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After more than twenty years of research, the molecular events of apoptotic cell death can be succinctly stated; different pathways, activated by diverse signals, increase the activity of proteases called caspases that rapidly and irreversibly dismantle condemned cell by cleaving specific substrates. In this time the ideas that apoptosis protects us from tumourigenesis and that cancer chemotherapy works by inducing apoptosis also emerged. Currently, apoptosis research is shifting away from the intracellular events within the dying cell to focus on the effect of apoptotic cells on surrounding tissues. This is producing counterintuitive data showing that our understanding of the role of apoptosis in tumourigenesis and cancer therapy is too simple, with some interesting and provocative implications. Here, we will consider evidence supporting the idea that dying cells signal their presence to the surrounding tissue and, in doing so, elicit repair and regeneration that compensates for any loss of function caused by cell death. We will discuss evidence suggesting that cancer cell proliferation may be driven by inappropriate or corrupted tissue-repair programmes that are initiated by signals from apoptotic cells and show how this may dramatically modify how we view the role of apoptosis in both tumourigenesis and cancer therapy.
Development and Validation of a Rapid and Reliable Method for TPMT Genotyping using real-time PCR
(2012)
The biological effects of bilirubin, still poorly understood, are concentration-dependent ranging from cell protection to toxicity. Here we present data that at high nontoxic physiological concentrations, bilirubin inhibits growth of proliferating human coronary artery smooth muscle cells by three events. It impairs the activation of Raf/ERK/MAPK pathway and the cellular Raf and cyclin D1 content that results in retinoblastoma protein hypophosphorylation on amino acids S608 and S780. These events impede the release of YY1 to the nuclei and its availability to regulate the expression of genes and to support cellular proliferation. Moreover, altered calcium influx and calpain II protease activation leads to proteolytical degradation of transcription factor YY1. We conclude that in the serum-stimulated human vascular smooth muscle primary cell cultures, bilirubin favors growth arrest, and we propose that this activity is regulated by its interaction with the Raf/ERK/MAPK pathway, effect on cyclin D1 and Raf content, altered retinoblastoma protein profile of hypophosphorylation, calcium influx, and YY1 proteolysis. We propose that these activities together culminate in diminished 5 S and 45 S ribosomal RNA synthesis and cell growth arrest. The observations provide important mechanistic insight into the molecular mechanisms underlying the transition of human vascular smooth muscle cells from proliferative to contractile phenotype and the role of bilirubin in this transition.
Gas chromatography with simultaneous flame-ionization detection (FID) and a nitrogen-phosphorus detection (NPD) as well as gas chromatography-mass spectrometry (GC/MS) has been used to characterize some long-chain primary alkyl amines and alkyl diamines after derivatization with trifluoroacetic anhydride (TFAA).
The criteria for assessing the quality of rubber materials are the polymer or copolymer composition and the additives. These additives include plasticizers, extender oils, carbon black, inorganic fillers, antioxidants, heat and light stabilizers, processing aids, cross-linking agents, accelerators, retarders, adhesives, pigments, smoke and flame retardants, and others. Determination of additives in polymers or copolymers generally requires the extraction of these substances from the matrix as a first step, which can be challenging, and the subsequent analysis of the extracted additives by gas chromatography (GC), GC–mass spectrometry (MS), high performance liquid chromatography (HPLC), HPLC–MS, capillary electrophoresis, thin-layer chromatography, and other analytical techniques. In the present work, nitrile rubber materials were studied using direct analytical flash pyrolysis hyphenated to GC and electrospray ionization MS in both scan and selected ion monitoring modes to demonstrate that this technique is a good tool to identify the organic additives in nitrile rubber.
Human mesenchymal stem cells (hMSCs) are considered a promising cell source for regenerative medicine, because they have the potential to differentiate into a variety of lineages among which the mesoderm-derived lineages such adipo- or osteogenesis are investigated best. Human MSCs can be harvested in reasonable to large amounts from several parts of the patient’s body and due to this possible autologous origin, allorecognition can be avoided. In addition, even in allogenic origin-derived donor cells, hMSCs generate a local immunosuppressive microenvironment, causing only a weak immune reaction. There is an increasing need for bone replacement in patients from all ages, due to a variety of reasons such as a new recreational behavior in young adults or age-related diseases. Adipogenic differentiation is another interesting lineage, because fat tissue is considered to be a major factor triggering atherosclerosis that ultimately leads to cardiovascular diseases, the main cause of death in industrialized countries. However, understanding the differentiation process in detail is obligatory to achieve a tight control of the process for future clinical applications to avoid undesired side effects. In this review, the current findings for adipo- and osteo-differentiation are summarized together with a brief statement on first clinical trials.
Nachhaltigkeitskonzepte sind kein selbstverständlicher Gegenstand der chemischen Hochschulausbildung. Der vorliegende Text fragt nach den Ursachen und zeigt anschließend Anschlussflächen für das Thema Nachhaltigkeit in der Chemieausbildung. Er stellt ein fachübergreifendes und zugleich fachbezogenes Konzept vor, welches Nachhaltigkeit zum Gegenstand für Chemiestudierende macht. Dieses ermöglicht den Studierenden einen subjektiv bedeutsamen Zugang zu den Fachinhalten. Es fördert Bewertungskompetenzen und Verantwortungsfähigkeit, schult die Sprachgewandtheit und erleichtert methodisch geführt die Reflexion auf Gegenstand und Selbstverständnis.
One of the most common problems in Regenerative Medicine is the regeneration of damaged bone with the aim of repairing or replacing lost or damaged bone tissue by stimulating the natural regenerative process. Particularly in the fields of orthopedic, plastic, reconstructive, maxillofacial and craniofacial surgery there is need for successful methods to restore bone. From a regenerative point of view two different bone replacement problems can be distinguished: large bone defects and small bone defects. Currently, no perfect system exists for the treatment of large bone defects.
People with type 2 Diabetes have an elevated risk for developing cardiovascular disease (CVD) for which dyslipidemia is the major contributor. Diabetic patients have characteristic pattern of dyslipidemia with decreased level of high density lipoprotein cholesterol (HDL-C) and elevated triglycerides (TG) level. However, in diabetes mellitus, low density lipoprotein cholesterol (LDL-C) which is used as one of the markers for the risk of CVD, is underestimated so in such cases the levels of non-High density lipoprotein cholesterol (non-HDL-C) can be a stronger predictor of CVD as it strongly correlates with atherogenic lipoproteins. Therefore, an attempt has been made to evaluate the level of non-HDL-C as a newer marker for the risk of cardiovascular disease and to fi nd out the pattern of dyslipidemia in diabetes mellitus. The present study comprised of 82 type 2 Diabetic cases and 81 non-diabetic controls. Among the diabetics, the majority of the subjects (61.0%) were HDL-C dyslipidemic. However, among the controls, the maximum numbers of individuals (40.7%) were TG dyslipidemic. Diabetics have signifi cantly elevated ratio of total cholesterol to high density lipoprotein cholesterol (TC/HDL-C) and the signifi cant increased levels of non-high density lipoprotein cholesterol (non-HDL-C) compared to controls which can be used as markers of dyslipidemia and can also be used to predict the risk of cardiovascular disease in type 2 Diabetes Mellitus.
In this work, preceramic papers containing 85 wt% Al2O3 were heat-treated at 1600 °C to obtain paper-derived ceramics. In order to increase the preceramic paper density prior to sintering, the papers were calendered at different roll temperatures and pressures. The influences of the calendering parameters on the microstructure and mechanical properties of the preceramic papers and the paper-derived ceramics were investigated. It was expected that especially the mechanical properties of the papers and derived ceramics would be improved by calendering.