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1.
Nature ; 592(7852): 93-98, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33568816

RESUMO

Long non-coding RNAs (lncRNAs) can be important components in gene-regulatory networks1, but the exact nature and extent of their involvement in human Mendelian disease is largely unknown. Here we show that genetic ablation of a lncRNA locus on human chromosome 2 causes a severe congenital limb malformation. We identified homozygous 27-63-kilobase deletions located 300 kilobases upstream of the engrailed-1 gene (EN1) in patients with a complex limb malformation featuring mesomelic shortening, syndactyly and ventral nails (dorsal dimelia). Re-engineering of the human deletions in mice resulted in a complete loss of En1 expression in the limb and a double dorsal-limb phenotype that recapitulates the human disease phenotype. Genome-wide transcriptome analysis in the developing mouse limb revealed a four-exon-long non-coding transcript within the deleted region, which we named Maenli. Functional dissection of the Maenli locus showed that its transcriptional activity is required for limb-specific En1 activation in cis, thereby fine-tuning the gene-regulatory networks controlling dorso-ventral polarity in the developing limb bud. Its loss results in the En1-related dorsal ventral limb phenotype, a subset of the full En1-associated phenotype. Our findings demonstrate that mutations involving lncRNA loci can result in human Mendelian disease.


Assuntos
Extremidades , Proteínas de Homeodomínio/genética , Deformidades Congênitas dos Membros/genética , RNA Longo não Codificante/genética , Deleção de Sequência/genética , Transcrição Gênica , Ativação Transcricional/genética , Animais , Linhagem Celular , Cromatina/genética , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Transgênicos
2.
Exp Parasitol ; 262: 108771, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38723847

RESUMO

Toxoplasmosis affects about one-third of the world's population. The disease treatment methods pose several side effects and do not efficiently eliminate the parasite, making the search for new therapeutic approaches necessary. We aimed to assess the anti-Toxoplasma gondii activity of four Copaifera oleoresins (ORs) and two isolated diterpene acids, named ent-kaurenoic and ent-polyalthic acid. We used HeLa cells as an experimental model of toxoplasmosis. Uninfected and infected HeLa cells were submitted to the treatments, and the parasite intracellular proliferation, cytokine levels and ROS production were measured. Also, tachyzoites were pre-treated and the parasite invasion was determined. Finally, an in silico analysis was performed to identify potential parasite targets. Our data show that the non-cytotoxic concentrations of ORs and diterpene acids controlled the invasion and proliferation of T. gondii in HeLa cells, thus highlighting the possible direct action on parasites. In addition, some compounds tested controlled parasite proliferation in an irreversible manner. An additional and non-exclusive mechanism of action involves the modulation of host cell components, by affecting the upregulation of the IL-6. Additionally, molecular docking suggested that ent-polyalthic acid has a high affinity for the active site of the TgCDPK1 protein. Copaifera ORs have great antiparasitic activity against T. gondii, and this effect can be partially explained by the presence of the isolated compounds ent-kaurenoic and ent-polyalthic acid.


Assuntos
Diterpenos , Fabaceae , Extratos Vegetais , Toxoplasma , Células HeLa , Humanos , Diterpenos/farmacologia , Diterpenos/isolamento & purificação , Diterpenos/química , Toxoplasma/efeitos dos fármacos , Toxoplasma/crescimento & desenvolvimento , Fabaceae/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Citocinas/metabolismo , Interleucina-6/metabolismo , Simulação de Acoplamento Molecular
3.
Chem Biodivers ; : e202400680, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748618

RESUMO

The study aimed to assess the chemical composition of Miconia ibaguensis leaves extracts and fractions obtained from the ethanolic extract (EE), along with evaluating their antifungal, antibacterial, antidiabetic, and antioxidant activities. The ethyl acetate fraction (EAF) exhibited potent antifungal activity against Candida spp (1.95 - 3.90 µg mL-1) and potent antioxidant activity in the DPPH (1.74 ± 0.07 µg mL-1), FRAP (654.01 ± 42.09 µmol ETrolox/gsample), and ORAC (3698.88 ± 37.28 µmol ETrolox/gsample) methods. The EE displayed inhibition against the α-amylase enzyme (8.42 ± 0.05 µg mL-1). Flavonoids, hydrolysable tannins, triterpenoids, and phenolic acids, identified in the EE and fractions via (-)-HPLC-ESI-MS/MS analysis, were found to contribute to the species' biological activity potentially. These findings suggest promising avenues for further research and potential applications in pharmacology and natural products, offering new possibilities in the fight against global health issues.

4.
Molecules ; 29(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38338388

RESUMO

Antibacterials derived from natural sources represent a fascinating and promising field of research in the quest for effective and sustainable solutions to bacterial infections [...].


Assuntos
Antibacterianos , Infecções Bacterianas , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico
5.
Metabolomics ; 19(8): 68, 2023 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-37486581

RESUMO

INTRODUCTION: Lantana trifolia L. (Verbenaceae) is a shrubby plant. In folk medicine, its leaves are used in the form of infusions and syrups to treat angina, coughs, and colds; they are also applied as tranquilizer. Previous studies have reported the antimicrobial potential of the compounds present in L. trifolia leaves. OBJECTIVES: To report the anti-Candida activities of the fractions obtained from the fruits and leaves of two L. trifolia specimens. METHODS: The L. trifolia fractions were submitted to UFLC-DAD-(+)-ESI-MS/MS, and the data were analyzed by using multivariate statistical tools (PCA, PLS-DA) and spectral similarity analyses based on molecular networking, which aided dereplication of the bioactive compounds. Additionally, NMR analyses were performed to confirm the chemical structure of some of the major compounds in the fractions. RESULTS: The ethyl acetate fractions presented MIC values lower than 100 µg mL-1 against the three Candida strains evaluated herein (C. albicans, C. tropicalis, and C. glabrata). Fractions FrPo AcOEt, FrPe AcOEt, and FrPe nBut had MIC values of 1.46, 2.93, and 2.93 µg mL-1 against C. glabrata, respectively. These values resembled the MIC value of amphotericin B, the positive control (0.5-1.0 µg mL-1), against this same strain. Cytotoxicity was measured and used to calculate the selectivity index. CONCLUSION: On the basis of our data, the most active fractions in the antifungal assay were more selective against C. glabrata than against non-infected cells. The analytical approach adopted here allowed us to annotate 29 compounds, nine of which were bioactive (PLS-DA results) and belong to the class of phenolic compounds.


Assuntos
Antineoplásicos , Lantana , Antifúngicos/farmacologia , Antifúngicos/análise , Espectrometria de Massas em Tandem , Lantana/química , Frutas , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Metabolômica , Folhas de Planta/química
6.
Exp Parasitol ; 250: 108534, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37100271

RESUMO

Due to the lack of efficient antiparasitic therapy and vaccines, as well as emerging resistance strains, congenital toxoplasmosis is still a public health issue worldwide. The present study aimed to assess the effects of an oleoresin obtained from the species Copaifera trapezifolia Hayne (CTO), and an isolated molecule found in the CTO, ent-polyalthic acid (ent-15,16-epoxy-8(17),13(16),14-labdatrien-19-oic acid) (named as PA), against T. gondii infection. We used human villous explants as an experimental model of human maternal-fetal interface. Uninfected and infected villous explants were exposed to the treatments; the parasite intracellular proliferation and the cytokine levels were measured. Also, T. gondii tachyzoites were pre-treated and the parasite proliferation was determined. Our findings showed that CTO and PA reduced efficiently the parasite growth with an irreversible action, but without causing toxicity to the villi. Also, treatments reduced the levels of IL-6, IL-8, MIF and TNF by villi, what configures a valuable treatment option for the maintenance of a pregnancy in an infectious context. In addition to a possible direct effect on parasites, our data suggest an alternative mechanism by which CTO and PA alter the villous explants environment and then impair parasite growth, since the pre-treatment of villi resulted in lower parasitic infection. Here, we highlighted PA as an interesting tool for the design of new anti-T. gondii compounds.


Assuntos
Fabaceae , Toxoplasma , Humanos , Gravidez , Feminino , Extratos Vegetais/farmacologia
7.
Anim Biotechnol ; 34(9): 5087-5096, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37975200

RESUMO

In vitro embryos production from prepubertal heifers can help contribute to breeding programs; however, strategies are necessary to increase their embryo production. The aim of this study was to investigate the effects of two nutritional plans on oocyte recovery, embryo production and growth performance of prepubertal Nelore heifers. Thirty-four Nelore heifers with age of 6.5 months were divided into two feeding treatments (NP1 and NP2). The NP1 diets served as the control and NP2 diets were formulated to contain an average of 1.22-fold more energy than NP1. After 3 months of supplementation, the animals underwent follicular aspiration (ovum pick-up, OPU) every 21 d for 3 months and embryos were produced in vitro. Wither height, chest depth, body weight and subcutaneous fat of animals were measured. The number of retrieved and viable oocytes per OPU were 1.49-fold and 1.42-fold greater in NP2 heifers (p = 0.018 and p = 0.049, respectively) than those in NP1 heifers. Heifers administered NP2 produced 29.7% blastocysts, a percentage higher than NP1 animals that produced 24.40% embryos (p < 0.05). Consequently, females in the NP2 treatment showed improved body development. These results indicate a positive effect of a higher energy diet on assisted reproduction and body development in prepubertal heifers.


Assuntos
Fertilização in vitro , Folículo Ovariano , Bovinos , Animais , Feminino , Fertilização in vitro/veterinária , Técnicas de Cultura Embrionária/veterinária , Oócitos , Suplementos Nutricionais
8.
Ren Fail ; 45(1): 2183044, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36856327

RESUMO

Eligibility and indication for autologous hematopoietic stem cell transplantation (HSCT) in patients with lymphoma are increasing. Acute kidney injury (AKI) is a known complication of HSCT with studies including a miscellaneous of hematological diagnoses and using different definitions of AKI. We aimed to evaluate incidence, risk factors and prognostic impact of AKI post-HSCT in patients with lymphoma submitted to autologous HSCT using the KDIGO classification with both serum creatinine and urinary output criteria. We performed a single-center retrospective cohort study including patients with lymphoma admitted for autologous HSCT. We used survival analysis with competing risks to evaluate cumulative incidence of AKI, AKI risk factors and AKI impact on disease-free survival. We used Cox regression for impact of AKI on overall survival. We used backward stepwise regression to create multivariable models. A total of 115 patients were included. Cumulative incidence of AKI: 63.7% 100 d post-HSCT. First diagnosis criteria: creatinine in 54.8%, urinary output in 41.1% and both in 4.1%. AKI highest stage: 1 in 57.5%, 2 in 17.8% and 3 in 24.7%. Variables independently associated with higher incidence of AKI were: use of nephrotoxic drugs (HR: 2.87, 95% CI: 1.07-7.65; p = 0.035), mucositis (HR: 1.95, 95% CI: 1.16-3.29; p = 0.012) and shock (HR: 2.63, 95% CI: 1.19-5.85; p = 0.017). Moderate to severe AKI was independently associated with lower overall survival (HR: 2.04, 95% CI: 1.06-3.94; p = 0.033). No association with relapse nor progression to chronic kidney disease (CKD) was found. AKI affects almost two thirds of patients with lymphomas submitted to autologous HSCT. Nephrotoxic drugs, mucositis and shock are important independent AKI risk factors. More than one third of AKI episodes are moderate to severe and these are associated with lower overall survival.


Assuntos
Injúria Renal Aguda , Transplante de Células-Tronco Hematopoéticas , Linfoma , Mucosite , Humanos , Creatinina , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Linfoma/complicações , Linfoma/terapia
9.
J Inherit Metab Dis ; 45(4): 769-781, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35279850

RESUMO

Congenital disorders of glycosylation type 1 (CDG-I) comprise a group of 27 genetic defects with heterogeneous multisystem phenotype, mostly presenting with nonspecific neurological symptoms. The biochemical hallmark of CDG-I is a partial absence of complete N-glycans on transferrin. However, recent findings of a diagnostic N-tetrasaccharide for ALG1-CDG and increased high-mannose N-glycans for a few other CDG suggested the potential of glycan structural analysis for CDG-I gene discovery. We analyzed the relative abundance of total plasma N-glycans by high resolution quadrupole time-of-flight mass spectrometry in a large cohort of 111 CDG-I patients with known (n = 75) or unsolved (n = 36) genetic cause. We designed single-molecule molecular inversion probes (smMIPs) for sequencing of CDG-I candidate genes on the basis of specific N-glycan signatures. Glycomics profiling in patients with known defects revealed novel features such as the N-tetrasaccharide in ALG2-CDG patients and a novel fucosylated N-pentasaccharide as specific glycomarker for ALG1-CDG. Moreover, group-specific high-mannose N-glycan signatures were found in ALG3-, ALG9-, ALG11-, ALG12-, RFT1-, SRD5A3-, DOLK-, DPM1-, DPM3-, MPDU1-, ALG13-CDG, and hereditary fructose intolerance. Further differential analysis revealed high-mannose profiles, characteristic for ALG12- and ALG9-CDG. Prediction of candidate genes by glycomics profiling in 36 patients with thus far unsolved CDG-I and subsequent smMIPs sequencing led to a yield of solved cases of 78% (28/36). Combined plasma glycomics profiling and targeted smMIPs sequencing of candidate genes is a powerful approach to identify causative mutations in CDG-I patient cohorts.


Assuntos
Defeitos Congênitos da Glicosilação , Defeitos Congênitos da Glicosilação/diagnóstico , Defeitos Congênitos da Glicosilação/genética , Glicômica , Glicosilação , Humanos , Manose , Manosiltransferases/genética , N-Acetilglucosaminiltransferases , Oligossacarídeos , Polissacarídeos/genética
10.
BMC Public Health ; 22(1): 2341, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36517802

RESUMO

BACKGROUND: Lifestyle factors are widely recognized as modifiers and major risk factors for non-communicable diseases. Previous studies on the prevalence of multimorbidity in Portugal predict an unfavourable reality. The aim of the present study was to analyse 1) the prevalence of multimorbidity in Portugal and 2) the association of individuals' lifestyles and sociodemographic factors with multimorbidity. METHODS: A cross-sectional, population-wide study was conducted on a representative sample of the general population of Portuguese adults aged ≥ 20 years. Categorical variables were described by their respective absolute and relative frequencies (n (%)). All variables with a p-value < 20% were included in the multiple logistic regression model. The variables were removed one by one in descending order of p-value (p) until the model contained only significant variables. The results are presented using the odds ratio and 95% confidence intervals. P-values ​​ < 5% were considered significant. RESULTS: The prevalence of multimorbidity was 48.9% (n = 436), and the odds of multimorbidity increased 4% (p < 0.001) for each year of increase in age. Participants with reasonable general health status had higher odds of multimorbidity (Odds ratio (OR) = 3.04; p < 0.001), and those with poor or very poor general health status had even higher odds (OR = 9.14; p < 0.001). Compared to those who never smoked, participants who quit smoking ≥ 1 year presented an increase of 91% (p = 0.005) in the odds of multimorbidity. Individuals with no good-quality sleep, non-moderate screen time, or non-moderate stress level had higher odds of multimorbidity (OR = 1.98; OR = 1.88; OR = 2.22, respectively. p < 0.001). CONCLUSIONS: This study presented a new approach to multimorbidity in Portugal. Population-based, multidimensional lifestyle interventions are needed. It seems necessary to optimize and adjust measures to prevent non-communicable diseases to improve health in Portugal. In the future, longitudinal studies will be an asset to reinforce and clarify these conclusions.


Assuntos
Multimorbidade , Doenças não Transmissíveis , Adulto , Humanos , Estudos Transversais , Portugal/epidemiologia , Doenças não Transmissíveis/epidemiologia , Fatores Sociodemográficos , Estilo de Vida , Prevalência
11.
Anim Biotechnol ; 33(6): 1014-1024, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33380273

RESUMO

Cells from different origins behave differently regarding the incorporation of exogenous DNA and formation of transgenic cells. Milk production of recombinant antibody may benefit from efficient transfection protocols to produce transgenic animals. In this context, the objective of this study was to verify the transfection potential of bovine mesenchymal stem cells from Wharton's jelly (MSC-WJ) and adipose tissue (MSC-AT), comparing co-transfection protocols with vectors pBC1-anti-CD3 and pEF-NEO-GFP, using transfection reagents Lipofectamine LTX with Plus Reagent or Xfect. Skin fibroblasts (FIB) were used as the control group. Forty-eight hours after transfection, neomycin was added and cells cultured for 2 weeks. Treated cells were submitted to fluorescence microscopy, flow cytometry, and PCR evaluations. Wharton's jelly cells were sensitive to treatments and started necrosis. In the flow cytometry assay, the median fluorescence was higher in adipocytes than fibroblasts, for both the Xfect (20.057 ± 1.620,7 and 10.601 ± 702,86, respectively, p < 0.05) and LTX (19.590 ± 113,84 and 10.518 ± 442,65, respectively, p < 0.05). These results, associated with evaluation of epifluorescence, demonstrated that adipocytes presented a better response to transfection than other cells, independent of the kit used. Performing PCR on co-transfected cells demonstrated the presence of anti-CD3, making this approach feasible for future experiments.


Assuntos
Células-Tronco Mesenquimais , Geleia de Wharton , Bovinos , Animais , Células Cultivadas , Geleia de Wharton/metabolismo , Transfecção , Adipócitos , Diferenciação Celular
12.
An Acad Bras Cienc ; 94(suppl 4): e20220150, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36228207

RESUMO

This study aimed to evaluate the air and water contamination level and to identify the microbes isolated from a rodent facility located at the Federal University of Uberlândia, Minas Gerais, Brazil. Colony forming units (CFU) per milliliter was used for monitoring water quantitatively; CFU per cubic meter was used for air monitoring. The isolated colonies were identified for qualitative monitoring. Due to absence of specific parameters for these facilities, the results were analyzed according to Brazilian and international standards, depending on which best suited each sample. The mean total number of microorganisms in water ranged from 0.015 ± 0.02 to 0.999 ± 0.91 CFU/mL. The number of microorganisms in air ranged from 9.1 ± 4.6 to 351.56 ± 158.2 CFU/m³. Forty-one microorganisms identified in the samples obtained from the rodent facility were potentially pathogenic or opportunistic for animals and humans (e.g., Corynebacterium spp.). We concluded that the water and air samples were contaminated with potentially pathogenic or opportunistic microorganisms that can harm rodents and humans. On the basis of our observations, specific sanitary standards suitable for these facilities should be developed for controlling microbial contamination, which will prevent zoonosis and ensure the reliability of scientific results obtained from animal experiments.


Assuntos
Microbiologia do Ar , Roedores , Animais , Brasil , Fungos , Humanos , Reprodutibilidade dos Testes , Água
13.
Chem Biodivers ; 19(4): e202200097, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35213780

RESUMO

This updated review article covers the literature between 2011 and 2021 on the antibacterial activity of EOs against the main bacteria that cause caries and periodontal diseases. The criteria to classify the in vitro antibacterial activity of EOs is updated and the most promising results are addressed.


Assuntos
Óleos Voláteis , Antibacterianos/farmacologia , Bactérias , Testes de Sensibilidade Microbiana , Óleos Voláteis/farmacologia
14.
Anaerobe ; 76: 102588, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35618163

RESUMO

OBJECTIVES: Periodontitis is a pathology resulting from complex interaction of microorganisms in the dental biofilm with the host's immune system. Increased use of antibiotics associated with their inappropriate use has increased resistance levels in anaerobic bacteria. Therefore, identifying new antimicrobial compounds, such as chalcones, is urgent. This study evaluates the antibacterial activity and the antibiofilm activity of 15 chalcones against the periodontopathogenic bacteria Prevotella nigrescens (ATCC 33563), P. oralis (ATCC 33269), Peptostreptococcus anaerobius (ATCC 27337), Actinomyces viscosus (ATCC 43146), Porphyromonas asaccharolytica (ATCC 25260), and Fusobacterium nucleatum (ATCC 25586). METHODS: The compounds were evaluated by minimum inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC) tests. RESULTS: Compounds 1-6 showed good antibacterial and antibiofilm activities against most of the evaluated bacteria: MIC was lower than or equal to 6.25 µg/mL, biofilm biomass was reduced by 95%, and the compounds at concentrations between 0.78 and 100 µg/mL totally inhibited cell viability. Among the tested chalcones, 3 stood out: it was effective against all the bacteria, as revealed by the MIC and MBIC results. CONCLUSIONS: Our results have consolidated a base for the development of new studies on the effects of the tested chalcones as agents to combat and to prevent periodontitis.


Assuntos
Chalconas , Periodontite , Antibacterianos/farmacologia , Bactérias , Biofilmes , Chalconas/farmacologia , Humanos , Testes de Sensibilidade Microbiana
15.
Odontology ; 110(3): 434-443, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34800212

RESUMO

To evaluate i) the inhibitory and bactericidal activity of cashew nut shell liquid (CNSL) and its isolated compounds (anacardic acid and cardol) against oral bacteria; ii) the biofilm formation inhibition, resin-dentin bond strength and physicochemical properties of a dental adhesive incorporated with these substances. The antibacterial effect of CNSL, anacardic acid, and cardol were assessed by determining the minimum inhibitory (MIC) and minimum bactericidal (MBC) concentrations. Effect in inhibiting biofilm formation of the adhesive incorporated with the substances (15 µg/ml) against a mixed-species biofilm of Streptococcus mutans and Candida Albicans and was determined by direct contact test. Additional Analysis included microtensile bond strength (µTBS) test, elastic modulus (EM), flexural strength (FS), degree of conversion (DC), water sorption (WS) and solubility (SL). The data were submitted to statistical analysis by one-way ANOVA and Tukey's test (p < 0.05). CNSL, anacardic acid and cardol showed antibacterial activity for all strains tested, with MIC and MBC values ranging from 3.12 to 25 µg/ml. There was no growth of colonies forming units in the adhesives incorporated with the substances. EM increased in the adhesive incorporated with anacardic acid, decreased after incorporation of cardol and it was not affected by incorporation of CNSL. The substances tested showed no effect in FS, DC, WS, SL and µTBS. In conclusion, the CNSL, anacardic acid and cardol showed antibacterial effects against oral bacteria and, the incorporation of substances did not reduce the performance of the adhesive.


Assuntos
Anacardium , Colagem Dentária , Anacardium/química , Antibacterianos/farmacologia , Cimentos Dentários/química , Dentina/química , Adesivos Dentinários/química , Teste de Materiais , Nozes/química , Cimentos de Resina/química , Cimentos de Resina/farmacologia , Streptococcus mutans , Resistência à Tração
16.
Molecules ; 27(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36364137

RESUMO

Helicobacter pylori is a Gram-negative, microaerophilic, curved-rod, flagellated bacterium commonly found in the stomach mucosa and associated with different gastrointestinal diseases. With high levels of prevalence worldwide, it has developed resistance to the antibiotics used in its therapy. Brazilian red propolis has been studied due to its biological properties, and in the literature, it has shown promising antibacterial activities. The aim of this study was to evaluate anti-H. pylori from the crude hydroalcoholic extract of Brazilian red propolis (CHEBRP). For this, in vitro determination of the minimum inhibitory and bactericidal concentration (MIC/MBC) and synergistic activity and in vivo, microbiological, and histopathological analyses using Wistar rats were carried out using CHEBRP against H. pylori strains (ATCC 46523 and clinical isolate). CHEBRP presented MIC/MBC of 50 and 100 µg/mL against H. pylori strains (ATCC 43526 and clinical isolate, respectively) and tetracycline MIC/MBC of 0.74 µg/mL. The association of CHEBRP with tetracycline had an indifferent effect. In the stomach mucosa of rats, all treatments performed significantly decreased the number of H. pylori, and a concentration of 300 mg/kg was able to modulate the inflammatory response in the tissue. Therefore, CHEBRP showed promising anti-H. pylori in in vitro and in vivo assays.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Própole , Ratos , Animais , Própole/farmacologia , Própole/uso terapêutico , Brasil , Ratos Wistar , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Imunidade , Tetraciclinas/farmacologia , Testes de Sensibilidade Microbiana , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia
17.
Mov Disord ; 36(7): 1654-1663, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33595142

RESUMO

BACKGROUND: Hereditary spastic paraplegia presents spasticity as the main clinical manifestation, reducing gait quality and producing incapacity. Management with botulinum toxin type A (BoNT-A) is not well elucidated. The objective of the current study was to evaluate the efficacy and safety of BoNT-A in patients with hereditary spastic paraplegias. METHODS: This was a double-blind, randomized, placebo-controlled crossover trial. Each participant was randomly assigned to receive 1 injection session of either BoNT-A (100 IU/2 mL of Prosigne in each adductor magnus and each triceps surae) or saline 0.9% (2 mL). The primary outcome measure was change from baseline in maximal gait velocity, and secondary outcome measures included changes in gait at self-selected velocity, spasticity, muscle strength, Spastic Paraplegia Rating Scale, pain, fatigue, and subjective perception of improvement. We also looked at adverse events reported by the patients. RESULTS: We enrolled 55 patients, 36 of whom were men and 41 with the pure phenotype. Mean age was 43 ± 13.4 years (range, 19-72 years), mean age of onset waws 27 ± 13.1 years (range, <1 to 55 yars), and mean disease duration was 17 ± 12.7 years (range, 1-62 years). Compared with baseline, we did not find significant differences between groups in primary and secondary outcomes, except for reduction in adductor tone (P = 0.01). The adverse events were transient and tolerable, and their incidence did not significantly differ between treatments (P = 0.17). CONCLUSIONS: BoNT-A was safe in patients with hereditary spastic paraplegias and reduced the adductor tone, but it was not able to produce functional improvement considering the doses, injection protocol, measures, and instruments used. © 2021 International Parkinson and Movement Disorder Society.


Assuntos
Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Paraplegia Espástica Hereditária , Adolescente , Adulto , Criança , Pré-Escolar , Método Duplo-Cego , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/tratamento farmacológico , Fármacos Neuromusculares/uso terapêutico , Paraplegia Espástica Hereditária/tratamento farmacológico , Resultado do Tratamento , Adulto Jovem
18.
J Peripher Nerv Syst ; 26(3): 290-297, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34190362

RESUMO

This study aimed to describe the clinical, genetic, and epidemiological features of Charcot-Marie-Tooth disease (CMT) in Brazilian patients from a tertiary center, and to compare our data with previously published findings. This retrospective observational study conducted between February 2015 and July 2020 evaluated 503 patients (94 families and 192 unrelated individuals), diagnosed with CMT. Clinical and neurophysiological data were obtained from electronic medical records and blood samples were used for genetic analyses. Multiplex ligation-dependent probe amplification was used to assess duplications/deletions in PMP22. Sanger sequencing of GJB1 was performed in cases of suspected demyelinating CMT. Targeted gene panel sequencing was used for the remaining negative demyelinating cases and all axonal CMT cases. The first decade of life was the most common period of disease onset. In all, 353 patients had demyelinating CMT, 39 had intermediate CMT, and 111 had axonal CMT. Pathogenic or likely pathogenic variants were identified in 197 index cases. The most common causative genes among probands were PMP22 (duplication) (n = 116, 58.88%), GJB1 (n = 23, 11.67%), MFN2 (n = 12, 6.09%), GDAP1 (n = 7, 3.55%), MPZ (n = 6, 3.05%), PMP22 (point mutation) (n = 6, 3.05%), NEFL (n = 3, 1.52%), SBF2 (n = 3, 1.52%), and SH3TC2 (n = 3, 1.52%). Other identified variants were ≤1% of index cases. This study provides further data on the frequency of CMT subtypes in a Brazilian clinical-based population and highlights the importance of rarer and previously undiagnosed variants in clinical practice.


Assuntos
Doença de Charcot-Marie-Tooth , Doença de Charcot-Marie-Tooth/epidemiologia , Doença de Charcot-Marie-Tooth/genética , Perfil Genético , Testes Genéticos , Humanos , Reação em Cadeia da Polimerase Multiplex , Mutação/genética , Proteínas/genética , Estudos Retrospectivos
19.
An Acad Bras Cienc ; 93(1): e20181265, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33886697

RESUMO

Blackberry is a species which has high potential to grow in an organic production system. However, there is scarce information on the behavior of cultivars and selections of this species conducted in an ecologically based system, a fact that makes it difficult to recommend cultivars for this production system. This study aimed to evaluate and characterize the phenology and productive aspects of six blackberry genotypes grown in an organic system, in Pelotas, Rio Grande do Sul (RS) state, Brazil. Evaluation of the following variables was carried out in the three first production cycles (2015-2016, 2016-2017 and 2017-2018): phenology, number of fruits.pl-¹, mean fruit yield.pl-¹, yield (kg.ha-¹), mean fruit mass (g) and soluble solid content (° Brix). Regarding phenology, genotype Black 112 was later than the others whereas Black 178 was the most precocious one. In the last year under evaluation, genotypes yielded around 10 ton.ha-¹, except Black 128 selection, which yielded approximately 6,767 ton.ha-¹. Genotypes Black 178, Black 112 and Black 145 and both cultivars BRS Xingu and Tupy exhibited potential to grow in an organic production system.


Assuntos
Rubus , Brasil , Frutas/genética , Genótipo
20.
An Acad Bras Cienc ; 93(1): e20181351, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33825788

RESUMO

Pecan trees require adequate soil moisture conditions to produce nuts with good yield and quality. Irrigation should be an important considered practice in orchards management plan, mainly in regions with water deficit periods. The objective of this research was to evaluate irrigation on pecan nuts growth and yield. This study was conducted in Uruguay, during the fast development phase until the pecan nuts harvest. Three irrigation treatments were used: 0 L (control), 70 L and 140 L plant-1 of water every two days, applied via drip irrigation in seven-year-old pecan trees of the cultivar Success. The number of nuts per cluster and nuts' diameter and length were evaluated during nut growth. After harvesting, peeled nuts' width and length were measured, and after peeling, the kernel length, width, height and filling and the kernel and peel percentage were evaluated. According to the results, it was possible to identify that periods of water deficit during pecan nuts development affected the kernel filling stageand size. Irrigation in pecan plants provides greater dimensions and nuts mass. With the use of 140 L plant-1, there was an increase in the nut mass of more than 100% in relation to the nuts from plants without irrigation.


Assuntos
Carya , Nozes , Uruguai
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