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1.
Oncol Ther ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38836997

ABSTRACT

INTRODUCTION: Biological monoclonal antibodies play a pivotal role in cancer treatment, with biosimilars significantly enhancing their accessibility. In Brazil's ethnically diverse setting, real-world evidence is crucial for assessing the effectiveness and applicability of these therapies in routine clinical practice. METHODS: We performed a multicentric, observational, prospective real-world study on biosimilar trastuzumab-dkst for adjuvant treatment of early HER2-positive breast cancer in Brazilian patients. Data were collected using a case-report form. RESULTS: Of the 176 recruited, we present data from the first 59 patients (mean age 51.7 ± 12.9 years) who had completed treatment with trastuzumab-dkst. The mean time from diagnosis to the first adjuvant treatment with trastuzumab-dkst was 5.5 ± 2.7 months. Of the patients, 59% of patients achieved at least a 30-month follow-up. The 31.7-month invasive disease-free survival rate (IDFS) was 94.5% (95% CI 83.9-98.2%) and median IDFS was not achieved, since only three patients had invasive disease recurrence. The overall survival rate was 100% until the last assessment. The observed adverse events were similar to those presented by other studies using biosimilar or reference trastuzumab. Four serious adverse events (8.5%) were observed. A reduction in left ventricular ejection fraction of at least 10% was observed in 16.9% of participants. There was no treatment interruption, and three participants (5.1%) had their trastuzumab-dkst dose reduced. CONCLUSION: Our study reinforces the existing pivotal data, underscoring the real-world efficacy and safety of biosimilar trastuzumab-dkst in the adjuvant treatment for early HER2-positive breast cancer. The preliminary long-term effectiveness and safety data we present further validate trastuzumab-dkst's role as a cost-saving alternative in oncological care. These findings have important implications for improving patient access to crucial treatments and for the more efficient use of healthcare resources. GOV REGISTRATION: NCT03892655.

2.
Sci Rep ; 14(1): 2572, 2024 01 31.
Article in English | MEDLINE | ID: mdl-38296985

ABSTRACT

Bacterial caseinolytic protease P subunit (ClpP) is important and vital for cell survival and infectivity. Recent publications describe and discuss the complex structure-function relationship of ClpP and its processive activity mediated by 14 catalytic sites. Even so, there are several aspects yet to be further elucidated, such as the paradoxical allosteric modulation of ClpP by peptidomimetic boronates. These compounds bind to all catalytic sites, and in specific conditions, they stimulate a dysregulated degradation of peptides and globular proteins, instead of inhibiting the enzymatic activity, as expected for serine proteases in general. Aiming to explore and explain this paradoxical effect, we solved and refined the crystal structure of native ClpP from Staphylococcus epidermidis (Se), an opportunistic pathogen involved in nosocomial infections, as well as ClpP in complex with ixazomib at 1.90 Å and 2.33 Å resolution, respectively. The interpretation of the crystal structures, in combination with complementary biochemical and biophysical data, shed light on how ixazomib affects the ClpP conformational state and activity. Moreover, SEC-SAXS and DLS measurements show, for the first time, that a peptidomimetic boronate compound also induces the assembly of the tetradecameric structure from isolated homomeric heptameric rings of a gram-positive organism.


Subject(s)
Glycine/analogs & derivatives , Peptidomimetics , Peptidomimetics/pharmacology , Scattering, Small Angle , X-Ray Diffraction , Boron Compounds/pharmacology , Boron Compounds/metabolism , Endopeptidase Clp/metabolism , Bacterial Proteins/metabolism
3.
Braz Oral Res ; 37: e002, 2023.
Article in English | MEDLINE | ID: mdl-36629588

ABSTRACT

Protease-activated receptor-2 (PAR2) is associated with the pathogenesis of many chronic diseases with inflammatory characteristics, including periodontitis. This study aimed to evaluate how the activation of PAR2 can affect the osteogenic activity of human periodontal ligament stem cells (PDLSCs) in vitro. PDLSCs collected from three subjects were treated in osteogenic medium for 2, 7, 14, and 21 days with trypsin (0.1 U/mL), PAR2 specific agonist peptide (SLIGRL-NH2) (100 nM), and PAR2 antagonist peptide (FSLLRY-NH2) (100 nM). Gene (RT-qPCR) expression and protein expression (ELISA) of osteogenic factors, bone metabolism, and inflammatory cytokines, cell proliferation, alkaline phosphatase (ALP) activity, alizarin red S staining, and supernatant concentration were assessed. Statistical analysis of the results with a significance level of 5% was performed. Activation of PAR2 led to decreases in cell proliferation and calcium deposition (p < 0.05), calcium concentration (p < 0.05), and ALP activity (p < 0.05). Additionally, PAR2 activation increased gene and protein expression of receptor activator of nuclear factor kappa-Β ligand (RANKL) (p < 0.05) and significantly decreased the gene and protein expression of osteoprotegerin (p <0. 05). Considering the findings, the present study demonstrated PAR2 activation was able to decrease cell proliferation, decreased osteogenic activity of PDLSCs, and upregulated conditions for bone resorption. PAR2 may be considered a promising target in periodontal regenerative procedures.


Subject(s)
Osteogenesis , Periodontal Ligament , Humans , Cell Differentiation , Receptor, PAR-2/metabolism , Calcium , Stem Cells , Cell Proliferation , Cells, Cultured
4.
Braz. oral res. (Online) ; 37: e002, 2023. graf
Article in English | LILACS-Express | LILACS, BBO - Dentistry | ID: biblio-1420947

ABSTRACT

Abstract Protease-activated receptor-2 (PAR2) is associated with the pathogenesis of many chronic diseases with inflammatory characteristics, including periodontitis. This study aimed to evaluate how the activation of PAR2 can affect the osteogenic activity of human periodontal ligament stem cells (PDLSCs) in vitro. PDLSCs collected from three subjects were treated in osteogenic medium for 2, 7, 14, and 21 days with trypsin (0.1 U/mL), PAR2 specific agonist peptide (SLIGRL-NH2) (100 nM), and PAR2 antagonist peptide (FSLLRY-NH2) (100 nM). Gene (RT-qPCR) expression and protein expression (ELISA) of osteogenic factors, bone metabolism, and inflammatory cytokines, cell proliferation, alkaline phosphatase (ALP) activity, alizarin red S staining, and supernatant concentration were assessed. Statistical analysis of the results with a significance level of 5% was performed. Activation of PAR2 led to decreases in cell proliferation and calcium deposition (p < 0.05), calcium concentration (p < 0.05), and ALP activity (p < 0.05). Additionally, PAR2 activation increased gene and protein expression of receptor activator of nuclear factor kappa-Β ligand (RANKL) (p < 0.05) and significantly decreased the gene and protein expression of osteoprotegerin (p <0. 05). Considering the findings, the present study demonstrated PAR2 activation was able to decrease cell proliferation, decreased osteogenic activity of PDLSCs, and upregulated conditions for bone resorption. PAR2 may be considered a promising target in periodontal regenerative procedures.

5.
Commun Biol ; 5(1): 805, 2022 08 11.
Article in English | MEDLINE | ID: mdl-35953531

ABSTRACT

SARS-CoV-2 papain-like protease (PLpro) covers multiple functions. Beside the cysteine-protease activity, facilitating cleavage of the viral polypeptide chain, PLpro has the additional and vital function of removing ubiquitin and ISG15 (Interferon-stimulated gene 15) from host-cell proteins to support coronaviruses in evading the host's innate immune responses. We identified three phenolic compounds bound to PLpro, preventing essential molecular interactions to ISG15 by screening a natural compound library. The compounds identified by X-ray screening and complexed to PLpro demonstrate clear inhibition of PLpro in a deISGylation activity assay. Two compounds exhibit distinct antiviral activity in Vero cell line assays and one inhibited a cytopathic effect in non-cytotoxic concentration ranges. In the context of increasing PLpro mutations in the evolving new variants of SARS-CoV-2, the natural compounds we identified may also reinstate the antiviral immune response processes of the host that are down-regulated in COVID-19 infections.


Subject(s)
Antiviral Agents , COVID-19 Drug Treatment , Allosteric Site , Antiviral Agents/pharmacology , Coronavirus Papain-Like Proteases , Humans , Papain/metabolism , Peptide Hydrolases/metabolism , SARS-CoV-2
6.
Braz Oral Res ; 36: e048, 2022.
Article in English | MEDLINE | ID: mdl-35442377

ABSTRACT

PAR1 is a G-coupled protein receptor that regulates several cellular metabolism processes, including differentiation and proliferation of osteogenic and cementogenic related cells and our group previously demonstrated the regenerative potential of PAR1 in human periodontal ligament stem cells (hPDLSCs). In this study, we hypothesized that PAR1 regulates the cementogenic differentiation of hPDLSCs. Our goal was to identify the intracellular signaling pathway underlying PAR1 activation in hPDSLC differentiation. hPDLSCs were isolated using the explant technique. Cells were cultured in an osteogenic medium (OST) (α-MEM, 15% fetal bovine serum, L-glutamine, penicillin, streptomycin, amphotericin B, dexamethasone, and beta-glycerophosphate). The hPDLSCs were treated with a specific activator of PAR1 (PAR1 agonist) and blockers of the MAPK/ERK and PI3K pathways for 2 and 7 days. The gene expression of CEMP1 was assessed by RT-qPCR. The activation of PAR1 by its agonist peptide led to an increase in CEMP1 gene expression when compared with OST control. MAPK/ERK blockage abrogated the upregulation of CEMP1 gene expression induced by PAR1 agonist (p < 0.05). PI3K blockage did not affect the gene expression of CEMP1 at any experimental time (p > 0.05). We concluded that CEMP1 gene expression increased by PAR1 activation is MAPK/ERK-dependent and PI3K independent, suggesting that PAR1 may regulate cementogenetic differentiation of hPDLSCs.


Subject(s)
MAP Kinase Signaling System , Receptor, PAR-1 , Cell Differentiation , Cells, Cultured , Gene Expression , Humans , Osteogenesis , Periodontal Ligament , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proteins , Receptor, PAR-1/genetics , Receptor, PAR-1/metabolism
7.
Braz. oral res. (Online) ; 36: e048, 2022. graf
Article in English | LILACS-Express | LILACS, BBO - Dentistry | ID: biblio-1374752

ABSTRACT

Abstract: PAR1 is a G-coupled protein receptor that regulates several cellular metabolism processes, including differentiation and proliferation of osteogenic and cementogenic related cells and our group previously demonstrated the regenerative potential of PAR1 in human periodontal ligament stem cells (hPDLSCs). In this study, we hypothesized that PAR1 regulates the cementogenic differentiation of hPDLSCs. Our goal was to identify the intracellular signaling pathway underlying PAR1 activation in hPDSLC differentiation. hPDLSCs were isolated using the explant technique. Cells were cultured in an osteogenic medium (OST) (α-MEM, 15% fetal bovine serum, L-glutamine, penicillin, streptomycin, amphotericin B, dexamethasone, and beta-glycerophosphate). The hPDLSCs were treated with a specific activator of PAR1 (PAR1 agonist) and blockers of the MAPK/ERK and PI3K pathways for 2 and 7 days. The gene expression of CEMP1 was assessed by RT-qPCR. The activation of PAR1 by its agonist peptide led to an increase in CEMP1 gene expression when compared with OST control. MAPK/ERK blockage abrogated the upregulation of CEMP1 gene expression induced by PAR1 agonist (p < 0.05). PI3K blockage did not affect the gene expression of CEMP1 at any experimental time (p > 0.05). We concluded that CEMP1 gene expression increased by PAR1 activation is MAPK/ERK-dependent and PI3K independent, suggesting that PAR1 may regulate cementogenetic differentiation of hPDLSCs.

8.
World J Stem Cells ; 13(6): 605-618, 2021 Jun 26.
Article in English | MEDLINE | ID: mdl-34249230

ABSTRACT

Inflammatory periodontal disease known as periodontitis is one of the most common conditions that affect human teeth and often leads to tooth loss. Due to the complexity of the periodontium, which is composed of several tissues, its regeneration and subsequent return to a homeostatic state is challenging with the therapies currently available. Cellular therapy is increasingly becoming an alternative in regenerative medicine/dentistry, especially therapies using mesenchymal stem cells, as they can be isolated from a myriad of tissues. Periodontal ligament stem cells (PDLSCs) are probably the most adequate to be used as a cell source with the aim of regenerating the periodontium. Biological insights have also highlighted PDLSCs as promising immunomodulator agents. In this review, we explore the state of knowledge regarding the properties of PDLSCs, as well as their therapeutic potential, describing current and future clinical applications based on tissue engineering techniques.

9.
Science ; 372(6542): 642-646, 2021 05 07.
Article in English | MEDLINE | ID: mdl-33811162

ABSTRACT

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput x-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (Mpro), which is essential for viral replication. In contrast to commonly applied x-ray fragment screening experiments with molecules of low complexity, our screen tested already-approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to Mpro In subsequent cell-based viral reduction assays, one peptidomimetic and six nonpeptidic compounds showed antiviral activity at nontoxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2.


Subject(s)
Allosteric Site , Antiviral Agents/chemistry , Catalytic Domain , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/chemistry , Drug Development , Protease Inhibitors/chemistry , SARS-CoV-2/enzymology , Animals , Antiviral Agents/pharmacology , Chlorocebus aethiops , Crystallography, X-Ray , Drug Evaluation, Preclinical , Protease Inhibitors/pharmacology , SARS-CoV-2/drug effects , Vero Cells , Virus Replication/drug effects
10.
Carbohydr Polym ; 260: 117814, 2021 May 15.
Article in English | MEDLINE | ID: mdl-33712158

ABSTRACT

Lytic polysaccharide monooxygenases (LPMOs), monocopper enzymes that oxidatively cleave recalcitrant polysaccharides, have important biotechnological applications. Thermothelomyces thermophilus is a rich source of biomass-active enzymes, including many members from auxiliary activities family 9 LPMOs. Here, we report biochemical and structural characterization of recombinant TtLPMO9H which oxidizes cellulose at the C1 and C4 positions and shows enhanced activity in light-driven catalysis assays. TtLPMO9H also shows activity against xyloglucan. The addition of TtLPMO9H to endoglucanases from four different glucoside hydrolase families (GH5, GH12, GH45 and GH7) revealed that the product formation was remarkably increased when TtLPMO9H was combined with GH7 endoglucanase. Finally, we determind the first low resolution small-angle X-ray scattering model of the two-domain TtLPMO9H in solution that shows relative positions of its two functional domains and a conformation of the linker peptide, which can be relevant for the catalytic oxidation of cellulose and xyloglucan.


Subject(s)
Cellulases/metabolism , Cellulose/metabolism , Enzyme Activation/radiation effects , Fungal Proteins/metabolism , Light , Mixed Function Oxygenases/metabolism , Sordariales/enzymology , Biomass , Catalysis , Cellulose/chemistry , Fungal Proteins/chemistry , Fungal Proteins/classification , Fungal Proteins/genetics , Glucans/chemistry , Glucans/metabolism , Mixed Function Oxygenases/chemistry , Mixed Function Oxygenases/classification , Mixed Function Oxygenases/genetics , Oxidation-Reduction , Phylogeny , Protein Domains , Recombinant Proteins/biosynthesis , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , Scattering, Small Angle , Stereoisomerism , Substrate Specificity , X-Ray Diffraction , Xylans/chemistry , Xylans/metabolism
11.
Appl Microbiol Biotechnol ; 104(19): 8309-8326, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32813063

ABSTRACT

Arabinanases from glycoside hydrolase family GH93 are enzymes with exo-activity that hydrolyze the α-1,5 bonds between arabinose residues present on arabinan. Currently, several initiatives aiming to use byproducts rich in arabinan such as pectin and sugar beet pulp as raw material to produce various compounds of interest are being developed. However, it is necessary to use robust enzymes that have an optimal performance under pH and temperature conditions used in the industrial processes. In this work, the first GH93 from the thermophilic fungus Thermothielavioides terrestris (Abn93T) was heterologously expressed in Aspergillus nidulans, purified and biochemically characterized. The enzyme is a thermophilic glycoprotein (optimum activity at 70 °C) with prolonged stability in acid pHs (4.0 to 6.5). The presence of glycosylation affected slightly the hydrolytic capacity of the enzyme, which was further increased by 34% in the presence of 1 mM CoCl2. Small-angle X-ray scattering results show that Abn93T is a globular-like-shaped protein with a slight bulge at one end. The hydrolytic mechanism of the enzyme was elucidated using capillary zone electrophoresis and molecular docking calculations. Abn93T has an ability to produce (in synergism with arabinofuranosidases) arabinose and arabinobiose from sugar beet arabinan, which can be explored as fermentable sugars and prebiotics. KEY POINTS: • Thermophilic exo-arabinanase from family GH93 • Molecular basis of arabinan depolymerization.


Subject(s)
Arabinose , Glycoside Hydrolases , Glycoside Hydrolases/genetics , Glycoside Hydrolases/metabolism , Molecular Docking Simulation , Sordariales , Substrate Specificity
12.
Sci Total Environ ; 729: 139085, 2020 Aug 10.
Article in English | MEDLINE | ID: mdl-32361428

ABSTRACT

The first COVID-19 case in Brazil was confirmed on February 25, 2020. On March 16, the state's governor declared public health emergency in the city of Rio de Janeiro and partial lockdown measures came into force a week later. The main goal of this work is to discuss the impact of the measures on the air quality of the city by comparing the particulate matter, carbon monoxide, nitrogen dioxide and ozone concentrations determined during the partial lockdown with values obtained in the same period of 2019 and also with the weeks prior to the virus outbreak. Concentrations varied with substantial differences among pollutants and also among the three studied monitoring stations. CO levels showed the most significant reductions (30.3-48.5%) since they were related to light-duty vehicular emissions. NO2 also showed reductions while PM10 levels were only reduced in the first lockdown week. In April, an increase in vehicular flux and movement of people was observed mainly as a consequence of the lack of consensus about the importance and need of social distancing and lockdown. Ozone concentrations increased probably due to the decrease in nitrogen oxides level. When comparing with the same period of 2019, NO2 and CO median values were 24.1-32.9 and 37.0-43.6% lower. Meteorological interferences, mainly the transport of pollutants from the industrial areas might have also impacted the results.


Subject(s)
Air Pollutants , Air Pollution , Betacoronavirus , Brazil , COVID-19 , Carbon Monoxide , Cities , Coronavirus Infections , Environmental Monitoring , Humans , Nitrogen Dioxide , Ozone , Pandemics , Particulate Matter , Pneumonia, Viral , SARS-CoV-2 , Sulfur Dioxide
13.
Nagy‐Reis, Mariana B.; Oshima, Júlia Emi de Faria; Kanda, Claudia Zukeran; Palmeira, Francesca Belem Lopes; Melo, Fabiano Rodrigues de; Morato, Ronaldo Gonçalves; Bonjorne, Lilian; Magioli, Marcelo; Leuchtenberger, Caroline; Rohe, Fabio; Lemos, Frederico Gemesio; Martello, Felipe; Alves‐Eigenheer, Milene; Silva, Rafaela Aparecida da; Santos, Juliana Silveira dos; Priante, Camila Fátima; Bernardo, Rodrigo; Rogeri, Patricia; Assis, Julia Camara; Gaspar, Lucas Pacciullio; Tonetti, Vinicius Rodrigues; Trinca, Cristiano Trapé; Ribeiro, Adauto de Souza; Bocchiglieri, Adriana; Hass, Adriani; Canteri, Adriano; Chiarello, Adriano Garcia; Paglia, Adriano Pereira; Pereira, Adriele Aparecida; Souza, Agnis Cristiane de; Gatica, Ailin; Medeiro, Akyllam Zoppi; Eriksson, Alan; Costa, Alan Nilo; González‐Gallina, Alberto; Yanosky, Alberto A; Cruz, Alejandro Jesus de la; Bertassoni, Alessandra; Bager, Alex; Bovo, Alex Augusto Abreu; Mol, Alexandra Cravino; Bezerra, Alexandra Maria Ramos; Percequillo, Alexandre; Vogliotti, Alexandre; Lopes, Alexandre Martins Costa; Keuroghlian, Alexine; Hartley, Alfonso Christopher Zúñiga; Devlin, Allison L.; Paula, Almir de; García‐Olaechea, Alvaro; Sánchez, Amadeo; Aquino, Ana Carla Medeiros Morato; Srbek‐Araujo, Ana Carolina; Ochoa, Ana Cecilia; Tomazzoni, Ana Cristina; Lacerda, Ana Cristyna Reis; Bacellar, Ana Elisa de Faria; Campelo, Ana Kellen Nogueira; Victoria, Ana María Herrera; Paschoal, Ana Maria de Oliveira; Potrich, Ana Paula; Gomes, Ana Paula Nascimento; Olímpio, Ana Priscila Medeiros; Costa, Ana Raissa Cunha; Jácomo, Anah Tereza de Almeida; Calaça, Analice Maria; Jesus, Anamélia Souza; Barban, Ananda de Barros; Feijó, Anderson; Pagoto, Anderson; Rolim, Anderson Claudino; Hermann, Andiara Paula; Souza, Andiara Silos Moraes de Castro e; Alonso, André Chein; Monteiro, André; Mendonça, André Faria; Luza, André Luís; Moura, André Luis Botelho; Silva, André Luiz Ferreira da; Lanna, Andre Monnerat; Antunes, Andre Pinassi; Nunes, André Valle; Dechner, Andrea; Carvalho, Andrea Siqueira; Novaro, Andres Jose; Scabin, Andressa Barbara; Gatti, Andressa; Nobre, Andrezza Bellotto; Montanarin, Anelise; Deffaci, Ângela Camila; Albuquerque, Anna Carolina Figueiredo de; Mangione, Antonio Marcelo; Pinto, Antonio Millas Silva; Pontes, Antonio Rossano Mendes; Bertoldi, Ariane Teixeira; Calouro, Armando Muniz; Fernandes, Arthur; Ferreira, Arystene Nicodemo; Ferreguetti, Atilla Colombo; Rosa, Augusto Lisboa Martins; Banhos, Aureo; Francisco, Beatriz da Silva de Souza; Cezila, Beatriz Azevedo; Beisiegel, Beatriz de Mello; Thoisy, Benoit de; Ingberman, Bianca; Neves, Bianca dos Santos; Pereira‐Silva, Brenda; Camargo, Bruna Bertagni de; Andrade, Bruna da Silva; Santos, Bruna Silva; Leles, Bruno; Campos, Bruno Augusto Torres Parahyba; Kubiak, Bruno Busnello; França, Bruno Rodrigo de Albuquerque; Saranholi, Bruno Henrique; Mendes, Calebe Pereira; Devids, Camila Cantagallo; Pianca, Camila; Rodrigues, Camila; Islas, Camila Alvez; Lima, Camilla Angélica de; Lima, Camilo Ribeiro de; Gestich, Carla Cristina; Tedesco, Carla Denise; Angelo, Carlos De; Fonseca, Carlos; Hass, Carlos; Peres, Carlos A.; Kasper, Carlos Benhur; Durigan, Carlos Cesar; Fragoso, Carlos Eduardo; Verona, Carlos Eduardo; Rocha, Carlos Frederico Duarte; Salvador, Carlos Henrique; Vieira, Carlos Leonardo; Ruiz, Carmen Elena Barragán; Cheida, Carolina Carvalho; Sartor, Caroline Charão; Espinosa, Caroline da Costa; Fieker, Carolline Zatta; Braga, Caryne; Sánchez‐Lalinde, Catalina; Machado, Cauanne Iglesias Campos; Cronemberger, Cecilia; Luna, Cecília Licarião; Vechio, Christine Del; Bernardo, Christine Steiner S.; Hurtado, Cindy Meliza; Lopes, Cíntia M.; Rosa, Clarissa Alves da; Cinta, Claudia Cristina; Costa, Claudia Guimaraes; Zárate‐Castañeda, Claudia Paola; Novaes, Claudio Leite; Jenkins, Clinton N.; Seixas, Cristiana Simão; Martin, Cristiane; Zaniratto, Cristiane Patrícia; López‐Fuerte, Cristina Fabiola; Cunha, Cristina Jaques da; Brito De‐Carvalho, Crizanto; Chávez, Cuauhtémoc; Santos, Cyntia Cavalcante; Polli, Daiana Jeronimo; Buscariol, Daiane; Carreira, Daiane Cristina; Galiano, Daniel; Thornton, Daniel; Ferraz, Daniel da Silva; Lamattina, Daniela; Moreno, Daniele Janina; Moreira, Danielle Oliveira; Farias, Danilo Augusto; Barros‐Battesti, Darci Moraes; Tavares, Davi Castro; Braga, David Costa; Gaspar, Denise Alemar; Friedeberg, Diana; Astúa, Diego; Silva, Diego Afonso; Viana, Diego Carvalho; Lizcano, Diego J.; Varela, Diego M.; Jacinavicius, Fernando de Castro; Andrade, Gabrielle Ribeiro de; Almeida, Maria Cristina Ferreira do Rosário; Onofrio, Valeria Castilho.
Ecology, v. 101, n. 11, e03128, nov. 2020
Article in English | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-3174

ABSTRACT

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non‐detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non‐governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peerreviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non‐detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio‐temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other largescale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data.

14.
São Paulo; s.n; 20200000. 95 p.
Thesis in Portuguese | LILACS, BBO - Dentistry | ID: biblio-1119585

ABSTRACT

O receptor ativado por protease do tipo 2 (PAR-2) está associado à patogênese de doenças inflamatórias crônicas, incluindo periodontite, e a ativação do PAR-2 desempenha papel relevante no processo inflamatório. O objetivo do presente estudo foi avaliar o efeito da ativação do PAR-2 na atividade osteogênica de células-tronco do ligamento periodontal humano (PDLSCs). PDLSCs obtidos de 3 sujeitos foram cultivados em meio controle ou em meio osteogênico por 2, 7, 14 e 21 dias. Proliferação celular, atividade da fosfatase alcalina (ALP), expressão gênica (qPCR) e expressão proteica (ensaio ELISA) de fatores osteogênicos e depósitos de cálcio, concentração de cálcio (sobrenadante) foram avaliados na presença de tripsina (0,1 U/ml), peptídeo agonista de PAR-2 (100nM), peptídeo antagonista de PAR-2 (100 nM) e peptídeo controle de PAR-2. A ativação do PAR-2 levou à alteração na proliferação celular, diminuição na formação de depósitos de cálcio (p <0,05), na concentração de cálcio (p<0,05) e atividade da ALP (p <0,05). Além disso, os ensaios de qPCR e ELISA mostraram que a ativação de PAR-2 pode aumentar a expressão gênica e protéica de RANKL (p<0,05) e diminuir a expressão gênica e proteica de OPG (p<0,05). Os resultados do presente estudo demonstram que a ativação do PAR-2 aumenta a proliferação e diminuem a atividade osteogênica dos PDLSCs, indicando que o PAR-2 pode ser um alvo importante a ser considerado no uso de células mesenquimais do ligamento periodontal em procedimentos regenerativos em periodontia.


Subject(s)
Mesenchymal Stem Cells
15.
Stem Cells Int ; 2019: 6857386, 2019.
Article in English | MEDLINE | ID: mdl-31281381

ABSTRACT

Protease-activated receptor 1 (PAR1) has been associated to tissue repair and bone healing. The aim of the present study was to evaluate the effect of PAR1 activation on the osteogenic activity of human periodontal ligament stem cells (PDLSCs). PDLSCs were cultured in the presence of PAR1-selective agonist peptide (100 nM), thrombin (0.1 U/mL), or PAR1 antagonist peptide (100 nM). Calcium deposits, calcium concentration (supernatant), alkaline phosphatase activity (ALP), cell proliferation, and gene (qPCR) and protein expression (ELISA assay) of osteogenic factors were assessed at 2, 7, and 14 days. PAR1 activation led to increased calcium deposits (p < 0.05), calcium concentration (p < 0.05), ALP activity (p < 0.05), and cell proliferation (p < 0.05). Further, PAR1 activation may increase gene and protein expression of Runx2 (p < 0.05) and OPG (p < 0.05). In conclusion, PAR1 activation increases osteogenic activity of PDLSCs, providing a possible new strategy for periodontal regenerative therapies.

16.
Environ Monit Assess ; 191(6): 369, 2019 May 16.
Article in English | MEDLINE | ID: mdl-31093831

ABSTRACT

In 2009, the city of Rio de Janeiro was announced as the host city of the 2016 Olympic Games (Rio 2016). For this event, the Brazilian government, in partnership with the International Olympic Committee (IOC), undertook the task of monitoring the air quality in the city. This study discusses the PM10, PM2.5, and O3 profiles at ten sampling sites located near the arenas in 2016, including during the Olympic Games period. At all sampling stations, the annual mean values of PM10 and PM2.5 were below either Brazilian air quality standards or United States Environmental Protection Agency (U.S. EPA) guidelines. In addition, no violations lasting 24 h were observed for particulate matter in 2016. Only two ozone episodes occurred in 2016, both in Campos dos Afonsos (163 and 195 µg m-3) near the extreme sports arena. However, during the pre-Olympic period (2013-2015), in the same area were registered 16, 81, and 18 violations per year, respectively. The results showed an improvement in air quality in Rio de Janeiro in 2016. The reduction in pollutant levels, especially O3 and PM2.5, is probably due to the conclusion of the structural construction of the Olympic arenas and efforts to improve urban mobility.


Subject(s)
Air Pollutants/analysis , Air Pollution/analysis , Environmental Monitoring/methods , Ozone/analysis , Particulate Matter/analysis , Sports , Brazil , Guidelines as Topic , Humans , United States , United States Environmental Protection Agency
17.
J Periodontol ; 89(12): 1383-1389, 2018 12.
Article in English | MEDLINE | ID: mdl-30005127

ABSTRACT

BACKGROUND: This study aimed to compare the periodontal status of liver transplant candidates (LTCs) with healthy controls. METHODS: Fifty liver transplant candidates (LTC group) and fifty patients without liver disease (control group) underwent a complete periodontal examination. The groups were matched according to sex, age, and smoking status. A structured questionnaire was applied to record demographic data, systemic health, and information related to liver disease. Full-mouth complete periodontal examination of six sites per tooth was performed: gingival recession (GR), probing depth (PD), attachment loss (AL), bleeding on probing (BOP), and visible plaque index (VPI). The groups were compared in regard to periodontal clinical variables. RESULTS: Patients with cirrhosis had greater prevalence of periodontitis than healthy controls (P < 0.001). In addition, they had greater mean percentage of sites with AL ≥3 mm (P = 0.008) and AL ≥5 mm (P = 0.023), greater mean AL (P = 0.003), greater mean gingival recession (P < 0.001), and more missing teeth than in the control group (P = 0.02). CONCLUSION: Liver transplant candidates presented greater prevalence, extent, and severity of periodontitis than matched control patients.


Subject(s)
Gingival Recession , Liver Transplantation , Periodontitis , Dental Plaque Index , Gingival Hemorrhage , Humans , Periodontal Attachment Loss , Periodontal Index
18.
Eur J Cancer ; 88: 21-30, 2018 01.
Article in English | MEDLINE | ID: mdl-29179134

ABSTRACT

PURPOSE: Chemoradiotherapy is the standard treatment for patients with inoperable locally advanced oesophageal cancer. We sought to assess the safety and efficacy of chemoradiation combined with nimotuzumab, a humanised antibody directed against epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: Untreated patients with inoperable locally advanced oesophageal cancer and no distant metastases were randomised to chemoradiotherapy (cisplatin and fluorouracil combined with external beam radiation) alone or in combination with nimotuzumab. The primary end-point was the endoscopic complete response (eCR) rate, and secondary end-points comprised quality of life (QoL) and safety. The combined eCR and pathologic complete response (cEPCR) and overall survival (OS) were also evaluated. RESULTS: We enrolled 107 patients with a mean age of 59 years, and 93% had squamous cell carcinoma. Toxicity was manageable in both arms with no important differences in adverse events (AEs). We performed post-treatment endoscopies in 67 patients, including 60 who had a biopsy. In the intent-to-treat population, the eCR rates with and without nimotuzumab were 47.2% and 33.3% (P = 0.17), respectively, and the cEPCR rates were 62.3% and 37.0% (P = 0.02), respectively. With a median follow-up of 14.7 months, the hazard ratio (HR) for OS was 0.68 (95% confidence interval (CI): 0.44-1.07; P = 0.09) with a median OS of 15.9 months for the nimotuzumab arm and 11.5 months for the control arm. Regarding QoL, a significant difference was observed for the physical subscale score (P = 0.03) with lower values for the control arm. CONCLUSION: Combined chemoradiotherapy plus nimotuzumab is safe for patients with locally advanced oesophageal cancer, it appears to increase the cEPCR rate, and without compromising QoL. CLINICAL TRIALS: Identification number: EF024-201; Trial registry: NCT01249352.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Esophageal Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Anemia/etiology , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Cisplatin/administration & dosage , Cisplatin/adverse effects , Esophageal Neoplasms/pathology , Fatigue/etiology , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Male , Middle Aged , Quality of Life , Survival Analysis
19.
Braz Oral Res ; 31: e8, 2017 01 16.
Article in English | MEDLINE | ID: mdl-28099577

ABSTRACT

The aim of this longitudinal prospective study was to evaluate the effects of periodontal treatment on the clinical, microbiological and immunological periodontal parameters, and on the systemic activity (ESSDAI) and subjective (ESSPRI) indexes in patients with primary Sjögren's Syndrome (pSS). Twenty-eight female patients were divided into four groups: pSS patients with or without chronic periodontitis (SCP, SC, respectively), and systemically healthy patients with or without chronic periodontitis (CP, C, respectively). Periodontal clinical examination and immunological and microbiological sample collection were performed at baseline, 30 and 90 days after nonsurgical periodontal treatment (NSPT). Levels of interleukin IL-1ß, IL-8 and IL-10 in saliva and gingival crevicular fluid (GCF) were evaluated by ELISA, as well as the expression of Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans, (Aa) Tannerella forsythia (Tf), and Treponema denticola (Td), by qPCR. Systemic activity and pSS symptoms were evaluated by ESSDAI and ESSPRI. NSPT resulted in improved periodontal clinical parameters in both SCP and CP groups (p>0.05). Pg, Aa, and Tf levels decreased after NSPT only in CP patients (p<0.05). Significantly greater levels of IL-10 in GCF were verified in both SCP and CP groups (p<0.05). SCP patients showed increased salivary flow rates and decreased ESSPRI scores after NSPT. In conclusion, NSPT in pSS patients resulted in improved clinical and immunological parameters, with no significant effects on microbiological status. pSS patients also showed increased salivary flow and lower ESSPRI scores after therapy. Therefore, it can be suggested that NSPT may improve the quality of life of pSS patients.


Subject(s)
Chronic Periodontitis/etiology , Chronic Periodontitis/therapy , Sjogren's Syndrome/complications , Adolescent , Adult , Aged , Bacterial Load , Case-Control Studies , Chronic Periodontitis/microbiology , Chronic Periodontitis/physiopathology , Enzyme-Linked Immunosorbent Assay , Female , Gingival Crevicular Fluid , Humans , Interleukins/analysis , Longitudinal Studies , Middle Aged , Polymerase Chain Reaction , Prospective Studies , Saliva/chemistry , Salivation/physiology , Secretory Rate , Sjogren's Syndrome/physiopathology , Time Factors , Treatment Outcome , Young Adult
20.
Braz. oral res. (Online) ; 31: e8, 2017. tab, graf
Article in English | LILACS | ID: biblio-839531

ABSTRACT

Abstract The aim of this longitudinal prospective study was to evaluate the effects of periodontal treatment on the clinical, microbiological and immunological periodontal parameters, and on the systemic activity (ESSDAI) and subjective (ESSPRI) indexes in patients with primary Sjögren’s Syndrome (pSS). Twenty-eight female patients were divided into four groups: pSS patients with or without chronic periodontitis (SCP, SC, respectively), and systemically healthy patients with or without chronic periodontitis (CP, C, respectively). Periodontal clinical examination and immunological and microbiological sample collection were performed at baseline, 30 and 90 days after nonsurgical periodontal treatment (NSPT). Levels of interleukin IL-1β, IL-8 and IL-10 in saliva and gingival crevicular fluid (GCF) were evaluated by ELISA, as well as the expression of Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans, (Aa) Tannerella forsythia (Tf), and Treponema denticola (Td), by qPCR. Systemic activity and pSS symptoms were evaluated by ESSDAI and ESSPRI. NSPT resulted in improved periodontal clinical parameters in both SCP and CP groups (p>0.05). Pg, Aa, and Tf levels decreased after NSPT only in CP patients (p<0.05). Significantly greater levels of IL-10 in GCF were verified in both SCP and CP groups (p<0.05). SCP patients showed increased salivary flow rates and decreased ESSPRI scores after NSPT. In conclusion, NSPT in pSS patients resulted in improved clinical and immunological parameters, with no significant effects on microbiological status. pSS patients also showed increased salivary flow and lower ESSPRI scores after therapy. Therefore, it can be suggested that NSPT may improve the quality of life of pSS patients.


Subject(s)
Humans , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Sjogren's Syndrome/complications , Chronic Periodontitis/etiology , Chronic Periodontitis/therapy , Saliva/chemistry , Salivation/physiology , Secretory Rate , Time Factors , Enzyme-Linked Immunosorbent Assay , Sjogren's Syndrome/physiopathology , Case-Control Studies , Polymerase Chain Reaction , Prospective Studies , Longitudinal Studies , Gingival Crevicular Fluid , Interleukins/analysis , Treatment Outcome , Chronic Periodontitis/physiopathology , Chronic Periodontitis/microbiology , Bacterial Load
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