Effect of Cytisus multiflorus in the control of Type-2 Diabetes

Medicinal plants display diverse pharmacological activities with marked therapeutic effects. Type-2 diabetes (T2D) remains a major health problem among industrialized countries, therefore the investigation of formulas to prevent or attenuate the metabolic syndrome, including new therapeutic agents. Currently the interest of medicinal plants is increasing. Portuguese native flora includes several plants known for their hypoglycemic properties. The aim of this work was to study the pharmacological effect of Cytisus multiflorus, one plant from the Portuguese flora traditionally used as an ethnopharmacological agent in diabetes control

Ankylosing Spondylitis Patients Have Impaired Osteoclast Gene Expression in Circulating Osteoclast Precursors

Introduction: Ankylosing spondylitis (AS) is typically characterized by focal bone over-growth and also by systemic bone loss. We hypothesize that the increased osteoproliferation found in AS might be partially due to reduced ability of osteoclast precursors (OCPs) to differentiate into osteoclasts (OCs). Therefore, our aim was to characterize bone remodeling and pro-osteoclastogenesis inflammatory environment, monocytes' phenotype, and in vitro osteoclast differentiation in AS patients. Methods: Patients with active AS without any ongoing therapy and age-and gender matched healthy donors were recruited. Receptor activator of nuclear factor-K13 (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations were assessed. Quantification of serum levels of bone turnover markers and cytokines, in vitro OC differentiation assay and quantitative reverse transcription real-time PCR for OC-specific genes were performed. Results: Pro-and anti-inflammatory cytokine serum levels were higher in AS patients than in controls. RANKL neutrophil expression was higher in AS patients when compared to healthy donors, but CD51/CD61 expression was lower in the classical monocyte subpopulation. Concerning osteoclastogenesis, we found no differences in the in vitro osteoclast differentiating potential of these cells when compared to healthy donors. However, we observed low expression of CSF1R, RANK, and NFATc1 in AS OCPs. Conclusion: Despite the high levels of pro-inflammatory cytokines present in AS patients, no differences in the number of OC or resorbed area were found between AS patients and healthy donors. Moreover, we observed that OCPs have low OC specific gene expression. These findings support our hypothesis of an impaired response of OCPs to pro-osteoclastogenic stimuli in vivo in AS patients.Peer reviewe

Comparison of PBO solvers in a dependency solving domain

Linux package managers have to deal with dependencies and conflicts of packages required to be installed by the user. As an NP-complete problem, this is a hard task to solve. In this context, several approaches have been pursued. Apt-pbo is a package manager based on the apt project that encodes the dependency solving problem as a pseudo-Boolean optimization (PBO) problem. This paper compares different PBO solvers and their effectiveness on solving the dependency solving problem.Comment: In Proceedings LoCoCo 2010, arXiv:1007.083

Influence of mixtures of acenaphthylene and benzo[a] anthracene on their degradation by Pleurotus ostreatus in sandy soil

Purpose Polycyclic aromatic hydrocarbons (PAHs) are a class of organic compounds commonly found as soil contaminants. Fungal degradation is considered as an environmentally friendly and cost-effective approach to remove PAHs from soil. Acenaphthylene (Ace) and Benzo[a]anthracene (BaA) are two PAHs that can coexist in soils; however, the influence of the presence of each other on their biodegradation has not been studied. The biodegradation of Ace and BaA, alone and in mixtures, by the white rot fungus Pleurotus ostreatus was studied in a sandy soil. Materials and methods Experimental microcosms containing soil spiked with different concentrations of Ace and BaAwere inoculated with P. ostreatus. Initial (t 0) and final (after 15 days of incubation) soil concentrations of Ace and BaA were determined after extraction of the PAHs. Results and discussion P. ostreatus was able to degrade 57.7% of the Ace in soil spiked at 30 mg kg−1 dry soil and 65.8% of Ace in soil spiked at 60 mg kg−1 dry soil. The degradation efficiency of BaA by P. ostreatus was 86.7 and 77.4% in soil spiked with Ace at 30 and 60 mg kg−1 dry soil, respectively. After 15 days of incubation, there were no significant differences in Ace concentration between soil spiked with Ace and soil spiked with Ace + BaA, irrespective of the initial soil concentration of both PAHs. There were also no differences in BaA concentration between soil spiked with BaA and soil spiked with BaA + Ace. Conclusions The results indicate that the fungal degradation of Ace and BaA was not influenced by the presence of each other’s PAH in sandy soil. Bioremediation of soils contaminated with Ace and BaA using P. ostreatus is a promising approach to eliminate these PAHs from the environment

Busca de inibidores da enzima glicossomal gliceraldeído 3-fosfato desidrogenase de Trypanosoma cruzi

The inhibitory activity of crude extracts of Meliaceae and Rutaceae plants on glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) enzyme from Trypanosoma cruzi was evaluated at 100 μg/mL. Forty-six extracts were tested and fifteen of them showed significant inhibitory activity (IA % > 50). The majority of the assayed extracts of Meliaceae plants (Cedrela fissilis, Cipadessa fruticosa and Trichilia ramalhoi) showed high ability to inhibit the enzymatic activity. The fractionation of the hexane extract from branches of C. fruticosa led to the isolation of three flavonoids: flavone, 7-methoxyflavone and 3',4',5',5,7-pentamethoxyflavone. The two last compounds showed high ability to inhibit the gGAPDH activity. Therefore, the assayed Meliaceae species could be considered as a promising source of lead compounds against Chagas' disease.Nesse trabalho foi avaliada a atividade inibitória sobre a enzima glicossomal gliceraldeído-3-fosfato desidrogenase de T. cruzi (gGAPDH) de extratos vegetais oriundos de plantas das famílias Meliaceae e Rutaceae, na concentração de 100 μg/mL. Foram testados 46 extratos, dos quais 15 apresentaram atividade inibitória significativa (% AI > 50). A maioria dos extratos de plantas da família Meliaceae (Cedrela fissilis, Cipadessa fruticosa e Trichilia ramalhoi) apresentou grande potencial em inibir a atividade enzimática. O fracionamento do extrato hexânico dos galhos de C. fruticosa permitiu o isolamento de três flavonóides: flavona, 7-metoxiflavona e 3',4',5',5,7-pentametoxiflavona. Os dois últimos foram ativos na inibição da atividade de gGAPDH. Desta forma, as três espécies de Meliaceae testadas podem ser consideradas promissoras na busca de compostos protótipos para o controle da doença de Chagas.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES)FINEP - Financiadora de Estudos e Projeto

Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis

© 2010 Cascão 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.Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and perpetuation of this disease. The main goal of this work was to determine whether cytokines driving neutrophil and Th17 activation are dysregulated in very early rheumatoid arthritis patients with less than 6 weeks of disease duration and before treatment (VERA). Methods: Cytokines related to neutrophil and Th17 activation were quantified in the serum of VERA and established RA patients and compared with other very early arthritis (VEA) and healthy controls. Synovial fluid (SF) from RA and osteoarthritis (OA) patients was also analyzed. Results: VERA patients had increased serum levels of cytokines promoting Th17 polarization (IL-1b and IL-6), as well as IL-8 and Th17-derived cytokines (IL-17A and IL-22) known to induce neutrophil-mediated inflammation. In established RA this pattern is more evident within the SF. Early treatment with methotrexate or corticosteroids led to clinical improvement but without an impact on the cytokine pattern. Conclusions: VERA patients already display increased levels of cytokines related with Th17 polarization and neutrophil recruitment and activation, a dysregulation also found in SF of established RA. 0 Thus, our data suggest that a cytokine-milieu favoring Th17 and neutrophil activity is an early event in RA pathogenesis.This work was supported by a grant from Sociedade Portuguesa de Reumatologia/Schering-Plough 2005. RAM and RC were funded by Fundação para a Ciência e a Tecnologia (FCT) SFRH/BD/30247/2006 and SFRH/BD/40513/2007, respectively. MMS-C was funded by Marie Curie Intra-European Fellowship PERG-2008-239422 and a EULAR Young Investigator Award

Potential impact on stroke

Funding Information: The funding agency that supported the work \u201CFunda\u00E7\u00E3o para a Ci\u00EAncia e Tecnologia\u201D (FCT) with four projects: Applied Molecular Biosciences Unit-UCIBIO (UID/Multi/04378/2019), iNOVA4Health - Programme in Translational Medicine (UID/Multi/04462/2013), LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy and PTDC/MEC-NEU/28750/2017 and the PhD scholarship for NLS (PD/BD/127819/2016). Publisher Copyright: © 2024 The AuthorsRemote ischemic conditioning (RIC) is a procedure consisting of short cycles of ischemia applied in a limb that activates endogenous protection in distant organs, such as the brain. Despite the promising outcomes of RIC, the biochemical factors governing inter-organ communication remain largely unexplored, particularly in humans. A pilot study on 20 healthy humans was performed to identify potential circulating biochemical factors involved in RIC signalling. Blood was collected before and immediately, 4 and 22 h after the end of RIC. To characterize the responses triggered by RIC, a combination of biochemical and proteomic analysis, along with functional in vitro tests in human cells, were performed. RIC did not alter the levels of nitric oxide, bilirubin and cell-free mitochondrial DNA. In contrast, carboxyhaemoglobin levels increased following RIC at all time points and young subset, suggesting endogenous production of carbon monoxide that is a cytoprotective gasotransmitter. Additionally, the levels of glutathione and cysteinylglycine bound to proteins also increased after RIC, while glutathione catabolism decreased. Plasma proteomic analysis identified overall 828 proteins. Several steps of statistical analysis (Student's t-test, repeated measures ANOVA, with Holm corrected pairwise p-values <0.05 threshold and fold change higher or lower than 100 %) leaded to the identification of 9 proteins with altered circulating levels in response to RIC at 4h and 22h. All 9 proteins are from extracellular space or exosomes, being involved in inflammation, angiogenesis or metabolism control. In addition, RIC-conditioned plasma from young subjects protected microglial cell culture against inflammatory stimuli, indicating an anti-inflammatory effect of RIC. Nevertheless, other functional tests in neurons or endothelial cells had no effect. Overall, we present some evidence for RIC-induced anti-inflammatory and antioxidant responses in healthy human subjects, in particular in young subjects. This study is a first step towards the disclosure of signalling factors involved in RIC-mediated inter-organ communication.publishersversionpublishe

Bioactivity screening of pinhão (Araucaria Angustifolia (Bertol.) Kuntze) seed extracts: the inhibition of cholinesterases and α-amylases, and cytotoxic and anti-inflammatory activities

The objective of this work was to determine the potential bioactive properties of extracts from bio-residues of pinhão (Araucaria angustifolia (Bertol.) Kuntze) seeds, namely the α-amylase and cholinesterase inhibition, cytotoxicity, and anti-inflammatory properties. The pinhão extracts evaluated were obtained from cooking water (CW) and as an ethanolic extract from residual pinhão seed shells (PS). Catechin was the major compound found in both extracts. The PS extract presented higher antioxidant levels and the better inhibition of human salivary and porcine pancreatic α-amylases when compared to the CW extract. Also, based on in vivo evaluations, the PS extract did not differ significantly from acarbose when compared to a control group. The most potent inhibitor of cholinesterases was the CW extract. No cytotoxicity toward normal cells was detected, and neither extract showed anti-inflammatory activity. The PS extract presented cytotoxic activity toward non-small-cell lung, cervical, hepatocellular and breast carcinoma cell lines. Overall, the results demonstrated the potential bioactivity of extracts obtained from pinhão bioresidues.The authors thank CNPq (Chamada Universal – MCTI/CNPq No. 28/2018, Process 421541/2018-0) and Fundação Araucária (convênio 039/2019) for financial support. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001. The authors thank Central Analítica Multiusuário da UTFPR Campo Mourão (CAMulti-CM) for analysis. Project POCI-01-0145-FEDER-006984 – Associated Laboratory LSRE-LCM was funded by FEDER funds through COMPETE2020 – Programa Operacional Competitividade e Internacionalização (POCI) and by national funds through FCT – Fundação para a Ciência e a Tecnologia. The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES to CIMO (UIDB/00690/2020). M. I. Dias and L. Barros would like to acknowledge national funding from FCT, P. I., through the institutional scientific employment program-contract.info:eu-repo/semantics/publishedVersio

Decrease of CD68 Synovial Macrophages in Celastrol Treated Arthritic Rats

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease characterized by cellular infiltration into the joints, hyperproliferation of synovial cells and bone damage. Available treatments for RA only induce remission in around 30% of the patients, have important adverse effects and its use is limited by their high cost. Therefore, compounds that can control arthritis, with an acceptable safety profile and low production costs are still an unmet need. We have shown, in vitro, that celastrol inhibits both IL-1β and TNF, which play an important role in RA, and, in vivo, that celastrol has significant anti-inflammatory properties. Our main goal in this work was to test the effect of celastrol in the number of sublining CD68 macrophages (a biomarker of therapeutic response for novel RA treatments) and on the overall synovial tissue cellularity and joint structure in the adjuvant-induced rat model of arthritis (AIA).FCT fellowship: (SFRH/BPD/92860/2013)