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

Localization of osteocalcin (BGP) during fish (Sparus aurata) development by in situ hybridization and immunohistochemistry: comparison between gene expression/protein distribution and skeletal mineralization

Osteocalcin (Bone Gla protein, BGP) is a small noncollagenous protein which is synthesized by osteoblasts and odontoblasts and is found exlusively in mineralized bony tissues. Although isolated for the first time in 1978, only recently has a function for this protein been suggested, specifically in controlling hydroxyapatite crystal growth. Appearance of osteocalcin could be linked to the presence of an hydroxyapatite-containing bony skeleton, since the protein was never found in cartilaginous fishes. Furthermore, within its primary sequence the amino acid residues known to be essential for its function are present in fish as well as in mammals, suggesting that function has been conserved over 400 million years of evolution. Taken totgether, these findings prompted us to study in detail the localization of osteocalcin gene expression in fish

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

Microalgae as potential sources of bioactive compounds for functional foods and pharmaceuticals

Microalgae are an untapped source of bioactive compounds with various biotechnological applications. Several species are industrially produced and commercialized for the feed or cosmetic industries, however, other applications in the functional food and pharmaceutical markets can be foreseen. In this study, nine industrial/commercial species were evaluated for in vitro antioxidant, calcium-chelating, anti-tumoral, and anti-inflammatory activities. The most promising extracts were fractionated yielding several promising fractions namely, of Tetraselmis striata CTP4 with anti-inflammatory activity (99.0 ± 0.8% reduction in TNF-α production in LPS stimulated human macrophages at 50 µg/mL), of Phaeodactylum Tricornutum with cytotoxicity towards cancerous cell lines (IC50 = 22.3 ± 1.8 µg/mL and 27.5 ± 1.6 µg/mL for THP-1 and HepG2, respectively) and of Porphyridium sp. and Skeletonema sp. with good chelating activity for iron, copper and calcium (IC50 = 0.047, 0.272, 0.0663 mg/mL and IC50 = 0.055, 0.240, 0.0850 mg/mL, respectively). These fractions were chemically characterized by GC–MS after derivatization and in all, fatty acids at various degrees of unsaturation were the most abundant compounds. Some of the species under study proved to be potentially valuable sources of antioxidant, metal chelators, anti-tumoral and anti-inflammatory compounds with possible application in the functional food and pharmaceutical industries.info:eu-repo/semantics/publishedVersio

Il monastero benedettino di S. Giorgio in Braida a Verona: nuove prospettive di ricerca sulla rifabbrica romanica (sec. XII)

L’attuale aspetto rinascimentale della chiesa di San Giorgio in Braida è frutto di una serie di interventi promossi dai canonici veneziani di San Giorgio in Alga a partire dalla fine del XV secolo. Il monastero benedettino, tuttavia, fu fondato nella metà dell’XI secolo e completamente ricostruito fra il terzo e il quarto decennio del secolo successivo per volere del vescovo Bernardo. L’articolo ripercorre le vicende storiche dell’istituzione in età medievale e rende nota l’esistenza di alcune parti della compagine romanica tuttora inedite, che permettono d’inserire il cantiere di San Giorgio in Braida nel contesto delle coeve manifestazioni architettoniche veronesi

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

Hope, optimism and survival in a randomized trial of chemotherapy for metastatic colorectal cancer

Purpose: Psychological responses to cancer are widely believed to affect survival. We investigated associations between hope, optimism, anxiety, depression, health utility and survival in patients starting first line chemotherapy for metastatic colorectal cancer. Methods: 429 subjects with metastatic colorectal cancer in a randomised controlled trial of chemotherapy, completed baseline questionnaires assessing: hopefulness, optimism, anxiety and depression and health utility. Hazard ratios (HR) and P-values were calculated with Cox models for overall survival (OS) and progression-free survival (PFS) in univariable and multivariable analyses. Results: Median follow-up was 31 months. Univariable analyses showed that OS was associated negatively with depression (HR 2.04, P<0.001), and positively with health utility (HR 0.56, P<0.001) and hopefulness (HR 0.75, P=0.013). In multivariable analysis, OS was also associated negatively with depression (HR 1.72, P<0.001), and positively with health utility (HR 0.73, P=0.014), but not with optimism, anxiety or hopefulness. PFS was not associated with hope, optimism, anxiety or depression in any analyses. Conclusions: Depression and health utility, but not optimism, hope, or anxiety were associated with survival after controlling for known prognostic factors in patients with advanced colorectal cancer. Further research is required to understand the nature of the relationship between depression and survival. If a causal mechanism is identified, this may lead to interventional possibilities