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1.
J Neurosci ; 43(40): 6816-6829, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37625855

RESUMO

Dysfunctions in growth hormone (GH) secretion increase the prevalence of anxiety and other neuropsychiatric diseases. GH receptor (GHR) signaling in the amygdala has been associated with fear memory, a key feature of posttraumatic stress disorder. However, it is currently unknown which neuronal population is targeted by GH action to influence the development of neuropsychiatric diseases. Here, we showed that approximately 60% of somatostatin (SST)-expressing neurons in the extended amygdala are directly responsive to GH. GHR ablation in SST-expressing cells (SSTΔGHR mice) caused no alterations in energy or glucose metabolism. Notably, SSTΔGHR male mice exhibited increased anxiety-like behavior in the light-dark box and elevated plus maze tests, whereas SSTΔGHR females showed no changes in anxiety. Using auditory Pavlovian fear conditioning, both male and female SSTΔGHR mice exhibited a significant reduction in fear memory. Conversely, GHR ablation in SST neurons did not affect memory in the novel object recognition test. Gene expression was analyzed in a micro punch comprising the central nucleus of the amygdala (CEA) and basolateral (BLA) complex. GHR ablation in SST neurons caused sex-dependent changes in the expression of factors involved in synaptic plasticity and function. In conclusion, GHR expression in SST neurons is necessary to regulate anxiety in males, but not female mice. GHR ablation in SST neurons also decreases fear memory and affects gene expression in the amygdala, although marked sex differences were observed. Our findings identified for the first time a neurochemically-defined neuronal population responsible for mediating the effects of GH on behavioral aspects associated with neuropsychiatric diseases.SIGNIFICANCE STATEMENT Hormone action in the brain regulates different neurological aspects, affecting the predisposition to neuropsychiatric disorders, like depression, anxiety, and posttraumatic stress disorder. Growth hormone (GH) receptor is widely expressed in the brain, but the exact function of neuronal GH action is not fully understood. Here, we showed that mice lacking the GH receptor in a group of neurons that express the neuropeptide somatostatin exhibit increased anxiety. However, this effect is only observed in male mice. In contrast, the absence of the GH receptor in somatostatin-expressing neurons decreases fear memory, a key feature of posttraumatic stress disorder, in males and females. Thus, our study identified a specific group of neurons in which GH acts to affect the predisposition to neuropsychiatric diseases.


Assuntos
Hormônio do Crescimento , Somatostatina , Feminino , Masculino , Camundongos , Animais , Somatostatina/metabolismo , Hormônio do Crescimento/metabolismo , Ansiedade , Medo , Receptores da Somatotropina/genética , Receptores da Somatotropina/metabolismo , Neurônios/metabolismo
2.
Mol Psychiatry ; 28(10): 4463-4473, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37452088

RESUMO

While our understanding of the molecular biology of Alzheimer's disease (AD) has grown, the etiology of the disease, especially the involvement of peripheral infection, remains a challenge. In this study, we hypothesize that peripheral infection represents a risk factor for AD pathology. To test our hypothesis, APP/PS1 mice underwent cecal ligation and puncture (CLP) surgery to develop a polymicrobial infection or non-CLP surgery. Mice were euthanized at 3, 30, and 120 days after surgery to evaluate the inflammatory mediators, glial cell markers, amyloid burden, gut microbiome, gut morphology, and short-chain fatty acids (SCFAs) levels. The novel object recognition (NOR) task was performed 30 and 120 days after the surgery, and sepsis accelerated the cognitive decline in APP/PS1 mice at both time points. At 120 days, the insoluble Aß increased in the sepsis group, and sepsis modulated the cytokines/chemokines, decreasing the cytokines associated with brain homeostasis IL-10 and IL-13 and increasing the eotaxin known to influence cognitive function. At 120 days, we found an increased density of IBA-1-positive microglia in the vicinity of Aß dense-core plaques, compared with the control group confirming the predictable clustering of reactive glia around dense-core plaques within 15 µm near Aß deposits in the brain. In the gut, sepsis negatively modulated the α- and ß-diversity indices evaluated by 16S rRNA sequencing, decreased the levels of SCFAs, and significantly affected ileum and colon morphology in CLP mice. Our data suggest that sepsis-induced peripheral infection accelerates cognitive decline and AD pathology in the AD mouse model.


Assuntos
Doença de Alzheimer , Microbioma Gastrointestinal , Sepse , Camundongos , Animais , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Doenças Neuroinflamatórias , RNA Ribossômico 16S , Camundongos Transgênicos , Amiloide , Citocinas , Placa Amiloide , Sepse/complicações , Peptídeos beta-Amiloides , Modelos Animais de Doenças
3.
J Oral Rehabil ; 51(8): 1521-1529, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38717007

RESUMO

BACKGROUND: Current clinical approaches to regenerate temporomandibular joint (TMJ) articulating cartilage defects only treat the symptoms (i.e. pain and dysfunction) and do not seek to restore joint integrity for long-term relief. Therefore, we investigated a novel self-assembling tissue-engineered cartilage to overcome this significant clinical issue for TMJ regenerative purposes. OBJECTIVES: Examine the maturation of dynamic self-regenerating cartilage (dSRC) using auricular chondrocytes and evaluate a novel combinatorial approach with fractional laser treatment and dSRC implantation for TMJ cartilage repair. MATERIALS AND METHODS: A suspension of 107 freshly harvested rabbit ear chondrocytes was cultured under a continuous reciprocating motion to form the dSRC. After 2, 4 and 8 weeks of culture, dSRC samples were stained with H&E, Safranin-O and Toluidine Blue. Immunohistochemistry (IHC) was performed for collagens type I and II. Channels (300-500 µm diameter and 1.2-1.5 mm depth) were created in six freshly harvested condyles using a fractional Erbium laser. Two groups were tested: dSRC in a laser-ablated lesion (experimental) and an empty laser-ablated channel (control). TMJ condyles were cultured for up to 8 weeks and analysed as described above. RESULTS: H&E staining showed a high cell density in dSRC compared to native cartilage. All dSRC groups demonstrated intense Safranin-O staining, indicating high glycosaminoglycan (GAG) production and intense Toluidine Blue staining showed high proteoglycan content. IHC confirmed that dSRC consisted predominantly of collagen type II. The experimental group showed improved cartilage repair at both time points compared to the empty channels. CONCLUSION: dSRC viability and successful matrix formation were demonstrated in vitro. The combination of fractional laser ablation and dSRC implantation enhanced cartilage repair.


Assuntos
Cartilagem Articular , Condrócitos , Regeneração , Articulação Temporomandibular , Engenharia Tecidual , Animais , Coelhos , Condrócitos/transplante , Engenharia Tecidual/métodos , Articulação Temporomandibular/cirurgia , Articulação Temporomandibular/patologia , Regeneração/fisiologia , Cartilagem Articular/cirurgia , Cartilagem Articular/patologia , Transtornos da Articulação Temporomandibular/cirurgia , Transtornos da Articulação Temporomandibular/fisiopatologia , Transtornos da Articulação Temporomandibular/terapia , Células Cultivadas , Cartilagem da Orelha/fisiologia , Técnicas In Vitro
4.
Genet Mol Biol ; 46(3 Suppl 1): e20230143, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38569056

RESUMO

Galileo is a transposon notoriously involved with inversions in Drosophila buzzatii by ectopic recombination. Although widespread in Drosophila, little is known about this transposon in other lineages of Drosophilidae. Here, the abundance of the canonical Galileo and its evolutionary history in Drosophilidae genomes was estimated and reconstructed across genera within its two subfamilies. Sequences of this transposon were masked in these genomes and their transposase sequences were recovered using BLASTn. Phylogenetic analyses were employed to reconstruct their evolutionary history and compare it to that of host genomes. Galileo was found in nearly all 163 species, however, only 37 harbored nearly complete transposase sequences. In the remaining, Galileo was found highly fragmented. Copies from related species were clustered, however horizontal transfer events were detected between the melanogaster and montium groups of Drosophila, and between the latter and the Lordiphosa genus. The similarity of sequences found in the virilis and willistoni groups of Drosophila was found to be a consequence of lineage sorting. Therefore, the evolution of Galileo is primarily marked by vertical transmission and long-term inactivation, mainly through the deletion of open reading frames. The latter has the potential to lead copies of this transposon to become miniature inverted-repeat transposable elements.

5.
Clin Sci (Lond) ; 137(6): 401-414, 2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-36942500

RESUMO

Sepsis is a life-threatening organ dysfunction triggered by a dysregulated host immune response to eliminate an infection. After the host immune response is activated, a complex, dynamic, and time-dependent process is triggered. This process promotes the production of inflammatory mediators, including acute-phase proteins, complement system proteins, cytokines, chemokines, and antimicrobial peptides, which are required to initiate an inflammatory environment for eliminating the invading pathogen. The physiological response of this sepsis-induced systemic inflammation can affect blood-brain barrier (BBB) function; subsequently, endothelial cells produce inflammatory mediators, including cytokines, chemokines, and matrix metalloproteinases (MMPs) that degrade tight junction (TJ) proteins and decrease BBB function. The resulting BBB permeability allows peripheral immune cells from the bloodstream to enter the brain, which then release a range of inflammatory mediators and activate glial cells. The activated microglia and astrocytes release reactive oxygen species (ROS), cytokines, chemokines, and neurochemicals, initiate mitochondrial dysfunction and neuronal damage, and exacerbate the inflammatory milieu in the brain. These changes trigger sepsis-associated encephalopathy (SAE), which has the potential to increase cognitive deterioration and susceptibility to cognitive decline later in life.


Assuntos
Células Endoteliais , Sepse , Humanos , Células Endoteliais/metabolismo , Encéfalo/metabolismo , Barreira Hematoencefálica/metabolismo , Sepse/complicações , Sepse/metabolismo , Citocinas/metabolismo , Quimiocinas/metabolismo , Mediadores da Inflamação/metabolismo
6.
Genome ; 66(7): 193-201, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37120861

RESUMO

Genome size evolution is known to be related with transposable elements, yet such relation in incipient species remains poorly understood. For decades, the willistoni subgroup of Drosophila has been a model for evolutionary studies because of the different evolutionary stages and degrees of reproductive isolation its species present. Our main question here was how speciation influences genome size evolution and the fraction of repetitive elements, with a focus on transposable elements. We quantitatively compared the mobilome of four species and two subspecies belonging to this subgroup with their genome size, and performed comparative phylogenetic analyses. Our results showed that genome size and the fraction of repetitive elements evolved according to the evolutionary history of these species, but the content of transposable elements showed some discrepancies. Signals of recent transposition events were detected for different superfamilies. Their low genomic GC content suggests that in these species transposable element mobilization might be facilitated by relaxed natural selection. Additionally, a possible role of the superfamily DNA/TcMar-Tigger in the expansion of these genomes was also detected. We hypothesize that the undergoing process of speciation could be promoting the observed increase in the fraction of repetitive elements and, consequently, genome size.


Assuntos
Elementos de DNA Transponíveis , Drosophila , Animais , Drosophila/genética , Tamanho do Genoma , Filogenia , Genômica , Evolução Molecular
7.
Clin Oral Investig ; 27(6): 2993-3000, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36781476

RESUMO

OBJECTIVE: Present a gnathodynamometer design that increases patient comfort, precision, and/or ease for the operator during bite force tests. MATERIALS AND METHODS: A bite tip capable of pivoting 180° was tested on senior dental students in a double-blind trial. The tests were performed in teeth 11 and 16 with the bite tip on the long axis of the clamp and at an angle of 90° to the clamp. The sample was composed of 24 students, 13 males and 11 females, randomly divided into two groups: the operator group (OP), which was composed of 12 students, 7 males and 5 females, and the test group (TI), which was composed of 12 students, 6 males and 6 females. The operator and participants were asked to evaluate comfort and precision/ease in positioning the bite tip by attributing scores from 0 (total discomfort) to 10 (total comfort) during the test. RESULTS: No difference was noted in tooth 11 (P > 0.05). In tooth 16, there was a statistically significant improvement (P < 0.01) for the participants tested and the operator using the pivoting bite tip. CONCLUSIONS: The pivoting bite tip showed no difference in the comfort of the participants and operator precision when testing incisors; however, the tip showed a difference for both conditions in the molar region. The gnathodynamometer geometry showed good results in participant comfort and operator precision when used in bite force tests of the incisors and molars. Further investigations are needed to confirm whether these improvements influence the mean value and maximum bite force measurement. CLINICAL RELEVANCE: Bite force measurement is a method for obtaining important data to check the functional conditions of the stomatognathic system. With the aging of the world population, it has become important to check the quality of life during aging. The pivoting bite tip improves the comfort and precision of bite tests for the participants tested and for the operator, respectively.


Assuntos
Força de Mordida , Qualidade de Vida , Masculino , Feminino , Humanos , Oclusão Dentária , Dente Molar , Incisivo
8.
An Acad Bras Cienc ; 94(suppl 2): e20210399, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35730896

RESUMO

The 2019 oil spill was the biggest in Brazilian history. Oil was found along more than 3,000 km of the Brazilian coastline, mainly in the Northeast, in more than 1,000 localities. This article analyzes the disaster's damage using a sample of interviewers who were impacted - fishers, tourism and beach hawkers - distributed along 40 of the affected municipalities in the Northeast Region of Brazil. The socio-economic indicators obtained by the research show that the impacts were not homogeneous between the segments and cities researched. Localities specialized in tourism and with a workforce relatively more specialized in fishing were the most affected. Accordingly, the populations of fishers and beach hawkers suffered the most severe impacts in terms of income reduction and the sale of products. These agents report a negative impact of the disaster on their work activities of 73% (fishers) and 65% (beach vendors), while the lodging and food sectors reported losses in about 38% of the cases. The interviewees' health indicators demonstrated that the volunteers at the oil spill clean- up suffered damage due to the exposure experienced, evidencing the public health emergency dimension of the disaster.


Assuntos
Desastres , Poluição por Petróleo , Brasil , Humanos , Poluição por Petróleo/efeitos adversos , Fatores Socioeconômicos
9.
Int J Mol Sci ; 23(16)2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-36012163

RESUMO

Leishmaniasis is a neglected tropical disease that kills more than 20,000 people each year. The chemotherapy available for the treatment of the disease is limited, and novel approaches to discover novel drugs are urgently needed. Herein, 2D- and 4D-quantitative structure-activity relationship (QSAR) models were developed for a series of oxazole and oxadiazole derivatives that are active against Leishmania infantum, the causative agent of visceral leishmaniasis. A clustering strategy based on structural similarity was applied with molecular fingerprints to divide the complete set of compounds into two groups. Hierarchical clustering was followed by the development of 2D- (R2 = 0.90, R2pred = 0.82) and 4D-QSAR models (R2 = 0.80, R2pred = 0.64), which showed improved statistical robustness and predictive ability.


Assuntos
Antiprotozoários , Leishmaniose Visceral , Antiprotozoários/química , Análise por Conglomerados , Humanos , Leishmaniose Visceral/tratamento farmacológico , Oxidiazóis/farmacologia , Oxidiazóis/uso terapêutico , Oxazóis/farmacologia , Oxazóis/uso terapêutico , Relação Quantitativa Estrutura-Atividade
10.
J Contemp Dent Pract ; 23(6): 618-622, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36259301

RESUMO

AIM: The aim of this study was to evaluate the profile of patients undergoing dental treatment in relation to cannabis use. MATERIALS AND METHODS: A comprehensive questionnaire was used to address the type of cannabis preparations, route of intake, frequency of usage, and potential reasoning for use (recreational vs medical use) of patients from the MGH Dental Group. RESULTS: Seventy-six adult patients completed the survey. Sixty-one percent of the participants were female, with the majority (59%) of the participants being ≥51 years or older. Twelve of the 76 participants (16%) were 18-30 years old. The remaining 19 patients (25%) who participated in the study were 31-50 years old. The sample included participants who were predominately non-Hispanic (63 patients, 83%) and White (59 patients, 78%). The majority of patients either had their first use of cannabis prior to 18 years of age (36%) or did not respond to this question (34%) at all. The predominant age at consistent cannabis use was 18-30 years (13%). The most common method of cannabis intake in the preceding year for participants was smoking, followed by ingesting, using cannabidiol (CBD), and vaping (least common). Recreational cannabis use was reported in 47% of the participants vs 28% of participants who reported cannabis intake for medical use. CONCLUSION: This preliminary study characterized the profile of patients undergoing dental treatment in relation to marijuana use. Diminishing restraints to cannabis use may affect the dental profession. CLINICAL SIGNIFICANCE: It is important for dentists to understand cannabis-related oral health conditions to provide customized patient treatments.


Assuntos
Canabidiol , Cannabis , Fumar Maconha , Maconha Medicinal , Adulto , Humanos , Feminino , Masculino , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Maconha Medicinal/uso terapêutico , Hospitais Gerais , Fumar Maconha/efeitos adversos , Analgésicos
12.
An Acad Bras Cienc ; 91(3): e20180226, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576912

RESUMO

Stable isotopes have been widely used in the literature both to discuss current ocean circulation processes, as well as to reconstitute paleoceanographic parameters. The distribution of oxygen and deuterium stable isotopes in seawater (δ18Osw and δDsw) at the Western Tropical South Atlantic border was investigated to better understand the main fractionation processes of these isotopes and establish a regional salinity and δ18Osw relation to improve the paleoceanographic knowledge in the region. This study was conducted during a quasi-synoptic oceanographic cruise in which 98 discrete seawater samples were collected in the core of the main water masses for stable isotope analysis. A strong correlation between δ18Osw and δD was found, which made it possible to extrapolate the results for δ18Osw to δD. Although it was not possible to distinguish the water masses based only on their isotopic signatures, the water masses had a strong salinity and δ18Osw relation, and compared with previous studies, a seasonal pattern was observed. Paleosalinity differences of up to 0.2 psu between Summer and Winter are reported. Considering the limitations of the current techniques to seasonally separate the samples for the paleoceanographic studies, an intermediate Mixing Line for the Tropical South Atlantic (SSS = 1.942* δ18Osw + 34.56) was proposed to reduce the estimated errors associated with these seasonal variations.


Assuntos
Isótopos de Oxigênio/química , Salinidade , Água do Mar/química , Clima Tropical , Oceano Atlântico , Brasil , Oceanografia , Estações do Ano , Temperatura
13.
Exp Mol Pathol ; 105(3): 352-356, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30343009

RESUMO

INTRODUCTION: Hybrid oncocytic/chromophobe tumor (HOCT) is a renal cell neoplasm displaying overlapping cellular and architectural features of both renal oncocytoma (RO) and chromophobe renal cell carcinoma (chRCC). It has been described in the context of oncocytosis, Birt-Hogg-Dubé syndrome, and also sporadically. Thus far, HOCT immunohischemical profile and cytogenetic alterations have been reported, but not epigenetic alterations. Herein, we characterize a HOCT case, including microRNA expression, comparing it to sporadic RO and chRCC. METHODS: An HOCT was entirely submitted. Representative paraffin blocks were selected for histochemical, immunohistochemical and FISH analyses. MicroRNAs were extracted from the two components separately and selected microRNA expression was performed. RESULTS: This 4 cm HOCT, from a 69 year-old female, was composed mainly by oncocytic cells with an insular distribution (RO-like) and areas of larger clarified cells (chRCC-like). The two areas displayed different features: RO-like areas showed negative colloidal iron staining, multifocal CD15, negative CK7, focal multiple tetrasomies, and higher miR21 expression; chRCC-like areas showed colloidal iron diffuse staining with moderate intensity, focal CD15 and CK7, no numeric chromosomic alterations, and higher miR141 and miR200b expression. CONCLUSION: microRNA expression in the two HOCT components is similar to its sporadic tumors counterparts. Morphologic, immunohistochemical, cytogenetic and epigenetic data on this case suggest either two independent pathogenic pathways or an early pathogenic divergence for RO-like and chRCC-like components of HOCT.


Assuntos
Adenoma Oxífilo/genética , Adenoma Oxífilo/patologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Idoso , Biomarcadores Tumorais/análise , Feminino , Humanos
14.
AAPS PharmSciTech ; 19(6): 2585-2597, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29916194

RESUMO

Amphotericin B (AmB), a potent antifungal drug, presents physicochemical characteristics that impair the development of suitable dosage forms. In order to overcome the AmB insolubility, several lipid carriers such as microemulsions have been developed. In this context, the bullfrog oil stands out as an eligible oily phase component, since its cholesterol composition may favor the AmB incorporation. Thus, the aim of this study was to develop a microemulsion based on bullfrog oil containing AmB. Moreover, its thermal stability, antifungal activity, and cytotoxicity in vitro were evaluated. The microemulsion formulation was produced using the pseudo-ternary phase diagram (PTPD) approach and the AmB was incorporated based on the pH variation technique. The antifungal activity was evaluated by determination of minimal inhibitory concentration (MIC) against different species of Candida spp. and Trichosporon asahii. The bullfrog oil microemulsion, stabilized with 16.8% of a surfactant blend, presented an average droplet size of 26.50 ± 0.14 nm and a polydispersity index of 0.167 ± 0.006. This system was able to entrap AmB up to 2 mg mL-1. The use of bullfrog oil as oily phase allowed an improvement of the thermal stability of the system. The MIC assay results revealed a growth inhibition for different strains of Candida spp. and were able to enhance the activity of AmB against T. asahii. The microemulsion was also able to reduce the AmB toxicity. Finally, the developed microemulsion showed to be a suitable system to incorporate AmB, improving the system's thermal stability, increasing the antifungal activity, and reducing the toxicity of this drug.


Assuntos
Anfotericina B/síntese química , Antifúngicos/síntese química , Portadores de Fármacos/síntese química , Emulsões/síntese química , Nanopartículas/química , Óleos/síntese química , Anfotericina B/administração & dosagem , Animais , Antifúngicos/administração & dosagem , Candida/efeitos dos fármacos , Candida/fisiologia , Portadores de Fármacos/administração & dosagem , Emulsões/administração & dosagem , Eritrócitos/efeitos dos fármacos , Eritrócitos/fisiologia , Humanos , Testes de Sensibilidade Microbiana/métodos , Nanopartículas/administração & dosagem , Óleos/administração & dosagem , Rana catesbeiana
15.
J Nanosci Nanotechnol ; 16(2): 1339-45, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27433584

RESUMO

The drawbacks related to the use of viral vectors in gene therapy have been stimulated the research in non-viral strategies such as cationic nanoemulsions. The aim of this work was to develop a stearylamine-containing nanoemulsion for gene therapy purpose. The formulation was chosen from a Pseudo-Ternary Phase Diagram and had its long-term stability assessed by Dynamic Light Scattering and Phase Analysis Light Scattering during 180 days at 4 degrees C, 25 degrees C and 40 degrees C. Besides, studies of sterilization and scale up of the product were conducted. It was demonstrated that the proposed system was stable up to 180 days when stored at 4 degrees C and could be sterilized by a 0.22 microm filter pore without changes on its characteristics. The scale up was possible by adjusting the volume to the sonication time. Because the nanoemulsion presented a droplet size smaller than 200 nm and a zeta potential higher than 30 mV, this system was able to correctly complex the plasmid model PIRES2-EGFP, as confirmed by the agarosis gel electrophoresis assay. The nanoemulsion toxicity evaluated over lung fetus human cells (MRC-5) was dose-dependent. However, it does not appear to be a limiting factor for further experiments aiming gene transfection. As a conclusion, stearylamine-containing cationic nanoemulsions can be used for gene therapy, since it presents suitable characteristics, stability and possibility of sterilization.


Assuntos
Aminas , Técnicas de Transferência de Genes , Nanopartículas/química , Plasmídeos , Aminas/química , Aminas/farmacologia , Linhagem Celular , Emulsões , Humanos , Plasmídeos/química , Plasmídeos/farmacologia
16.
An Acad Bras Cienc ; 88(2): 933-40, 2016 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-27192196

RESUMO

This study aims to verify the effects of coconut oil supplementation (COS) in the body composition and lipid profile of rats submitted to physical exercise. The animals (n=6 per group) were randomly assigned to: G1=Sedentary and Non-supplemented (Control Group), G2=Sedentary and Supplemented, G3=Exercised and Non-supplemented and G4=Exercised and Supplemented. The COS protocol used was 3 mL/Kg of body mass by gavage for 28 days. The physical exercise was the vertical jumping training for 28 days. It was determined the body mass parameters, Lee Index, blood glucose and lipid profile. The COS did not interfere with body mass, but the lean body mass was lower in G3 compared to G2. The final Lee Index classified G1 and G2 as obese (>30g/cm). The lipid profile showed total cholesterol was decreased in G3, LDL-c concentration was decreased in G2, triglycerides, VLDL-c and HDL-c concentrations were increased in G2 and G4 in relation to G1 and G3. The COS decreased LDL-c/HDL-c ratio. In conclusion, the COS associated or not to physical exercise worsen others lipid parameters, like triglycerides and VLDL-c level, showing the care with the use of lipid supplements.


Assuntos
Composição Corporal/efeitos dos fármacos , Óleo de Coco/farmacologia , Animais , Óleo de Coco/administração & dosagem , Lipídeos/análise , Obesidade/diagnóstico , Condicionamento Físico Animal , Distribuição Aleatória , Ratos , Triglicerídeos/análise
17.
Arch Oral Biol ; 159: 105875, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38160519

RESUMO

OBJECTIVE: To assess the outcomes of several rodent animal models for studying tooth extraction-related medication-related osteonecrosis of the jaw (MRONJ). DESIGN: After a search of the databases, 2004 articles were located, and 118 corroborated the inclusion factors (in vivo studies in rodents evaluating tooth extraction as a risk factor for the development of MRONJ). RESULTS: Numerous studies attempting to establish an optimal protocol to induce MRONJ were found. Zoledronic acid (ZA) was the most used drug, followed by alendronate (ALN). Even when ZA did not lead to the development of MRONJ, its effect compromised the homeostasis of the bone and soft tissue. The association of other risk factors (dexamethasone, diabetes, and tooth-related inflammatory dental disease) besides tooth extraction also played a role in the development of MRONJ. In addition, studies demonstrated a relationship between cumulative dose and MRONJ. CONCLUSIONS: Both ZA and ALN can lead to MRONJ in rodents when equivalent human doses (in osteoporosis or cancer treatment) are used. Local oral risk factors and tooth-related inflammatory dental disease increase the incidence of MRONJ in a tooth extraction-related rodent model.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Animais , Humanos , Difosfonatos/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Roedores , Ácido Zoledrônico/efeitos adversos , Extração Dentária/efeitos adversos , Modelos Animais , Alendronato/efeitos adversos
18.
Zootaxa ; 5399(1): 1-18, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38221179

RESUMO

The Drosophila flavopilosa group comprises morphologically cryptic species that are ecologically restricted to feeding, breeding and ovipositing on flowers of Cestrum and Sessea (Solanaceae). Previous studies confirmed the monophyly of the group and the success of DNA barcoding in identifying a subset of its species, but several others remain yet to be evaluated. Furthemore, the taxonomy of the group remains incomplete, with only nine of the 17 species assigned to subgroups. Here, we accessed the phylogenetic relationships and spatio-temporal evolutionary patterns of the flavopilosa group based on a mitochondrial and two nuclear genes, providing the first molecular support to the subdivision of the group and suggesting a new taxonomic scheme for its species. Barcoding proved to be an effective tool, as all species were reciprocally monophyletic and different analyses of species delimitation yielded congruent results. The close relationship of D. flavopilosa with D. cestri and D. cordeiroi was strongly supported, suggesting that the latter should be placed in the flavopilosa subgroup together with the first. Furthermore, D. mariaehelenae was positioned as sister to D. incompta, supporting its inclusion in the nesiota subgroup. Despite new taxonomic assignments, the synapomorphic status of the diagnostic characters proposed for both subgroups was supported. Based on them, each of the remaining species were placed into one of both subgroups. Divergence time estimates suggest that their diversification coincided with the divergence of Sessea and Cestrum, providing an interesting case of coevolution.


Assuntos
Drosophila , Melhoramento Vegetal , Animais , Drosophila/genética , Filogenia , Evolução Biológica , Mitocôndrias/genética
19.
Sci Rep ; 14(1): 8991, 2024 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637583

RESUMO

COVID-19 is a multisystemic disease caused by the SARS-CoV-2 airborne virus, a member of the Coronaviridae family. It has a positive sense single-stranded RNA genome and encodes two non-structural proteins through viral cysteine-proteases processing. Blocking this step is crucial to control virus replication. In this work, we reported the synthesis of 23 statine-based peptidomimetics to determine their ability to inhibit the main protease (Mpro) activity of SARS-CoV-2. Among the 23 peptidomimetics, 15 compounds effectively inhibited Mpro activity by 50% or more, while three compounds (7d, 8e, and 9g) exhibited maximum inhibition above 70% and IC50 < 1 µM. Compounds 7d, 8e, and 9g inhibited roughly 80% of SARS-CoV-2 replication and proved no cytotoxicity. Molecular docking simulations show putative hydrogen bond and hydrophobic interactions between specific amino acids and these inhibitors. Molecular dynamics simulations further confirmed the stability and persisting interactions in Mpro's subsites, exhibiting favorable free energy binding (ΔGbind) values. These findings suggest the statine-based peptidomimetics as potential therapeutic agents against SARS-CoV-2 by targeting Mpro.


Assuntos
COVID-19 , Proteases 3C de Coronavírus , Peptidomiméticos , Humanos , SARS-CoV-2/metabolismo , Peptidomiméticos/farmacologia , Simulação de Acoplamento Molecular , Inibidores de Proteases/química , Aminoácidos , Simulação de Dinâmica Molecular , Antivirais/farmacologia , Antivirais/química
20.
Micromachines (Basel) ; 15(4)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38675287

RESUMO

DNA data storage based on synthetic oligonucleotides is a major attraction due to the possibility of storage over long periods. Nowadays, the quantity of data generated has been growing exponentially, and the storage capacity needs to keep pace with the growth caused by new technologies and globalization. Since DNA can hold a large amount of information with a high density and remains stable for hundreds of years, this technology offers a solution for current long-term data centers by reducing energy consumption and physical storage space. Currently, research institutes, technology companies, and universities are making significant efforts to meet the growing need for data storage. DNA data storage is a promising field, especially with the advancement of sequencing techniques and equipment, which now make it possible to read genomes (i.e., to retrieve the information) and process this data easily. To overcome the challenges associated with developing new technologies for DNA data storage, a message encoding and decoding exercise was conducted at a Brazilian research center. The exercise performed consisted of synthesizing oligonucleotides by the phosphoramidite route. An encoded message, using a coding scheme that adheres to DNA sequence constraints, was synthesized. After synthesis, the oligonucleotide was sequenced and decoded, and the information was fully recovered.

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