Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Third International Conference on 3Rs Research and Progress, Vishakhapatnam, 2022

Alternatives to Laboratory Animals, Год журнала: 2023, Номер 51(4), С. 263 - 288

Опубликована: Июнь 6, 2023

Animal experimentation has been integral to drug discovery and development safety assessment for many years, since it provides insights into the mechanisms of efficacy toxicity (e.g. pharmacology, pharmacokinetics pharmacodynamics). However, due species differences in physiology, metabolism sensitivity drugs, animal models can often fail replicate effects drugs chemicals human patients, workers consumers. Researchers across globe are increasingly applying Three Rs principles by employing innovative methods research testing. The concept focuses on: replacement with vitro silico or studies), on reduction number animals required achieve objectives, refinement existing experimental practices eliminating distress enhancing wellbeing). For last two Oncoseek Bio-Acasta Health, a 3-D cell culture-based cutting-edge translational biotechnology company, organised an annual International Conference 3Rs Research Progress. This series global conferences aims bring together researchers diverse expertise interests, platform where they share discuss their promote according principles. In November 2022, 3rd international conference, Advances Models Cutting-Edge Alternatives, took place at GITAM University Vishakhapatnam (AP, India) hybrid format (i.e. online in-person). These conference proceedings provide details presentations, which were categorised under five different topic sessions. It also describes special interactive session strategies preclinical oncology, was held end first day.

Язык: Английский

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Olfactory dysfunction in chronic rhinosinusitis: insights into the underlying mechanisms and treatments

Expert Review of Clinical Immunology, Год журнала: 2023, Номер 19(8), С. 993 - 1004

Опубликована: Июль 11, 2023

Olfactory dysfunction (OD) is a typical symptom of chronic rhinosinusitis (CRS), which adversely affects the patient's quality life and results in mood depression. Studies investigating impairment olfactory epithelium (OE) have indicated that inflammation-induced cell damage OE plays vital role development OD. Consequently, glucocorticoids biologics are beneficial management OD CRS patients. However, mechanisms underlying patients not been fully elucidated.This review focuses on Additionally, methods used for detection olfaction both currently available potentially new clinical treatments reviewed.Chronic inflammation impairs only sensory neurons but also non-neuronal cells responsible regeneration support neurons. The current treatment mainly aimed at attenuating preventing inflammation. Strategies use combinations these therapies may achieve greater efficacy restoration damaged consequently better

Язык: Английский

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Beyond chemicals: Opportunities and challenges of integrating non-chemical stressors in adverse outcome pathways

ALTEX, Год журнала: 2023, Номер unknown

Опубликована: Янв. 1, 2023

The adverse outcome pathways (AOPs) were developed to accelerate evidence-based chemical risk assessment by leveraging data from new approach methodologies. Thanks their stressor-agnostic approach, AOPs seen as instrumental in other fields. Here, we present that report non-chemical stressors along with the challenges encountered for development. Challenges regarding linked nanomaterials include non-specific molecular initiating events, limited understanding of nanomaterial biodistribution, and needs adaptations silico modeling testing systems. Development radiation face how incorporate ionizing events type, dose rate, energy deposition, account targeting multiple macromolecules. COVID-19 required inclusion SARS-CoV-2-specific replicative steps capture essential driving disease. Developing evaluate efficacy toxicity cell therapies necessitates addressing cellular nature therapeutic function stressor. Finally, emerging biological like microbial pesticides can learn AOPs. We further discuss needed expand AOP applicability beyond chemicals are mainly at levels while downstream key tissue or organ level, such inflammation, shared many initiated various stressors. In conclusion, although it is challenging integrate within AOPs, this expands opportunities real-world scenarios, identify vulnerable individuals, bridge knowledge on mechanisms adversity. Plain language summaryThe pathway (AOP) framework was help predict whether have toxic effects humans. Structuring available information an accessible database reduce animal testing. usually path interaction a stressor, chemical, human body outcome, e.g., disease symptom. concept has now been expanded nanomaterials, radiation, viruses, cells used treat patients, microorganisms employed pesticides. use these need be accommodated point out share inflammation By integrating into framework, scenarios where people may exposed different stressor types considered, individuals identified, compounded.

Язык: Английский

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Bioinspired nanoplatforms for human-machine interfaces: Recent progress in materials and device applications

Biotechnology Advances, Год журнала: 2023, Номер 70, С. 108297 - 108297

Опубликована: Дек. 6, 2023

Язык: Английский

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Human-derived air–liquid interface cultures decipher Alzheimer’s disease–SARS-CoV-2 crosstalk in the olfactory mucosa

Journal of Neuroinflammation, Год журнала: 2023, Номер 20(1)

Опубликована: Дек. 14, 2023

Abstract Background The neurological effects of the coronavirus disease 2019 (COVID-19) raise concerns about potential long-term consequences, such as an increased risk Alzheimer's (AD). Neuroinflammation and other AD-associated pathologies are also suggested to increase serious SARS-CoV-2 infection. Anosmia is a common symptom reported in COVID-19 early AD. olfactory mucosa (OM) important for perception smell proposed site viral entry brain. However, little known infection at OM individuals with Methods To address this gap, we established 3D vitro model from primary cells derived cognitively healthy AD individuals. We cultured air–liquid interface (ALI) study under controlled experimental conditions. Primary ALI expressed angiotensin-converting enzyme 2 (ACE-2), neuropilin-1 (NRP-1), several receptor were highly vulnerable Infection was determined by secreted RNA content confirmed nucleocapsid protein (NP) infected immunocytochemistry. Differential responses individuals-derived sequencing. Results indicate that donors do not differ susceptibility wild-type virus. transcriptomic signatures distinct. Specifically, patients virus showed levels oxidative stress, desensitized inflammation immune responses, alterations genes associated olfaction. These results imply may be greater experiencing severe outcomes infection, potentially driven pre-existing neuroinflammation. Conclusions sheds light on interplay between pathology Altered contribute unique symptoms more course, notable involvement Furthermore, research emphasizes need targeted interventions enhance crucial better comprehend relationship AD, COVID-19, anosmia. It highlights importance ongoing develop effective treatments those high Graphical

Язык: Английский

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The Adverse Outcome Pathway Framework Applied to Neurological Symptoms of COVID-19

Cells, Год журнала: 2022, Номер 11(21), С. 3411 - 3411

Опубликована: Окт. 28, 2022

Several reports have shown that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has potential to also be neurotropic. However, mechanisms by which SARS-CoV-2 induces neurologic injury, including neurological and/or psychological symptoms, remain unclear. In this review, available knowledge on neurobiological underlying COVID-19 was organized using AOP framework. Four AOPs leading adverse outcomes (AO), anosmia, encephalitis, stroke, and seizure, were developed. Biological key events (KEs) identified induce these AOs included binding ACE2, blood–brain barrier (BBB) disruption, hypoxia, neuroinflammation, oxidative stress. The modularity of allows construction networks visualize core pathways recognize neuroinflammation BBB disruption as shared mechanisms. Furthermore, impact modulating multiscale factors such age, stress, nutrition, poverty, food insecurity discussed. Organizing existing along an framework can represent a valuable tool understand disease identify data gaps potentially contribute treatment, prevention. This AOP-aligned approach facilitates synergy between experts from different backgrounds, while fast-evolving disruptive nature emphasizes need for interdisciplinarity cross-community research.

Язык: Английский

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CIAO: a living experiment in interdisciplinary large-scale collaboration facilitated by the Adverse Outcome Pathway framework

Frontiers in Public Health, Год журнала: 2023, Номер 11

Опубликована: Авг. 10, 2023

Introduction The CIAO project was launched in Spring 2020 to address the need make sense of numerous and disparate data available on COVID-19 pathogenesis. Based a crowdsourcing model large-scale collaboration, has exploited Adverse Outcome Pathway (AOP) knowledge management framework built support chemical risk assessment driven by mechanistic understanding biological perturbations at different organizational levels. Hence AOPs might have real potential integrate produced through approaches from disciplines as experienced context COVID-19. In this study, we aim effectiveness AOP (i) supporting an interdisciplinary collaboration for viral disease (ii) working conceptual mediator collaboration. Methods We used survey disseminated among participants, workshop open all interested contributors, series interviews with some participants self-reflection processes. Results supported genuine interdisciplinarity exchange knowledge. provided common reference point discussion diagram assisted making explicit what are perspectives brought about pathways. AOP-Wiki showed up many aspects its usability those not already world AOPs. Meanwhile their use highlighted needed adaptations. new Wiki elements modulating factors potentially most disruptive one. Regarding how well that is successful when there strong central impetus clarity terms early possible. Discussion Extrapolate approach related processes other areas science where could foster systematic organization exciting perspective.

Язык: Английский

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Exposure to urban particulate matter alters responses of olfactory mucosal cells to SARS-CoV-2 infection

Environmental Research, Год журнала: 2024, Номер 249, С. 118451 - 118451

Опубликована: Фев. 8, 2024

Respiratory viruses have a significant impact on health, as highlighted by the COVID-19 pandemic. Exposure to air pollution can contribute viral susceptibility and be associated with severe outcomes, suggested recent epidemiological studies. Furthermore, exposure particulate matter (PM), an important constituent of pollution, is linked adverse effects brain, including cognitive decline Alzheimer's disease (AD). The olfactory mucosa (OM), tissue located at rooftop nasal cavity, directly exposed inhaled in direct contact brain. Increasing evidence OM dysfunction related neuropathogenesis infection demonstrates importance elucidating interplay between pollutants OM. This study examined subacute urban PM 0.2 10–2.5 SARS-CoV-2 using primary human cells obtained from cognitively healthy individuals diagnosed AD. were subsequently infected virus presence pollutants. entry receptors replication, toxicological endpoints, cytokine release, oxidative stress markers, amyloid beta levels measured. did not enhance expression or cellular load cells. However, PM-exposed SARS-CoV-2-infected showed alterations immune responses when compared only These changes are highly pronounced AD results suggest that does increase vitro, but it alter virus, particularly Understanding provide insight for development public health policies interventions reduce negative influences exposure.

Язык: Английский

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An overview of immune safety avatar: mimicking the effects of immunomodulatory therapies on the immune system

Journal of Immunotoxicology, Год журнала: 2024, Номер 21(sup1)

Опубликована: Дек. 9, 2024

Innovative therapeutics like biologicals that modulate the immune system are on rise. However, their immune-modulating characteristics can also lead sometimes to induction of adverse effects, by triggering unintended reactions. Due complexity and target-specificity such therapeutics, these drug-induced events could remain undetected during non-clinical development, if test systems are, for example, animal-based, only emerge in clinical development when tested humans subsequently discontinuance otherwise promising drug candidates. To identify effects human at an early stage, new approaches, assays, technologies needed. The Medicine Initiative (IMI) cooperation Immune Safety Avatar (imSAVAR) project aims develop a tool integrated safety assessment immune-modulatory therapeutic drugs trial applications. achieve this goal, imSAVAR has relied Adverse Outcome Pathway (AOP) framework gather knowledge structured approach design, select or develop, needed, appropriate prediction immune-related outcomes. So far, consortium identified "mode action" certain classes needed improved risk assessment, including chimeric antigen receptor T cells (CAR cells), checkpoint inhibitors (ICIs), recombinant proteins (e.g. interleukin [IL]-2), linked those outcomes formulated literature-based AOPs (irAOPs). Models measure immune-specific perturbations were selected, adjusted, newly developed. work described special issue

Язык: Английский

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Embryology and Clinical Development of the Human Olfactory System

Journal of Pediatric Neurology, Год журнала: 2023, Номер 22(01), С. 001 - 007

Опубликована: Март 30, 2023

Abstract The olfactory system is unique as a special sensory in its developmental neuroanatomy and function. Neonatal reflexes can be detected the fetus from 30 weeks gestation tested term preterm neonates older children. Most efferent axons bulb terminate anterior nucleus within tract, with secondary projections to amygdala, hypothalamus, hippocampus, entorhinal cortex (parahippocampal gyrus), tertiary also insula other cortical regions. tract incorporate an intrinsic thalamic equivalent. may primary generating auras some cases of temporal lobe epilepsy. Developmental malformations involve isolated or part complex cerebral genetic syndromes. Primary neural tumors arise nerve. Impaired olfaction occurs neonatal hypoxic/ischemic metabolic encephalopathies. Loss sense smell are early symptoms neurodegenerative diseases viral respiratory including coronavirus disease 2019. Testing cranial nerve I easy reliable at all ages, recommended selected suspected brain encephalopathy.

Язык: Английский

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