Growth, photosynthetic pigments, phenolic content and biological activities of Foeniculum vulgare Mill., Anethum graveolens L. and Pimpinella anisum L. (Apiaceae) in response to zinc

The effect of zinc (Zn) on phenols, antioxidant activities (free radicals' scavenging activities, inhibition of lipid peroxidation, chelating activity and reducing power), and enzyme inhibition activities of acetylcholinesterase, lipoxygenase and tyrosinase of anise, dill and two cultivars of fennel [Latina" (F-L) and "Doux de Florence" (F-DF)] aqueous extracts was evaluated for the first time. At the same time, growth and photosynthetic pigment contents were also estimated. A significant decrease in all growth parameters, such as plant height, fresh and dry weights of aerial parts and roots was statistically proved in the presence of 2 mM Zn. An enhancement of Zn accumulation was observed, particularly in aerial part. Exposure to 2 mM Zn induced quantitative changes in the phenols of all tested extracts. In fennel extracts, a decrease of phenol content was observed when treated with Zn, whereas an increase was found in dill and anise extracts submitted to Zn treatment. All samples, either in the presence or absence of Zn, showed antioxidant activity, independent on the tested assay, with the exception of the cultivar F-DF (treated and non-treated), which was unable to scavenge NO radicals. Zn-treated dill and anise presented usually higher antioxidant activity. Concerning inhibitory activities against acetylcholinesterase, lipoxygenase and tyrosinase enzymes, both treated and non-treated F-DF did not inhibit acetylcholinesterase activity. Zinc-treated F-DF was also unable to inhibit lipoxygenase activity. The remaining species presented capacity for inhibiting those enzymes and tyrosinase as well, but their abilities varied in response to Zn excess.Portuguese National Funding Agency for Science, Research and Technology (Fundacao para a Ciencia e a Tecnologia - FCTPortugal) [UID/BIA/04325/2013-MEDTBIO, UID/Multi/04326/2013]info:eu-repo/semantics/publishedVersio

SATISFAÇÃO DOS CLIENTES DO SUPERMERCADO SÃO PAULO DO MUNICÍPIO DE ALFENAS NO SUL DE MINAS GERAIS

O tema da satisfação do consumidor vem sendo estudado desde os primórdios do marketing. O estudo pretende demonstrar o nível de satisfação e detectar pontos de insatisfação dos clientes com os serviços prestados pelo Supermercado São Paulo, procurando corrigir o que poderia estar errado e, conseqüentemente, oferecer um feedback sobre a opinião dos consumidores aos gestores deste supermercado em estudo.---------------------------------------------The objetive of this paper was to identify the satisfaction level from the Sâo Paulo, and more specifically, identify the consumers characteristics, analyze the possible insatisfactions from the services offered, analyze the satisfaction level fom the employers attendance service to customers and indentify if the custumers thinks it is necessary to include additional service in the market offer this organization.Satisfação, Consumidor, Supermercados, Satisfaction, Customer, Supermarket, Agribusiness,

Helminth Parasites From the Stomach of Conger Eel, Conger conger, From Madeira Island, Atlantic Ocean

Geographic variations in the diversity and prevalence of helminth parasites of fish call provide important clues as to the relatedness of fish populations. In the present work, the stomachs of 64 conger eels, Conger conger, collected during 1999 and 2000, were examined for the presence of parasites. Four fish were infected with L3 stages of the nematode Anisakis simplex s.l. (Anisakidae), 1 with the nematode Cristitectus congeri (Cystidicolidae), 1 with the acanthocephalan Rhadinorhynchus pristis, 17 with postlarvae of Sphyriocephalus tergestinus (Eucestoda: Trypanorhyncha), and 55 with Lecithochirium spp. (Digenea: Hemiuridae). The hemiurids were the most abundant parasites, with a total of 385 individuals recovered. Strong aggregated distributions were found for both the digeneans, Lecithochirium musculus and Lecithochirium fusiforme, with variance-to-mean ratios (s(2)/x) and index of discrepancy (D) 13.98 and 0.672 (for L. musculus) and 8.08 and 0.90 for L. fusiforme, respectively. Intensity of L. musculus, L. fusforme, and S. tergestinus showed significant relationships with depth of capture. Differences in number of species and prevalence were found between Madeira and the Atlantic coasts of the Iberian Peninsula

Non-Random Phases in Non-Trivial Topologies

We present a new technique for constraining the topology of the universe. The method exploits the existence of correlations in the phases of the spherical harmonic coefficients of the CMB temperature pattern associated with matched pairs of circles seen in the sky in universes with non-trivial topology. The method is computationally faster than all other statistics developed to hunt for these matched circles. We applied the method to a range of simulations with topologies of various forms and on different scales. A characteristic form of phase correlation is found in the simulations. We also applied the method to preliminary CMB maps derived from WMAP, but the separation of topological effects from, e.g., foregrounds is not straightforward.Comment: 5 pages, accepted for publication in MNRA

Therapeutic targeting of PD-1/PD-L1 blockade by novel small-molecule inhibitors recruits cytotoxic T cells into solid tumor microenvironment

© Author(s) (or their employer(s)) 2022.This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.Background: Inhibiting programmed cell death protein 1 (PD-1) or PD-ligand 1 (PD-L1) has shown exciting clinical outcomes in diverse human cancers. So far, only monoclonal antibodies are approved as PD-1/PD-L1 inhibitors. While significant clinical outcomes are observed on patients who respond to these therapeutics, a large proportion of the patients do not benefit from the currently available immune checkpoint inhibitors, which strongly emphasize the importance of developing new immunotherapeutic agents. Methods: In this study, we followed a transdisciplinary approach to discover novel small molecules that can modulate PD-1/PD-L1 interaction. To that end, we employed in silico analyses combined with in vitro, ex vivo, and in vivo experimental studies to assess the ability of novel compounds to modulate PD-1/PD-L1 interaction and enhance T-cell function. Results: Accordingly, in this study we report the identification of novel small molecules, which like anti-PD-L1/PD-1 antibodies, can stimulate human adaptive immune responses. Unlike these biological compounds, our newly-identified small molecules enabled an extensive infiltration of T lymphocytes into three-dimensional solid tumor models, and the recruitment of cytotoxic T lymphocytes to the tumor microenvironment in vivo, unveiling a unique potential to transform cancer immunotherapy. Conclusions: We identified a new promising family of small-molecule candidates that regulate the PD-L1/PD-1 signaling pathway, promoting an extensive infiltration of effector CD8 T cells to the tumor microenvironment.C and RCA are supported by the Fundação para a Ciência e a Tecnologia, Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES) (PhD grants PD/BD/128238/2016 (RCA) and SFRH/BD/131969/2017 (BC)). The authors thank the funding received from the European Structural & Investment Funds through the COMPETE Programme and from National Funds through FCT under the Programme grant LISBOA-01-0145-FEDER016405 - SAICTPAC/0019/2015 (HF and RCG). HFF and RCA received additional support from FCT-MCTES (UIDB/04138/2020, PTDC/BTM-SAL/4350/2021 and UTAPEXPL/NPN/0041/2021; EXPL/MED-QUI/1316/2021, respectively). The MultiNano@MBM project was supported by The Israeli Ministry of Health, and FCTMCTES, under the frame of EuroNanoMed-II (ENMed/0051/2016; HF and RS-F). HF and RS-F thank the generous financial support from ‘La Caixa’ Foundation under the framework of the Healthcare Research call 2019 (NanoPanther; LCF/PR/HR19/52160021), as well as CaixaImpulse (Co-Vax; LCF/TR/CD20/52700005). MP thanks the financial support from Liga Portuguesa Contra o Cancro – Nucleo Regional do Sul and ‘iNOVA4Health – UIDB/04462/2020’, a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência. RS-F thanks the following funding agencies for their generous support: the European Research Council (ERC) Advanced Grant Agreement No. (835227)–3DBrainStrom, ERC PoC Grant Agreement no. 862580 – 3DCanPredict, The Israel Science Foundation (Grant No. 1969/18), The Melanoma Research Alliance (MRA Established Investigator Award n°615808), the Israel Cancer Research Fund (ICRF) Professorship award (n° PROF-18-682), and the Morris Kahn Foundation.info:eu-repo/semantics/publishedVersio

Piperine decreases pilocarpine-induced convulsions by GABAergic mechanisms

Piperine, an alkaloid present in the Piper genus, was shown to have an anticonvulsant activity, evaluated by the pilocarpine-induced model, in mice. Pilocarpine (350 mg/kg, i.p.) was administered 30 min after piperine (2.5, 5, 10 and 20 mg/kg, i.p.) which significantly increased latencies to 1st convulsion and to death, and percentage of survivals. These parameters were also increased in the pilocarpine groups pretreated with atropine plus piperine (10 and 2.5 mg/kg, respectively), as related to the pilocarpine group. However, they were not altered in the pilocarpine groups pretreated with memantine (a NMDA-type glutamate receptors blocker, 2 mg/kg, p.o.) or nimodipine (a calcium channel blocker, 10 mg/kg, p.o.), both associated with piperine (1 or 2.5 mg/kg), as compared to the piperine plus pilocarpine group. Moreover, the pilocarpine group pretreated with diazepam (which binds to the GABA(A) receptor, 0.2 and 0.5 mg/kg, i.p.) plus piperine (1 and 2.5 mg/kg) significantly increased latency to the 1st convulsion, as related to the pilocarpine group, suggesting that the GABAergic system is involved with the piperine action. Furthermore, the piperine effect was blocked by flumazenil (2 mg/kg, i.p.), a benzodiazepine antagonist. Untreated P350 animals showed decreased striatal DA and increased DOPAC and HVA levels that were not affected in the piperine plus pilocarpine groups. Piperine increased striatal levels of GABA, glycine and taurine, and reversed pilocarpine-induced increases in nitrite contents in sera and brain. Hippocampi from the untreated pilocarpine group showed an increased number of TNF-alpha immunostained cells in all areas, as opposed to the pilocarpine group pretreated with piperine. Taken together, piperine anticonvulsant effects are the result of its anti-inflammatory and antioxidant actions, as well as TNF-alpha reduction. in addition, piperine effects on inhibitory amino acids and on the GABAergic system may certainly contribute to the drug anticonvulsant activity. (C) 2013 Elsevier Inc. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)FMJ, Fac Med Estacio Juazeiro Norte, Fortaleza, Ceara, BrazilUniversidade Federal de São Paulo, UNIFESP, São Paulo, BrazilUniv Fed Ceara, Fac Med, UFC, Fortaleza, Ceara, BrazilUniversidade Federal de São Paulo, UNIFESP, São Paulo, BrazilWeb of Scienc

Effectiveness and long-term retention of anti-tumour necrosis factor treatment in juvenile and adult patients with juvenile idiopathic arthritis: data from Reuma.pt

Methods. We prospectively collected patient and disease characteristics from patients with JIA who started biological therapy. Adverse events were collected during the follow-up period. Predictors of response at 1 year and drug retention rates were assessed at 4 years of treatment for the first biologic agent.Results. A total of 812 JIA patients [65% females, mean age at JIA onset 6.9 years (s.d. 4.7)], 227 received biologic therapy; 205 patients (90.3%) were treated with an anti-TNF as the first biologic. All the parameters used to evaluate disease activity, namely number of active joints, ESR and Childhood HAQ/HAQ, decreased significantly at 6 months and 1 year of treatment. The mean reduction in Juvenile Disease Activity Score 10 (JADAS10) after 1 year of treatment was 10.4 (s.d. 7.4). According to the definition of improvement using the JADAS10 score, 83.3% respond to biologic therapy after 1 year. Fourteen patients discontinued biologic therapies due to adverse events. Retention rates were 92.9% at 1 year, 85.5% at 2 years, 78.4% at 3 years and 68.1% at 4 years of treatment. Among all JIA subtypes, only concomitant therapy with corticosteroids was found to be univariately associated with withdrawal of biologic treatment (P = 0.016).Conclusion. Biologic therapies seem effective and safe in patients with JIA. In addition, the retention rates for the first biologic agent are high throughout 4 years

description of the methodological approach

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