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1.
Trends Biochem Sci ; 47(9): 732-735, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35418348

RESUMO

Alternative histone acylations integrate gene expression with cellular metabolic states. Recent measurements of cellular acyl-coenzyme A (acyl-CoA) pools highlight the potential that histone post-translational modifications (PTMs) contribute directly to the regulation of metabolite pools. A metabolite-centric view throws new light onto roles and evolution of histone PTMs.


Assuntos
Cromatina , Histonas , Acil Coenzima A/metabolismo , Acilação , Histonas/metabolismo , Processamento de Proteína Pós-Traducional
2.
Mol Cell Proteomics ; 23(7): 100799, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38866077

RESUMO

Histone posttranslational modifications (PTMs) have crucial roles in a multitude of cellular processes, and their aberrant levels have been linked with numerous diseases, including cancer. Although histone PTM investigations have focused so far on methylations and acetylations, alternative long-chain acylations emerged as new dimension, as they are linked to cellular metabolic states and affect gene expression through mechanisms distinct from those regulated by acetylation. Mass spectrometry is the most powerful, comprehensive, and unbiased method to study histone PTMs. However, typical mass spectrometry-based protocols for histone PTM analysis do not allow the identification of naturally occurring propionylation and butyrylation. Here, we present improved state-of-the-art sample preparation and analysis protocols to quantitate these classes of modifications. After testing different derivatization methods coupled to protease digestion, we profiled common histone PTMs and histone acylations in seven mouse tissues and human normal and tumor breast clinical samples, obtaining a map of propionylations and butyrylations found in different tissue contexts. A quantitative histone PTM analysis also revealed a contribution of histone acylations in discriminating different tissues, also upon perturbation with antibiotics, and breast cancer samples from the normal counterpart. Our results show that profiling only classical modifications is limiting and highlight the importance of using sample preparation methods that allow the analysis of the widest possible spectrum of histone modifications, paving the way for deeper insights into their functional significance in cellular processes and disease states.


Assuntos
Neoplasias da Mama , Histonas , Processamento de Proteína Pós-Traducional , Histonas/metabolismo , Humanos , Animais , Camundongos , Neoplasias da Mama/metabolismo , Feminino , Espectrometria de Massas/métodos , Acilação , Especificidade de Órgãos , Acetilação , Proteômica/métodos
3.
Mol Psychiatry ; 27(11): 4800-4808, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36071110

RESUMO

Dementia is more prevalent in Blacks than in Whites, likely due to a combination of environmental and biological factors. Paradoxically, clinical studies suggest an attenuation of APOE ε4 risk of dementia in African ancestry (AFR), but a dearth of neuropathological data preclude the interpretation of the biological factors underlying these findings, including the association between APOE ε4 risk and Alzheimer's disease (AD) pathology, the most frequent cause of dementia. We investigated the interaction between African ancestry, AD-related neuropathology, APOE genotype, and functional cognition in a postmortem sample of 400 individuals with a range of AD pathology severity and lack of comorbid neuropathology from a cohort of community-dwelling, admixed Brazilians. Increasing proportions of African ancestry (AFR) correlated with a lower burden of neuritic plaques (NP). However, for individuals with a severe burden of NP and neurofibrillary tangles (NFT), AFR proportion was associated with worse Clinical Dementia Rating sum of boxes (CDR-SOB). Among APOE ε4 carriers, the association between AFR proportion and CDR-SOB disappeared. APOE local ancestry inference of a subset of 309 individuals revealed that, in APOE ε4 noncarriers, non-European APOE background correlated with lower NP burden and, also, worse cognitive outcomes than European APOE when adjusting by NP burden. Finally, APOE ε4 was associated with worse AD neuropathological burden only in a European APOE background. APOE genotype and its association with AD neuropathology and clinical pattern are highly influenced by ancestry, with AFR associated with lower NP burden and attenuated APOE ε4 risk compared to European ancestry.


Assuntos
Doença de Alzheimer , Apolipoproteína E4 , Humanos , Apolipoproteína E4/genética , Doença de Alzheimer/patologia , Emaranhados Neurofibrilares/genética , Emaranhados Neurofibrilares/patologia , Placa Amiloide/genética , Placa Amiloide/patologia , Genótipo , Fatores Biológicos , Cognição
4.
Prep Biochem Biotechnol ; 52(4): 443-451, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34370621

RESUMO

Chitooligosaccharides (COS) have a great potential to be used by pharmaceutical industry due to their many biological activities. The use of enzymes to produce them is very advantageous, however it still faces many challenges, such as discovering new strains capable to produce enzymes that are able to generate bioactive oligosaccharides. In the present study a purification protein protocol was performed to purify chitosanases produced by Bacillus toyonensis CCT 7899 for further chitosan hydrolysis. The produced chitooligosaccharides were characterized by mass spectroscopy (MS) and their antiedematogenic effect was investigated through carrageenan-induced paw edema model. The animals were treated previously to inflammation by intragastric route with COS at 30, 300 and 600 mg/kg. The purification protocol showed a good performance for the chitosanases purification using 0.20 M NaCl solution to elute it, with a 9.54-fold purification factor. The treatment with COS promoted a decrease of paw edema at all evaluated times and the AUC0-4h, proving that COS produced showed activity in acute inflammation like commercial anti-inflammatory Dexamethasone (corticosteroid). Therefore, the strategy used to purification was successfully applied and it was possible to generate bioactive oligosaccharides with potential pharmacological use.


Assuntos
Bacillus , Quitosana , Animais , Bacillus/metabolismo , Quitina/metabolismo , Quitosana/química , Edema/induzido quimicamente , Edema/tratamento farmacológico , Glicosídeo Hidrolases/metabolismo , Inflamação , Oligossacarídeos/metabolismo
5.
Mol Biol Evol ; 37(6): 1647-1656, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32128591

RESUMO

The Transatlantic Slave Trade transported more than 9 million Africans to the Americas between the early 16th and the mid-19th centuries. We performed a genome-wide analysis using 6,267 individuals from 25 populations to infer how different African groups contributed to North-, South-American, and Caribbean populations, in the context of geographic and geopolitical factors, and compared genetic data with demographic history records of the Transatlantic Slave Trade. We observed that West-Central Africa and Western Africa-associated ancestry clusters are more prevalent in northern latitudes of the Americas, whereas the South/East Africa-associated ancestry cluster is more prevalent in southern latitudes of the Americas. This pattern results from geographic and geopolitical factors leading to population differentiation. However, there is a substantial decrease in the between-population differentiation of the African gene pool within the Americas, when compared with the regions of origin from Africa, underscoring the importance of historical factors favoring admixture between individuals with different African origins in the New World. This between-population homogenization in the Americas is consistent with the excess of West-Central Africa ancestry (the most prevalent in the Americas) in the United States and Southeast-Brazil, with respect to historical-demography expectations. We also inferred that in most of the Americas, intercontinental admixture intensification occurred between 1750 and 1850, which correlates strongly with the peak of arrivals from Africa. This study contributes with a population genetics perspective to the ongoing social, cultural, and political debate regarding ancestry, admixture, and the mestizaje process in the Americas.


Assuntos
População Negra/genética , Escravização/história , Pool Gênico , Genoma Humano , Migração Humana/história , África , América , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , Humanos , Filogeografia
6.
Genome Res ; 28(7): 1090-1095, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29903722

RESUMO

EPIGEN-Brazil is one of the largest Latin American initiatives at the interface of human genomics, public health, and computational biology. Here, we present two resources to address two challenges to the global dissemination of precision medicine and the development of the bioinformatics know-how to support it. To address the underrepresentation of non-European individuals in human genome diversity studies, we present the EPIGEN-5M+1KGP imputation panel-the fusion of the public 1000 Genomes Project (1KGP) Phase 3 imputation panel with haplotypes derived from the EPIGEN-5M data set (a product of the genotyping of 4.3 million SNPs in 265 admixed individuals from the EPIGEN-Brazil Initiative). When we imputed a target SNPs data set (6487 admixed individuals genotyped for 2.2 million SNPs from the EPIGEN-Brazil project) with the EPIGEN-5M+1KGP panel, we gained 140,452 more SNPs in total than when using the 1KGP Phase 3 panel alone and 788,873 additional high confidence SNPs (info score ≥ 0.8). Thus, the major effect of the inclusion of the EPIGEN-5M data set in this new imputation panel is not only to gain more SNPs but also to improve the quality of imputation. To address the lack of transparency and reproducibility of bioinformatics protocols, we present a conceptual Scientific Workflow in the form of a website that models the scientific process (by including publications, flowcharts, masterscripts, documents, and bioinformatics protocols), making it accessible and interactive. Its applicability is shown in the context of the development of our EPIGEN-5M+1KGP imputation panel. The Scientific Workflow also serves as a repository of bioinformatics resources.


Assuntos
Genoma Humano/genética , Brasil , Biologia Computacional/métodos , Genômica/métodos , Haplótipos/genética , Humanos , América Latina , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos Testes , Software , Fluxo de Trabalho
7.
Int J Obes (Lond) ; 45(5): 1017-1029, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33633342

RESUMO

BACKGROUND/OBJECTIVES: Admixed populations are a resource to study the global genetic architecture of complex phenotypes, which is critical, considering that non-European populations are severely underrepresented in genomic studies. Here, we study the genetic architecture of BMI in children, young adults, and elderly individuals from the admixed population of Brazil. SUBJECTS/METHODS: Leveraging admixture in Brazilians, whose chromosomes are mosaics of fragments of Native American, European, and African origins, we used genome-wide data to perform admixture mapping/fine-mapping of body mass index (BMI) in three Brazilian population-based cohorts from Northeast (Salvador), Southeast (Bambuí), and South (Pelotas). RESULTS: We found significant associations with African-associated alleles in children from Salvador (PALD1 and ZMIZ1 genes), and in young adults from Pelotas (NOD2 and MTUS2 genes). More importantly, in Pelotas, rs114066381, mapped in a potential regulatory region, is significantly associated only in females (p = 2.76e-06). This variant is rare in Europeans but with frequencies of ~3% in West Africa and has a strong female-specific effect (95% CI: 2.32-5.65 kg/m2 per each A allele). We confirmed this sex-specific association and replicated its strong effect for an adjusted fat mass index in the same Pelotas cohort, and for BMI in another Brazilian cohort from São Paulo (Southeast Brazil). A meta-analysis confirmed the significant association. Remarkably, we observed that while the frequency of rs114066381-A allele ranges from 0.8 to 2.1% in the studied populations, it attains ~9% among women with morbid obesity from Pelotas, São Paulo, and Bambuí. The effect size of rs114066381 is at least five times higher than the FTO SNPs rs9939609 and rs1558902, already emblematic for their high effects. CONCLUSIONS: We identified six candidate SNPs associated with BMI. rs114066381 stands out for its high effect that was replicated and its high frequency in women with morbid obesity. We demonstrate how admixed populations are a source of new relevant phenotype-associated genetic variants.


Assuntos
Índice de Massa Corporal , Genética Populacional , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Alelos , Brasil , Criança , Pré-Escolar , Mapeamento Cromossômico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Sequências Reguladoras de Ácido Nucleico , Fatores Sexuais , Adulto Jovem
8.
Mar Drugs ; 19(2)2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33673266

RESUMO

The global rise of infectious disease outbreaks and the progression of microbial resistance reinforce the importance of researching new biomolecules. Obtained from the hydrolysis of chitosan, chitooligosaccharides (COSs) have demonstrated several biological properties, including antimicrobial, and greater advantage over chitosan due to their higher solubility and lower viscosity. Despite the evidence of the biotechnological potential of COSs, their effects on trypanosomatids are still scarce. The objectives of this study were the enzymatic production, characterization, and in vitro evaluation of the cytotoxic, antibacterial, antifungal, and antiparasitic effects of COSs. NMR and mass spectrometry analyses indicated the presence of a mixture with 81% deacetylated COS and acetylated hexamers. COSs demonstrated no evidence of cytotoxicity upon 2 mg/mL. In addition, COSs showed interesting activity against bacteria and yeasts and a time-dependent parasitic inhibition. Scanning electron microscopy images indicated a parasite aggregation ability of COSs. Thus, the broad biological effect of COSs makes them a promising molecule for the biomedical industry.


Assuntos
Anti-Infecciosos/farmacologia , Antiparasitários/farmacologia , Quitina/análogos & derivados , Anti-Infecciosos/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antiparasitários/química , Quitina/química , Quitina/farmacocinética , Quitosana , Microscopia Eletrônica de Varredura , Oligossacarídeos , Fatores de Tempo
9.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638973

RESUMO

The search for promising biomolecules such as chitooligosaccharides (COS) has increased due to the need for healing products that act efficiently, avoiding complications resulting from exacerbated inflammation. Therefore, this study aimed to produce COS in two stages of hydrolysis using chitosanases derived from Bacillus toyonensis. Additionally, this study aimed to structurally characterize the COS via mass spectrometry, to analyze their biocompatibility in acute toxicity models in vivo, to evaluate their healing action in a cell migration model in vitro, to analyze the anti-inflammatory activity in in vivo models of xylol-induced ear edema and zymosan-induced air pouch, and to assess the wound repair action in vivo. The structural characterization process pointed out the presence of hexamers. The in vitro and in vivo biocompatibility of COS was reaffirmed. The COS stimulated the fibroblast migration. In the in vivo inflammatory assays, COS showed an antiedematogenic response and significant reductions in leukocyte migration, cytokine release, and protein exudate. The COS healing effect in vivo was confirmed by the significant wound reduction after seven days of the experiment. These results indicated that the presence of hexamers influences the COS biological properties, which have potential uses in the pharmaceutical field due to their healing and anti-inflammatory action.


Assuntos
Anti-Inflamatórios/administração & dosagem , Materiais Biocompatíveis/administração & dosagem , Quitosana/administração & dosagem , Otopatias/tratamento farmacológico , Edema/tratamento farmacológico , Oligossacarídeos/administração & dosagem , Cicatrização/efeitos dos fármacos , Células 3T3 , Animais , Anti-Inflamatórios/química , Bacillus/enzimologia , Materiais Biocompatíveis/química , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Citocinas/metabolismo , Modelos Animais de Doenças , Otopatias/induzido quimicamente , Edema/induzido quimicamente , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Glicosídeo Hidrolases/química , Hidrólise , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Oligossacarídeos/química
10.
BMC Biotechnol ; 20(1): 55, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066751

RESUMO

BACKGROUND: Buriti oil presents numerous health benefits, but due to its lipophilic nature and high oxidation, it is impossible to incorporate it into aqueous food matrices. Thus, the present study evaluated whether powder nanoparticles based on porcine gelatin (OPG) and in combination with sodium alginate (OAG) containing buriti oil obtained by O/W emulsification followed by freeze-drying enabled water dispersibility and preserved or increased the antimicrobial activity of the oil. RESULTS: OPG presented spherical shape, smooth surface, smaller particle size and polydispersity index [51.0 (6.07) nm and 0.40 (0.05)], and better chemical interaction between the nonpolar amino acids and the hydrophobic oil chain. OPG also presented a higher dispersibility percentage [85.62% (7.82)] than OAG [50.19% (7.24)] (p < 0.05), and significantly increased the antimicrobial activity of the oil by 59, 62, and 43% for Pseudomonas aeruginosa, Klebsiella pneumonia, and Staphylococcus aureus, respectively. CONCLUSIONS: Thus, nanoencapsulation in gelatin is a promising strategy to increase the potential to use buriti oil in foods.


Assuntos
Anti-Infecciosos/farmacologia , Arecaceae/química , Gelatina/química , Gelatina/farmacologia , Nanopartículas/química , Água/química , Aminoácidos , Animais , Anti-Infecciosos/química , Carotenoides , Ácidos Graxos , Interações Hidrofóbicas e Hidrofílicas , Hidroxibenzoatos/análise , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Extratos Vegetais/farmacologia , Óleos de Plantas , Suínos
11.
Int J Mol Sci ; 21(18)2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32927660

RESUMO

Collagen prolyl 4-hydroxylase 1 (C-P4H1) is an α-ketoglutarate (α-KG)-dependent dioxygenase that catalyzes 4-hydroxylation of proline on collagen. C-P4H1-induced prolyl hydroxylation is required for proper collagen deposition and cancer metastasis. Therefore, targeting C-P4H1 is considered a potential therapeutic strategy for collagen-related cancer progression and metastasis. However, no C-P4H1 inhibitors are available for clinical testing, and the high content assay is currently not available for C-P4H1 inhibitor screening. In the present study, we developed a high-throughput screening assay by quantifying succinate, a byproduct of C-P4H-catalyzed hydroxylation. C-P4H1 is the major isoform of collagen prolyl 4-hydroxylases (CP4Hs) that contributes the majority prolyl 4-hydroxylase activity. Using C-P4H1 tetramer purified from the eukaryotic expression system, we showed that the Succinate-GloTM Hydroxylase assay was more sensitive for measuring C-P4H1 activity compared with the hydroxyproline colorimetric assay. Next, we performed high-throughput screening with the FDA-approved drug library and identified several new C-P4H1 inhibitors, including Silodosin and Ticlopidine. Silodosin and Ticlopidine inhibited C-P4H1 activity in a dose-dependent manner and suppressed collagen secretion and tumor invasion in 3D tissue culture. These C-P4H1 inhibitors provide new agents to test clinical potential of targeting C-P4H1 in suppressing cancer progression and metastasis.


Assuntos
Antineoplásicos/análise , Ensaios de Triagem em Larga Escala/métodos , Inibidores de Prolil-Hidrolase/análise , Antineoplásicos/química , Linhagem Celular Tumoral , Humanos , Indóis/química , Ticlopidina/química
12.
J Clin Periodontol ; 46(4): 457-469, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30854670

RESUMO

AIM: This study evaluated the effects of 5-fluorouracil (5-FU) and cisplatin (CIS) in healthy periodontal tissues and in the early stages of experimental periodontitis (EP) in rats. METHODS: One hundred and eighty male rats were divided into three groups, which were submitted to the following systemic treatments: physiological saline solution (PSS); CIS and 5FU. Each group was subdivided into two subgroups: without (NEP) and with (EP) induction of EP. Animals were euthanized at 3, 5 and 7 days post-treatment. Histological, histometric (percentage of bone in the furcation [PBF]) and immunohistochemical (for tumour necrosis factor-α, interleukin-1ß and receptor activator of nuclear factor-κB ligand) analyses were performed. Data were statistically analysed. RESULTS: CIS-NEP and 5FU-NEP showed more inflammation than PSS-NEP at 3, 5 and 7 days. CIS-EP and 5FU-EP showed more inflammation and lower PBF than PSS-EP at all periods of evaluation. 5FU-EP showed lower PBF than CIS-EP at 5 and 7 days. CONCLUSION: 5-FU and CIS exacerbated periodontal inflammation and aggravated the progression of EP in its early stages.


Assuntos
Perda do Osso Alveolar , Antineoplásicos , Periodontite , Animais , Inflamação , Masculino , Ratos , Ratos Wistar
13.
Mem Inst Oswaldo Cruz ; 113(12): e180328, 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30517210

RESUMO

BACKGROUND Human herpesvirus 2 (HHV-2) have DNA genome with a limited genetic variability and have been classified into two clades. OBJECTIVES To identify and characterise six HHV-2 isolates derived from Brazilian women. METHODS HHV-2 isolates were performed polymerase chain reaction (PCR) and sequencing of 2250 pb of the glycoprotein B (gB) coding regions. FINDINGS Four HHV-2 isolates were classified into clade B, while the remaining two, derived from HIV-1 co-infected women, showed a notable genetic divergence (> 1%). MAIN CONCLUSION The results reveal novel HHV-2 variants. The impact of these novel variants on HHV-2 pathogenesis and HIV/HHV-2 coinfection need to be investigated.


Assuntos
Genes Virais/genética , Infecções por HIV/virologia , HIV-1 , Herpes Genital/virologia , Herpesvirus Humano 2/genética , Brasil , Coinfecção/virologia , Feminino , Infecções por HIV/complicações , Herpes Genital/complicações , Humanos , Filogenia , Reação em Cadeia da Polimerase
14.
Clin Oral Investig ; 22(1): 361-367, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28536783

RESUMO

OBJECTIVE: The aim of this study was to investigate the biocompatibility of methylene blue at different pH levels through the method of implantation in subcutaneous tissue. MATERIALS AND METHODS: Eighty-four sterilized polyethylene tubes were allocated in the subcutaneous tissue of 28 rats, each one receiving four tubes, set into four groups: group tube (G-T)-empty tube, fibrin group (G-F)-tube filled with fibrin sponge, group methylene blue pH 7 (G-MB/pH 7)-tube filled with fibrin sponge soaked by methylene blue (100 µg/ml) at pH 7.0, and group methylene blue pH 1 (G-MB/pH 1)-tube filled with fibrin sponge and soaked by methylene blue (100 µg/ml) at pH 1.0. After 7, 15, and 30 days, seven animals from each group were euthanized, and the tubes involved by the surrounding tissue were removed and fixed with 4% buffered formaldehyde solution. The collected pieces were processed and histological sections (4 µm) were stained with hematoxylin and eosin and analyzed by light microscopy. Scores were assigned to analysis of histopathologic parameters. The results were statistically analyzed by the Kruskal-Wallis test (p ≤ 0.05). RESULTS: At 7 and 30 days, the G-MB/pH 1 group showed no significant difference in the G-T control group, while G-MB/pH 7 had a significant increase on tissue reaction, also when compared to G-T. At 15 days, there was no statistical difference between the groups. CONCLUSION: Within the limits of this study, it is concluded that methylene blue at pH 1.0 provides better biocompatibility than at pH 7.0.


Assuntos
Materiais Biocompatíveis/farmacologia , Azul de Metileno/farmacologia , Tela Subcutânea/efeitos dos fármacos , Animais , Fibrina/farmacologia , Concentração de Íons de Hidrogênio , Inflamação , Linfócitos , Macrófagos , Teste de Materiais , Ratos , Ratos Wistar , Soluções
15.
Implant Dent ; 26(1): 137-144, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27548110

RESUMO

OBJECTIVE: This study aimed to perform a systematic review of the effectiveness of nonsurgical treatment associated with different adjuvant therapies on periimplantitis. MATERIALS AND METHODS: Different individuals, following a research process, performed a network research of controlled and randomized controlled clinical trials on PubMed, Embase/MEDLINE, with 20 years' time constraint and the last search in January 2016. RESULTS: From 108 articles found by the first search, they analyzed 10 full texts, and in none did they find a standard control group. When compared, mechanical therapies combined with adjuvant therapy decreased prevalence of periimplant ratios; however, some groups showed unsatisfactory results, mainly related to the probing depth and bleeding index. When comparing debridement with other nonsurgical therapies (Er:YAG, Vector, air abrasive with amino acid glycine powder), increased periimplant levels were noticed in the test and control groups, although in different periods. CONCLUSION: Despite the improvement in the periimplant indices, there is no sufficient evidence to score the best results or even to choose the best association for nonsurgical treatment of periimplantitis; hence, more trials are necessary to answer this question.


Assuntos
Peri-Implantite/terapia , Desbridamento Periodontal/métodos , Humanos , Resultado do Tratamento
16.
J Sep Sci ; 39(4): 709-16, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26638991

RESUMO

This study presents a system for expanded bed adsorption for the purification of chitosanase from broth extract in a single step. A chitosanase-producing strain was isolated and identified as Bacillus cereus C-01 and used to produce chitosanases. The expanded bed adsorption conditions for chitosanase purification were optimized statistically using STREAMLINE(TM) DEAE and a homemade column (2.6 × 30.0 cm). Dependent variables were defined by the quality criteria purification factor (P) and enzyme yield to optimize the chromatographic process. Statistical analyses showed that the optimum conditions for the maximum P were 150 cm/h load flow velocity, 6.0 cm settled bed height, and 7.36 cm distributor height. Distributor height had a strong influence on the process, considerably affecting both the P and enzyme yield. Optimizing the purification variables resulted in an approximately 3.66-fold increase in the P compared with the value under nonoptimized conditions. This system is promising for the recovery of chitosanase from B. cereus C-01 and is economically viable because it promotes the reduction steps.


Assuntos
Bacillus cereus/enzimologia , Glicosídeo Hidrolases/isolamento & purificação , Adsorção , Soluções Tampão , Quitosana/química , Cromatografia/métodos , Etanolaminas , Glicosídeo Hidrolases/química , Hidrodinâmica , Concentração de Íons de Hidrogênio , Microbiologia Industrial/métodos , Ligantes , Peso Molecular , Análise de Regressão
17.
Microsc Microanal ; 20(1): 296-304, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24230481

RESUMO

In this work the leaf anatomy of three species of Ficus section Americanae (Miq.) Miq. from Brazil, whose leaves and latex are used in folk medicine is reported. The work was carried out using light and scanning electron microscopy in order to characterize these species and to evaluate their taxonomic significance, and also contribute to the quality control of their ethnodrugs. The three species (Ficus cyclophylla, Ficus elliotiana, and Ficus caatingae) showed hypostomatic leaves, anomocytic stomata, straight epidermal cell outlines, and a dorsiventral mesophyll. Some micro-morphological characters such as density and distribution of epicuticular waxes, glandular trichomes, the length and width of stomata, as well as the palisade of mesophyll and petiole outlines proved to be the most useful and distinctive characters for the separation of species. These may contribute as additional support for the taxonomy of the section and for the quality control of their ethnodrugs.


Assuntos
Ficus , Folhas de Planta , Brasil , Ficus/anatomia & histologia , Ficus/química , Ficus/citologia , Histocitoquímica , Microscopia Eletrônica de Varredura , Epiderme Vegetal/anatomia & histologia , Epiderme Vegetal/química , Epiderme Vegetal/citologia , Folhas de Planta/anatomia & histologia , Folhas de Planta/química , Folhas de Planta/citologia , Ceras/química
18.
Cells ; 13(17)2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39273065

RESUMO

Prostate apoptosis response-4 (Par-4, also known as PAWR) is a ubiquitously expressed tumor suppressor protein that induces apoptosis selectively in cancer cells, while leaving normal cells unaffected. Our previous studies indicated that genetic loss of Par-4 promoted hepatic steatosis, adiposity, and insulin-resistance in chow-fed mice. Moreover, low plasma levels of Par-4 are associated with obesity in human subjects. The mechanisms underlying obesity in rodents and humans are multi-faceted, and those associated with adipogenesis can be functionally resolved in cell cultures. We therefore used pluripotent mouse embryonic fibroblasts (MEFs) or preadipocyte cell lines responsive to adipocyte differentiation cues to determine the potential role of Par-4 in adipocytes. We report that pluripotent MEFs from Par-4-/- mice underwent rapid differentiation to mature adipocytes with an increase in lipid droplet accumulation relative to MEFs from Par-4+/+ mice. Knockdown of Par-4 in 3T3-L1 pre-adipocyte cultures by RNA-interference induced rapid differentiation to mature adipocytes. Interestingly, basal expression of PPARγ, a master regulator of de novo lipid synthesis and adipogenesis, was induced during adipogenesis in the cell lines, and PPARγ induction and adipogenesis caused by Par-4 loss was reversed by replenishment of Par-4. Mechanistically, Par-4 downregulates PPARγ expression by directly binding to its upstream promoter, as judged by chromatin immunoprecipitation and luciferase-reporter studies. Thus, Par-4 transcriptionally suppresses the PPARγ promoter to regulate adipogenesis.


Assuntos
Células 3T3-L1 , Adipócitos , Adipogenia , Proteínas Reguladoras de Apoptose , PPAR gama , Animais , PPAR gama/metabolismo , PPAR gama/genética , Adipogenia/genética , Camundongos , Adipócitos/metabolismo , Adipócitos/citologia , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Reguladoras de Apoptose/genética , Diferenciação Celular , Humanos , Transcrição Gênica , Regiões Promotoras Genéticas/genética , Fibroblastos/metabolismo
19.
PLoS One ; 18(5): e0284497, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37167233

RESUMO

OBJECTIVE: The aim of this study was to evaluate the effectiveness of hand debridement (HD) versus ultrasonic dental scaler (UDS) for the treatment of experimental periodontitis (EP) in rats. MATERIAL AND METHODS: Thirty 3-month-old male rats were used. EP was induced around the mandibular first molars (right and left). Seven days after induction, the treatments with either HD (n = 30) or UDS (n = 30) were randomly performed in each molar. Euthanasia were performed at 7, 15, and 30 days after treatment. Histometric (percentage of bone in the furcation [PBF]), histopathological, and immunohistochemical (for detection of tartrate-resistant acid phosphatase [TRAP] and osteocalcin [OCN]). Parametric data (PBF and TRAP) was analyzed by One-way ANOVA followed by Tukey's post-test. OCN was analyzed by Kruskal-Wallis followed by Student-Newman-Keuls post-test. The level of significance was 5%. RESULTS: Group HD presented higher PBF and lower TRAP-immunolabeling at 30 days as compared with UDS in the same period (p≤0.05). Group HD presented higher OCN immunolabeling at 30 days as compared with 7 and 15 days (p≤0.05). Persistent and exacerbated inflammatory process was observed in some specimens from group UDS at 30 days, as well as the bone trabeculae presented irregular contour, surrounded by many active osteoclasts. CONCLUSION: Nonsurgical periodontal therapy with HD resulted in higher PBF and lower expression of TRAP as compared with UDS. Also, HD increased the expression of OCN over time.


Assuntos
Perda do Osso Alveolar , Periodontite , Ratos , Masculino , Animais , Ratos Wistar , Perda do Osso Alveolar/patologia , Ultrassom , Periodontite/patologia , Projetos de Pesquisa
20.
Nutr Hosp ; 40(2): 419-427, 2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-36880723

RESUMO

Introduction: Introduction: changes in dietary/energetic composition during the critical period of development (pregnancy/lactation) or even during meal times may contribute to changes in metabolic and behavioral parameters such as feeding behavior. Objective: the study aimed to examine the repercussions of time-restricted feeding on feeding behavior and on some parameters of glycemic and lipemic metabolism of the offspring of adult rats whose mothers were fed a westernized diet during pregnancy and lactation. Methods: initially, 43 male Wistar rats were used. At 60 days of life, the rats were divided into 4 groups: C: control group; RC: control group with time-restricted feeding; W: westernized diet during pregnancy/lactation group; RW: westernized diet group during pregnancy/lactation group with time-restricted feeding. The following parameters were evaluated: behavioral sequence of satiety (BSS), biochemical parameters, and abdominal fat. Results: findings highlighted a high level of abdominal fat in the groups whose mothers were submitted to a westernized diet, as well as hypertriglyceridemia, and clear differences in feed rate and meal length. This study showed that the westernized diet ingested by mothers during pregnancy and lactation induced hyperlipidemia and changes in the feeding behavior of their adult offspring. Conclusions: these changes may be responsible for eating disorders and risk factors for metabolism disturbance-related diseases.


Introducción: Introducción: los cambios en la composición dietética/energética durante el período crítico de desarrollo (embarazo/lactancia) o incluso durante las comidas pueden contribuir a cambios en los parámetros metabólicos y conductuales como el comportamiento alimentario. Objetivo: el estudio tuvo como objetivo examinar las repercusiones de la alimentación restringida en el tiempo sobre el comportamiento alimentario y sobre algunos parámetros del metabolismo glucémico y lipémico de crías de ratas adultas cuyas madres fueron alimentadas con una dieta occidentalizada durante el embarazo y la lactancia. Métodos: inicialmente se utilizaron 43 ratas Wistar macho. A los 60 días de vida, las ratas se agruparon en 4 grupos: C: grupo de control; RC: grupo de control con alimentación restringida en el tiempo; W: grupo de dieta occidentalizada durante el embarazo/lactancia; RW: grupo de dieta occidentalizada durante el embarazo y la lactancia con alimentación restringida en el tiempo. Se evaluaron los siguientes parámetros: secuencia conductual de saciedad (BSS), parámetros bioquímicos y grasa abdominal. Resultados: destacó una grasa abdominal elevada en los grupos cuyas madres fueron sometidas a una dieta occidentalizada, así como hipertrigliceridemia y una diferencia evidente en la tasa de alimentación y la duración de la comida. Este estudio demostró que la dieta occidentalizada ingerida por las madres durante el embarazo y la lactancia induce hiperlipidemia y cambios en el comportamiento alimentario de las crías adultas. Conclusiones: estos cambios pueden ser responsables de trastornos alimentarios y factores de riesgo de enfermedades relacionadas con alteraciones del metabolismo.


Assuntos
Fenômenos Fisiológicos da Nutrição Materna , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Feminino , Humanos , Ratos , Masculino , Animais , Ratos Wistar , Dieta , Comportamento Alimentar , Ingestão de Alimentos , Lactação , Dieta Hiperlipídica
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