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1.
Res Sq ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38746402

RESUMO

Background X-linked Dystonia-Parkinsonism(XDP) is an adult-onset neurodegenerative disorder that results in the loss of striatal medium spiny neurons (MSNs). XDP is associated with disease-specific mutations in and around the TAF1 gene. This study highlights the utility of directly reprogrammed MSNs from fibroblasts of affected XDP individuals as a platform that captures cellular and epigenetic phenotypes associated with XDP-related neurodegeneration. In addition, the current study demonstrates the neuroprotective effect of SAK3 currently tested in other neurodegenerative diseases. Methods XDP fibroblasts from three independent patients as well as age- and sex-matched control fibroblasts were used to generate MSNs by direct neuronal reprogramming using miRNA-9/9*-124 and thetranscription factors CTIP2 , DLX1 -P2A- DLX2 , and MYT1L . Neuronal death, DNA damage, and mitochondrial health assays were carried out to assess the neurodegenerative state of directly reprogrammed MSNs from XDP patients (XDP-MSNs). RNA sequencing and ATAC sequencing were performed to infer changes in the transcriptomic and chromatin landscapesof XDP-MSNs compared to those of control MSNs (Ctrl-MSNs). Results Our results show that XDP patient fibroblasts can be successfully reprogrammed into MSNs and XDP-MSNs display several degenerative phenotypes, including neuronal death, DNA damage, and mitochondrial dysfunction, compared to Ctrl-MSNs reprogrammed from age- and sex-matched control individuals' fibroblasts. In addition, XDP-MSNs showed increased vulnerability to TNFα -toxicity compared to Ctrl-MSNs. To dissect the altered cellular state in XDP-MSNs, we conducted transcriptomic and chromatin accessibility analyses using RNA- and ATAC-seq. Our results indicate that pathways related to neuronal function, calcium signaling, and genes related to other neurodegenerative diseases are commonly altered in XDP-MSNs from multiple patients. Interestingly, we found that SAK3, a T-type calcium channel activator, that may have therapeutic values in other neurodegenerative disorders, protected XDP-MSNs from neuronal death. Notably, we found that SAK3-mediated alleviation of neurodegeneration in XDP-MSNs was accompanied by gene expression changes toward Ctrl-MSNs.

2.
Soc Sci Med ; 352: 117019, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38810507

RESUMO

This study addresses the challenge of low blood donation rates in developing countries by examining the effectiveness of a barrier-removal incentive-a one-day transportation voucher-to promote blood donation. Utilizing a longitudinal dataset of 23,750 donors from a Brazilian blood collection agency (BCA) collected between March 2018 and May 2020, we examine the short and long-term effects of this campaign on donation rates. Our results show that the incentive had a large positive influence on both donation attempts and successful donations on the day of the campaign. However, the short-term success of the intervention had an unintended consequence: the significant increase in prospective donors' waiting time at the BCA during the intervention day, which may help explain the negative impact on return rates in the 24-month follow-up. Despite these opposing outcomes, the net effect of the one-day blood donation incentive was still positive, offering valuable insights for BCAs aiming to enhance donor recruitment and retention strategies and emphasizing the need to balance immediate benefits with potential long-term impacts.


Assuntos
Doadores de Sangue , Motivação , Humanos , Doadores de Sangue/psicologia , Doadores de Sangue/estatística & dados numéricos , Masculino , Feminino , Adulto , Brasil , Pessoa de Meia-Idade , Estudos Longitudinais , Comportamento Social
3.
Biomed Pharmacother ; 174: 116564, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38608525

RESUMO

During resolution of inflammation, specialized proresolving mediators (SPMs), including resolvins, are produced to restore tissue homeostasis. We hypothesized that there might be a dysregulation of SPMs pathways in pathological vascular remodeling and that resolvin D2 (RvD2) might prevent vascular remodeling and contractile and endothelial dysfunction in a model of obesity and hypertension. In aortic samples of patients with or without abdominal aortic aneurysms (AAA), we evaluated gene expression of enzymes involved in SPMs synthesis (ALOXs), SPMs receptors and pro-inflammatory genes. In an experimental model of aortic dilation induced by high fat diet (HFD, 60%, eighteen weeks) and angiotensin II (AngII) infusion (four weeks), we studied the effect of RvD2 administration in aorta and small mesenteric arteries structure and function and markers of inflammation. In human macrophages we evaluated the effects of AngII and RvD2 in macrophages function and SPMs profile. In patients, we found positive correlations between AAA and obesity, and between AAA and expression of ALOX15, RvD2 receptor GPR18, and pro-inflammatory genes. There was an inverse correlation between the expression of aortic ALOX15 and AAA growth rate. In the mice model, RvD2 partially prevented the HFD plus AngII-induced obesity and adipose tissue inflammation, hypertension, aortic and mesenteric arteries remodeling, hypercontratility and endothelial dysfunction, and the expression of vascular proinflammatory markers and cell apoptosis. In human macrophages, RvD2 prevented AngII-induced impaired efferocytosis and switched SPMs profile. RvD2 might represent a novel protective strategy in preventing vascular damage associated to hypertension and obesity likely through effects in vascular and immune cells.


Assuntos
Ácidos Docosa-Hexaenoicos , Hipertensão , Camundongos Endogâmicos C57BL , Obesidade , Remodelação Vascular , Animais , Masculino , Humanos , Ácidos Docosa-Hexaenoicos/farmacologia , Hipertensão/metabolismo , Hipertensão/tratamento farmacológico , Obesidade/complicações , Obesidade/metabolismo , Remodelação Vascular/efeitos dos fármacos , Camundongos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Dieta Hiperlipídica/efeitos adversos , Angiotensina II , Aneurisma da Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Camundongos Obesos , Vasoconstrição/efeitos dos fármacos , Inflamação/patologia , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Modelos Animais de Doenças
4.
Phys Rev E ; 109(3-1): 034307, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38632723

RESUMO

We study the ordering dynamics of nonlinear voter models with multiple states, also providing a discussion of the two-state model. The rate with which an individual adopts an opinion scales as the qth power of the number of the individual's neighbors in that state. For q>1 the dynamics favor the opinion held by the most agents. The ordering to consensus is driven by deterministic drift, and noise plays only a minor role. For q<1 the dynamics favors minority opinions, and for multistate models the ordering proceeds through a noise-driven succession of metastable states. Unlike linear multistate systems, the nonlinear model cannot be reduced to an effective two-state model. We find that the average density of active interfaces in the model with multiple opinion states does not show a single exponential decay in time for q<1, again at variance with the linear model. This highlights the special character of the conventional (linear) voter model, in which deterministic drift is absent. As part of our analysis, we develop a pair approximation for the multistate model on graphs, valid for any positive real value of q, improving on previous approximations for nonlinear two-state voter models.

5.
An Acad Bras Cienc ; 96(1): e20220610, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38451592

RESUMO

The main objective of this study was to evaluate the effects of supplementation the diet of pigs with grape pomace preserved in silage form (GPS) and its interaction with indoor and outdoor production systems, with and without access to vegetation, on the attributes of meat quality produced. Analyzes of proximal composition, cholesterol content, fatty acid profile, shear force, texture profile and sensory analysis were performed. During cold storage, oxidative stability and objective color were analyzed. Statistical analysis was performed in a 3x2 factorial design (production systems (S) x GPS-feed (F)) and the interaction between them (S*F). The results showed that there was no interaction between the production system and GPS feeding for the attributes evaluated. The proximate composition and fatty acid profile of the muscle remained unchanged. Additionally, it provides higher subjective and objective tenderness, higher red color intensity, and reduces lipid oxidation under refrigeration. The supplementation of pig feed with GPS improve the quality of the meat and constitute a sustainable alternative for the winemaking residue.


Assuntos
Vitis , Animais , Suínos , Criopreservação , Ácidos Graxos , Metabolismo dos Lipídeos , Carne
6.
Cells ; 13(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474387

RESUMO

The involvement of central and peripheral inflammation in the pathogenesis and prognosis of major depressive disorder (MDD) has been demonstrated. The increase of pro-inflammatory cytokines (interleukin (IL)-1ß, IL-6, IL-18, and TNF-α) in individuals with depression may elicit neuroinflammatory processes and peripheral inflammation, mechanisms that, in turn, can contribute to gut microbiota dysbiosis. Together, neuroinflammation and gut dysbiosis induce alterations in tryptophan metabolism, culminating in decreased serotonin synthesis, impairments in neuroplasticity-related mechanisms, and glutamate-mediated excitotoxicity. This review aims to highlight the inflammatory mechanisms (neuroinflammation, peripheral inflammation, and gut dysbiosis) involved in the pathophysiology of MDD and to explore novel anti-inflammatory therapeutic approaches for this psychiatric disturbance. Several lines of evidence have indicated that in addition to antidepressants, physical exercise, probiotics, and nutraceuticals (agmatine, ascorbic acid, and vitamin D) possess anti-inflammatory effects that may contribute to their antidepressant properties. Further studies are necessary to explore the therapeutic benefits of these alternative therapies for MDD.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Doenças Neuroinflamatórias , Disbiose/tratamento farmacológico , Antidepressivos/farmacologia , Inflamação/metabolismo , Anti-Inflamatórios/uso terapêutico
7.
Sci Rep ; 14(1): 4036, 2024 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-38369633

RESUMO

Strategies to separately manufacture arterial-scale tissue engineered vascular grafts and microvascular networks have been well-established, but efforts to bridge these two length scales to create hierarchical vasculature capable of supporting parenchymal cell functions or restoring perfusion to ischemic tissues have been limited. This work aimed to create multiscale vascular constructs by assessing the capability of macroscopic vessels isolated from mice to form functional connections to engineered capillary networks ex vivo. Vessels of venous and arterial origins from both thoracic and femoral locations were isolated from mice, and then evaluated for their abilities to sprout endothelial cells (EC) capable of inosculating with surrounding human cell-derived microvasculature within bulk fibrin hydrogels. Comparing aortae, vena cavae, and femoral vessel bundles, we identified the thoracic aorta as the rodent macrovessel that yielded the greatest degree of sprouting and interconnection to surrounding capillaries. The presence of cells undergoing vascular morphogenesis in the surrounding hydrogel attenuated EC sprouting from the macrovessel compared to sprouting into acellular hydrogels, but ultimately sprouted mouse EC interacted with human cell-derived capillary networks in the bulk, yielding chimeric vessels. We then integrated micromolded mesovessels into the constructs to engineer a primitive 3-scale vascular hierarchy comprising capillaries, mesovessels, and macrovessels. Overall, this study yielded a primitive hierarchical vasculature suitable as proof-of-concept for regenerative medicine applications and as an experimental model to better understand the spontaneous formation of host-graft vessel anastomoses.


Assuntos
Células Endoteliais , Engenharia Tecidual , Humanos , Animais , Camundongos , Microvasos , Capilares , Hidrogéis , Neovascularização Fisiológica
8.
Int J Mol Sci ; 24(23)2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38069198

RESUMO

Major depressive disorder (MDD) has a high prevalence and is a major contributor to the global burden of disease. This psychiatric disorder results from a complex interaction between environmental and genetic factors. In recent years, the role of the gut microbiota in brain health has received particular attention, and compelling evidence has shown that patients suffering from depression have gut dysbiosis. Several studies have reported that gut dysbiosis-induced inflammation may cause and/or contribute to the development of depression through dysregulation of the gut-brain axis. Indeed, as a consequence of gut dysbiosis, neuroinflammatory alterations caused by microglial activation together with impairments in neuroplasticity may contribute to the development of depressive symptoms. The modulation of the gut microbiota has been recognized as a potential therapeutic strategy for the management of MMD. In this regard, physical exercise has been shown to positively change microbiota composition and diversity, and this can underlie, at least in part, its antidepressant effects. Given this, the present review will explore the relationship between physical exercise, gut microbiota and depression, with an emphasis on the potential of physical exercise as a non-invasive strategy for modulating the gut microbiota and, through this, regulating the gut-brain axis and alleviating MDD-related symptoms.


Assuntos
Transtorno Depressivo Maior , Microbioma Gastrointestinal , Humanos , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Maior/tratamento farmacológico , Disbiose , Inflamação , Exercício Físico
9.
J Surg Educ ; 80(12): 1877-1884, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37634977

RESUMO

OBJECTIVE: To evaluate the effect of home residency programs on outcomes in the otolaryngology residency match DESIGN: A retrospective online survey study during the 2015, 2018, 2019, 2020, and 2021 match cycles was conducted. All available otolaryngology residency positions listed by the National Resident Matching Program were compared with publicly available spreadsheets containing the following information: matriculated applicant name, medical school, whether the final match institution was the matriculated applicant's home program (HP), whether the matriculated applicant had completed an away rotation at their final matched institution (designated away institution, AI), or neither (designated Other Institution, OI). SETTING: Nonclinical survey study using publicly available spreadsheets containing The Match data from 2015 to 2021 located online at Otomatch.com. PARTICIPANTS: Newly matched United States otolaryngology-head and neck surgery residents completing the Otomatch.com survey RESULTS: A total of 1771 matched OHNS applicants were identified. Fifty-one percent of students were affiliated with their matched institution, with 25% of students matching at HPs, and 26% matching at AIs. Students with home programs had an increased likelihood of remaining in the same geographic region compared to students without home programs (OR 1.742 95% CI [1.21-2.506], p = 0.003). Applicants with HPs matched at significantly larger residency programs (p < 0.001). CONCLUSIONS: This study found that a majority of residents match at an institution with which they were affiliated, either their home program or away institution. Applicants with HPs are more likely to remain in the same geographic region as their medical school, and to match into larger residency programs compared to applicants without HPs.


Assuntos
Internato e Residência , Otolaringologia , Humanos , Estados Unidos , Estudos Retrospectivos , Estudantes , Inquéritos e Questionários , Otolaringologia/educação
10.
Sci Rep ; 13(1): 13726, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37608002

RESUMO

Paragonimiasis is a zoonotic, food-borne trematode infection that affects 21 million people globally. Trematodes interact with their hosts via extracellular vesicles (EV) that carry protein and RNA cargo. We analyzed EV in excretory-secretory products (ESP) released by Paragonimus kellicotti adult worms cultured in vitro (EV ESP) and EV isolated from lung cyst fluid (EV CFP) recovered from infected gerbils. The majority of EV were approximately 30-50 nm in diameter. We identified 548 P. kellicotti-derived proteins in EV ESP by mass spectrometry and 8 proteins in EV CFP of which 7 were also present in EV ESP. No parasite-derived proteins were reliably detected in EV isolated from plasma samples. A cysteine protease (MK050848, CP-6) was the most abundant protein found in EV CFP in all technical and biological replicates. Immunolocalization of CP-6 showed strong labeling in the tegument of P. kellicotti and in the adjacent cyst and lung tissue that contained worm eggs. It is likely that CP-6 present in EV is involved in parasite-host interactions. These results provide new insights into interactions between Paragonimus and their mammalian hosts, and they provide potential clues for development of novel diagnostic tools and treatments.


Assuntos
Cistos , Vesículas Extracelulares , Paragonimus , Animais , Proteoma , Gerbillinae , Pulmão
11.
Pharmaceuticals (Basel) ; 16(7)2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37513925

RESUMO

Ketamine, a racemic mixture of esketamine (S-ketamine) and arketamine (R-ketamine), has received particular attention for its rapid antidepressant and antisuicidal effects. NMDA receptor inhibition has been indicated as one of the main mechanisms of action of the racemic mixture, but other pharmacological targets have also been proposed. This study aimed to explore the possible multiple targets of ketamine enantiomers related to their antidepressant and antisuicidal effects. To this end, targets were predicted using Swiss Target Prediction software for each ketamine enantiomer. Targets related to depression and suicide were collected by the Gene Cards database. The intersections of targets were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Network pharmacology analysis was performed using Gene Mania and Cytoscape software. Molecular docking was used to predict the main targets of the network. The results indicated that esketamine and arketamine share some biological targets, particularly NMDA receptor and phosphodiesterases 3A, 7A, and 5A but have specific molecular targets. While esketamine is predicted to interact with the GABAergic system, arketamine may interact with macrophage migration inhibitory factor (MIF). Both ketamine enantiomers activate neuroplasticity-related signaling pathways and show addiction potential. Our results identified novel, poorly explored molecular targets that may be related to the beneficial effects of esketamine and arketamine against depression and suicide.

12.
Am J Otolaryngol ; 44(4): 103904, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37148847

RESUMO

OBJECTIVE: Otolaryngology (OTO) is a competitive specialty, and medical school factors outside an applicant's control, such as presence of OTO student resources and an affiliated OTO residency program, can impact the competitiveness of a student's application. This study sought to evaluate the extent of OTO resources United States (U.S.) allopathic medical schools provide to help their students be successful, and to evaluate for medical school factors which may bias toward inequitable distribution of student OTO resources. METHODS: A 48-question cross-sectional survey evaluating the extent of OTO resources was distributed by email to LCME accredited U.S. allopathic medical schools in 2020 and 2021. RESULTS: Schools with residency programs and where faculty were employed through an OTO or surgery department were more likely to have an Otolaryngology Interest Group (OIG), an Otolaryngology Medical Student Education Director (OMSED), and were more likely to provide opportunities for OTO research.


Assuntos
Internato e Residência , Otolaringologia , Estudantes de Medicina , Humanos , Estados Unidos , Faculdades de Medicina , Estudos Transversais , Otolaringologia/educação
13.
Ann Otol Rhinol Laryngol ; 132(11): 1412-1417, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37010056

RESUMO

OBJECTIVES: With an ever-expanding medical knowledge base and requirements for clinical training, medical schools struggle to incorporate subspecialty education, such as otolaryngology (OTO), into curricula. This study aims to assess the current state of OTO education, and evaluate factors contributing to the extent of OTO teaching in United States (U.S.) medical schools. METHODS: A 48-question survey evaluated the extent and practices of OTO teaching. The survey was distributed by email to all 155 LCME accredited U.S. allopathic medical schools in 2020 and 2021. RESULTS: Sixty-eight unique responses were received (43.9% of U.S. allopathic medical schools). 36.8% (n = 25) of schools reported having formal expectations of OTO knowledge in their core curriculum. Only 1 school (1.5%) had a required OTO rotation; the majority of schools offered an optional third or fourth year clerkship rotation (76.5% and 95.6%, respectively). Schools with residency programs and who employ their faculty through an OTO or surgery department were more likely to have otolaryngologists teach basic science lectures and the Head & Neck exam, offer an optional third year rotation, and have formal expectations of rotating students. CONCLUSIONS: Medical schools with residency programs and who employ their faculty through an OTO or surgery department have more robust OTO curricula. Despite the ubiquity of OTO presentations across specialties, incorporation of OTO knowledge in U.S. medical school curricula remains variable, and at times limited.


Assuntos
Internato e Residência , Otolaringologia , Estados Unidos , Humanos , Faculdades de Medicina , Estudos Transversais , Currículo , Otolaringologia/educação
14.
Sci Total Environ ; 879: 163256, 2023 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-37011689

RESUMO

Sponges from South America and Antarctica are evolutionarily closely related. Specific symbiont signatures that could differentiate these two geographic regions are unknown. This study aimed to investigate the microbiome diversity of sponges from South America and Antarctica. In total 71 sponge specimens were analyzed (Antarctica: N = 59, 13 different species; South America: N = 12, 6 different species). Illumina 16S rRNA sequences were generated (2.88 million sequences; 40K ± 29K/sample). The most abundant symbionts were heterotrophic (94.8 %) and belonged mainly to Proteobacteria and Bacteroidota. EC94 was the most abundant symbiont and dominated the microbiome of some species (70-87 %), comprising at least 10 phylogroups. Each of the EC94 phylogroups was specific to one genus or species of sponge. Furthermore, South America sponges had higher abundance of photosynthetic microorganisms (2.3 %) and sponges from Antarctica, the highest abundance of chemosynthetic (5.5 %). Sponge symbionts may contribute to the function of their hosts. The unique features from each of these two regions (e.g., light, temperature, and nutrients) possibly stimulate distinct microbiome diversity from sponges biogeographically distributed across continents.


Assuntos
Microbiota , Fotossíntese , RNA Ribossômico 16S/genética , Regiões Antárticas , Bacteroidetes/genética , Filogenia
15.
ISA Trans ; 139: 49-59, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37055262

RESUMO

This paper presents a new methodology to obtain prediction regions of the output of a dynamical system. The proposed approach uses stored past outputs of the system and it is entirely data-based. Only two hyperparameters are necessary to apply the proposed methodology. These scalars are chosen so that the size of the obtained regions is minimized while fulfilling the desired empirical probability in a validation set. In this paper, methods to optimally estimate both hyperparameters are provided. The provided prediction regions are convex and checking if a given point belongs to a computed prediction region amounts to solving a convex optimization problem. Also, approximation methods to build ellipsoidal prediction regions are provided. These approximations are useful when explicit descriptions of the regions are necessary. Finally, some numerical examples and comparisons for the case of a non-linear uncertain kite system are provided to prove the effectiveness of the proposed methodology.

16.
Aquat Toxicol ; 257: 106434, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36870176

RESUMO

Titanium dioxide nanoparticles-multiwalled carbon nanotubes (TiO2-MWCNT) nanohydrid has an enhanced photocatalytic activity across the visible light with promising applications in environmental remediation, solar energy devices and antimicrobial technologies. However, it is necessary to evaluate the toxicological effects of TiO2-MWCNT towards safe and sustainable development of nanohybrids. In this work, we studied the cytotoxicity, protein corona formation and cellular internalisation of TiO2-MWCNT on fibroblasts derived from gonadal rainbow trout tissue (RTG-2) for the first time. This nanohydrid did not show any toxicity effect on RTG-2 cells up to 100 mg L-1 after 24 h of exposure as monitored by alamar blue, neutral red and trypan blue assays (in presence or absence of foetal bovine serum, FBS). Futhermore, cryo-transmission electron microscopy analysis demonstrated that TiO2 particles is attached on nanotube surface after FBS-protein corona formation in cell culture medium. Raman spectroscopy imaging showed that TiO2-MWCNT can be internalised by RTG-2 cells. This work is a novel contribution towards better understanding the nanobiointeractions of nanohydrids linked to their in vitro effects on fish cells in aquatic nanoecotoxicology.


Assuntos
Nanopartículas , Nanotubos de Carbono , Coroa de Proteína , Poluentes Químicos da Água , Animais , Coroa de Proteína/química , Nanotubos de Carbono/toxicidade , Nanotubos de Carbono/química , Poluentes Químicos da Água/toxicidade , Linhagem Celular , Nanopartículas/toxicidade , Peixes , Titânio/toxicidade , Titânio/química
17.
Metab Brain Dis ; 38(3): 819-829, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36862275

RESUMO

Alzheimer's disease (AD) is the most common cause of dementia. In recent years, several studies have robustly shown that neuroinflammation plays a crucial role in the pathophysiology of this disease. The co-localization of amyloid-ß plaques near activated glial cells and the increased levels of inflammatory cytokines in AD patients indicate the involvement of the neuroinflammatory process in AD progression. Considering that pharmacological treatment remains a challenge for the management of this disease, compounds with anti-inflammatory and antioxidant properties are promising therapeutic strategies. In this context, vitamin D has gained attention in the last few years due to its neuroprotective property and the high prevalence of vitamin D deficiency in the population. Herein, in this narrative review we present the possible contribution of the antioxidant and anti-inflammatory properties of vitamin D for its neuroprotective effects, and the clinical and preclinical data dealing with the effects of vitamin D in AD, focusing mainly on the neuroinflammatory process.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Antioxidantes/uso terapêutico , Doenças Neuroinflamatórias , Peptídeos beta-Amiloides , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
18.
Chem Biol Interact ; 375: 110440, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-36878458

RESUMO

Guanosine has been reported to elicit antidepressant-like responses in rodents, but if these actions are associated with its ability to afford neuroprotection against glutamate-induced toxicity still needs to be fully understood. Therefore, this study investigated the antidepressant-like and neuroprotective effects elicited by guanosine in mice and evaluated the possible involvement of NMDA receptors, glutamine synthetase, and GLT-1 in these responses. We found that guanosine (0.05 mg/kg, but not 0.01 mg/kg, p. o.) was effective in producing an antidepressant-like effect and protecting hippocampal and prefrontocortical slices against glutamate-induced damage. Our results also unveiled that ketamine (1 mg/kg, but not 0.1 mg/kg, i. p, an NMDA receptor antagonist) effectively elicited antidepressant-like actions and protected hippocampal and prefrontocortical slices against glutamatergic toxicity. Furthermore, the combined administration of sub-effective doses of guanosine (0.01 mg/kg, p. o.) with ketamine (0.1 mg/kg, i. p.) promoted an antidepressant-like effect and augmented glutamine synthetase activity and GLT-1 immunocontent in the hippocampus, but not in the prefrontal cortex. Our results also showed that the combination of sub-effective doses of ketamine and guanosine, at the same protocol schedule that exhibited an antidepressant-like effect, effectively abolished glutamate-induced damage in hippocampal and prefrontocortical slices. Our in vitro results reinforce that guanosine, ketamine, or sub-effective concentrations of guanosine plus ketamine protect against glutamate exposure by modulating glutamine synthetase activity and GLT-1 levels. Finally, molecular docking analysis suggests that guanosine might interact with NMDA receptors at the ketamine or glycine/d-serine co-agonist binding sites. These findings provide support for the premise that guanosine has antidepressant-like effects and should be further investigated for depression management.


Assuntos
Ketamina , Fármacos Neuroprotetores , Animais , Camundongos , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Sistema X-AG de Transporte de Aminoácidos/farmacologia , Antidepressivos/farmacologia , Depressão/metabolismo , Glutamato-Amônia Ligase/metabolismo , Glutamato-Amônia Ligase/farmacologia , Ácido Glutâmico/farmacologia , Guanosina/farmacologia , Guanosina/metabolismo , Hipocampo , Ketamina/farmacologia , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Transportador 2 de Aminoácido Excitatório
19.
Int J Mol Sci ; 24(3)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36768554

RESUMO

The product specificity and mechanistic peculiarities of two allene oxide synthases, tomato LeAOS3 (CYP74C3) and maize ZmAOS (CYP74A19), were studied. Enzymes were vortexed with linoleic acid 9-hydroperoxide in a hexane-water biphasic system (20-60 s, 0 °C). Synthesized allene oxide (9,10-epoxy-10,12-octadecadienoic acid; 9,10-EOD) was trapped with ethanol. Incubations with ZmAOS produced predominantly 9,10-EOD, which was converted into an ethanolysis product, (12Z)-9-ethoxy-10-oxo-12-octadecenoic acid. LeAOS3 produced the same trapping product and 9(R)-α-ketol at nearly equimolar yields. Thus, both α-ketol and 9,10-EOD appeared to be kinetically controlled LeAOS3 products. NMR data for 9,10-EOD (Me) preparations revealed that ZmAOS specifically synthesized 10(E)-9,10-EOD, whereas LeAOS3 produced a roughly 4:1 mixture of 10(E) and 10(Z) isomers. The cyclopentenone cis-10-oxo-11-phytoenoic acid (10-oxo-PEA) and the Favorskii-type product yields were appreciable with LeAOS3, but dramatically lower with ZmAOS. The 9,10-EOD (free acid) kept in hexane transformed into macrolactones but did not cyclize. LeAOS3 catalysis is supposed to produce a higher proportion of oxyallyl diradical (a valence tautomer of allene oxide), which is a direct precursor of both cyclopentenone and cyclopropanone. This may explain the substantial yields of cis-10-oxo-PEA and the Favorskii-type product (via cyclopropanone) with LeAOS3. Furthermore, 10(Z)-9,10-EOD may be produced via the reverse formation of allene oxide from oxyallyl diradical.


Assuntos
Óxidos , Solanum lycopersicum , Zea mays , Hexanos
20.
J Food Sci ; 88(2): 666-680, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36617682

RESUMO

In this work, the Amazonian native acai fruit, a superfruit recognized worldwide, was used through a simple operation of maceration in alcohol vinegar to transform it into an attractive and functional product containing the acai natural colorant and its bioactive compounds. The variables studied were the proportion of alcohol vinegar to acai (8:2 and 1:1) and maceration period (7, 14, and 21 days). The final vinegar was subjected to the determination of color parameters, antioxidant capacity (DPPH, ABTS), total phenolics content (TPC), volatile compounds extracted by stir bar sorptive extraction and identified by gas-chromatography-mass spectrometry analysis. The alcohol vinegars macerated with acai presented the color according to the content of acai added and maceration period employed, whereas antioxidant capacity and TPC were comparable to vinegars elaborated from fruits and red wine. Sixty volatiles compounds classified into five chemical groups were identified. The principal volatile compounds which contributed to the aroma in the products were 3-methyl-1-butanol, phenylethyl alcohol, benzaldehyde, o-cymene, p-cymenene, isoamyl acetate, and ethyl acetate. The most attractive product regarding the parameters studied was obtained from the use of the proportion of 1:1 of alcohol vinegar:acai and maceration period of 14 days. This product retained the most similar color to acai in natura, the highest values for antioxidant capacity measured by ABTS and TPC while being rich in volatile compounds due to the contributions mainly of alcohols, esters, aldehydes, and terpenes. PRACTICAL APPLICATION: This work demonstrates the feasibility to produce an alcohol vinegar with an attractive color and functional properties by the addition of acai resulting in to a wide spectrum of chemical compounds of acai through a very simple operation of maceration during 14 days of a proportion of 1:1 of alcohol vinegar:acai.


Assuntos
Ácido Acético , Euterpe , Ácido Acético/análise , Antioxidantes/química , Etanol/análise , Frutas/química , Fenóis/análise
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