Sofia Beghi  Malgorzata Furmanik  Armand Jaminon  Rogier Veltrop  Nikolas Rapp  Kanin Wichapong  Elham Bidar  Annamaria Buschini  Leon J. Schurgers 《International journal of molecular sciences》2022,23(24)

Cardiovascular disease is the major cause of death worldwide. The success of medication and other preventive measures introduced in the last century have not yet halted the epidemic of cardiovascular disease. Although the molecular mechanisms of the pathophysiology of the heart and vessels have been extensively studied, the burden of ischemic cardiovascular conditions has risen to become a top cause of morbidity and mortality. Calcium has important functions in the cardiovascular system. Calcium is involved in the mechanism of excitation–contraction coupling that regulates numerous events, ranging from the production of action potentials to the contraction of cardiomyocytes and vascular smooth muscle cells. Both in the heart and vessels, the rise of intracellular calcium is sensed by calmodulin, a protein that regulates and activates downstream kinases involved in regulating calcium signalling. Among them is the calcium calmodulin kinase family, which is involved in the regulation of cardiac functions. In this review, we present the current literature regarding the role of calcium/calmodulin pathways in the heart and vessels with the aim to summarize our mechanistic understanding of this process and to open novel avenues for research.  相似文献   

    

Alexey Afoshin  Svetlana Tishchenko  Azat Gabdulkhakov  Irina Kudryakova  Inna Galemina  Dmitry Zelenov  Elena Leontyevskaya  Sofia Saharova  Natalya Leontyevskaya 《International journal of molecular sciences》2022,23(24)

The crystal structure of the Lysobacter capsici VKM B−2533^T β-lytic protease (Blp), a medicinally promising antimicrobial enzyme, was first solved. Blp was established to possess a folding characteristic of the M23 protease family. The groove of the Blp active site, as compared with that of the LasA structural homologue from Pseudomonas aeruginosa, was found to have amino acid differences. Biochemical analysis revealed no differences in the optimal reaction conditions for manifesting Blp and LasA bacteriolytic activities. At the same time, Blp had a broader range of action against living and autoclaved target cells. The results suggest that the distinction in the geometry of the active site and the charge of amino acid residues that form the active site groove can be important for the hydrolysis of different peptidoglycan types in target cells.  相似文献   

    

Ana M. S. Costa  Nadya V. Dencheva  Sofia G. Caridade  Zlatan Z. Denchev  Joo F. Mano 《Advanced Materials Interfaces》2016,3(16)

  相似文献   

    

Sofia Nilsson  Aida Alvinius  Ann Enander 《突发事故与危机管理杂志》2016,24(1):14-26

The aim of this study was to identify and analyze the ways in which images and reactions of the public are described and framed in media articles and reports. Reporting from six major events affecting the Swedish public was studied using a thematic method of analysis. The results show three dynamic interrelated processes at work simultaneously in framing the public: identification, characterization and evaluation. A significant contribution of this study is the emphasis on how this often subtle and implicit framing influences the portrayal of human reactions, thus possibly influencing the expectations and evaluations of both the public in general and crisis managers in particular.  相似文献   

    

Sofia Sofroniadou  Ioanna Revela  Alexandros Kouloubinis  Ioanna Makriniotou  Sinodi Zerbala  Despina Smirloglou  Petros Kalocheretis  Apostolos Drouzas  George Samonis  Christos Iatrou 《Hemodialysis international. International Symposium on Home Hemodialysis》2017,21(4):498-506

Introduction: Ethanol lock solution has been mainly administered in paediatric and home parenteral nutrition patients in order to prevent catheter related blood stream infections (CRBSI). Its utility in hemodialysis (HD) patients with non‐tunneled‐uncuffed catheter (NTC) has been poorly explored. Methods: We conducted a prospective randomized study in chronic HD patients requiring a newly inserted NTC‐while awaiting for the maturation of an already established arteriovenous fistula (AVF) or arteriovenous graft (AVG) or tunneled‐cuffed catheter insertion. Patients were randomized in two groups: Group A, where the lock solution was ethanol 70% + unfractionated heparin 2000 U/mL and group B, that received only unfractionated heparin 2000 U/mL. Primary end point was CRBSIs whereas exit site infections, thrombotic and bleeding episodes were the secondary end points. Findings: One hundred three HD patients were enrolled in the study (group A, n = 52; group B, n = 51). The median number of catheter days was 32 for group A (range: 23–39) and 34 (range: 27–40) for group B with no statistically significant difference between the two groups. Group A (ethanol + heparin) demonstrated 4/52 episodes (7.69%) of CRBSI whereas Group B (heparin) 11/51 episodes (21.57%) (P = 0.04). CRBSI rates per 1000 catheter days were 2.53/1000 catheter days for group A and 6.7/1000 catheter days for group B (P = 0.04). Mean cumulative infection‐free catheter survival in the ethanol group did not differ significantly compared to the heparin group (log‐rank test = 2.99, P = 0.08). Thrombotic episodes did not differ between the two groups. Discussion: Locking of NTCs in HD patients with ethanol 70% + unfractionated heparin reduces CRBSI rates without increasing the thrombotic episodes.  相似文献   

    

Sofia Municoy  Pablo E. Antezana  Claudio J. Pérez  Martin G. Bellino  Martín F. Desimone 《应用聚合物科学杂志》2021,138(18):50330

The development of advanced biocidal agents stands as a global challenge, focused on the increasing demand of new biomaterials with local and gradual release of antimicrobial agents. This is the first time that three well-known materials are strategically combined to develop a novel biomaterial with long-term bactericidal activity that avoids burst release and toxic effects, by the incorporation of silver nanoparticles in liposomes and the subsequent incorporation of these assemblies in collagen hydrogels. These systems show improved mechanical properties and prolonged inhibitory effect on the growth of Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria, while remaining highly biocompatible for epithelial cells. In fact, the hybrid biocomposite prevents bacterial colonization for at least 72 h, allowing at the same time eukaryotic cell proliferation. As a result, this new bactericidal biomaterial provides a new alternative to improve current treatments of bacterial infections with many implications in significant applications, such as wound therapy and tissue regeneration.  相似文献   

    

Gemma Di Pompo  Margherita Cortini  Roberto Palomba  Valentina Di Francesco  Elena Bellotti  Paolo Decuzzi  Nicola Baldini  Sofia Avnet 《International journal of molecular sciences》2021,22(11)

In the tumor microenvironment, mesenchymal stromal cells (MSCs) are key modulators of cancer cell behavior in response to several stimuli. Intratumoral acidosis is a metabolic trait of fast-growing tumors that can induce a pro-tumorigenic phenotype in MSCs through the activation of the NF-κB-mediated inflammatory pathway, driving tumor clonogenicity, invasion, and chemoresistance. Recent studies have indicated that curcumin, a natural ingredient extracted from Curcuma longa, acts as an NF-κB inhibitor with anti-inflammatory properties. In this work, highly proliferating osteosarcoma cells were used to study the ability of curcumin to reduce the supportive effect of MSCs when stimulated by acidosis. Due to the poor solubility of curcumin in biological fluids, we used spherical polymeric nanoparticles as carriers (SPN-curc) to optimize its uptake by MSCs. We showed that SPN-curc inhibited the release of inflammatory cytokines (IL6 and IL8) by acidity-stimulated MSCs at a higher extent than by free curcumin. SPN-curc treatment was also successful in blocking tumor stemness, migration, and invasion that were driven by the secretome of acid-stressed MSCs. Overall, these data encourage the use of lipid–polymeric nanoparticles encapsulating NF-κB inhibitors such as curcumin to treat cancers whose progression is stimulated by an activated mesenchymal stroma.  相似文献   

    

Ana Sofia Carvalho  Henrique Baeta  Andreia F. A. Henriques  Mostafa Ejtehadifar  Erin M. Tranfield  Ana Laura Sousa  Ana Farinho  Bruno Costa Silva  Jos Cabeadas  Paula Gameiro  Maria Gomes da Silva  Hans Christian Beck  Rune Matthiesen 《International journal of molecular sciences》2021,22(20)

The role of extracellular vesicles (EVs) proteome in diffuse large B-cell lymphoma (DLBCL) pathology, subclassification, and patient screening is unexplored. We analyzed by state-of-the-art mass spectrometry the whole cell and secreted extracellular vesicles (EVs) proteomes of different molecular subtypes of DLBCL, germinal center B cell (GCB subtype), and activated B cell (ABC subtype). After quality control assessment, we compared whole-cell and secreted EVs proteomes of the two cell-of-origin (COO) categories, GCB and ABC subtypes, resulting in 288/1115 significantly differential expressed proteins from the whole-cell proteome and 228/608 proteins from EVs (adjust p-value < 0.05/p-value < 0.05). In our preclinical model system, we demonstrated that the EV proteome and the whole-cell proteome possess the capacity to separate cell lines into ABC and GCB subtypes. KEGG functional analysis and GO enrichment analysis for cellular component, molecular function, and biological process of differential expressed proteins (DEP) between ABC and GCB EVs showed a significant enrichment of pathways involved in immune response function. Other enriched functional categories for DEPs constitute cellular signaling and intracellular trafficking such as B-cell receptor (BCR), Fc_gamma R-mediated phagocytosis, ErbB signaling, and endocytosis. Our results suggest EVs can be explored as a tool for patient diagnosis, follow-up, and disease monitoring. Finally, this study proposes novel drug targets based on highly expressed proteins, for which antitumor drugs are available suggesting potential combinatorial therapies for aggressive forms of DLBCL. Data are available via ProteomeXchange with identifier PXD028267.  相似文献   

    

Rune Matthiesen  Paula Gameiro  Andreia Henriques  Cristian Bodo  Maria Carolina Strano Moraes  Bruno Costa-Silva  Jos Cabeadas  Maria Gomes da Silva  Hans Christian Beck  Ana Sofia Carvalho 《International journal of molecular sciences》2022,23(21)

Diffuse large B cell lymphoma (DLBCL) is an aggressive B cell lymphoma characterized by a heterogeneous behavior and in need of more accurate biological characterization monitoring and prognostic tools. Extracellular vesicles are secreted by all cell types and are currently established to some extent as representatives of the cell of origin. The present study characterized and evaluated the diagnostic and prognostic potential of plasma extracellular vesicles (EVs) proteome in DLBCL by using state-of-the-art mass spectrometry. The EV proteome is strongly affected by DLBCL status, with multiple proteins uniquely identified in the plasma of DLBCL. A proof-of-concept classifier resulted in highly accurate classification with a sensitivity and specificity of 1 when tested on the holdout test data set. On the other hand, no proteins were identified to correlate with non-germinal center B-cell like (non-GCB) or GCB subtypes to a significant degree after correction for multiple testing. However, functional analysis suggested that antigen binding is regulated when comparing non-GCB and GCB. Survival analysis based on protein quantitative values and clinical parameters identified multiple EV proteins as significantly correlated to survival. In conclusion, the plasma extracellular vesicle proteome identifies DLBCL cancer patients from healthy donors and contains potential EV protein markers for prediction of survival.  相似文献   

    

Ekaterina Blinova  Egor Turovsky  Elena Eliseikina  Alexandra Igrunkova  Elena Semeleva  Grigorii Golodnev  Rita Termulaeva  Olga Vasilkina  Sofia Skachilova  Yan Mazov  Kirill Zhandarov  Ekaterina Simakina  Konstantin Belanov  Saveliy Zalogin  Dmitrii Blinov 《International journal of molecular sciences》2022,23(21)

A non-surgical pharmacological approach to control cellular vitality and functionality during ischemic and/or reperfusion-induced phases of strokes remains extremely important. The synthesis of 2-ethyl-6-methyl-3-hydroxypyridinium gammalactone-2,3-dehydro-L-gulonate (3-EA) was performed using a topochemical reaction. The cell-protective effects of 3-EA were studied on a model of glutamate excitotoxicity (GluTox) and glucose-oxygen deprivation (OGD) in a culture of NMRI mice cortical cells. Ca²⁺ dynamics was studied using fluorescent bioimaging and a Fura-2 probe, cell viability was assessed using cytochemical staining with propidium iodide, and gene expression was assessed by a real-time polymerase chain reaction. The compound anti-ischemic efficacy in vivo was evaluated on a model of irreversible middle cerebral artery (MCA) occlusion in Sprague-Dawley male rats. Brain morphological changes and antioxidant capacity were assessed one week after the pathology onset. The severity of neurological disorder was evaluated dynamically. 3-EA suppressed cortical cell death in a dose-dependent manner under the excitotoxic effect of glutamate and ischemia/reoxygenation. Pre-incubation of cerebral cortex cells with 10–100 µM 3-EA led to significant stagnation in Ca²⁺ concentration in a cytosol ([Ca2+]i) of neurons and astrocytes suffering GluTox and OGD. Decreasing intracellular Ca²⁺ and establishing a lower [Ca2+]i baseline inhibited necrotic cell death in an acute experiment. The mechanism of 3-EA cytoprotective action involved changes in the baseline and ischemia/reoxygenation-induced expression of genes encoding anti-apoptotic proteins and proteins of the oxidative status; this led to inhibition of the late irreversible stages of apoptosis. Incubation of brain cortex cells with 3-EA induced an overexpression of the anti-apoptotic genes BCL-2, STAT3, and SOCS3, whereas the expression of genes regulating necrosis and inflammation (TRAIL, MLKL, Cas-1, Cas-3, IL-1β and TNFa) were suppressed. 3-EA 18.0 mg/kg intravenous daily administration for 7 days following MCA occlusion preserved rats’ cortex neuron population, decreased the severity of neurological deficit, and spared antioxidant capacity of damaged tissues. 3-EA demonstrated proven short-term anti-ischemic activity in vivo and in vitro, which can be associated with antioxidant activity and the ability to target necrotic and apoptotic death. The compound may be considered a potential neuroprotective molecule for further pre-clinical investigation.  相似文献