The POU5F1 gene codes for the OCT4 transcription factor, which is one of the key regulators of pluripotency. Its transcription, alternative splicing, and alternative translation leading to the synthesis of the active, nuclear localized OCT4A has been described in detail. Much less, however, is known about actively transcribed OCT4 pseudogenes, several of which display high homology to OCT4A and can be expressed and translated into proteins. Using RT-PCR followed by pseudogene-specific restriction digestion, cloning, and sequencing we discriminate between OCT4A and transcripts for pseudogenes 1, 3 and 4. We show that expression of OCT4 and its pseudogenes follows a developmentally-regulated pattern in differentiating hESCs, indicating a tight regulatory relationship between them. We further demonstrate that differentiated human cells from a variety of tissues express exclusively pseudogenes. Expression of OCT4A can, however be triggered in adult differentiated cells by oxygen and FGF2-dependent mechanisms.
COBISS.SI-ID: 31179993
During the discovery of mechanisms that govern immune activation and suppression, immune tolerance always came second in the scientific timeline. This has subsequently shaped the advances in the clinical translation of DC therapy protocols used for immunostimulation or immunosuppression. With several hundred clinical trials already registered within the U.S. National Institutes of Health for the use of DCs in cancer vaccination, only a few involve TolDCs for use as negative vaccines. However, as a result of the strong scientific rationale from preclinical and clinical trials, the use of negative vaccination in organ transplantation is likely on its way to reach the extent of the use of positive cancer vaccines in the future. As the underlying mechanisms emerge, the role of DCs in the induction of transplant tolerance is recognized unambiguously as central in the bidirectional communication with various types of immune cells. This is achieved by a complex interplay of numerous tolerogenic signals involving regulatory cytokines and other surface-bound or soluble inhibitory molecules associated with corresponding inhibitory signaling cascades. A detailed understanding of these processes will accelerate the advances of clinical immunologists in translating their knowledge from bench to bedside. In this review, we present the role of TolDCs as well as the most recent findings concerning associated molecular and cellular mechanisms that shape the balance between regulatory and effector immune responses during organ transplantation.
COBISS.SI-ID: 3534449
Background. Glioblastoma multiforme (GBM) is a brain tumour with a very high patient mortality rate, with a median survival of 47 weeks. This might be improved by the identification of novel diagnostic, prognostic and predictive therapy-response biomarkers, preferentially through the monitoring of the patient blood. The aim of this study was to define the impact of GBM in terms of alterations of the plasma protein levels in these patients. Materials and methods. We used a commercially available antibody array that includes 656 antibodies to analyse blood plasma samples from 17 healthy volunteers in comparison with 17 blood plasma samples from patients with GBM. Results. We identified 11 plasma proteins that are statistically most strongly associated with the presence of GBM. These proteins belong to three functional signalling pathways: T-cell signalling and immune responses; cell adhesion and migration; and cell-cycle control and apoptosis. Thus, we can consider this identified set of proteins as potential diagnostic biomarker candidates for GBM. In addition, a set of 16 plasma proteins were significantly associated with the overall survival of these patients with GBM. Guanine nucleotide binding protein alpha (GNAO1) was associated with both GBM presence and survival of patients with GBM. Conclusions. Antibody array analysis represents a useful tool for the screening of plasma samples for potential cancer biomarker candidates in small-scale exploratory experiments; however, clinical validation of these candidates requires their further evaluation in a larger study on an independent cohort of patients.
COBISS.SI-ID: 31525081
Introduction. Total extrusion and loss of the talus is a rare injury with a wide choice of appropriate treatment, but rarely resulting in a fully functional recovery. We report on an uncommon case, both for the severity of the injury and for the uncommon treatment due to the patient's rejection of secondary surgery. Case presentation We treated a 16-year-old Caucasian man with the most extreme variant of a totally extruded and lost talus, accompanied with complex injury of the soft tissues of the ankle and foot. The treatment included urgent microvascular foot reimplantation, microvascular muscle free flap transfer, platelet grofth factors, and temporary fixation. This kind of injury should typically be treated by tibiocalcaneal arthrodesis. However, this was not performed, as after the successful early stages of the treatment he strongly objected to another surgery due to his fully functional status and the successful therapeutic results of our early treatment. Conclusions The injury described in this case study would ordinarily be treated by amputation, but due to the well-executed treatment in the early stages after the injury, the outcome was satisfying. Surprisingly and against our expectations, the late results of the treatment were successful even without arthrodesis. He is now 37 years old and has a functional foot 21 years after the injury.
COBISS.SI-ID: 31775705
OBJECTIVES: Bone tissue regeneration requires a source of viable, proliferative cells with osteogenic differentiation capacity. Periodontal surgeries represent an opportunity to procure small amounts of autologous tissues for primary cell isolation. Our objective was to assess the potential of human alveolar bone as a source of autologous osteogenic cells for tissue engineering and biomaterials and drug testing studies. MATERIALS AND METHODS: Alveolar bone tissue was obtained from 37 patients undergoing routine periodontal surgery. Tissue harvesting and cell isolation procedures were optimized to isolate viable cells. Primary cells were subcultured and characterized with respect to their growth characteristics, gene expression of osteogenic markers, alkaline phosphatase activity and matrix mineralization, under osteogenic stimulation. RESULTS: Alveolar bone cells were successfully isolated from 28 of the 30 samples harvested with bone forceps, and from 2 of the 5 samples obtained by bone drilling. The yield of cells in primary cultures was variable between the individual samples, but was not related to the site of tissue harvesting and the patient age. In 80% of samples (n = 5), the primary cells proliferated steadily for eight subsequent passages, reaching cumulative numbers over 10(10) cells. Analyses confirmed stable gene expression of alkaline phosphatase, osteopontin and osteocalcin in early and late cell passages. In osteogenic medium, the cells from late passages increased alkaline phosphatase activity and accumulated mineralized matrix, indicating a mature osteoblastic phenotype. CONCLUSIONS: Primary alveolar bone cells exhibited robust proliferation and retained osteogenic phenotype during in vitro expansion, suggesting that they can be used as an autologous cell source for bone regenerative therapies and various in vitro studies.
COBISS.SI-ID: 513984119