Role of glucose as a modulator of anabolic and catabolic gene expression in normal and osteoarthritic human chondrocytes

Cartilage matrix homeostasis involves a dynamic balance between numerous signals that modulate chondrocyte functions. This study aimed at elucidating the role of the extracellular glucose concentration in modulating anabolic and catabolic gene expression in normal and osteoarthritic (OA) human chondrocytes and its ability to modify the gene expression responses induced by pro-anabolic stimuli, namely Transforming Growth Factor-β (TGF). For this, we analyzed by real time RT-PCR the expression of articular cartilage matrix-specific and non-specific genes, namely collagen types II and I, respectively. The expression of the matrix metalloproteinases (MMPs)-1 and -13, which plays a major role in cartilage degradation in arthritic conditions, and of their tissue inhibitors (TIMP) was also measured. The results showed that exposure to high glucose (30 mM) increased the mRNA levels of both MMPs in OA chondrocytes, whereas in normal ones only MMP-1 increased. Collagen II mRNA was similarly increased in normal and OA chondrocytes, but the increase lasted longer in the later. Exposure to high glucose for 24 h prevented TGF-induced downregulation of MMP-13 gene expression in normal and OA chondrocytes, while the inhibitory effect of TGF on MMP-1 expression was only partially reduced. Other responses were not significantly modified. In conclusion, exposure of human chondrocytes to high glucose, as occurs in vivo in diabetes mellitus patients and in vitro for the production of engineered cartilage, favors the chondrocyte catabolic program. This may promote articular cartilage degradation, facilitating OA development and/or progression, as well as compromise the quality and consequent in vivo efficacy of tissue engineered cartilage

Differential effects of the essential oils of Lavandula luisieri and Eryngium duriaei subsp. juresianum in cell models of two chronic inflammatory diseases

CONTEXT: Effective drugs to treat osteoarthritis (OA) and inflammatory bowel disease (IBD) are needed. OBJECTIVE: To identify essential oils (EOs) with anti-inflammatory activity in cell models of OA and IBD. MATERIALS AND METHODS: EOs from Eryngium duriaei subsp. juresianum (M. Laínz) M. Laínz (Apiaceae), Laserpitium eliasii subsp. thalictrifolium Sennen & Pau (Apiaceae), Lavandula luisieri (Rozeira) Rivas-Martínez (Lamiaceae), Othantus maritimus (L.) Hoff. & Link (Asteraceae), and Thapsia villosa L. (Apiaceae) were analyzed by GC and GC/MS. The anti-inflammatory activity of EOs (5-200 μg/mL) was evaluated by measuring inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB) activation (total and phosphorylated IκB-α), in primary human chondrocytes and the intestinal cell line, C2BBe1, stimulated with interleukin-1β (IL-1β) or interferon-γ (IFN-γ), IL-1β and tumor necrosis factor-α (TNF-α), respectively. RESULTS: The EO of L. luisieri significantly reduced iNOS (by 54.9 and 81.0%, respectively) and phosphorylated IκB-α (by 87.4% and 62.3%, respectively) in both cell models. The EO of E. duriaei subsp. juresianum caused similar effects in human chondrocytes, but was inactive in intestinal cells, even at higher concentrations. The EOs of L. eliasii subsp. thalictrifolium and O. maritimus decreased iNOS expression by 45.2 ± 8.7% and 45.2 ± 6.2%, respectively, in C2BBe1 cells and were inactive in chondrocytes. The EO of T. villosa was inactive in both cell types. DISCUSSION AND CONCLUSION: This is the first study showing anti-inflammatory effects of the EOs of L. luisieri and E. duriaei subsp. juresianum. These effects are specific of the cell type and may be valuable to develop new therapies or as sources of active compounds with improved efficacy and selectivity towards OA and IBD

Modulation of Myocardial Stiffness by beta-Adrenergic Stimulation Its Role in Normal and Failing Heart

The acute effects of ß-adrenergic stimulation on myocardial stiffness were evaluated. New-Zealand white rabbits were treated with saline (control group) or doxorubicin to induce heart failure (HF) (DOXO-HF group). Effects of isoprenaline (10 -10-1 -5 M), a non-selective ß-adrenergic agonist, were tested in papillary muscles from both groups. In the control group, the effects of isoprenaline were also evaluated in the presence of a damaged endocardial endothelium, atenolol (ßi-adrenoceptor antagonist), ICI-118551 (ßz-adrenoceptor antagonist), KT-5720 (PKA inhibitor), L-NNA (NO-synthase inhibitor), or indomethacin (cyclooxygenase inhibitor). Passive length-tension relations were constructed before and after adding isoprenaline (10 -5 M). In the control group, isoprenaline increased resting muscle length up to 1.017±0.006 L/L max. Correction of resting muscle length to its initial value resulted in a 28.5±3.1% decrease of resting tension, indicating decreased muscle stiffness, as confirmed by the isoprenaline-induced right-downward shift of the passive lengthtension relation. These effects were modulated by ßr and ß 2adrenoceptors and PKA. In DOXO-HF group, the effect on myocardial stiffness was significantly decreased. We conclude that ß-adrenergic stimulation is a relevant mechanism of acute neurohumoral modulation of the diastolic function. Furthermore, this study clarifies the mechanisms by which myocardial stiffness is decreased. (c) 2011 Institute of Physiology v.v.i., Academy of Sciences of the Czech Republic, Prague, Czech Republic

Influence of P53 on the radiotherapy response of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it has a poor prognosis and few therapeutic options. Radiotherapy is one of the most effective forms of cancer treatment, and P53 protein is one of the key molecules determining how a cell responds to radiotherapy. The aim of this study was to determine the therapeutic efficacy of iodine-131 in three human HCC cell lines

SYNTHESIS OF CHIRALS REGIOISOMERS FROM D-MANNITOL: OBTAINMENT OF A ACETYLENIC ALCOHOLS MIXTURE.

SYNTHESIS OF CHIRALS REGIOISOMERS FROM D-MANNITOL: OBTAINMENT OF A ACETYLENIC ALCOHOLS MIXTURE. The synthesis of chiral acetylenic regioisomers was described by using an appropriate intermediate such as isopropylidene glycerol, a synthon widely used in the enantioselective syntheses. This intermediate was prepared from D-mannitol. The nine obtained compounds have been characterized by their respective spectral data. The mixture of chiral acetylenic alcohols showed activity against Escherichia coli when tested through the monitoring of CO(2) released during microbial respiration by using a conductimetric system.3292355235

Expression and clinical relevance of SOX9 in gastric cancer

Gastric cancer is one of the most frequent tumours and the third leading cause of cancer-related death worldwide. The investigation of new biomarkers that can predict patient outcome more accurately and allow better treatment and follow-up decisions is of crucial importance. SOX9 (sex-determining region Y (SRY)-box 9) is a regulator of cell fate decisions in embryogenesis and adulthood. Here, we sought to ascertain the relevance of SOX9 transcription factor as a prognostic marker in gastric cancer. SOX9 expression was analyzed by immunohistochemistry in 333 gastric adenocarcinoma cases, and its association with clinicopathological and follow-up data was evaluated. SOX9 nuclear expression was absent in 17% of gastric cancer cases and predicted worse disease-free survival (P = 0 03). SOX9 expression was associated with lower risk of relapse in Cox univariable analysis (HR = 0 58; 95% CI = 0 35-0.97; P = 0 04). The prognostic value of SOX9 was more pronounced in tumours with expansive growth (P = 0 01) or with venous invasion (P = 0 02). Two validation cohorts from the Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) confirmed that low SOX9 expression was significantly associated with poor patient outcome. In conclusion, we have identified SOX9 as a biomarker of disease relapse in gastric cancer patients. Further experiments are needed to elucidate its biological relevance at the cellular level.The authors wish to acknowledge the tumour and tissue bank at Hospital de São João for providing all the means to collect the human tissue samples included in this study. This work was supported by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). This work was also financed by the projects NORTE-01-0145-FEDER-000003 (DOCnet) and NORTE-07-0124-FEDER-000029 supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). BP and RB acknowledge FCT for financial support (grants SFRH/BPD/109794/2015 and SFRH/BPD/68276/2010, respectively)

Эксплуатационные показатели качества транспортной телекоммуникационной первичной сети Украины

Приведены статистические данные о количестве, причинах и характере повреждений подземных волоконно-оптических линий связи, которые являются основой транспортной телекоммуникационной первичной сети на примере Донецкой и Луганской областей за период с 2001 по 2010 годы. Сравнение значений этих характеристик со значениями аналогичных параметров за 2001—2005 гг. позволяет разработать рекомендации по повышению надежности телекоммуникационных сетей.В роботі наведено статистичні дані про кількість, причини та характер пошкоджень підземних волоконно-оптичних ліній зв’язку, які є основою транспортної телекомунікаційної первинної мережі, на прикладі Донецької та Луганської областей за період з 2001 по 2010 рр. Порівняння значень цих характеристик із значеннями аналогічних характеристик за 2001—2005 рр. дозволяє розробити рекомендації по підвищенню надійності телекомунікаціїйних мереж.The paper presents statistical data on the number, nature and causes of the damage to underground fiber-optic communication lines, on which the transport telecommunication primary network is based, using an example of Donetsk and Lugansk regions for the period between 2001 and 2010. Comparison of these characteristics with the values of similar parameters over 2001—2005 allows to develop recommendations for the improvement of the reliability of telecommunication networks

Mechanisms of Psychological Distress following War in the Former Yugoslavia: The Role of Interpersonal Sensitivity

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This study was funded by a grant from the European Commission, contract number INCO-CT-2004-509176. AN was supported by a Clinical Early Career Research Fellowship (113295) and a Project Grant (104288

TEORIAS DE ENFERMAGEM: IMPORTÂNCIA DA CORRETA APLICAÇÃO DOS CONCEITOS

Theoretical-reflexive research, whose aim is to analyze the clarity of concept stimulus in the Roy Model, for best comprehension in nursing practice. It was developed in three phases: 1- Search of studies that utilized the Roy Model; 2- Conducted reading for comprehension of the concept stimulus and 3- Analysis of clarity of the concept. The three studies were conducted at master level. The analysis of the studies shows deficiency in the clarity of the concept stimulus, being predominant the ambiguity in the classification and differentiation of the focal and contextual stimuli, without the existence of consistency and uniformity. The need arises to deepen the theories of nursing for adequate application in the areas of research: nursing education and practice, optimizing and improving its use, as well as, enabling the comprehension of determined concepts that are not sufficiently clear. The worries that arise among the nurses will provide a more profound approach to the study, enabling the advance of theories, as well as new findings, leading to necessary changes.  Investigación teórico-reflexiva cuyo objetivo fue analizar la claridad del concepto estímulo según el  modelo de Roy, para mayor comprensión en la práctica de enfermería. Desarrollada en tres etapas: 1ª- Levantamiento de estudios que utilizaron el Modelo de Roy; 2ª - Lectura dirigida hacia la comprensión del concepto estímulo y 3ª - Análisis de la claridad del concepto. Fueron utilizados tres estudios, a  nivel de maestrado. El análisis de los estudios demuestra deficiencia en la claridad del concepto estímulo, predominando ambigüedad en la clasificación y diferenciación de los estímulos focales y contextuales, sin consistencia y uniformidad. Se evidencia la necesidad de profundizar en las teorías de enfermería, para su aplicación adecuada en las áreas de investigación, enseñanza y práctica, optimizando y mejorando su uso, además de posibilitar la comprensión de determinados conceptos no suficientemente claros. Las inquietudes surgidas entre los enfermeros podrán motivar un abordaje más profundo de los estudios, posibilitando el avance de las teorías, así  como nuevos descubrimientos, dirigiendo los cambios necesariosPesquisa teórico-reflexiva, objetivando analisar a clareza do conceito estímulo no modelo de Roy, para maior compreensão na prática de enfermagem. Desenvolvido em três etapas: 1ª- Levantamento de estudos que utilizaram o Modelo de Roy; 2ª - Leitura dirigida para a compreensão do conceito estímulo e 3ª - Análise da clareza do conceito. Foram utilizados três estudos, em nível de mestrado. A análise dos estudos demonstra deficiência na clareza do conceito estímulo, predominando ambigüidade na classificação e diferenciação dos estímulos focais e contextuais, não existindo consistência e uniformidade. Evidencia-se a necessidade do aprofundamento nas teorias de enfermagem, para a aplicação adequada nas áreas de pesquisa, ensino e prática, otimizando e aprimorando seu uso, além de possibilitar a compreensão de determinados conceitos, não suficientemente claros. As inquietações surgidas entre os enfermeiros poderão proporcionar o aprofundamento nos estudos, possibilitando o avanço das teorias, assim como novos achados, direcionando as mudanças necessárias

Assessment of a novel, capsid-modified adenovirus with an improved vascular gene transfer profile

<p>Background: Cardiovascular disorders, including coronary artery bypass graft failure and in-stent restenosis remain significant opportunities for the advancement of novel therapeutics that target neointimal hyperplasia, a characteristic of both pathologies. Gene therapy may provide a successful approach to improve the clinical outcome of these conditions, but would benefit from the development of more efficient vectors for vascular gene delivery. The aim of this study was to assess whether a novel genetically engineered Adenovirus could be utilised to produce enhanced levels of vascular gene expression.</p> <p>Methods: Vascular transduction capacity was assessed in primary human saphenous vein smooth muscle and endothelial cells using vectors expressing the LacZ reporter gene. The therapeutic capacity of the vectors was compared by measuring smooth muscle cell metabolic activity and migration following infection with vectors that over-express the candidate therapeutic gene tissue inhibitor of matrix metalloproteinase-3 (TIMP-3).</p> <p>Results: Compared to Adenovirus serotype 5 (Ad5), the novel vector Ad5T*F35++ demonstrated improved binding and transduction of human vascular cells. Ad5T*F35++ mediated expression of TIMP-3 reduced smooth muscle cell metabolic activity and migration in vitro. We also demonstrated that in human serum samples pre-existing neutralising antibodies to Ad5T*F35++ were less prevalent than Ad5 neutralising antibodies.</p> <p>Conclusions: We have developed a novel vector with improved vascular transduction and improved resistance to human serum neutralisation. This may provide a novel vector platform for human vascular gene transfer.</p&gt