bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-dependent effect of high-fructose and high-fat diets on lipid metabolism and lipid accumulation in liver and kidney of rats
Authors: de Castro Uberdan Guilherme Mendes , dos Santos Robson Augusto Souza Augusto Souza , Silva Marcelo Eustáquio , de Lima Wanderson Geraldo , Campagnole-Santos Maria José , Alzamora Andréia Carvalho 
Published: September 2013

Abstract

Background
The metabolic syndrome (MS) is characterized by variable coexistence of metabolic and pathophysiological alterations which are important risk factors for developing of type II diabetes and/or cardiovascular diseases. Increased of MS patients in worldwide has stimulated the development of experimental models. However, it is still challenging to find an dietetic model that most closely approximates human MS and, in addition, is not yet fully established the effect of different diets of MS in lipid metabolism in rats of different ages. The aim of this study was to evaluate the effect of different diets of MS in lipid metabolism and ectopic fat deposition and define the most appropriate diet for inducing the characteristic disturbances of the human MS in rats of different ages.

Methods
Young (4 weeks old) and adult rats (12 weeks old) were given a high-fat (FAT) or high-fructose diet (FRU) for 13 weeks and biochemical, physiological, histological and biometric parameters were evaluated.

Results
In young rats, the FAT diet induced increased mean blood pressure (MAP) and heart rate (HR), body weight after 6 to 10 weeks, and in the 13th week, increased the liver, mesenteric, retroperitoneal and epididymal fat weights, fasting glucose, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and reduced HDL cholesterol; and also induced non-alcoholic fatty liver disease (NAFLD) and renal inflammatory infiltrates. In adult rats, the FRU diet induced transient elevations of MAP and HR in the 6th week, and, at 13 weeks, increased fasting glucose, triglycerides, total cholesterol, AST and ALT; increased liver, kidneys and retroperitoneal fat weights; and induced macrovesicular and microvesicular NAFLD, the presence of fat cells in the kidney, glomerular sclerosis, and liver and kidney inflammation. Additionally, the FAT and FRU diets induced, respectively, increases in liver glycogen in adults and young rats.

Conclusions
Our data show that FRU diet in adult rats causes biggest change on metabolism of serum lipids and lipid accumulation in liver and kidney, while the FAT diet in young rats induces elevation of MAP and HR and higher increased visceral lipid stores, constituting the best nutritional interventions to induce MS in rats.
Sarcoidosis lymphoma syndrome - the value of PET-CT in the diagnosis
Authors: Kis Adrian , Eszes Noemi , Tamasi Lilla , Losonczy Gyorgy , Csekeo Attila , Csomor Judit , Muller Veronika 
Published: September 2013

Abstract
We report a 52-year-old patient who developed B-cell non-Hodgkin’s lymphoma subsequent to sarcoidosis. Sarcoidosis was diagnosed 16 years ago and remained asymptomatic for 14 years after steroid treatment. She presented with new symptoms of arthralgia, photosensitivity, butterfly erythema, autoimmune antibodies (ANA, chromatin positivity) associated with progression of the known left upper lobe lesion on the chest X-ray suggesting primary autoimmune disease (systemic lupus erythematosus). As steroid treatment was not effective, we started bolus cyclophosphamide therapy after which progression was seen on the chest X-ray. Computed tomography (CT)-guided needle biopsy confirmed malignancy of indefinable origin. Despite of the well-known fluorodeoxyglucose (FDG) avidity in active sarcoidosis, a FDG-positron emission tomography (PET) scan was performed to stage the primary tumour. Intensive FDG uptake was detected in the affected lung segment, with moderate uptake in mediastinal lymph nodes. The patient underwent left upper lobectomy. The histology showed pulmonary mucosa-associated lymphoma (bronchus-associated lymphoid tissue (BALT) lymphoma) in the lung tissue, while only sarcoidosis was present in the mediastinal lymph nodes. Bone marrow biopsy was negative.
The association between sarcoidosis and lymphoma is known as sarcoidosis lymphoma syndrome, which is a rare disease. PET-CT was helpful in the differentiation of sarcoidosis and malignancy in this patient. It is important to be aware of the risk of lymphoma in sarcoidosis and FDG-PET, used for adequate purpose, can help the diagnosis.
Direct transdifferentiation of spermatogonial stem cells to morphological, phenotypic and functional hepatocyte-like cells via the ERK1/2 and Smad2/3 signaling pathways and the inactivation of cyclin A, cyclin B and cyclin E
Authors: Zhang Zhenzhen , Gong Yuehua , Guo Ying , Hai Yanan , Yang Hao , Yang Shi , Liu Yang , Ma Meng , Liu Linhong , Li Zheng , Gao Wei-Qiang , He Zuping 
Published: September 2013

Abstract

Background
Severe shortage of liver donors and hepatocytes highlights urgent requirement of extra-liver and stem cell source of hepatocytes for treating liver-related diseases. Here we hypothesized that spermatogonial stem cells (SSCs) can directly transdifferentiate to hepatic stem-like cells capable of differentiating into mature hepatocyte-like cells in vitro without an intervening pluripotent state.

Results
SSCs first changed into hepatic stem-like cells since they resembled hepatic oval cells in morphology and expressed Ck8, Ck18, Ck7, Ck19, OV6, and albumin. Importantly, they co-expressed CK8 and CK19 but not ES cell markers. Hepatic stem-like cells derived from SSCs could differentiate into small hepatocytes based upon their morphological features and expression of numerous hepatic cell markers but lacking of bile epithelial cell hallmarks. Small hepatocytes were further coaxed to differentiate into mature hepatocyte-like cells, as identified by their morphological traits and strong expression of Ck8, Ck18, Cyp7a1, Hnf3b, Alb, Ta t, Ttr, albumin, and CYP1A2 but not Ck7 or CK19. Notably, these differentiated cells acquired functional attributes of hepatocyte-like cells because they secreted albumin, synthesized urea, and uptake and released indocyanine green. Moreover, phosphorylation of ERK1/2 and Smad2/3 rather than Akt was activated in hepatic stem cells and mature hepatocytes. Additionally, cyclin A, cyclin B and cyclin E transcripts and proteins but not cyclin D1 or CDK1 and CDK2 transcripts or proteins were reduced in mature hepatocyte-like cells or hepatic stem-like cells derived from SSCs compared to SSCs.

Conclusions
SSCs can transdifferentiate to hepatic stem-like cells capable of differentiating into cells with morphological, phenotypic and functional characteristics of mature hepatocytes via the activation of ERK1/2 and Smad2/3 signaling pathways and the inactivation of cyclin A, cyclin B and cyclin E. This study thus provides an invaluable source of mature hepatocytes for treating liver-related diseases and drug toxicity screening and offers novel insights into mechanisms of liver development and cell reprogramming.
AMP-activated protein kinase activation mediates CCL3-induced cell migration and matrix metalloproteinase-2 expression in human chondrosarcoma
Authors: Hsu Chin-Jung , Wu Min-Huan , Chen Chin-Yuan , Tsai Chun-Hao , Hsu Horng-Chaung , Tang Chih-Hsin 
Published: September 2013

Abstract
Chemokine (C-C motif) ligand 3 (CCL3), also known as macrophage inflammatory protein-1α, is a cytokine involved in inflammation and activation of polymorphonuclear leukocytes. CCL3 has been detected in infiltrating cells and tumor cells. Chondrosarcoma is a highly malignant tumor that causes distant metastasis. However, the effect of CCL3 on human chondrosarcoma metastasis is still unknown. Here, we found that CCL3 increased cellular migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells. Pre-treatment of cells with the MMP-2 inhibitor or transfection with MMP-2 specific siRNA abolished CCL3-induced cell migration. CCL3 has been reported to exert its effects through activation of its specific receptor, CC chemokine receptor 5 (CCR5). The CCR5 and AMP-activated protein kinase (AMPK) inhibitor or siRNA also attenuated CCL3-upregulated cell motility and MMP-2 expression. CCL3-induced expression of MMP-2 and migration were also inhibited by specific inhibitors, and inactive mutants of AMPK, p38 mitogen activated protein kinase (p38 or p38-MAPK), and nuclear factor κB (NF-κB) cascades. On the other hand, CCL3 treatment demonstrably activated AMPK, p38, and NF-κB signaling pathways. Furthermore, the expression levels of CCL3, CCR5, and MMP-2 were correlated in human chondrosarcoma specimens. Taken together, our results indicate that CCL3 enhances the migratory ability of human chondrosarcoma cells by increasing MMP-2 expression via the CCR5, AMPK, p38, and NF-κB pathways.
Over-expression of the special AT rich sequence binding protein 1 (SATB1) promotes the progression of nasopharyngeal carcinoma: association with EBV LMP-1 expression
Authors: Shen Zhihua , Zeng Yumei , Guo Junli , Wu Yanxia , Jiang Xiaofan , Ding Ranran , Wu Changli , Li Rujia , Luo Botao , Zeng Chao , Jiang Hanguo , Jie Wei 
Published: September 2013

AbstractBackgroundSpecial AT rich sequence binding protein 1 (SATB1) plays a crucial role in the biology of various types of human cancer. However, the role of SATB1 in human nasopharyngeal carcinoma (NPC) remains unknown. In the present study, we sought to investigate the contribution of aberrant SATB1 expression in the progression of NPC and its association with the Epstein Barr virus (EBV)-encoded latent membrane protein 1 (LMP-1).MethodsImmunohistochemical analysis was performed to detect SATB1 and LMP-1 protein in clinical samples, and the association of SATB1 protein expression with patient clinicopathological characteristics and LMP-1 expression were analyzed. SATB1 expression profiles were evaluated in well-differentiated NPC cell line CNE1, poorly-differentiated CNE2Z, undifferentiated C666-1 and immortalized nasopharyngeal epithelia NP-69 cells using quantitative RT-PCR, western blotting and fluorescent staining. After inhibition the SATB1 expression by using SATB1 specific small interfering RNA in these cell lines, the change of cell proliferation was investigated by western blotting analysis of PCNA (proliferating cell nuclear antigen) expression and CCK-8 assay, and the cell migration was assessed by Transwell migration assay. Finally, the expressions of SATB1 and PCNA were examined in CNE1 cells that forced LMP-1 expression by fluorescent staining and RT-PCR.ResultsImmunohistochemical analysis revealed that SATB1 protein expression was elevated in NPC tissues compared to benign nasopharyngeal tissues (P = 0.005). Moreover, high levels of SATB1 protein expression were positively correlated with clinical stage (P = 0.025), the status of lymph node metastasis (N classification) (P = 0.018), distant metastasis (M classification) (P = 0.041) and LMP-1 expression status (r = 2.35,P < 0.01) in NPC patients.In vitroexperiments demonstrated that an inverse relationship between SATB1 expression and NPC differentiation status, with SATB1 weakly expressed in NP-69 cells and CNE1 cells, and significant increasingly expressed in CNE-2Z and C666-1 cells. Targeted knockdown of SATB1 expression obviously attenuated the proliferation and migration of highly SATB1-expressing CNE2Z and C666-1 cells, but not NP-69 and CNE1 cells. Interestingly, forced LMP-1 expression in CNE1 cells led to a surprisingly increasing SATB1 expression and nuclear location, companying with an up-regulated PCNA expression.ConclusionsOur results reveal that EBV LMP-1-mediated over-expression of SATB1 is associated with NPC progression, suggesting SATB1 may represent a promising biomarker and therapeutic target for NPC.
MicroRNAs induced in melanoma treated with combination targeted therapy of Temsirolimus and Bevacizumab
Authors: Wagenseller Aubrey G , Shada Amber , D’Auria Kevin M , Murphy Cheryl , Sun Dandan , Molhoek Kerrington R , Papin Jason A , Dutta Anindya , Slingluff Jr Craig L 
Published: September 2013

Abstract

Background
Targeted therapies directed at commonly overexpressed pathways in melanoma have clinical activity in numerous trials. Little is known about how these therapies influence microRNA (miRNA) expression, particularly with combination regimens. Knowledge of miRNAs altered with treatment may contribute to understanding mechanisms of therapeutic effects, as well as mechanisms of tumor escape from therapy. We analyzed miRNA expression in metastatic melanoma tissue samples treated with a novel combination regimen of Temsirolimus and Bevacizumab. Given the preliminary clinical activity observed with this combination regimen, we hypothesized that we would see significant changes in miRNA expression with combination treatment.

Methods
Using microarray analysis we analyzed miRNA expression levels in melanoma samples from a Cancer Therapy Evaluation Program-sponsored phase II trial of combination Temsirolimus and Bevacizumab in advanced melanoma, which elicited clinical benefit in a subset of patients. Pre-treatment and post-treatment miRNA levels were compared using paired t-tests between sample groups (patients), using a p-value < 0.01 for significance.

Results
microRNA expression remained unchanged with Temsirolimus alone; however, expression of 15 microRNAs was significantly upregulated (1.4 to 2.5-fold) with combination treatment, compared to pre-treatment levels. Interestingly, twelve of these fifteen miRNAs possess tumor suppressor capabilities. We identified 15 putative oncogenes as potential targets of the 12 tumor suppressor miRNAs, based on published experimental evidence. For 15 of 25 miRNA-target mRNA pairings, changes in gene expression from pre-treatment to post-combination treatment samples were inversely correlated with changes in miRNA expression, supporting a functional effect of those miRNA changes. Clustering analyses based on selected miRNAs suggest preliminary signatures characteristic of clinical response to combination treatment and of tumor BRAF mutational status.

Conclusions
To our knowledge, this is the first study analyzing miRNA expression in pre-treatment and post-treatment human metastatic melanoma tissue samples. This preliminary investigation suggests miRNAs that may be involved in the mechanism of action of combination Temsirolimus and Bevacizumab in metastatic melanoma, possibly through inhibition of oncogenic pathways, and provides the preliminary basis for further functional studies of these miRNAs.
Electrochemically hydrogenated TiO2 nanotubes with improved photoelectrochemical water splitting performance
Authors: Xu Chen , Song Ye , Lu Linfeng , Cheng Chuanwei , Liu Dongfang , Fang Xiaohong , Chen Xiaoyuan , Zhu Xufei , Li Dongdong 
Published: September 2013

Abstract
One-dimensional anodic titanium oxide (ATO) nanotube arrays hold great potential as photoanode for photoelectrochemical (PEC) water splitting. In this work, we report a facile and eco-friendly electrochemical hydrogenation method to modify the electronic and PEC properties of ATO nanotube films. The hydrogenated ATO (ATO-H) electrodes present a significantly improved photocurrent of 0.65 mA/cm2 in comparison with that of pristine ATO nanotubes (0.29 mA/cm2) recorded under air mass 1.5 global illumination. The incident photon-to-current efficiency measurement suggests that the enhanced photocurrent of ATO-H nanotubes is mainly ascribed to the improved photoactivity in the UV region. We propose that the electrochemical hydrogenation induced surface oxygen vacancies contribute to the substantially enhanced electrical conductivity and photoactivity.
Comparing sociocultural features of cholera in three endemic African settings
Authors: Schaetti Christian , Sundaram Neisha , Merten Sonja , Ali Said M , Nyambedha Erick O , Lapika Bruno , Chaignat Claire-Lise , Hutubessy Raymond , Weiss Mitchell G 
Published: September 2013

Abstract

Background
Cholera mainly affects developing countries where safe water supply and sanitation infrastructure are often rudimentary. Sub-Saharan Africa is a cholera hotspot. Effective cholera control requires not only a professional assessment, but also consideration of community-based priorities. The present work compares local sociocultural features of endemic cholera in urban and rural sites from three field studies in southeastern Democratic Republic of Congo (SE-DRC), western Kenya and Zanzibar.

Methods
A vignette-based semistructured interview was used in 2008 in Zanzibar to study sociocultural features of cholera-related illness among 356 men and women from urban and rural communities. Similar cross-sectional surveys were performed in western Kenya (n = 379) and in SE-DRC (n = 360) in 2010. Systematic comparison across all settings considered the following domains: illness identification; perceived seriousness, potential fatality and past household episodes; illness-related experience; meaning; knowledge of prevention; help-seeking behavior; and perceived vulnerability.

Results
Cholera is well known in all three settings and is understood to have a significant impact on people’s lives. Its social impact was mainly characterized by financial concerns. Problems with unsafe water, sanitation and dirty environments were the most common perceived causes across settings; nonetheless, non-biomedical explanations were widespread in rural areas of SE-DRC and Zanzibar. Safe food and water and vaccines were prioritized for prevention in SE-DRC. Safe water was prioritized in western Kenya along with sanitation and health education. The latter two were also prioritized in Zanzibar. Use of oral rehydration solutions and rehydration was a top priority everywhere; healthcare facilities were universally reported as a primary source of help. Respondents in SE-DRC and Zanzibar reported cholera as affecting almost everybody without differentiating much for gender, age and class. In contrast, in western Kenya, gender differentiation was pronounced, and children and the poor were regarded as most vulnerable to cholera.

Conclusions
This comprehensive review identified common and distinctive features of local understandings of cholera. Classical treatment (that is, rehydration) was highlighted as a priority for control in the three African study settings and is likely to be identified in the region beyond. Findings indicate the value of insight from community studies to guide local program planning for cholera control and elimination.
Immunophenotypic features and t(14;18) (q32;q21) translocation of Chinese follicular lymphomas helps to distinguish subgroups
Authors: Zhang Fen , Yan Li-Xu , Lin Su-Xia , Ye Zi-Yin , Zhuang Heng-Guo , Yun Jing-Ping , Lin Han-Liang , Luo Dong-Lan , Xu Fang-Ping , Luo Xin-Lan , Cheng Jie , Zhang Ke-Ping , Liu Yan-Hui 
Published: September 2013

Abstract

Background
The revised 2008 World Health Organization classification maintains a histological grading system (grades 1–3) for follicular lymphoma (FL). The value of grading FL has been debated. This study will yield deeper insights into the morphologic, immunophenotypic characterization and t(14;18) translocation in FL and explore their significance of diagnosis of Chinese FL subgroups.

Methods
We retrospectively reviewed the FL diagnoses according to the 2008 WHO classification in all diagnostic specimens from a multicentric cohort of 122 Chinese patients. Upon review, 115 cases proved to be truly FL. CD10, BCL6, MUM1, BCL2 and t(14;18) (q32;q21) translocation were detected by Envision immunostaining technique and fluorescence in situ hybridization.

Results
FL1 has larger proportion of follicular pattern (93.0%) than that of FL2 (73.7%, P = 0.036), FL3B (63.6%, P = 0.003) and FL3A (77.4%, P = 0.053), although the last P value was more than 0.05 (Pearson’s chi-squared test). Areas of DLBCL were present in 25.8% (8/31) of FL3A and more frequent in FL3B (59.1%, 13/22; P = 0.015). The positivity of CD10 and BCL2 in FL1-2 were significantly higher than those in FL3 (P < 0.001, P = 0.043, respectively). The positivity of MUM1 in FL1-2 was significantly lower than that in FL3 (10.2% vs. 51.0%; P < 0.001). Furthermore the positivity of MUM1 in FL3A was significantly lower than that in FL3B (37.9% vs. 68.2%; P = 0.032). The positivity of t(14;18) was higher in FL1-2 than in FL3 (73.5% vs. 35.6%, P < 0.001), and was higher in FL3A than in FL3B (51.9% vs. 11.1%, P = 0.005). t(14;18) was significantly correlated with CD10+ (R = 0.453, P < 0.001) and MUM1+ (R = -0.482, P < 0.001).

Conclusions
FL1 and FL2 were immunophenotypically and genomically similar, while FL3A and FL3B were partly immunophenotypically similar but morphologically, genomically distinct. FL3A was genomically closer to FL1-2, whereas FL3A was genomically closer DLBCL. Thus we hypothesize that FL may in fact be a heterogeneous indolent lymphoma encompassing entities with distinct molecular pathogenesis and genetic characteristics. Immunohistochemical and genetic characterization helps to distinguish subgroups of FLs.

Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1334018129864616.
Dosimetric impact of reduced nozzle-to-isocenter distance in intensity-modulated proton therapy of intracranial tumors in combined proton-carbon fixed-nozzle treatment facilities
Authors: Jelen Urszula , Bubula Marta E , Ammazzalorso Filippo , Engenhart-Cabillic Rita , Weber Uli , Wittig Andrea 
Published: September 2013

Abstract

Background
In combined proton-carbon fixed-nozzle treatment facilities with raster scanning delivery, the scattering of proton pencil beams caused by nozzle elements and the relatively large nozzle-to-isocenter distance cause a beam broadening. This may pose limitations to the achievable dose conformity. One way to counteract this effect is by delivering the treatment in a position closer to the nozzle than the room isocenter. Purpose of this study was to assess the potential dosimetric benefit of such solution, in terms of dose conformity and normal tissue sparing, in intensity-modulated proton therapy (IMPT) of intracranial tumors.

Material and methods
For 12 patients with intracranial lesions, IMPT-plans were created at two treatment positions: nozzle-to-treatment-isocenter distance: 100 cm (room isocenter) and nozzle-to-treatment-isocenter distance: 60 cm. The resulting plans were compared in terms of dose distributions, dose-volume histograms and selected dosimetric indexes.

Results
With comparable target coverage, statistically significant normal tissue sparing was achieved through the reduction of the distance between nozzle and treatment isocenter. The decrease in mean dose (Dmean) was 12.5% to the whole brain, 16.2% to the brainstem, 9.7% and 15.4% to the temporal lobes, 10.0% and 12.9% to the hippocampi, 11.8% and 12.5% to the optic nerves and 0.2% to the chiasm. The volume receiving at least 10% of the prescribed dose (V10%) was reduced by more than 10% for most organs at risk (OARs). The maximum dose (Dnear-max) values to most OARs remained without significant difference.

Conclusion
A reduced distance between nozzle and treatment isocenter leads to steeper lateral dose gradients and significantly reduces the volume of OARs adjacent to the target, which receives low to intermediate doses. Technical solutions shifting the treatment isocenter closer to the nozzle should be considered in clinical situations, where critical OARs are adjacent to the beam channel and where the integral dose should be minimized.