Abstract
Age increases the risk for cognitive impairment and is the single major risk factor for Alzheimer’s disease (AD), the most prevalent form of dementia in the elderly. The pathophysiological ...processes triggered by aging that render the brain vulnerable to dementia involve, at least in part, changes in inflammatory mediators. Here we show that lipoxin A4 (LXA4), a lipid mediator of inflammation resolution known to stimulate endocannabinoid signaling in the brain, is reduced in the aging central nervous system. We demonstrate that genetic suppression of 5-lipoxygenase (5-LOX), the enzyme mediating LXA4 synthesis, promotes learning impairment in mice. Conversely, administration of exogenous LXA4 attenuated cytokine production and memory loss induced by inflammation in mice. We further show that cerebrospinal fluid LXA4 is reduced in patients with dementia and positively associated with cognitive performance, brain-derived neurotrophic factor (BDNF), and AD-linked amyloid-β. Our findings suggest that reduced LXA4 levels may lead to vulnerability to age-related cognitive disorders and that promoting LXA4 signaling may comprise an effective strategy to prevent early cognitive decline in AD.
Neural crest stem cells (NCPCs) have been shown to differentiate into various cell types and tissues during embryonic development, including sensory neurons. The few studies addressing the generation ...of NCPCs and peripheral sensory neurons (PSNs) from human induced pluripotent stem cells (hiPSCs), generated sensory cells without displaying robust activity. Here, we describe an efficient strategy for hiPSCs differentiation into NCPCs and functional PSNs using chemically defined media and factors to achieve efficient differentiation, confirmed by the expression of specific markers. After 10 days hiPSCs differentiated into NCPCs, cells were then maintained in neural induction medium containing defined growth factors for PSNs differentiation, followed by 10 days in neonatal human epidermal keratinocytes- (HEKn-) conditioned medium (CM). We observed a further increase in PSN markers expression and neurites length after CM treatment. The resulting neurons elicited action potentials after current injection and released substance P (SP) in response to nociceptive agents such as anandamide and resiniferatoxin. Anandamide induced substance P release via activation of TRPV1 and not CB1. Transcriptomic analysis of the PSNs revealed the main dorsal root ganglia neuronal markers and a transcriptional profile compatible with C fiber-low threshold mechanoreceptors. TRPV1 was detected by immunofluorescence and RNA-Seq in multiple experiments. In conclusion, the developed strategy generated PSNs useful for drug screening that could be applied to patient-derived hiPSCs, consisting in a powerful tool to model human diseases
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•SARS-CoV-2 infection of neural tissue is non-permissive.•SARS-CoV-2 infection can elicit inflammatory response and cell damage.•Increasing virus amount and incubation times do not ...elicit permissive infection.•Divergences in viral sequences may explain differences in neural cell infectivity.
Coronavirus disease 2019 (COVID-19) was initially described as a viral infection of the respiratory tract. It is now known, however, that several other organs are affected, including the brain. Neurological manifestations such as stroke, encephalitis, and psychiatric conditions have been reported in COVID-19 patients, but the neurotropic potential of the virus is still debated. Herein, we sought to investigate SARS-CoV-2 infection in human neural cells. We demonstrated that SARS-CoV-2 infection of neural tissue is non-permissive, however, it can elicit inflammatory response and cell damage. These findings add to the hypothesis that most of the neural damage caused by SARS-CoV-2 infection is due to a systemic inflammation leading to indirect harmful effects on the central nervous system despite the absence of local viral replication.
Axon guidance is required for the establishment of brain circuits. Whether much of the molecular basis of axon guidance is known from animal models, the molecular machinery coordinating axon growth ...and pathfinding in humans remains to be elucidated. The use of induced pluripotent stem cells (iPSC) from human donors has revolutionized in vitro studies of the human brain. iPSC can be differentiated into neuronal stem cells which can be used to generate neural tissue-like cultures, known as neurospheres, that reproduce, in many aspects, the cell types and molecules present in the brain. Here, we analyzed quantitative changes in the proteome of neurospheres during differentiation. Relative quantification was performed at early time points during differentiation using iTRAQ-based labeling and LC-MS/MS analysis. We identified 6438 proteins, from which 433 were downregulated and 479 were upregulated during differentiation. We show that human neurospheres have a molecular profile that correlates to the fetal brain. During differentiation, upregulated pathways are related to neuronal development and differentiation, cell adhesion, and axonal guidance whereas cell proliferation pathways were downregulated. We developed a functional assay to check for neurite outgrowth in neurospheres and confirmed that neurite outgrowth potential is increased after 10 days of differentiation and is enhanced by increasing cyclic AMP levels. The proteins identified here represent a resource to monitor neurosphere differentiation and coupled to the neurite outgrowth assay can be used to functionally explore neurological disorders using human neurospheres as a model.
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•Quantitative proteomic analysis of human neurospheres during differentiation using isobaric labeling (iTRAQ).•Axon guidance proteins are increased during differentiation.•Increased neurite outgrowth during differentiation is shown in a neuron outgrowth assay.•Neuron outgrowth in neurospheres is regulated by PKA and cAMP.•Axon guidance proteins related to neurological disorders are highlighted.
A pesquisa adotou a fotografia como recurso para revisitar memórias individuais e coletivas e identificar significados que compõem o lugar a partir da percepção dos moradores da Área de Proteção ...Ambiental (APA) Rota do Sol, Rio Grande do Sul (RS). Os participantes dispuseram suas coleções de fotografias, que junto às narrativas mostraram as percepções e relações de pertencimento com o local, servindo de base à compreensão e interpretação dos significados que compõem o lugar. Deste modo tomamos a fotografia como um dispositivo de narrativas e, à luz da iconologia, realizamos uma discussão sobre a memória e os significados de relevância trazidos pelos participantes, dispostos em 2 macrotemas: Araucária: um significado simbólico associado ao afetos, às emoções e à memória (3.1) e As mudanças no uso do solo influenciando a produção, o trabalho e a organização social (3.2). Deste modo, identificando elementos que mantém viva a cultura local. Para embasar as discussões partimos do estudo teórico-epistemológico em relação ao uso da fotografia como instrumento de pesquisa e dispositivo de memória, bem como, exploramos o conceito de paisagem. O estudo nos possibilitou entender as relações que ligam as pessoas ao lugar, as formas de produção, trabalho e organização social, mediante dados da memória coletiva não antes analisados. O uso da fotografia possibilitou levantar informações que vão muito além do plano objetivo na imagem impressa, proporcionando explorar e analisar os aspectos implícitos e subjetivos e reconhecer significados importantes à comunidade local.
Cette recherche utilise la photographie en tant que ressource pour revisiter les mémoires individuelles et collectives, et identifier les significations qui constituent le lieu, à partir de la perception des habitants de la zone de protection de l'environnement Rota do Sol, Rio Grande do Sul. Les participants ont mis à disposition leurs collections de photos, et, à travers leurs récits, ont montré leurs perceptions et relations d'appartenance à ce lieu, constituant comme référence pour la compréhension et interprétation des significations qui constituent la zone. Ainsi, nous avons adopté la photographie comme un dispositif de récits et, en fonction de l'iconologie, nous avons réalisé une discussion sur la mémoire et ses significations pertinentes apportées par les participants, réparties en deux macro-thèmes : Araucária: une signification symbolique associée aux affections, aux émotions et à la mémoire (3.1) et aux changements dans l'utilisation des terres influençant la production, le travail et l'organisation sociale (3.2). Nous sommes partis de l'étude théorique-épistémologique sur l'usage de la photographie comme instrument de recherche et dispositif de mémoire, comme base de discussion, mais nous avons exploré également le concept de paysage. L'étude nous a permis de comprendre les relations qui lient les personnes au lieu, les modes de production, travail et organisation social, à travers des données sur la mémoire collective analysées auparavant. L'usage de la photographie rend alors possible l'apport d'informations qui va bien plus loin que le niveau objectif de l'image imprimée, en nous offrant une exploration et analyse d'aspects implicites et subjectifs et la reconnaissance de l'importance de la communauté locale.
The research adopted the photograph as a resource to revisit individual and collective memories and to identify meanings that make up the place from the perception of the residents of the Environmental Protection Area (APA) Rota do Sol, Rio Grande do Sul, Rio Grande do Sul, Brazil (BR). The participants arranged their collections of photographs, which together with the narratives showed the perceptions and relations of belonging to the place, serving as a basis for understanding and interpreting the meanings that make up the place. In this way we take the photograph as a device of narratives and, in the light of the iconology, we carried out a discussion about the memory and the relevance meanings brought by the participants in 2 macro themes: Araucária: a symbolic meaning associated with affections, emotions and memory (3.1) and Changes in land use influencing production, work and social organization (3.2). To support the discussions we start with the theoretical-epistemological study of the use of photography as a research tool and memory device, as well as exploring the concept of landscape. The study allowed us to understand the relationships that bind people to the place, the forms of production, work and social organization, through data from the collective memory not previously analyzed.The use of photography made it possible to gather information that goes far beyond the objective plan in the printed image, allowing to explore and analyze the implicit and subjective aspects and to recognize important meanings to the local community.
Dentists play a fundamental role in the early diagnosis of oral leishmaniasis. Although these lesions are rare at oral mucosa, this is one of the manifestations sites of the disease This study ...reports seven clinical cases of orofacial mucocutaneous leishmaniasis. All had leishmaniasis diagnosis confirmed by laboratory tests, with orofacial involvement. Five out of the seven cases were males, and in four cases, patients had associated comorbidities. Late diagnosis was observed, resulting in treatment delay and increased hospitalization stay. One patient had severe psychological consequences due to facial deformity. The lack of differential diagnosis due the great variability of clinical presentation of the lesions and frequent unspecific histopathology represent a challenge for the dentist. In two reported cases, there were unspecific biopsy results. This series of cases highlights the importance of a multidisciplinary approach in the diagnosis and treatment of oral and perioral leishmaniasis. Patients with atypical lesions, originating from or living in endemic regions, should be investigated for leishmaniasis. These procedures could avoid delays in diagnosis and decrease the risk of disease dissemination.
SARS-CoV-2 infects cardiac cells and causes heart dysfunction. Conditions such as myocarditis and arrhythmia have been reported in COVID-19 patients. The Sigma-1 receptor (S1R) is a ubiquitously ...expressed chaperone that plays a central role in cardiomyocyte function. S1R has been proposed as a therapeutic target because it may affect SARS-CoV-2 replication; however, the impact of the inhibition of S1R in human cardiomyocytes remains to be described. In this study, we investigated the consequences of S1R inhibition in iPSC-derived human cardiomyocytes (hiPSC-CM). SARS-CoV-2 infection in hiPSC-CM was productive and reduced cell survival. S1R inhibition decreased both the number of infected cells and viral particles after 48 hours. S1R inhibition also prevented the release of pro-inflammatory cytokines and cell death. Although the S1R antagonist NE-100 triggered those protective effects, it compromised cytoskeleton integrity by downregulating the expression of structural-related genes and reducing beating frequency. Our findings suggest that the detrimental effects of S1R inhibition in human cardiomyocytes' integrity may abrogate its therapeutic potential against COVID and should be carefully considered.
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can infect several organs, especially impacting respiratory capacity. Among the ...extrapulmonary manifestations of COVID-19 is myocardial injury, which is associated with a high risk of mortality. Myocardial injury, caused directly or indirectly by SARS-CoV-2 infection, can be triggered by inflammatory processes that lead to damage to the heart tissue. Since one of the hallmarks of severe COVID-19 is the "cytokine storm", strategies to control inflammation caused by SARS-CoV-2 infection have been considered. Cannabinoids are known to have anti-inflammatory properties by negatively modulating the release of pro-inflammatory cytokines. Herein, we investigated the effects of the cannabinoid agonist WIN 55,212-2 (WIN) in human iPSC-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2. WIN did not modify angiotensin-converting enzyme II protein levels, nor reduced viral infection and replication in hiPSC-CMs. On the other hand, WIN reduced the levels of interleukins six, eight, 18 and tumor necrosis factor-alpha (TNF-α) released by infected cells, and attenuated cytotoxic damage measured by the release of lactate dehydrogenase (LDH). Our findings suggest that cannabinoids should be further explored as a complementary therapeutic tool for reducing inflammation in COVID-19 patients.
Retinal layers and symptoms and inflammation in schizophrenia Carriello, Marcelo Alves; Costa, Diogo F. Bornancin; Alvim, Pedro Henrique Pereira ...
European archives of psychiatry and clinical neuroscience,
08/2024, Letnik:
274, Številka:
5
Journal Article
Recenzirano
Schizophrenia is a neurodevelopmental disorder that affects brain structure and function. The retina, as well as the brain, consists of neuronal and glial cells packed in layers. Cortical volume and ...brain thickness are associated with inflammatory biomarkers, however, no study has been performed associating inflammatory biomarkers and retina in schizophrenia. our study aims to compare the retinal macular thickness and volume and peripapillary thickness in patients with schizophrenia and controls, and associate it to symptoms of schizophrenia, to interleukin-6 (IL-6) and C Reactive Protein (CRP) levels. Optical coherence tomography was performed to assess retinal layer thickness and volume, and CRP and IL-6 levels were measured in patients with schizophrenia and controls. Positive, negative, and general symptoms of schizophrenia were measured with the Positive and Negative Syndrome Scale (PANSS). A linear regression controlling for confounding factors was performed. 70 subjects were included, 35 patients, and 35 controls matched for sex and age. Patients with schizophrenia presented a significantly lower macular volume (
p
< 0.05) and thickness (< 0.05) than controls. PANSS positive, general and total scores were associated with retinal nerve fiber layer (RNFL) thickness (
p
< 0.05). There was no association between inflammatory markers (CRP and IL-6) levels and the retinal layer. A reduction in macular volume and thickness was found in patients with schizophrenia. The severity of schizophrenia symptoms was associated with RNFL thickness. CRP and IL-6 are not associated with retinal thickness/volume in schizophrenia or controls.
Abstract
Introduction Tympanoplasty is a reparative surgery that has multiple indications. The aid of a microscope or an endoscope is necessary to carry out the procedure. The classic method utilizes ...the microscope; however, in the recent decades, the endoscope has been popular. Although many articles try to compare these two techniques, there is still no robust evidence that confirms the superiority of either technique. In the present work, we seek to perform a systematic review contribute with this.
Objectives The present systematic review attempted to compare endoscopic and microscopic surgery techniques and to discover whether there would be superiority in the results of any of them, based on data currently available in the literature.
Data Synthesis The objectives of the present review were organized according to the PICO planning and strategy adapted for systematic reviews. The inclusion and exclusion criteria were established aiming to select only select primary data. The main medical databases were searched using an optimized search string with appropriate descriptors. The searched databases were MEDLINE, LILACS, SciELO, and EMBASE. A total of 99 studies were selected and 38 were fully assessed after the inclusion criteria were applied. All included articles were reviewed by all authors and their results were discussed and summarized.
Conclusion The endoscopic technique was shown to be a safer technique comparable in effectiveness to the use of microscopy. In addition, it provides possible advantages such as shortening the surgical time and better postoperative pain outcomes.
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