroke outcome (infarct size and neurological deficit scores) evaluated at either 24 or 72 hours after stroke showed no differences between the two genotypes. Verge deletion leads to decreased edema formation after ischemia; however acute stroke outcomes were unchanged.
Branching of the p-nitrophenol (PNP) degradation pathway in burkholderia sp. Strain SJ98: Evidences from genetic characterization of PNP gene cluster
Authors: Vikram Surendra , Pandey Janmejay , Bhalla Nidhi , Pandey Gunjan , Ghosh Anuradha , Khan Fazlurrahman , Jain Rakesh K , Raghava Gajendra PS 
Published: June 2012

Abstract
Aerobic microbial degradation of p-nitrophenol (PNP) has been classically shown to proceed via ‘Hydroquinone (HQ) pathway’ in Gram-negative bacteria, whereas in Gram-positive PNP degraders it proceed via ‘Benzenetriol (BT) pathway’. These pathways are characterized by the ring cleavage of HQ and BT as terminal aromatic intermediates respectively. Earlier reports on PNP degradation have indicated these pathways to be mutually exclusive. We report involvement of both ‘HQ’ and ‘BT’ ring cleavage pathways in PNP degradation by Burkholderia sp. strain SJ98. Genetic characterization of an ~41 Kb DNA fragment harboring PNP degradation gene cluster cloned and sequenced from strain SJ98 showed presence of multiple orfs including pnpC and pnpD which corresponded to previously characterized ‘benzenetriol-dioxygenase (BtD)’ and ‘maleylacetate reductase (MaR)’ respectively. This gene cluster also showed presence of pnpE1 and pnpE2, which shared strong sequence identity to cognate sub-units of ‘hydroquinone dioxygenase’ (HqD). Heterologous expression and biochemical characterization ascertained the identity of PnpE1 and PnpE2. In in vitro assay reconstituted heterotetrameric complex of PnpE1 and PnpE2 catalyzed transformation of hydroquinone (HQ) into corresponding hydroxymuconic semialdehyde (HMS) in a substrate specific manner. Together, these results clearly establish branching of PNP degradation in strain SJ98. We propose that strain SJ98 presents a useful model system for future studies on evolution of microbial degradation of PNP.
Polyclonal HER2-specific antibodies induced by vaccination mediate receptor internalization and degradation in tumor cells
Authors: Ren Xiu-Rong , Wei Junping , Lei Gangjun , Wang Jiangbo , Lu Jiuyi , Xia Wenle , Spector Neil , Barak Larry S , Clay Timothy M , Osada Takuya , Hamilton Erika , Blackwell Kimberly , Hobeika Amy C , Morse Michael A , Lyerly H Kim , Chen Wei 
Published: June 2012

Abstract
Introduction
Sustained HER2 signaling at the cell surface is an oncogenic mechanism in a significant proportion of breast cancers. While clinically effective therapies targeting HER2 such as mAbs and tyrosine kinase inhibitors exist, tumors overexpressing HER2 eventually progress despite treatment. Thus, abrogation of persistent HER2 expression at the plasma membrane to synergize with current approaches may represent a novel therapeutic strategy.

Methods
We generated polyclonal anti-HER2 antibodies (HER2-VIA) by vaccinating mice with an adenovirus expressing human HER2, and assessed their signaling effects in vitro and anti-tumor effects in a xenograft model. In addition, we studied the signaling effects of human HER2-specific antibodies induced by vaccinating breast cancer patients with a HER2 protein vaccine.

Results
HER2-VIA bound HER2 at the plasma membrane, initially activating the downstream kinases extracellular signal-regulated protein kinase 1/2 and Akt, but subsequently inducing receptor internalization in clathrin-coated pits in a HER2 kinase-independent manner, followed by ubiquitination and degradation of HER2 into a 130 kDa fragment phosphorylated at tyrosine residues 1,221/1,222 and 1,248. Following vaccination of breast cancer patients with the HER2 protein vaccine, HER2-specific antibodies were detectable and these antibodies bound to cell surface-expressed HER2 and inhibited HER2 signaling through blocking tyrosine 877 phosphorylation of HER2. In contrast to the murine antibodies, human anti-HER2 antibodies induced by protein vaccination did not mediate receptor internalization and degradation.

Conclusion
These data provide new insight into HER2 trafficking at the plasma membrane and the changes induced by polyclonal HER2-specific antibodies. The reduction of HER2 membrane expression and HER2 signaling by polyclonal antibodies induced by adenoviral HER2 vaccines supports human clinical trials with this strategy for those breast cancer patients with HER2 therapy-resistant disease.