Dataset Information

Insights Regarding the Role of Inflammasomes in Leukemia: What Do We Know?

ABSTRACT: Inflammation is a physiological mechanism of the immune response and has an important role in maintaining the hematopoietic cell niche in the bone marrow. During this process, the participation of molecules produced by innate immunity cells in response to a variety of pathogen-associated molecular patterns and damage-associated molecular patterns is observed. However, chronic inflammation is intrinsically associated with leukemogenesis, as it induces DNA damage in hematopoietic stem cells and contributes to the creation of the preleukemic clone. Several factors influence the malignant transformation within the hematopoietic microenvironment, with inflammasomes having a crucial role in this process, in addition to acting in the regulation of hematopoiesis and its homeostasis. Inflammasomes are intracellular multimeric complexes responsible for the maturation and secretion of the proinflammatory cytokines interleukin-1β and interleukin-18 and the cell death process via pyroptosis. Therefore, dysregulation of the activation of these complexes may be a factor in triggering several diseases, including leukemias, and this has been the subject of several studies in the area. In this review, we summarized the current knowledge on the relationship between inflammation and leukemogenesis, in particular, the role of inflammasomes in different types of leukemias, and we describe the potential therapeutic targets directed at inflammasomes in the leukemic context.

SUBMITTER: Alves-Hanna FS

PROVIDER: S-EPMC10421713 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Insights Regarding the Role of Inflammasomes in Leukemia: What Do We Know?

Alves-Hanna Fabíola Silva FS Crespo-Neto Juniel Assis JA Nogueira Glenda Menezes GM Pereira Daniele Sá DS Lima Amanda Barros AB Ribeiro Thaís Lohana Pereira TLP Santos Vitória Giovanna Rodrigues VGR Fonseca Joey Ramone Ferreira JRF Magalhães-Gama Fábio F Sadahiro Aya A Costa Allyson Guimarães AG

Journal of immunology research 20230804

Inflammation is a physiological mechanism of the immune response and has an important role in maintaining the hematopoietic cell niche in the bone marrow. During this process, the participation of molecules produced by innate immunity cells in response to a variety of pathogen-associated molecular patterns and damage-associated molecular patterns is observed. However, chronic inflammation is intrinsically associated with leukemogenesis, as it induces DNA damage in hematopoietic stem cells and co ...[more]

PMID: 37577033

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Project description:BackgroundGuidelines encourage engagement in self-care activities for osteoarthritis (OA), but there are gaps in consumers' knowledge about suitable choices for self-care. Community pharmacists are in an ideal position to contribute to OA management through screening and supporting evidence-based pain management choices. Prior research established an association between health literacy and advice-seeking and appropriateness of analgesics choices (both lower in participants with limited health literacy) amongst people living with OA. This article explores the implications of these data for pharmacists in OA management.MethodsA national online survey was conducted amongst 628 adults aged 45-74 years, currently residing in Australia, with self-reported symptoms of OA. All data were collected using a customized online questionnaire, which was completed only once. 'Self-reported symptoms of OA' was based on six validated screening questions to identify people with OA without a formal clinical diagnosis.ResultsRespondents matched the typical profile of people diagnosed with OA; more than half were female (56%), knees (59%) and hips (31%) were the primary affected joints and 74% were either overweight or obese. Self-identification of OA was limited (41%). Overall, 38% self-managed their pain, and limited health literacy was associated with less advice-seeking. Efficacy and ease of use were the main reasons cited for prompting use across all classes of nonprescription analgesic, with less than 20% reporting recommendation from a pharmacist. Participants were managing their pain with an average of 1.74 (95% confidence interval: 1.60-1.88) analgesics, but 73% reported inadequate pain relief and 54% had disrupted sleep.ConclusionOur findings highlight three key themes: lack of self-identification of OA, suboptimal pain relief and limited use of the community pharmacist as a source of management advice. Equipping community pharmacists with tools to identify OA could bridge this gap. More research is needed to determine if it will improve consumers' ability to appropriately manage OA pain.Patient or public contributionConsumers living with OA contributed to the study outcomes, reviewed the survey questionnaire for face validity and advised on plain language terminology.

Project description:Obsessive compulsive (OC) symptoms involve excessive information gathering (e.g., checking, reassurance-seeking), and uncertainty about possible, often catastrophic, future events. Here we propose that these phenomena are the result of excessive uncertainty regarding state transitions (transition uncertainty): a computational impairment in Bayesian inference leading to a reduced ability to use the past to predict the present and future, and to oversensitivity to feedback (i.e. prediction errors). Using a computational model of Bayesian learning under uncertainty in a reversal learning task, we investigate the relationship between OC symptoms and transition uncertainty. Individuals high and low in OC symptoms performed a task in which they had to detect shifts (i.e. transitions) in cue-outcome contingencies. Modeling subjects' choices was used to estimate each individual participant's transition uncertainty and associated responses to feedback. We examined both an optimal observer model and an approximate Bayesian model in which participants were assumed to attend (and learn about) only one of several cues on each trial. Results suggested the participants were more likely to distribute attention across cues, in accordance with the optimal observer model. As hypothesized, participants with higher OC symptoms exhibited increased transition uncertainty, as well as a pattern of behavior potentially indicative of a difficulty in relying on learned contingencies, with no evidence for perseverative behavior. Increased transition uncertainty compromised these individuals' ability to predict ensuing feedback, rendering them more surprised by expected outcomes. However, no evidence for excessive belief updating was found. These results highlight a potential computational basis for OC symptoms and obsessive compulsive disorder (OCD). The fact the OC symptoms predicted a decreased reliance on the past rather than perseveration challenges preconceptions of OCD as a disorder of inflexibility. Our results have implications for the understanding of the neurocognitive processes leading to excessive uncertainty and distrust of past experiences in OCD.

Dataset Information

Insights Regarding the Role of Inflammasomes in Leukemia: What Do We Know?

Publications

Insights Regarding the Role of Inflammasomes in Leukemia: What Do We Know?

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