Phytotherapics in tissue healing and its interface with professionals of health in Brazil / Fitoterápicos na cicatrização de tecidos e sua interface com profissionais de saúde no Brasil

The World Health Organization and many other national health conferences have stimulated the use of phytotherapeutics and medicinal plants in primary health care in Brazil. Phytotherapeutics and the use of medicinal plants are part of the folk medicine practice, which complements the treatment that is usually employed by lower income population. There is a growing interest in researches about improving the knowledge of plants’ medicinal properties used in tissue healing. This process occurs as a biological response after injury, where uncountable signaling pathways are stimulated to restore the homeostasis of the affected structure. It is observed that Brazil has been developing important researches to improve the knowledge of plants’ medicinal properties favoring a greater prescription by the health professionals and also a better use by the population. Phototherapeutics act in tissue repair in different ways, and the present review describes the use of these in healing in experimental researches and its interface with professionals of health. In this research, we checked scientific articles (Medline, Scielo, Lilacs, Coordination of Superior Level Staff Improvement (CAPES), PubMed and Google Scholar) published between years 2000 and 2018. Companies, researchers, professionals of health and the general population have shown an interest in phytotherapeutics compounds as alternatives for the treatment of various conditions and the healing of injuries. This is due to the lower side effects, easy access and low cost of herbal medicines compared to allopathic medicines and the rich biodiversity from the Brazilian flora. However, it is necessary for the health professionals training and motivation, aiming at a correct and safe prescription and the use of herbal medicines in tissue healing, as well as the insertion of this practice into their professional qualification.

Association of physical activity with physical function and quality of life in people with hip and knee osteoarthritis: longitudinal analysis of a population-based cohort

Hip and knee osteoarthritis (HKOA) is a chronic disease characterized by joint pain that leads to reduced physical function and health-related quality of life (HRQoL). At present, no cure is available. Clinical trials indicate that people with HKOA benefit from physical activity in several health-related outcomes. However, few studies have evaluated the long-term positive effect of regular physical activity. This study analyzed participants with HKOA from a nationwide population-based cohort (EpiDoC Cohort) to assess the impact of physical activity on patients' physical function and HRQoL over a long-term follow-up. The regular weekly frequency of intentional physical activity was self-reported as non-frequent (0 times/week), frequent (1-2 times/week), or very frequent (≥ 3 times/week). This study followed 1086 participants over a mean period of 4.7 ± 3.4 years, during which 6.3% and 14.9% of participants reported frequent and very frequent physical activity, respectively. Using linear mixed models, we found that frequent (β = - 0.101 [- 0.187, - 0.016]; β = 0.039 [- 0.002, 0.080]) and very frequent physical activity (β = - 0.061 [- 0.118, - 0.004]; β = 0.057 [0.029, 0.084]) were associated with improved physical function and HRQoL over time, respectively, when compared with non-frequent exercise, adjusting for years to baseline, sex, age, years of education, body mass index, multimorbidity, hospitalizations, clinical severity, and unmanageable pain levels. These findings raise awareness of the importance of maintaining exercise/physical activity long term to optimize HRQoL and physical function. Further studies must address barriers and facilitators to improve the adoption of regular physical activity among citizens with HKOA.info:eu-repo/semantics/publishedVersio

Retinal blood vessels extraction using probabilistic modelling

© 2014 Kaba et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.The analysis of retinal blood vessels plays an important role in detecting and treating retinal diseases. In this review, we present an automated method to segment blood vessels of fundus retinal image. The proposed method could be used to support a non-intrusive diagnosis in modern ophthalmology for early detection of retinal diseases, treatment evaluation or clinical study. This study combines the bias correction and an adaptive histogram equalisation to enhance the appearance of the blood vessels. Then the blood vessels are extracted using probabilistic modelling that is optimised by the expectation maximisation algorithm. The method is evaluated on fundus retinal images of STARE and DRIVE datasets. The experimental results are compared with some recently published methods of retinal blood vessels segmentation. The experimental results show that our method achieved the best overall performance and it is comparable to the performance of human experts.The Department of Information Systems, Computing and Mathematics, Brunel University

Pro-inflammatory polarization and colorectal cancer modulate alternative and intronic polyadenylation in primary human macrophages

Macrophages are essential cells of the immune system that alter their inflammatory profile depending on their microenvironment. Alternative polyadenylation in the 3'UTR (3'UTR-APA) and intronic polyadenylation (IPA) are mechanisms that modulate gene expression, in particular in cancer and activated immune cells. Yet, how polarization and colorectal cancer (CRC) cells microenvironment affect 3'UTR-APA and IPA in primary human macrophages remains unknown. Here, primary human monocytes were isolated from healthy donors, differentiated and polarized into a pro-inflammatory state and ChrRNA-Seq and 3'RNA-Seq were performed to quantify gene expression and characterize new 3’UTR-APA and IPA mRNA isoforms. Our results show that polarization of human macrophages from naïve to a pro-inflammatory state causes a marked increase both in proximal polyA site selection in the 3'UTR and in IPA events, in genes relevant for macrophage functions. Additionally, we found a negative correlation between differential gene expression and IPA during pro-inflammatory polarization of primary human macrophages. As macrophages are abundant immune cells in the CRC microenvironment that either promote or abrogate cancer progression, we investigated how indirect exposure to CRC cells affects macrophage gene expression and 3'UTR-APA and IPA mRNA events. Co-culture with CRC cells alters the inflammatory phenotype of macrophages, increases the expression of pro tumoral genes and induce 3’UTR-APA alterations. Notably, some of these gene expression differences were also found in tumour-associated macrophages of CRC patients, indicating that they are physiological relevant. Upon macrophage pro inflammatory polarization SRSF12 is the pre-mRNA processing gene that is most upregulated. After SRSF12 knockdown in M1 macrophages there is a global downregulation of gene expression, in particular in genes involved in gene expression regulation and in immune responses. Our results reveal new 48 3’UTR-APA and IPA mRNA isoforms produced during pro-inflammatory polarization of primary human macrophages and CRC co-culture that may be used in the future as diagnostic or therapeutic tools

Characterization of two heparan sulphate-binding sites in the mycobacterial adhesin Hlp

<p>Abstract</p> <p>Background</p> <p>The histone-like Hlp protein is emerging as a key component in mycobacterial pathogenesis, being involved in the initial events of host colonization by interacting with laminin and glycosaminoglycans (GAGs). In the present study, nuclear magnetic resonance (NMR) was used to map the binding site(s) of Hlp to heparan sulfate and identify the nature of the amino acid residues directly involved in this interaction.</p> <p>Results</p> <p>The capacity of a panel of 30 mer synthetic peptides covering the full length of Hlp to bind to heparin/heparan sulfate was analyzed by solid phase assays, NMR, and affinity chromatography. An additional active region between the residues Gly46 and Ala60 was defined at the N-terminal domain of Hlp, expanding the previously defined heparin-binding site between Thr31 and Phe50. Additionally, the C-terminus, rich in Lys residues, was confirmed as another heparan sulfate binding region. The amino acids in Hlp identified as mediators in the interaction with heparan sulfate were Arg, Val, Ile, Lys, Phe, and Thr.</p> <p>Conclusion</p> <p>Our data indicate that Hlp interacts with heparan sulfate through two distinct regions of the protein. Both heparan sulfate-binding regions here defined are preserved in all mycobacterial Hlp homologues that have been sequenced, suggesting important but possibly divergent roles for this surface-exposed protein in both pathogenic and saprophic species.</p

Adenosine A2A receptor modulation of hippocampal CA3-CA1 synapse plasticity during associative learning in behaving mice

© 2009 Nature Publishing Group All rights reservedPrevious in vitro studies have characterized the electrophysiological and molecular signaling pathways of adenosine tonic modulation on long-lasting synaptic plasticity events, particularly for hippocampal long-term potentiation(LTP). However, it remains to be elucidated whether the long-term changes produced by endogenous adenosine in the efficiency of synapses are related to those required for learning and memory formation. Our goal was to understand how endogenous activation of adenosine excitatory A2A receptors modulates the associative learning evolution in conscious behaving mice. We have studied here the effects of the application of a highly selective A2A receptor antagonist, SCH58261, upon a well-known associative learning paradigm - classical eyeblink conditioning. We used a trace paradigm, with a tone as the conditioned stimulus (CS) and an electric shock presented to the supraorbital nerve as the unconditioned stimulus(US). A single electrical pulse was presented to the Schaffer collateral–commissural pathway to evoke field EPSPs (fEPSPs) in the pyramidal CA1 area during the CS–US interval. In vehicle-injected animals, there was a progressive increase in the percentage of conditioning responses (CRs) and in the slope of fEPSPs through conditioning sessions, an effect that was completely prevented (and lost) in SCH58261 (0.5 mg/kg, i.p.)-injected animals. Moreover, experimentally evoked LTP was impaired in SCH58261- injected mice. In conclusion, the endogenous activation of adenosine A2A receptors plays a pivotal effect on the associative learning process and its relevant hippocampal circuits, including activity-dependent changes at the CA3-CA1 synapse.This study was supported by grants from the Spanish Ministry of Education and Research (BFU2005-01024 and BFU2005-02512), Spanish Junta de Andalucía (BIO-122 and CVI-02487), and the Fundación Conocimiento y Cultura of the Pablo de Olavide University (Seville, Spain).B. Fontinha was in receipt of a studentship from a project grant (POCI/SAU-NEU/56332/2004) supported by Fundação para a Ciência e Tecnologia (FCT, Portugal), and of an STSM from Cost B30 concerted action of the EU

Congenital Disorders of Glycosylation in Portugal—Two Decades of Experience

Objective: To describe the clinical, biochemical, and genetic features of both new and previously reported patients with congenital disorders of glycosylation (CDGs) diagnosed in Portugal over the last 20 years. Study design: The cohort includes patients with an unexplained multisystem or single organ involvement, with or without psychomotor disability. Serum sialotransferrin isoforms and, whenever necessary, apolipoprotein CIII isoforms and glycan structures were analyzed. Additional studies included measurement of phosphomannomutase (PMM) activity and analysis of lipid-linked oligosaccharides in fibroblasts. Sanger sequencing and massive parallel sequencing were used to identify causal variants or the affected gene, respectively. Results: Sixty-three individuals were diagnosed covering 14 distinct CDGs; 43 patients diagnosed postnatally revealed a type 1, 14 a type 2, and 2 a normal pattern on serum transferrin isoelectrofocusing. The latter patients were identified by whole exome sequencing. Nine of them presented also a hypoglycosylation pattern on apolipoprotein CIII isoelectrofocusing, pointing to an associated O-glycosylation defect. Most of the patients (62%) are PMM2-CDG and the remaining carry pathogenic variants in ALG1, ATP6AP1, ATP6AP2, ATP6V0A2, CCDC115, COG1, COG4, DPAGT1, MAN1B1, SLC35A2, SRD5A3, RFT1, or PGM1. Conclusions: Portuguese patients with CDGs are presented in this report, some of them showing unique clinical phenotypes. Among the 14 genes mutated in Portuguese individuals, 8 are shared with a previously reported Spanish cohort. However, regarding the mutational spectrum of PMM2-CDG, the most frequent CDG, a striking similarity between the 2 populations was found, as only 1 mutated allele found in the Portuguese group has not been reported in Spain.info:eu-repo/semantics/publishedVersio