Browsing by Subject "318 Medical biotechnology"

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  • Wrzaczek, Michael; Brosche, Mikael; Kollist, Hannes; Kangasjärvi, Jaakko (2009)
    Reactive oxygen species (ROS) have important functions in plant stress responses and development. In plants, ozone and pathogen infection induce an extracellular oxidative burst that is involved in the regulation of cell death. However, very little is known about how plants can perceive ROS and regulate the initiation and the containment of cell death. We have identified an Arabidopsis thaliana protein, GRIM REAPER (GRI), that is involved in the regulation of cell death induced by extracellular ROS. Plants with an insertion in GRI display an ozone-sensitive phenotype. GRI is an Arabidopsis ortholog of the tobacco flower-specific Stig1 gene. The GRI protein appears to be processed in leaves with a release of an N-terminal fragment of the protein. Infiltration of the N-terminal fragment of the GRI protein into leaves caused cell death in a superoxide-and salicylic acid-dependent manner. Analysis of the extracellular GRI protein yields information on how plants can initiate ROS-induced cell death during stress response and development.
  • Vroomans, Renske M. A.; Hogeweg, Paulien; ten Tusscher, Kirsten H. W. J. (2018)
    BackgroundSegmentation, the subdivision of the major body axis into repeated elements, is considered one of the major evolutionary innovations in bilaterian animals. In all three segmented animal clades, the predominant segmentation mechanism is sequential segmentation, where segments are generated one by one in anterior-posterior order from a posterior undifferentiated zone. In vertebrates and arthropods, sequential segmentation is thought to arise from a clock-and-wavefront-type mechanism, where oscillations in the posterior growth zone are transformed into a segmental prepattern in the anterior by a receding wavefront. Previous evo-devo simulation studies have demonstrated that this segmentation type repeatedly arises, supporting the idea of parallel evolutionary origins in these animal clades. Sequential segmentation has been studied most extensively in vertebrates, where travelling waves have been observed that reflect the slowing down of oscillations prior to their cessation and where these oscillations involve a highly complex regulatory network. It is currently unclear under which conditions this oscillator complexity and slowing should be expected to evolve, how they are related and to what extent similar properties should be expected for sequential segmentation in other animal species.ResultsTo investigate these questions, we extend a previously developed computational model for the evolution of segmentation. We vary the slope of the posterior morphogen gradient and the strength of gene expression noise. We find that compared to a shallow gradient, a steep morphogen gradient allows for faster evolution and evolved oscillator networks are simpler. Furthermore, under steep gradients, damped oscillators often evolve, whereas shallow gradients appear to require persistent oscillators which are regularly accompanied by travelling waves, indicative of a frequency gradient. We show that gene expression noise increases the likelihood of evolving persistent oscillators under steep gradients and of evolving frequency gradients under shallow gradients. Surprisingly, we find that the evolutions of oscillator complexity and travelling waves are not correlated, suggesting that these properties may have evolved separately.ConclusionsBased on our findings, we suggest that travelling waves may have evolved in response to shallow morphogen gradients and gene expression noise. These two factors may thus also be responsible for the observed differences between different species within both the arthropod and chordate phyla.
  • Wolf, Maija; Korja, Miikka; Karhu, Ritva; Edgren, Henrik; Kilpinen, Sami; Ojala, Kalle; Mousses, Spyro; Kallioniemi, Anne; Haapasalo, Hannu (2010)
    Neuroblastoma has successfully served as a model system for the identification of neuroectoderm-derived oncogenes. However, in spite of various efforts, only a few clinically useful prognostic markers have been found. Here, we present a framework, which integrates DNA, RNA and tissue data to identify and prioritize genetic events that represent clinically relevant new therapeutic targets and prognostic biomarkers for neuroblastoma.
  • Fusciello, Manlio; Fontana, Flavia; Tähtinen, Siri; Capasso, Cristian; Feola, Sara; da Silva Lopes Martins, Beatriz; Chiaro, Jacopo; Peltonen, Karita; Ylösmäki, Leena; Ylösmäki, Erkko; Hamdan Hissaoui, Firas; Kari, Otto K.; Ndika, Joseph; Alenius, Harri; Urtti, Arto; Hirvonen, Jouni T.; Santos, Hélder A.; Cerullo, Vincenzo (2019)
    Virus-based cancer vaccines are nowadays considered an interesting approach in the field of cancer immunotherapy, despite the observation that the majority of the immune responses they elicit are against the virus and not against the tumor. In contrast, targeting tumor associated antigens is effective, however the identification of these antigens remains challenging. Here, we describe ExtraCRAd, a multi-vaccination strategy focused on an oncolytic virus artificially wrapped with tumor cancer membranes carrying tumor antigens. We demonstrate that ExtraCRAd displays increased infectivity and oncolytic effect in vitro and in vivo. We show that this nanoparticle platform controls the growth of aggressive melanoma and lung tumors in vivo both in preventive and therapeutic setting, creating a highly specific anti-cancer immune response. In conclusion, ExtraCRAd might serve as the next generation of personalized cancer vaccines with enhanced features over standard vaccination regimens, representing an alternative way to target cancer.
  • Taavitsainen, Eveliina; Kortesoja, Maarit; Bruun, Tanja; Johansson, Niklas G; Hanski, Leena (2020)
    Antibiotic-tolerant persister bacteria involve frequent treatment failures, relapsing infections and the need for extended antibiotic treatment. The virulence of an intracellular human pathogen C. pneumoniae is tightly linked to its propensity for persistence and means for its chemosensitization are urgently needed. In the current work, persistence of C. pneumoniae clinical isolate CV6 was studied in THP-1 macrophages using quantitative PCR and quantitative culture. A dibenzocyclooctadiene lignan schisandrin reverted C. pneumoniae persistence and promoted productive infection. The concomitant administration of schisandrin and azithromycin resulted in significantly improved bacterial eradication compared to sole azithromycin treatment. In addition, the closely related lignan schisandrin C was superior to azithromycin in eradicating the C. pneumoniae infection from the macrophages. The observed chemosensitization of C. pneumoniae was associated with the suppression of cellular glutathione pools by the lignans, implying to a previously unknown aspect of chlamydia-host interactions. These data indicate that schisandrin lignans induce a phenotypic switch in C. pneumoniae, promoting the productive and antibiotic-susceptible phenotype instead of persistence. By this means, these medicinal plant -derived compounds show potential as adjuvant therapies for intracellular bacteria resuscitation.
  • Abdollahzadeh, Ali; Belevich, Ilya; Jokitalo, Eija; Tohka, Jussi; Sierra, Alejandra (2019)
  • Zhang, Liucheng; Xiang, Yi; Zhang, Hongbo; Cheng, Liying; Mao, Xiyuan; An, Ning; Zhang, Lu; Zhou, Jinxiong; Deng, Lianfu; Zhang, Yuguang; Sun, Xiaoming; Santos, Hélder A.; Cui, Wenguo (2020)
    Inspired by drying‐driven curling of apple peels, hydrogel‐based micro‐scaled hollow tubules are proposed in article number 1903553 by Yuguang Zhang, Xiaoming Sun, Hélder A. Santos, Wenguo Cui, and co‐workers for biomimicking microvessels with diameters of 50–500 μm, which promote microcirculation and improve the survival of random skin flaps. The 3D‐shape‐morphing technique is of great flexibility and potential to lay the foundation for the construction of complex vascular networks, such as Y‐branches, anastomosis rings, and triangle loops.
  • Lakanmaa, Riitta-Liisa; Suominen, Tarja; Ritmala-Castren, Marita; Vahlberg, Tero; Leino-Kilpi, Helena (2015)
    Critical care patients benefit from the attention of nursing personnel with a high competence level. The aim of the study was to describe and evaluate the self-assessed basic competence of intensive care unit nurses and related factors. A cross-sectional survey design was used. A basic competence scale (Intensive and Critical Care Nursing Competence Scale version 1, Likert scale 1-5, 1 = poor and 5 = excellent) was employed among Finnish intensive care unit nurses (n = 431). Intensive care unit nurses' self-assessed basic competence was good (mean 4.19, SD 0.40). The attitude and value base of basic competence was excellent whereas experience base was the poorest compared to the knowledge base and skill base of intensive and critical care nursing. The strongest factor explaining nurses' basic competence was their experience of autonomy in nursing care (F value 60.85, beta 0.11, SE 0.01, and P
  • Chilov, Dmitri; Sinjushina, Natalia; Saarimäki-Vire, Jonna Marianne; Taketo, Makoto M.; Partanen, Juha (2010)
  • Capasso, Cristian; Hirvinen, Mari; Cerullo, Vincenzo (2013)
    Viral vectors have been extensively studied due to their great transduction efficiency compared to non-viral vectors. These vectors have been used extensively in gene therapy, enabling the comprehension of, not only the advantages of these vectors, but also the limitations, such as the activation of the immune system after vector administration. Moreover, the need to control the target of the vector has led to the development of chemical and non-chemical modifications of the vector surface, allowing researchers to modify the tropism and biodistribution profile of the vector, leading to the production of viral vectors able to target different tissues and organs. This review describes recent non-genetic modifications of the surfaces of viral vectors to decrease immune system activation and to control tissue targeting. The developments described herein provide opportunities for applications of gene therapy to treat acquired disorders and genetic diseases and to become useful tools in regenerative medicine.
  • Jolma, Arttu; Zhang, Jilin; Mondragon, Estefania; Morgunova, Ekaterina; Kivioja, Teemu; Laverty, Kaitlin U.; Yin, Yimeng; Zhu, Fangjie; Bourenkov, Gleb; Morris, Quaid; Hughes, Timothy R.; Maher III, Louis James; Taipale, Jussi (2020)
    RNA-binding proteins (RBPs) regulate RNA metabolism at multiple levels by affecting splicing of nascent transcripts, RNA folding, base modification, transport, localization, translation, and stability. Despite their central role in RNA function, the RNA-binding specificities of most RBPs remain unknown or incompletely defined. To address this, we have assembled a genome-scale collection of RBPs and their RNA-binding domains (RBDs) and assessed their specificities using high-through-put RNA-SELEX (HTR-SELEX). Approximately 70% of RBPs for which we obtained a motif bound to short linear sequenc-es, whereas similar to 30% preferred structured motifs folding into stem-loops. We also found that many RBPs can bind to multiple distinctly different motifs. Analysis of the matches of the motifs in human genomic sequences suggested novel roles for many RBPs. We found that three cytoplasmic proteins-ZC3H12A, ZC3H12B, and ZC3H12C-bound to motifs resembling the splice donor sequence, suggesting that these proteins are involved in degradation of cytoplasmic viral and/or unspliced transcripts. Structural analysis revealed that the RNA motif was not bound by the conventional C3H1 RNA-binding domain of ZC3H12B. Instead, the RNA motif was bound by the ZC3H12B's PilT N terminus (PIN) RNase domain, revealing a po-tential mechanism by which unconventional RBDs containing active sites or molecule-binding pockets could interact with short, structured RNA molecules. Our collection containing 145 high-resolution binding specificity models for 86 RBPs is the largest systematic resource for the analysis of human RBPs and will greatly facilitate future analysis of the various bi-ological roles of this important class of proteins.
  • Fontana, Flavia; Santos, Helder A. (Springer International Publishing AG, 2021)
    Advances in Experimental Medicine and Biology
  • Ortega-Paino, Eva; Tupasela, Aaro (Edward Elgar, 2019)
  • Nowak, Jessika; Visnovsky, Sandra B.; Pitman, Andrew R.; Cruz, Cristina D.; Palmer, Jon; Fletcher, Graham C.; Flint, Steve (2021)
    Listeria monocytogenes is a ubiquitous foodborne pathogen that results in a high rate of mortality in sensitive and immunocompromised people. Contamination of food with L. monocytogenes is thought to occur during food processing, most often as a result of the pathogen producing a biofilm that persists in the environment and acting as the source for subsequent dispersal of cells onto food. A survey of seafoodprocessing plants in New Zealand identified the persistent strain 15G01, which has a high capacity to form biofilms. In this study, a transposon library of L. monocytogenes 15G01 was screened for mutants with altered biofilm formation, assessed by a crystal violet assay, to identify genes involved in biofilm formation. This screen identified 36 transposants that showed a significant change in biofilm formation compared to the wild type. The insertion sites were in 27 genes, 20 of which led to decreased biofilm formation and seven to an increase. Two insertions were in intergenic regions. Annotation of the genes suggested that they are involved in diverse cellular processes, including stress response, autolysis, transporter systems, and cell wall/membrane synthesis. Analysis of the biofilms produced by the transposants using scanning electron microscopy and fluorescence microscopy showed notable differences in the structure of the biofilms compared to the wild type. In particular, inactivation of uvrB and mltD produced coccoid-shaped cells and elongated cells in long chains, respectively, and the mgtB mutant produced a unique biofilm with a sandwich structure which was reversed to the wild-type level upon magnesium addition. The mltD transposant was successfully complemented with the wild-type gene, whereas the phenotypes were not or only partially restored for the remaining mutants. IMPORTANCE The major source of contamination of food with Listeria monocytogenes is thought to be due to biofilm formation and/or persistence in food-processing plants. By establishing as a biofilm, L. monocytogenes cells become harder to eradicate due to their increased resistance to environmental threats. Understanding the genes involved in biofilm formation and their influence on biofilm structure will help identify new ways to eliminate harmful biofilms in food processing environments. To date, multiple genes have been identified as being involved in biofilm formation by L. monocytogenes; however, the exact mechanism remains unclear. This study identified four genes associated with biofilm formation by a persistent strain. Extensive microscopic analysis illustrated the effect of the disruption of mgtB, clsA, uvrB, and mltD and the influence of magnesium on the biofilm structure. The results strongly suggest an involvement in biofilm formation for the four genes and provide a basis for further studies to analyze gene regulation to assess the specific role of these biofilm-associated genes.
  • Fontana, Flavia; Bartolo, Raquel; Santos, Helder A. (Springer International Publishing AG, 2021)
    Advances in Experimental Medicine and Biology
    During the last 20+ years, research into the biomedical application of nanotechnology has helped in reshaping cancer treatment. The clinical use of several passively targeted nanosystems resulted in improved quality of care for patients. However, the therapeutic efficacy of these systems is not superior to the original drugs. Moreover, despite extensive investigations into actively targeted nanocarriers, numerous barriers still remain before their successful clinical translation, including sufficient blood-stream circulation time and efficient tumor targeting. The combination of synthetic nanomaterials with biological elements (e.g., cells, cell membranes, and macromolecules) is presently the cutting-edge research in cancer nanotechnology. The features provided by the biological moieties render the particles with prolonged bloodstream circulation time and homotopic targeting to the tumor site. Moreover, cancer cell membranes serve as sources of neoantigens, useful in the formulation of nanovaccines. In this chapter, we will discuss the advantages of biohybrid nanosystems in cancer chemotherapy, immunotherapy, and combined therapy, as well as highlight their preparation methods and clinical translatability.
  • Rauniyar, Khusbu; Jha, Sawan Kumar; Jeltsch, Markku Michael (2018)
    Because virtually all tissues contain blood vessels, the importance of hemevascularization has been long recognized in regenerative medicine and tissue engineering. However, the lymphatic vasculature has only recently become a subject of interest. Central to the task of growing a lymphatic network are lymphatic endothelial cells (LECs), which constitute the innermost layer of all lymphatic vessels. The central molecule that directs proliferation and migration of LECs during embryogenesis is vascular endothelial growth factor C (VEGF-C). VEGF-C is therefore an important ingredient for LEC culture and attempts to (re)generate lymphatic vessels and networks. During its biosynthesis VEGF-C undergoes a stepwise proteolytic processing, during which its properties and affinities for its interaction partners change. Many of these fundamental aspects of VEGF-C biosynthesis have only recently been uncovered. So far, most—if not all—applications of VEGF-C do not discriminate between different forms of VEGF-C. However, for lymphatic regeneration and engineering purposes, it appears mandatory to understand these differences, since they relate, e.g., to important aspects such as biodistribution and receptor activation potential. In this review, we discuss the molecular biology of VEGF-C as it relates to the growth of LECs and lymphatic vessels. However, the properties of VEGF-C are similarly relevant for the cardiovascular system, since both old and recent data show that VEGF-C can have a profound effect on the blood vasculature.
  • Jain, Ashvi Sanjay; Pawar, Pranita Subhash; Sarkar, Aira; Junnuthula, Vijayabhaskarreddy; Dyawanapelly, Sathish (2021)
    Among the various types of nanoparticles and their strategy for synthesis, the green synthesis of silver nanoparticles has gained much attention in the biomedical, cellular imaging, cosmetics, drug delivery, food, and agrochemical industries due to their unique physicochemical and biological properties. The green synthesis strategies incorporate the use of plant extracts, living organisms, or biomolecules as bioreducing and biocapping agents, also known as bionanofactories for the synthesis of nanoparticles. The use of green chemistry is ecofriendly, biocompatible, nontoxic, and cost-effective. We shed light on the recent advances in green synthesis and physicochemical properties of green silver nanoparticles by considering the outcomes from recent studies applying SEM, TEM, AFM, UV/Vis spectrophotometry, FTIR, and XRD techniques. Furthermore, we cover the antibacterial, antifungal, and antiparasitic activities of silver nanoparticles.
  • Terracciano, M; De Stefano, L.; Almeida Santos, Helder; Martucci, N.M.; Ruggiero, I.; Rendina, I.; Migliaccio, N.; Lamberti, A.; Rea, I. (INTECHopen, 2016)
    Diatomite is a natural porous silica material of sedimentary origin, formed by remains of diatom skeletons called “frustules.” The abundance in many areas of the world and the peculiar physico-chemical properties made diatomite an intriguing material for several applications ranging from food production to pharmaceutics. However, diatomite is a material still rarely used in biomedical applications. In this chapter, the properties of diatom frustules reduced to nanoparticles, with an average diameter less than 350 nm, as potential drug vectors are described. Their biocompatibility, cellular uptake, and capability to transport molecules inside cancer cells are discussed. Preliminary studies of in vivo toxicity are also presented.
  • Pitkänen, S.; Paakinaho, K.; Pihlman, H.; Ahola, N.; Hannula, M.; Asikainen, S.; Manninen, M.; Morelius, M.; Keränen, P.; Hyttinen, J.; Kellomäki, M.; Laitinen-Vapaavuori, O.; Miettinen, S. (2019)
    Most synthetic bone grafts are either hard and brittle ceramics or paste-like materials that differ in applicability from the gold standard autologous bone graft, which restricts their widespread use. Therefore, the aim of the study was to develop an elastic, highly porous and biodegradable beta-tricalciumphosphate/poly(L-lactide-co-epsilon-caprolactone) (beta-TCP/PLCL) composite for bone applications using supercritical CO2 foaming. Ability to support osteogenic differentiation was tested in human adipose stem cell (hASC) culture for 21 d. Biocompatibility was evaluated for 24 weeks in a rabbit femur-defect model. Foamed composites had a high ceramic content (50 wt%) and porosity (65-67 %). After 50 % compression, in an aqueous environment at 37 degrees C, tested samples returned to 95 % of their original height. Hydrolytic degradation of beta-TCP/PLCL composite, during the 24-week follow-up, was very similar to that of porous PLCL scaffold both in vitro and in vivo. Osteogenic differentiation of hASCs was demonstrated by alkaline phosphatase activity analysis, alizarin red staining, soluble collagen analysis, immunocytochemical staining and qRT-PCR. In vitro, hASCs formed a pronounced mineralised collagen matrix. A rabbit femur defect model confirmed biocompatibility of the composite. According to histological Masson-Goldner's trichrome staining and micro-computed tomography, beta-TCP/PLCL composite did not elicit infection, formation of fibrous capsule or cysts. Finally, native bone tissue at 4 weeks was already able to grow on and in the beta-TCP/PLCL composite. The elastic and highly porous beta-TCP/PLCL composite is a promising bone substitute because it is osteoconductive and easy-to-use and mould intraoperatively.
  • Jahromi, Leila Pourtalebi; Shahbazi, Mohammad-Ali; Maleki, Aziz; Azadi, Amir; Santos, Helder A. (2021)
    Over the past decades, considerable attention has been dedicated to the exploitation of diverse immune cells as therapeutic and/or diagnostic cell-based microrobots for hard-to-treat disorders. To date, a plethora of therapeutics based on alive immune cells, surface-engineered immune cells, immunocytes' cell membranes, leukocyte-derived extracellular vesicles or exosomes, and artificial immune cells have been investigated and a few have been introduced into the market. These systems take advantage of the unique characteristics and functions of immune cells, including their presence in circulating blood and various tissues, complex crosstalk properties, high affinity to different self and foreign markers, unique potential of their on-demand navigation and activity, production of a variety of chemokines/cytokines, as well as being cytotoxic in particular conditions. Here, the latest progress in the development of engineered therapeutics and diagnostics inspired by immune cells to ameliorate cancer, inflammatory conditions, autoimmune diseases, neurodegenerative disorders, cardiovascular complications, and infectious diseases is reviewed, and finally, the perspective for their clinical application is delineated.