Direct Optical Coupling to an Unoccupied Dirac Surface State in the Topological Insulator Bi2_2Se3_3

We characterize the occupied and unoccupied electronic structure of the topological insulator Bi$_2$Se$_3$ by one-photon and two-photon angle-resolved photoemission spectroscopy and slab band structure calculations. We reveal a second, unoccupied Dirac surface state with similar electronic structure and physical origin to the well-known topological surface state. This state is energetically located 1.5 eV above the conduction band, which permits it to be directly excited by the output of a Ti:Sapphire laser. This discovery demonstrates the feasibility of direct ultrafast optical coupling to a topologically protected, spin-textured surface state.Comment: Accepted to Physical Review Letter

A dual role for GRP in cardiovascular disease

Management and prevention of cardiovascular disease (CVD) represents one of the major health challenges worldwide. CVD is the leading cause of death globally despite all research efforts on last decades regarding the molecular mechanisms and processes involved on its development and progression. Chronic Kidney Disease (CKD) is an independent risk factor and promotor of CVD events, representing a considerable economic cost for the health system. CVD is the leading cause of death in all CKD stages, accounting for half the number of deaths in this population.info:eu-repo/semantics/publishedVersio

Vitamin K as a powerful micronutrient in aging and age-related diseases: pros and cons from clinical studies

Vitamin K is a multifunctional micronutrient implicated in age-related diseases such as cardiovascular diseases, osteoarthritis and osteoporosis. Although vitamin K-dependent proteins (VKDPs) are described to have a crucial role in the pathogenesis of these diseases, novel roles have emerged for vitamin K, independently of its role in VKDPs carboxylation. Vitamin K has been shown to act as an anti-inflammatory by suppressing nuclear factor κB (NF-κB) signal transduction and to exert a protective effect against oxidative stress by blocking the generation of reactive oxygen species. Available clinical evidences indicate that a high vitamin K status can exert a protective role in the inflammatory and mineralization processes associated with the onset and progression of age-related diseases. Also, vitamin K involvement as a protective super-micronutrient in aging and 'inflammaging' is arising, highlighting its future use in clinical practice. In this review we summarize current knowledge regarding clinical data on vitamin K in skeletal and cardiovascular health, and discuss the potential of vitamin K supplementation as a health benefit. We describe the clinical evidence and explore molecular aspects of vitamin K protective role in aging and age-related diseases, and its involvement as a modulator in the interplay between pathological calcification and inflammation processes.Agência financiadora Portuguese Society of Nephrology (SPN) Portuguese national funds from FCT-Foundation for Science and Technology UID/Multi/04326/2019info:eu-repo/semantics/publishedVersio

Identification of Proteins with Potential Osteogenic Activity Present in the Water-Soluble Matrix Proteins from Crassostrea gigas Nacre Using a Proteomic Approach

Nacre, when implanted in vivo in bones of dogs, sheep, mice, and humans, induces a biological response that includes integration and osteogenic activity on the host tissue that seems to be activated by a set of proteins present in the nacre water-soluble matrix (WSM). We describe here an experimental approach that can accurately identify the proteins present in the WSM of shell mollusk nacre. Four proteins (three gigasin-2 isoforms and a cystatin A2) were for the first time identified in WSM of Crassostrea gigas nacre using 2DE and LC-MS/MS for protein identification. These proteins are thought to be involved in bone remodeling processes and could be responsible for the biocompatibility shown between bone and nacre grafts. These results represent a contribution to the study of shell biomineralization process and opens new perspectives for the development of new nacre biomaterials for orthopedic applications

Gla-rich protein is involved in the cross-talk between calcification and inflammation in osteoarthritis

Osteoarthritis (OA) is a whole-joint disease characterized by articular cartilage loss, tissue inflammation, abnormal bone formation and extracellular matrix (ECM) mineralization. Disease-modifying treatments are not yet available and a better understanding of osteoarthritis pathophysiology should lead to the discovery of more effective treatments. Gla-rich protein (GRP) has been proposed to act as a mineralization inhibitor and was recently shown to be associated with OA in vivo. Here, we further investigated the association of GRP with OA mineralization-inflammation processes. Using a synoviocyte and chondrocyte OA cell system, we showed that GRP expression was up-regulated following cell differentiation throughout ECM calcification, and that inflammatory stimulation with IL-1 beta results in an increased expression of COX2 and MMP13 and up-regulation of GRP. Importantly, while treatment of articular cells with gamma-carboxylated GRP inhibited ECM calcification, treatment with either GRP or GRP-coated basic calcium phosphate (BCP) crystals resulted in the down-regulation of inflammatory cytokines and mediators of inflammation, independently of its gamma-carboxylation status. Our results strengthen the calcification inhibitory function of GRP and strongly suggest GRP as a novel anti-inflammatory agent, with potential beneficial effects on the main processes responsible for osteoarthritis progression. In conclusion, GRP is a strong candidate target to develop new therapeutic approaches

Gla Rich Protein (GRP) is associated to osteoarthritis being highly accumulated in the joint tissues and synovial fluid

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Mentalization for Offending Adult Males (MOAM): study protocol for a randomized controlled trial to evaluate mentalization-based treatment for antisocial personality disorder in male offenders on community probation

Background Antisocial personality disorder (ASPD), although associated with very significant health and social burden, is an under-researched mental disorder for which clinically effective and cost-effective treatment methods are urgently needed. No intervention has been established for prevention or as the treatment of choice for this disorder. Mentalization-based treatment (MBT) is a psychotherapeutic treatment that has shown some promising preliminary results for reducing personality disorder symptomatology by specifically targeting the ability to recognize and understand the mental states of oneself and others, an ability that is compromised in people with ASPD. This paper describes the protocol of a multi-site RCT designed to test the effectiveness and cost-effectiveness of MBT for reducing aggression and alleviating the wider symptoms of ASPD in male offenders subject to probation supervision who fulfil diagnostic criteria for ASPD. Methods Three hundred and two participants recruited from a pool of offenders subject to statutory supervision by the National Probation Service at 13 sites across the UK will be randomized on a 1:1 basis to 12 months of probation plus MBT or standard probation as usual, with follow-up to 24 months post-randomization. The primary outcome is frequency of aggressive antisocial behaviour as assessed by the Overt Aggression Scale – Modified. Secondary outcomes include violence, offending rates, alcohol use, drug use, mental health status, quality of life, and total service use costs. Data will be gathered from police and criminal justice databases, NHS record linkage, and interviews and self-report measures administered to participants. Primary analysis will be on an intent-to-treat basis; per-protocol analysis will be undertaken as secondary analysis. The primary outcome will be analysed using hierarchical mixed-effects linear regression. Secondary outcomes will be analysed using mixed-effects linear regression, mixed-effects logistic regression, and mixed-effects Poisson models for secondary outcomes depending on whether the outcome is continuous, binary, or count data. A cost-effectiveness and cost-utility analysis will be undertaken. Discussion This definitive, national, multi-site trial is of sufficient size to evaluate MBT to inform policymakers, service commissioners, clinicians, and service users about its potential to treat offenders with ASPD and the likely impact on the population at risk

Acción de la terapia láser sobre la actividad enzimática mitocondrial en un modelo de miopatía experimental.

Las hipótesis sobre el mecanismo de acción del láser de baja intensidad (LLLT: Low Level Laser Teraphy), Helio-Neón (He-Ne) y Arseniuro de Galio (As.Ga), se centran en la mitocondria. Se evaluó el efecto de LLLT en miopatía experimental, valorando la actividad de: citrato sintasa (CI) y los complejos I-IV de la cadena respiratoria mitocondrial (CRM). Se utilizaron 70 ratashembras, cepa Wistar, distribuidas en 7 grupos: A) control, B) injuriado y sacrificado a las 24 hs., C) injuriado y sacrificado a los 10 días, D) injuriado + láser de He-Ne, E) injuriado + láser de As.Ga, F) láser de He-Ne y G) láser de As.Ga. La miopatía se indujo con carragenina, inyectada en un miembro posterior. Las variables fueron determinadas por espectrofotometría. LLLT se realizó durante 10 días consecutivos (9,5 J/cm2).El análisis estadístico se realizó aplicando ANOVA-test de Fisher (p<0.05). El láser de He.Ne por si solo aumentó significativamente (p < 0.05) la actividad de CI y disminuyó la actividad del complejo IV de la CRM (p < 0.05). El láser por si solo aumentó la actividad de CI y disminuyó los complejos II (p<0.001) y IV (0.05). LLLT en miopatía inflamatoria tuvo efecto normo-regulador de la actividad enzimática mitocondrial.Action of laser therapy on mitochondrial enzyme activity in amodel of experimental myopathy.AbstractHypotheses about the mechanism of action of low level laser (LLLT: Low Level Laser therapy), Helium-Neon (He-Ne) and gallium arsenide (As.Ga) focus in the mitochondria. The effect of LLLT in experimental myopathy, evaluating the activity: citrate synthase (CI) and complex I-IV of the mitochondrial respiratory chain (CRM). We used 70 female rats, Wistar strain, divided into 7 groups: A) control, B) injured and sacrificed at 24 hours, C) injured and sacrificed at 10 days, D) injured + He-Ne laser, E) As. Ga injured + laser, F) He-Ne laser and G) laser As.Ga. Myopathy was induced by carrageenan injected into the left hind foot. The variables were determined by spectrophotometry. LLLT was performed for 10 consecutive days (9.5 J/cm2).Statistical analysis was performed using ANOVA-Fisher test (p <0.05). He.Ne laser alone was significantly increased (p <0.05) CI activity and decreased activity of complex IV of the MCA (p <0.05). The laser alone increased CI and decreased activity ofcomplex II (p <0.001) and IV (0.05). LLLT was effective in inflammatory myopathy normal-regulating mitochondrial enzyme activityKey words: Myopathy; Helium Neon laser; Gallium Arsenide laser; Mitochondrial respiratory chai

Use of an innovative system and nanotechnology-based strategy for therapeutic applications of Gla-rich protein (GRP)

Introduction: Gla-rich protein (GRP) is a vitamin K-dependent protein (VKDP) acting as a calcification inhibitor and anti-inflammatory agent in cardiovascular and articular systems, and THP1 monocyte/macrophage cells [1,2]. Calcification and inflammation processes are known to be involved in the etiology of several calcification-related chronic inflammatory diseases such as atherosclerosis, CKD and osteoarthritis, in a complex bi-directional interplay that drives disease progression. Here, we developed an innovative system to produce human c-carboxylated GRP (cGRP), and a nanotechnology strategy based on GRP loading into extracellular vesicles (EVs) as a gold standard delivery system for GRP in therapeutic applications. Materials and methods: Human GRP protein was co-expressed with c-carboxylase enzyme (GGCX), vitamin K oxidoreductase (GGCX) and furin, in the insect cell baculovirus system in the presence of vitamin K. GRP released in the cell culture media was characterized by mass spectrometry based techniques and Western blot analysis. EVs released by the insect cells overexpressing GRP were isolated by ultracentrifugation, and characterized for GRP content through TEM-immunogold staining, Western blot, ELISA, qPCR. Functional assays using isolated EVs containing GRP were performed in primary vascular smooth muscle cells (VSMCs) and THP1 monocyte/macrophage cells, for anti-mineralizing and anti-inflammatory screening.Results: GRP released in the cell culture media when co-expressed with GGCX, VKOR and furin in the presence of vitamin K, is processed at the pro-peptide and contain Gla residues. EVs released by the insect cells in this system were shown to be loaded with GRP protein and mRNA, and capable of reducing ECM calcium deposition of calcifying VSMCs and the production of TNFa in THP1 monocyte/macrophage cells stimulated with LPS. Discussion and conclusions: While the successful production of human cGRP constitutes a major achievement, this innovative methodology will open new opportunities for the production of other biological active VKDPs. Furthermore, EVs loaded with GRP were shown to have anti-mineralizing and anti-inflammatory properties, with promising therapeutic potentialities for calcification-related chronic inflammatory diseases.Portuguese Foundation for Science and Technology (EU/PID1003201)info:eu-repo/semantics/publishedVersio