bluuebunny/crossref_metadata_2025_split huggingface dataset:
Herbal compound triptolide synergistically enhanced antitumor activity of amino-terminal fragment of urokinase
Authors: Lin Yuli , Peng Nana , Li Jianping , Zhuang Hongqin , Hua Zi-Chun 
Published: June 2013

AbstractBackgroundUrokinase (uPA) and its receptor (uPAR) play an important role in tumour growth and metastasis, and overexpression of these molecules is strongly correlated with poor prognosis in a variety of malignant tumours. Targeting the excessive activation of this system as well as the proliferation of the tumour vascular endothelial cell would be expected to prevent tumour neovasculature and halt tumour development. The amino terminal fragment (ATF) of urokinase has been confirmed effective to inhibit the proliferation, migration and invasiveness of cancer cells via interrupting the interaction of uPA and uPAR. Triptolide (TPL) is a purified diterpenoid isolated from the Chinese herbTripterygium wilfordiiHook F that has shown antitumor activities in various cancer cell types. However, its therapeutic application is limited by its toxicity in normal tissues and complications caused in patients. In this study, we attempted to investigate the synergistic anticancer activity of TPL and ATF in various solid tumour cells.MethodsUsingin vitroandin vivoexperiments, we investigated the combined effect of TPL and ATF at a low dosage on cell proliferation, cell apoptosis, cell cycle distribution, cell migration, signalling pathways, xenograft tumour growth and angiogenesis.ResultsOur data showed that the sensitivity of a combined therapy using TPL and ATF was higher than that of TPL or ATF alone. Suppression of NF-κB transcriptional activity, activation of caspase-9/caspase-3, cell cycle arrest, and inhibition of uPAR-mediated signalling pathway contributed to the synergistic effects of this combination therapy. Furthermore, using a mouse xenograft model, we demonstrated that the combined treatment completely suppressed tumour growth by inhibiting angiogenesis as compared with ATF or TPL treatment alone.ConclusionsOur study suggests that lower concentration of ATF and TPL used in combination may produce a synergistic anticancer efficacy that warrants further investigation for its potential clinical applications.
Association of CETP Taq1B and -629C > A polymorphisms with coronary artery disease and lipid levels in the multi-ethnic Singaporean population
Authors: Lu Yongjian , Tayebi Naeimeh , Li Hongzhe , Saha Nilmani , Yang Hongyuan , Heng Chew-Kiat 
Published: June 2013

Abstract

Background
Hyperlipidaemia is a major risk factor for coronary artery disease (CAD) and cholesteryl ester transfer protein (CETP) gene polymorphisms are known to be associated with lipid profiles.

Methods
In this study, we investigated the association of two polymorphisms in the CETP, Taq1B (rs708272) and -629C > A (rs1800775), with CAD and lipid levels HDL-C in 662 CAD + cases and 927 controls from the Singapore population comprising Chinese, Malays and Indians.

Results

TaqB2 frequency was significantly lowest in the Malays (0.43) followed by Chinese (0.47) and highest in the Indians (0.56) in the controls. The B2 allele frequency was significantly lower in the Chinese CAD + cases compared to the controls (p = 0.002). The absence of the B2 allele was associated with CAD with an OR 2.0 (95% CI 1.2 to 3.4) after adjustment for the confounding effects of age, smoking, BMI, gender, hypertension, dyslipidemia and diabetes mellitus. The B2 allele was significantly associated with higher plasma HDL-C levels in the Chinese men after adjusting for confounders. Associations with plasma apoA1 levels were significant only in the Chinese men for Taq1B and -629C > A. In addition, the Taq1B polymorphism was only associated with plasma Apo B and Lp(a) in the Malay men. Significant associations were only found in non-smoking subjects with BMI <50th percentile. In this study, the LD coefficients between the Taq1B and -629C > A polymorphisms seemed to be weak.

Conclusion
The absence the Taq1B2 allele was associated with CAD in the Chinese population only and the minor allele of the Taq1B polymorphism of the CETP gene was significantly associated with higher plasma HDL-C levels in Chinese men.
Targeting of Acyl-CoA synthetase 5 decreases jejunal fatty acid activation with no effect on dietary long-chain fatty acid absorption
Authors: Meller Nahum , Morgan Michelle E , Wong Winifred PS , Altemus Jessica B , Sehayek Ephraim 
Published: June 2013

Abstract

Background
The absorption of dietary long chain fatty acids (LCFA) largely occurs in the jejunum. LCFA are activated via conjugation with Coenzyme A (CoA), a reaction catalyzed by Acyl-CoA synthetases (ACS). Acyl-CoA sythesis is critical for dietary LCFA absorption; yet, the jejunal ACS enzymes that catalyze the reaction are largely unknown.

Findings
High throughput mRNA sequencing of the mouse jejunum revealed that the expression of acyl-CoA synthetase 5 (Acsl5) and fatty-acid transport protein 4 (Fatp4) largely exceeded all other annotated ACS genes that activate LCFA. Interestingly, Acsl5 knockout (KO) mice displayed a decrease of 60% in jejunal total long chain acyl-CoA synthesis rate. Nevertheless, and despite of this decrease, dietary LCFA absorption and body-weight gain in response to high fat diet remained unaffected.

Conclusion
Acsl5 is a major activator of dietary LCFA, yet in Acsl5 KO mice residual ACS activity is sufficient for maintaining a normal LCFA absorption. Our findings provide further evidence for a robust small intestine LCFA absorption capacity.
Pure mucinous carcinoma of the breast: clinicopathologic characteristics and long-term outcome among Taiwanese women
Authors: Tseng Hsin-Shun , Lin Che , Chan Szu-Erh , Chien Su-Yu , Kuo Shou-Jen , Chen Shou-Tung , Chang Tsai-Wang , Chen Dar-Ren 
Published: June 2013

Abstract

Background
Pure mucinous carcinoma (MC) is found in about 3.5% of all newly diagnosed breast cancer patients in Taiwan. MC is a relatively rare malignancy of breast cancer, and its nature, behaviors, treatment pattern and long-term follow-up are not well understood. The study aimed to investigate the incidence rate, treatment patterns, and prognostic factors of MC of the breast and the clinical long-term outcomes compared with infiltrating ductal carcinoma not otherwise specified (IDC) in the middle and south Taiwanese women.

Methods
Data from 93 patients with breast MC were retrospectively reviewed and the clinicopathologic characteristics and survival status were compared with those of 2,674 patients with IDC.

Results
The expression of hormonal receptor was higher in MC than those in IDC (P <0.001). MC also demonstrated lower Her2/neu gene over-expression (P = 0.023), less axillary lymph node involvement (P <0.0001), lymphovascular invasion (P <0.0001) and higher 10-year overall survival rate (P = 0.042), when compared with those of IDC.

Conclusion
Our data confirm the less aggressive behavior of MC compared to IDC. MC showed favorable clinicopathologic characteristics in tumor grade, hormone receptor status and lymph node involvement in the middle and south Taiwanese women.
Carbon dots: a safe nanoscale substance for the immunologic system of mice
Authors: Gao Zhongcai , Shen Guangxia , Zhao Xiunan , Dong Na , Jia Peiyuan , Wu Junhua , Cui Daxiang , Zhang Yingge , Wang Yuxia 
Published: June 2013

AbstractWe aimed at investigating the effect of carbon dots on the BALB/c mice immune system. Mice were respectively treated with different doses of carbon dots and saline. At 1 and 9 days after intravenous administration of carbon dots, splenocyte proliferation, subpopulation of the peripheral lymphocytes, and induction of primary immune responses in mice were investigated. The results showed that high dose of carbon dots could promote the percentages of CD3+ and interferon-γ (IFN-γ) secretion and decrease the proportions of CD4+/CD8+ on the first day after administration. At 9 days post exposure, the proliferation of splenocytes had a significant increase. IFN-γ secretion and proportions of CD3+/CD19+ were also found to have an obvious promotion, and both the percentages of CD4+ and CD8+ T lymphocytes were raised, whereas the expression of cytokines made little change in the treated groups, except for IL-12 which had a slight increase in the 50-mg/kg group. The weight coefficients and histological analysis of the spleen and thymus of the treated mice exerted fewer differences compared with those from the control mice. It suggests that carbon dots could influence the immune functions of normal BALB/c mice by inducing Th1 and Tc responses and that these effects were not enough to induce the morphological change of the immune organs.
Clade C HIV-1 isolates circulating in Southern Africa exhibit a greater frequency of dicysteine motif-containing Tat variants than those in Southeast Asia and cause increased neurovirulence
Authors: Rao Vasudev R , Neogi Ujjwal , Talboom Joshua S , Padilla Ligia , Rahman Mustafizur , Fritz-French Cari , Gonzalez-Ramirez Sandra , Verma Anjali , Wood Charles , Ruprecht Ruth M , Ranga Udaykumar , Azim Tasnim , Joska John , Eugenin Eliseo , Shet Anita , Bimonte-Nelson Heather , Tyor William R , Prasad Vinayaka R 
Published: June 2013

AbstractBackgroundHIV-1 Clade C (Subtype C; HIV-1C) is responsible for greater than 50% of infections worldwide. Unlike clade B HIV-1 (Subtype B; HIV-1B), which is known to cause HIV associated dementia (HAD) in approximately 15% to 30% of the infected individuals, HIV-1C has been linked with lower prevalence of HAD (0 to 6%) in India and Ethiopia. However, recent studies report a higher prevalence of HAD in South Africa, Zambia and Botswana, where HIV-1C infections predominate. Therefore, we examined whether Southern African HIV-1C is genetically distinct and investigated its neurovirulence. HIV-1 Tat protein is a viral determinant of neurocognitive dysfunction. Therefore, we focused our study on the variations seen intatgene and its contribution to HIV associated neuropathogenesis.ResultsA phylogenetic analysis oftatsequences of Southern African (South Africa and Zambia) HIV isolates with those from the geographically distant Southeast Asian (India and Bangladesh) isolates revealed that Southern Africantatsequences are distinct from Southeast Asian isolates. The proportion of HIV − 1C variants with an intact dicysteine motif in Tat protein (C30C31) was significantly higher in the Southern African countries compared to Southeast Asia and broadly paralleled the high incidence of HAD in these countries. Neuropathogenic potential of a Southern African HIV-1C isolate (from Zambia; HIV-1C1084i), a HIV-1C isolate (HIV-1IndieC1) from Southeast Asia and a HIV-1B isolate (HIV-1ADA) from the US were tested usingin vitroassays to measure neurovirulence and a SCID mouse HIV encephalitis model to measure cognitive deficits.In vitroassays revealed that the Southern African isolate, HIV-1C1084iexhibited increased monocyte chemotaxis and greater neurotoxicity compared to Southeast Asian HIV-1C. In neurocognitive tests, SCID mice injected with MDM infected with Southern African HIV-1C1084ishowed greater cognitive dysfunction similar to HIV-1B but much higher than those exposed to Southeast Asian HIV − 1C.ConclusionsWe report here, for the first time, that HIV-1C from Southern African countries is genetically distinct from Southeast Asian HIV-1C and that it exhibits a high frequency of variants with dicysteine motif in a key neurotoxic HIV protein, Tat. Our results indicate that Tat dicysteine motif determines neurovirulence. If confirmed in population studies, it may be possible to predict neurocognitive outcomes of individuals infected with HIV-1C by genotyping Tat.
Two novel PIWI families: roles in inter-genomic conflicts in bacteria and Mediator-dependent modulation of transcription in eukaryotes
Authors: Burroughs A Maxwell , Iyer Lakshminarayan M , Aravind L 
Published: June 2013

Abstract

Background
The PIWI module, found in the PIWI/AGO superfamily of proteins, is a critical component of several cellular pathways including germline maintenance, chromatin organization, regulation of splicing, RNA interference, and virus suppression. It binds a guide strand which helps it target complementary nucleic strands.

Results
Here we report the discovery of two divergent, novel families of PIWI modules, the first such to be described since the initial discovery of the PIWI/AGO superfamily over a decade ago. Both families display conservation patterns consistent with the binding of oligonucleotide guide strands. The first family is bacterial in distribution and is typically encoded by a distinctive three-gene operon alongside genes for a restriction endonuclease fold enzyme and a helicase of the DinG family. The second family is found only in eukaryotes. It is the core conserved module of the Med13 protein, a subunit of the CDK8 subcomplex of the transcription regulatory Mediator complex.

Conclusions
Based on the presence of the DinG family helicase, which specifically acts on R-loops, we infer that the first family of PIWI modules is part of a novel RNA-dependent restriction system which could target invasive DNA from phages, plasmids or conjugative transposons. It is predicted to facilitate restriction of actively transcribed invading DNA by utilizing RNA guides. The PIWI family found in the eukaryotic Med13 proteins throws new light on the regulatory switch through which the CDK8 subcomplex modulates transcription at Mediator-bound promoters of highly transcribed genes. We propose that this involves recognition of small RNAs by the PIWI module in Med13 resulting in a conformational switch that propagates through the Mediator complex.

Reviewers
This article was reviewed by Sandor Pongor, Frank Eisenhaber and Balaji Santhanam.
Mitral commissurotomy through the left ventricle apical orifice with Heart Ware left ventricular assist device implantation
Authors: Mohite Prashant Nanasaheb , Zych Bartlomiej , Popov Aron Frederik , Patil Nikhil , Luthra Suvitesh , Hedger Mike , Simon Andre Ruediger , Amrani Mohammed 
Published: June 2013

Abstract
Diseased, replaced or repaired mitral valve can lead to restricted blood flow to left ventricle and inadequate flow in left ventricular assist device (LVAD). A middle age woman with ‘burnt out’ hypertrophic cardiomyopathy had mitral valve repair for mitral regurgitation. She needed LVAD to support severe decompensating heart failure. Repaired mitral valve posed a risk of restricted flow through the device. Mitral commissurotomy was performed on beating heart through the left ventricular apical hole created for insertion of inflow cannula of LVAD.
The influence of applying insurance medicine guidelines for depression on disability assessments
Authors: Schellart Antonius JM , Zwerver Feico , Anema Johannes R , Van derBeek Allard J 
Published: June 2013

Abstract

Background
In the current study we report on the effects of an implementation strategy in the form of a training programme on the assessed work limitations of a client with depression by insurance physicians (IPs) participating in a RCT. These assessed work limitations of a client were in the form of scores on the List of Functional Abilities (LFA).

Method
We conducted a randomised controlled trial (RCT) for IPs in which we compared the intervention of a specially developed training programme with the usual methods of implementation and training currently used. The outcome was the mean sum score and the inter-rater reliability (Intraclass Correlation Coefficient, ICC) of the LFA scores. These LFA scores were scored by the IPs participating in the RCT for the work limitations of the cases presented in different videos, two videos before the training and two after the training of the intervention group.

Results
At baseline, the intervention group (IG) consisted of 21 IPs and the control group (CG) of 19. For one participant of the IG and for one of the CG the LFAs of the two case reports after training were not available. Before training the sum scores for the first case report did not differ significantly between the groups, while the mean sum score was higher in the IG than in the CG for the second case report. For both case reports after training a higher score was found in the IG than in the CG. The inter-rater reliability measured for the two case reports before training was about the same in the IG and the CG: 0.64 and 0.65, respectively. For the two case reports after training, the ICC was higher in the IG than in the CG: 0.69 and 0.54, respectively. This difference was not significant however.

Conclusion
It would appear that the implementation of a specially designed training programme on guidelines for depression may lead to greater inter-rater reliability in the assessments by insurance physicians of the work limitations of clients with depression. It is, however, important to note that insurance physicians who receive training may find more work limitations than those who do not.

Trial registration
Netherlands’ Trial Register NTR1863
T and B lymphocytes in the brains of dogs with concomitant seropositivity to three pathogenic protozoans: Leishmania chagasi, Toxoplasma gondii and Neospora caninum
Authors: Sakamoto Keila Priscilla , de Melo Guilherme Dias , Machado Gisele Fabrino 
Published: June 2013

Abstract

Background
Visceral leishmaniasis is a disease with great variability regarding the clinical manifestations in humans and dogs. Chronically infected dogs may develop neurological disorders, however, there are few reports that characterize the lesions and make clear the pathogenesis of the canine cerebral leishmaniasis. Concomitant with Leishmania chagasi, dogs may be infected by opportunistic pathogens, such as Toxoplasma gondii and Neospora caninum, which may contribute to the occurrence of lesions in the central nervous system. Hence, we aimed to compare the T and B lymphocytes population in the brains of infected dogs with seropositivity to L. chagasi, T. gondii and N. caninum concurrently (n = 24), seropositivity only to L. chagasi (n = 31), and seropositivity to T. gondii and N. caninum (n = 16). Uninfected dogs were used as control (n = 10).

Results
Inflammatory lesions, characterised by mononuclear cell accumulation, composed mainly of CD3+ T lymphocytes predominated in several encephalic regions of the dogs from all the three infected groups, with no difference among them (P = 0.0004), whereas CD79α+ B lymphocytes were detected in very small intensity and presented no difference among groups (P = 0.5313). Furthermore, no association among diseases was detected at the serological enquire.

Conclusions
We demonstrate that the peripheral infection by L. chagasi per se can promote the influx of lymphocytes within the nervous milieu as occurs during Toxoplasma and Neospora infections, and the concomitant seropositivity against these pathogens does not exacerbate the inflammatory brain lesions. Therefore, these findings give additional support that the brain should be included in the list of organs affected by visceral leishmaniasis and that even asymptomatic infected dogs may develop brain lesions.
The antiretroviral agent saquinavir enhances hTERT expression and telomerase activity in human T leukaemia cells in vitro
Authors: Adamo Riccardo , Comandini Alessandro , Aquino Angelo , Bonmassar Laura , Guglielmi Loredana , Bonmassar Enzo , Franzese Ornella 
Published: June 2013

AbstractBackgroundSaquinavir, a protease inhibitor utilized in HIV infection, shows antitumor activity in various experimental models. In previous studies performed in our laboratory the drug was found to induce a substantial increase of telomerase activity in normal peripheral blood mononuclear cells. Aim of the present investigation was to test whether saquinavir was able to increase telomerase activity and the expression of the catalytic subunit of telomerase, hTERT, in human malignant hematopoietic cells.MethodsHuman Jurkat CD4+T cell leukaemia cell line was used throughout the present study. The antiproliferative effect of saquinavir was tested by the MTT assay. Telomerase activity was determined according to the telomeric repeat amplification protocol. The expression of hTERT mRNA was semi-quantitative evaluated by RT-PCR amplification and quantitative Real Time PCR. The binding of the transcription factor c-Myc to its specific E-Box DNA binding-site ofhTERTpromoter was analyzed by Electophoretic Mobility Shift Assay (EMSA). The amount of c-Myc in cytoplasm and nucleus of leukemia cells was determined by Western Blot analysis, and c-Myc down-regulation was obtained by siRNA transfection.ResultsSaquinavir produced a substantial increase of telomerase activity in Jurkat cells in vitro without increasing but rather reducing target cell proliferation rate. Telomerase up-regulation appeared to be the result of enhanced expression of hTERT. Saquinavir-mediated up-regulation of hTERT gene was the result of the increased binding of proteins to the E-Box sequence of the promoter. Moreover, saquinavir amplified the expression of c-Myc especially in the nuclear cell fraction. The direct influence of saquinavir on this transcription factor was also demonstrated by the antagonistic effect of the drug on siRNA induced c-Myc suppression. Since c-Myc is the main responsible for hTERT transcription, these findings suggest that the main mechanism underlying saquinavir-induced telomerase activation is mediated by c-Myc up-regulation.ConclusionsSaquinavir augments hTERT expression while inhibiting leukemic cell growth. Experimental evidences show that this effect is mediated by saquinavir-influenced increase of c-Myc levels. This could have relevance in terms of enhanced hTERT-dependent tumor cell immunogenicity and suggests new paharmacological approaches interfering with c-Myc dependent pathways.
A framework incorporating the impact of exposure scenarios and application conditions on risk assessment of chemicals applied to skin
Authors: Dancik Yuri , Troutman John A , Jaworska Joanna 
Published: June 2013

AbstractPurpose1. To develop a framework for exposure calculation via the dermal route to meet the needs of 21st century toxicity testing and refine current approaches; 2. To demonstrate the impact of exposure scenario and application conditions on the plasma concentration following dermal exposure.MethodA workflow connecting a dynamic skin penetration model with a generic whole-body physiologically-based pharmacokinetic (PBPK) model was developed. The impact of modifying exposure scenarios and application conditions on the simulated steady-state plasma concentration and exposure conversion factor was investigated for 9 chemicals tested previously in dermal animal studies which did not consider kinetics in their experimental designs.ResultsBy simulating the animal study scenarios and exposure conditions, we showed that 7 studies were conducted with finite dose exposures, 1 with both finite and infinite dose exposures (in these 8 studies, an increase in the animal dose resulted in an increase in the simulated steady-state plasma concentrations (Cp,ss)), while 1 study was conducted with infinite dose exposures only (an increase in the animal dose resulted in identicalCp,ss). Steady-state plasma concentrations were up to 30-fold higher following an infinite dose scenario vs. a finite dose scenario, and up to 40-fold higher with occlusion vs. without. Depending on the chemical, the presence of water as a vehicle increased or decreased the steady-state plasma concentration, the largest difference being a factor of 16.ConclusionsThe workflow linking Kasting’s model of skin penetration and whole-body PBPK enables estimation of plasma concentrations for various applied doses, exposure scenarios and application conditions. Consequently, it provides a quantitative, mechanistic tool to refine dermal exposure calculations methodology for further use in risk assessment.