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mRNA is a new class of drugs that has the potential to revolutionize the treatment of brain tumors. Thanks to the COVID-19 mRNA vaccines and numerous therapy-based clinical trials, it is now clear that lipid nanoparticles (LNPs) are a clinically viable means to deliver RNA therapeutics. However, LNP-mediated mRNA delivery to brain tumors remains elusive. Over the past decade, numerous studies have shown that tumor cells communicate with each other via small extracellular vesicles, which are around 100 nm in diameter and consist of lipid bilayer membrane similar to synthetic lipidbased nanocarriers. We hypothesized that rationally designed LNPs based on extracellular vesicle mimicry would enable efficient delivery of RNA therapeutics to brain tumors without undue toxicity. We synthesized LNPs using four components similar to the formulation used in the mRNA COVID19 vaccines (Moderna and Pfizer): ionizable lipid, cholesterol, helper lipid and polyethylene glycol (PEG)-lipid. For the in vitro screen, we tested ten classes of helper lipids based on their abundance in extracellular vesicle membranes, commercial availability, and large-scale production feasibility while keeping rest of the LNP components unchanged. The transfection kinetics of GFP mRNA encapsulated in LNPs and doped with 16 mol% of helper lipids was tested using GL261, U87 and SIM-A9 cell lines. Several LNP formations resulted in stable transfection (upto 5 days) of GFP mRNA in all the cell lines tested in vitro. The successful LNP candidates (enabling >80% transfection efficacy) were then tested in vivo to deliver luciferase mRNA to brain tumors via intrathecal administration in a syngeneic glioblastoma (GBM) mouse model, which confirmed luciferase expression in brain tumors in the cortex. LNPs were then tested to deliver Cre recombinase mRNA in syngeneic GBM mouse model genetically modified to express tdTomato under LoxP marker cassette that enabled identification of LNP targeted cells. mRNA was successfully delivered to tumor cells (70-80% transfected) and a range of different cells in the tumor microenvironment, including tumor-associated macrophages (80-90% transfected), neurons (31- 40% transfected), neural stem cells (39-62% transfected), oligodendrocytes (70-80% transfected) and astrocytes (44-76% transfected). Then, LNP formulations were assessed for delivering Cas9 mRNA and CD81 sgRNA (model protein) in murine syngeneic GBM model to enable gene editing in brain tumor cells. Sanger sequencing showed that CRISPR-Cas9 editing was successful in ~94% of brain tumor cells in vivo. In conclusion, we have developed a library of safe LNPs that can transfect GBM cells in vivo with high efficacy. This technology can potentially be used to develop novel mRNA therapies for GBM by delivering single or multiple mRNAs and holds great potential as a tool to study brain tumor biology.
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Objective: Although the neurological and olfactory symptoms of coronavirus disease 2019 have been identified, the neurotropic properties of the causative virus, severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), remain unknown. We sought to identify the susceptible cell types and potential routes of SARS-CoV-2 entry into the central nervous system, olfactory system, and respiratory system. Method(s): We collected single-cell RNA data from normal brain and nasal epithelium specimens, along with bronchial, tracheal, and lung specimens in public datasets. The susceptible cell types that express SARS-CoV-2 entry genes were identified using single-cell RNA sequencing and the expression of the key genes at protein levels was verified by immunohistochemistry. We compared the coexpression patterns of the entry receptor angiotensin-converting enzyme 2 (ACE2) and the spike protein priming enzyme transmembrane serine protease (TMPRSS)/cathepsin L among the specimens. Result(s): The SARS-CoV-2 entry receptor ACE2 and the spike protein priming enzyme TMPRSS/cathepsin L were coexpressed by pericytes in brain tissue;this coexpression was confirmed by immunohistochemistry. In the nasal epithelium, ciliated cells and sustentacular cells exhibited strong coexpression of ACE2 and TMPRSS. Neurons and glia in the brain and nasal epithelium did not exhibit coexpression of ACE2 and TMPRSS. However, coexpression was present in ciliated cells, vascular smooth muscle cells, and fibroblasts in tracheal tissue;ciliated cells and goblet cells in bronchial tissue;and alveolar epithelium type 1 cells, AT2 cells, and ciliated cells in lung tissue. Conclusion(s): Neurological symptoms in patients with coronavirus disease 2019 could be associated with SARS-CoV-2 invasion across the blood-brain barrier via pericytes. Additionally, SARS-CoV-2-induced olfactory disorders could be the result of localized cell damage in the nasal epithelium.Copyright © Wolters Kluwer Health, Inc. All rights reserved.
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One of the symptoms of a new coronavirus infection (COVID-19) is a complete or partial violation of the sense of smell. The aim of the work is to analyze the published results of scientific research on the mechanisms of olfactory impairment in COVID-19. Material and methods. Research was conducted for publications in Pubmed on the problem of olfactory impairment in COVID-19 using terms indexed by MeSH. The systematic review was compiled in accordance with the checklist Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA). Results. Publication's analysis has shown that the existing ideas about conductive anosmia are insufficient to explain the causes of olfactory impairment caused by SARS-CoV-2. It has been established that ACE2 and TMPRSS2 receptors located on the surface of target cells are necessary for the penetration of a new coronavirus. It is known that these receptors are mainly located on the cells of the olfactory epithelium. The main hypothesis of olfactory impairment in COVID-19 is that anosmia/hyposmia is caused by damage not to neuronal cells (as previously assumed), but to the olfactory epithelium. There is no confirmation of the point of view about the damage of SARS-CoV-2 olfactory bulbs and olfactory neurons, since they do not express receptor proteins for the virus on their surface.Copyright © 2022 by the authors.
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Introduction: Encephalopathy and delirium are common following coronavirus infection [1], and the associated neuroinflammation often results in long-term behavioral and cognitive impairment. Neurovirulent cytokines (NVC) are strongly implicated in the pathogenesis of coronavirus encephalopathy [2]. We hypothesized that characterizing the abnormal signaling in NVC exposed neurons will enable us to identify targets to treat encephalopathy and prevent its downstream effects. Method(s): We incubated primary mouse neocortical cultures in NVC known to be increased in coronavirus encephalopathy (TNF-alpha, IL-1beta, IL-6, IL-12 and IL-15). Using whole-cell patch clamp methods, we tested how neuronal function was impacted by 22-28-h exposure to NVC. Result(s): We found that NVC depolarized the resting membrane potential (RMP), reduced the firing threshold of neocortical neurons, and increased baseline spontaneous action potential (AP) firing. NVC altered the sensitivity (or input-output properties) of single neurons to changes in their microenvironment. Specifically, decreasing external Ca2+ and Mg2+ from physiological to low (1.1-0.2 mM) levels increased evoked AP firing in control, but not following exposure to NVC. AP firing threshold and spontaneous firing rates returned to control levels 1 h after NVC wash-out. However, the RMP and attenuated sensitivity of evoked APs to changes in the microenvironment remained persistently abnormal suggesting two distinct mechanisms were at play. Interestingly, hyperpolarizing the RMP reversed this altered response. Conclusion(s): Sustained exposure to NVC reversibly depolarizes neocortical neuronal RMP, altering excitability and the ability of neurons to respond to microenvironment changes. By characterizing the pathogenesis of the underlying changes in neuronal function in our model of coronavirus encephalopathy we will identify intervenable drug targets.
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Purpose: Disability in knee osteoarthritis (KOA) is known to be largely due to pain, the mechanism of which is complex and multidimensional with alterations in nociceptive processing in the peripheral and central nervous system (CNS) leading to persistent pain. Current clinical practice guidelines for KOA provide strong recommendations for education and exercise including land-based or mind-body approaches. However, individually these strategies are only moderately effective. One potential reason for this is a lack of understanding of their underlying mechanisms and how their combination might impact nervous system modulation. Neuromuscular exercise is known to improve lower extremity strength. Mind-body approaches as well as pain neuroscience education (PNE) are uniquely positioned to potentially reverse CNS adaptations by inducing positive neuroplastic changes and improving descending modulation of pain resulting in decreased pain. To our knowledge, neuromuscular exercise, mind-body techniques, and PNE have not been studied in combination. We therefore aimed to establish the feasibility of an intervention consisting of these three elements referred to as Pain Informed Movement (PIM). The results of this study will inform necessary modifications for a two-arm pilot randomized controlled trial (RCT). Method(s): This study was a single-arm feasibility trial with a nested qualitative component and the primary feasibility outcome of complete follow up. Inclusion criteria: age >= 40 years, KOA clinical diagnosis or people fulfilling the NICE diagnostic criteria, and average pain intensity >=3/10 on the numeric pain rating scale. PIM consisted of twice weekly in-person exercise sessions and a third home exercise session for 8 weeks. In addition, PNE, provided as online videos, covered the following topics: purpose of pain, neurophysiological changes associated with pain, movement guidelines when pain persists, mind-body techniques to impact neurophysiology and support moving with ease that included breath awareness and regulation, muscle tension regulation, awareness of pain related thoughts and emotions, and relaxation. The mind-body techniques and the PNE topics were implemented during the group exercise sessions that included evidence-based neuromuscular exercises aimed at improving sensorimotor control and functionality of the knee joint. Participants completed questionnaires and in-person assessments at baseline and at program completion. Assessments included weight and height, chair stands as a measure of functional leg strength, and conditioned pain modulation to assess efficiency of the descending modulatory pathways. Participants also had their blood drawn to monitor changes in brain derived neurotrophic factor (BDNF), a marker of neuroplasticity. Questionnaires included the Pain Catastrophizing Scale, Hospital Anxiety and Depression Scale, the Knee Injury and Osteoarthritis Outcome Score - function and pain subscales, Chronic Pain Self Efficacy scale, pain intensity rated in the past 24 hours, the past week, and worst pain in the past 24 hours. Secondary feasibility outcomes included acceptability of the intervention, burden of assessments, recruitment rate, compliance rate, adherence rate, and self-reported adverse events. Feasibility findings were evaluated against a-priori success criteria. In the qualitative component, participants were invited to an online focus group and were asked about their experience and perceptions of the program. Interview recordings were analyzed using thematic content analysis to identify suggestions for program modification. Result(s): In total, 19 participants (mean age 63.3 years (SD 10.5), 73% female) were enrolled, with a complete follow up rate of 74% (n=14) for our primary objective, indicating that modifications would be needed to proceed. Of the 5 dropouts, only one was study related. We will be adding additional inclusion criteria of: ability to get up and down from the floor independently, and no use of mobility aids. Adherence to in-person treatment sessions was 91%, hich indicates proceeding with the protocol for the next phase (i.e., pilot RCT). Some absences were due to unmodifiable factors (e.g., COVID-19). We will make protocol amendments for the purpose of improving the adherence rate to include 'no planned absences'. All other success criteria were met: recruitment rate, compliance to exercise sessions, program acceptability, duration, frequency, and delivery, likelihood of recommending the program to others and taking the program again, burden, and adverse events (Table 1). Analysis of the focus groups revealed that the video content pertaining to the mind-body techniques would benefit from on screen demonstrations by the instructor to assist with participants' execution of breath and muscle tension regulation. The majority of participants improved in most of the physical assessment outcomes and questionnaires (Table 2). Conclusion(s): The PIM program is feasible, acceptable, not burdensome, does not cause adverse events, and had an excellent compliance rate. Minor modifications are needed to optimize enrolment and adherence rates. Although improvements in pain, function, and psychological measures were observed, the feasibility nature of this study precludes any conclusions regarding efficacy. A pilot two-arm RCT will be conducted to establish the feasibility and explore potential effects of PIM when compared to conventional neuromuscular exercise and standard OA education. [Formula presented] [Formula presented]Copyright © 2023
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The ongoing corona virus disease 2019 (COVID-19) pandemic has led to an urgent demand for appropriate models depicting host-pathogen interactions and disease severity-dependent immune responses. Amongst various animal models, hamster species are particularly valuable as they are permissive to develop a moderate (Mesocricetus auratus) or severe (Phodopus roborovskii) disease course following infection. Here, we use single-cell ribonucleic acid sequencing of white blood cells to dissect cell-specific changes in moderate and severe disease courses of hamsters infected with severe acute respiratory syndrome coronavirus 2. To determine universal and species-specific transcriptional responses, the generated datasets were integrated with two publicly available datasets of human COVID-19 patients (Schulte-Schrepping et al. 2020 and Su et al. 2020) featuring all disease severities. Datasets were integrated using the R package Harmony and the Python package scGen enabling the prediction of disease states through different species using an autoencoder neural network architecture. Specifically, application of a low dimensional latent space embedding allows capturing most relevant transcriptome data structures, identifying shift vectors from healthy to diseased cells as well as interspecies differences. Preliminary results show that interspecies integration of hamster and human data is achievable, and major cell types were identified throughout the datasets. Training of a neuronal network on human blood monocytes enables the prediction of transcriptomic disease severity specific patterns, paving the way for extended analyses involving several cell types and species. In addition to in-depth analysis of COVID-19 signatures in blood of hamsters and humans, successfully established workflows could subsequently be used to study the pathology of extensive lung diseases, shedding light on cellular mechanisms in the transition from healthy to diseased cellular states.
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Background: Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. Method(s): We performed a broad translational investigation, employing brain imaging and cognitive tests in 81 living COVID-19 patients (mildly infected individuals) as well as flow cytometry, respirometry, microscopy, proteomics, and metabolomics in postmortem brain samples, and in preclinical in vitro and ex vivo models. Result(s): We observed orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms in living individuals. Postmortem brain tissue from 26 individuals who died of COVID-19 revealed histopathological signs of brain damage. Five individuals out of the 26 exhibited foci of SARS- CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a non-canonical mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that significantly reduces neuronal viability. Conclusion(s): Our data support the model in which COVID-19 alter cortical thickness, promoting psychiatric symptoms. In addition, SARS-CoV-2 is able to reach the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients. Funding Source: Sao Paulo Research Foundation (FAPESP) Keywords: COVID-19, Anxiety, Astrocytes, Multi-omics, Brain Magnetic Resonance Imaging (MRI)Copyright © 2023
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The COVID-19 pandemic spread around the world due to the enormous transmission of the SARS-CoV-2 among humans. COVID-19 represents a threat to global public health. The entry of this virus into cells is greatly facilitated by the presence of angiotensin-converting enzyme 2 (ACE2) in the cell membrane. Today we do not have a precise understanding of how this receptor expresses in the brain during human development and, as a consequence, we do not know whether neural cells in the developing brain are susceptible to infection. We review the knowledge about ACE2 expression in the developing human brain, with special attention to the fetal stage. This stage corresponds to the period of the cerebral cortex formation. Therefore, SARS-CoV-2 infection during the fetal period may alter the normal development of the cerebral cortex. Although few cases have been published demonstrating vertical transmission of SARS-CoV-2 infection, the large number of infected young people may represent a problem which requires health surveillance, due to the possibility of cognitive alterations and abnormalities in the development of cortical circuits that may represent a predisposition to mental problems later in life.Copyright © 2023, Instituto de Investigaciones Medicas. All rights reserved.
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The monoamine hypothesis of depression has dominated treatment for decades, but for some with treatment-resistant depression, alternative approaches are needed. This article discusses some of the other mechanisms involved in depression and how novel treatments could address these.Copyright © 2023 Wiley Interface Ltd.
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The pandemic outbreak of coronavirus disease (COVID-19) has emerged as the most threat-ening public health challenge. The clinical presentation ranges from asymptomatic and mild clinical symptoms to acute respiratory-distress syndrome (ARDS) and death. Apart from the respiratory system, other organ systems like cardiovascular, renal, and gastrointestinal systems are also involved. Cytokine storm is a condition of systemic inflammatory cytokine rampage through the bloodstream leading to life-threatening complications. There is an urgent need for the prevention of infection and effective man-agement. Yoga is a profound science with both immunity-boosting and immune-modulating capacity. We propose that yoga-based intervention may aid in improving health with its immunity-boosting potential and preventing the exuberant inflammatory cytokine storm, thus reducing the severity of the disease. It can also reduce stress, anxiety, and co-morbid depression by promoting neuroplasticity and prevents persistent activation of the hypothalamus pituitary adrenal axis and thus may reduce disease severity. It may also enhance the immunity of caretakers and make them more emotionally resilient. Thus, yoga can be useful for enhancing immunity, stress reduction and may prevent the exaggerated immune response to the cytokine storm.Copyright © 2021 Bentham Science Publishers.
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Introduction: Machine learning (ML) plays a significant role in the fight against the COVID-19 (officially known as SARS-CoV-2) pandemic. ML techniques enable the rapid detection of patterns and trends in large datasets. Therefore, ML provides efficient methods to generate knowledge from structured and unstructured data. This potential is particularly significant when the pandemic affects all aspects of human life. It is necessary to collect a large amount of data to identify methods to prevent the spread of infection, early detection, reduction of consequences, and finding appropriate medicine. Modern information and communication technologies (ICT) such as the Internet of Things (IoT) allow the collection of large amounts of data from various sources. Thus, we can create predictive ML-based models for assessments, predictions, and decisions. Method(s): This is a review article based on previous studies and scientifically proven knowledge. In this paper, bibliometric data from authoritative databases of research publications (Web of Science, Scopus, PubMed) are combined for bibliometric analyses in the context of ML applications for COVID-19. Aim(s): This paper reviews some ML-based applications used for mitigating COVID-19. We aimed to identify and review ML potentials and solutions for mitigating the COVID-19 pandemic as well as to present some of the most commonly used ML techniques, algorithms, and datasets applied in the context of COVID-19. Also, we provided some insights into specific emerging ideas and open issues to facilitate future research. Conclusion(s): ML is an effective tool for diagnosing and early detection of symptoms, predicting the spread of a pandemic, developing medicines and vaccines, etc.Copyright © 2022 Sciendo. All rights reserved.
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Background: For the first time in December 2019, as reported in the Wuhan city of China, COVID-19 deadly virus spread rapidly around the world and the first cases were seen in Turkey on March 11, 2020. On the same day, a pandemic was declared by the World Health Organization due to the rapid spread of the disease throughout the world. Method(s): In this study, a multilayered perception feed-forward back propagation neural network has been designed for predicting the spread and mortality rate of the COVID-19 virus in Turkey. COVID-19 data from six different countries were used in the design of the artificial neural network, which has 15 neurons in its hidden layer. 70% of these optimized data were used for training, 20% for validation, and 10% for testing. Result(s): The simulation results showed that the COVID-19 virus in Turkey, between day 20 and 37, was the fastest to rise. The number of cases for the 20th day was predicted to be 13.845. Conclusion(s): As for the death rate, it was predicted that a rapid rise would start on the 20th day and a slowdown around the 43rd day and progress towards the zero case point. The death rate for the 20th day was predicted to be 170 and for the 43rd day it was 1,960s.Copyright © 2021 Bentham Science Publishers.
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Introduction: (IFITM3) is an innate immune protein that has been identified as a novel gamma-secretase (gammas) modulator. FYN is a kinase that stabilizes IFITM3 on the membrane, primes APP for amyloidogenic gammas processing and mediates tau oligomerization. The purpose of this study is to explore the role of FYN and IFITM3 in AD and COVID-19, expanding on previous research from our group. Method(s): A 520 gene signature containing FYN and IFITM3 (termed Ia) was extracted from a previously published meta-analysis of Alzheimer's disease (AD) bulk- and single nuclei sequencing data. Exploratory analyses involved meta-analysis of bulk and single cell RNA data for IFITM3 and FYN differential expression per CNS site and cellular type. Confirmatory analyses, gene set enrichment analysis (GSEA) on Ia was performed to detect overlapping enriched biological networks between COVID-19 with AD. Result(s): Bulk RNA data analysis revealed that IFITM3 and FYN were overexpressed in two CNS regions in AD vs. Controls: the temporal cortex Wilcoxon p-value=1.3e-6) and the parahippocampal cortex Wilcoxon p-value=0.012). Correspondingly, single cell RNA analysis of IFITM3 and FYN revealed that it was differentially expressed in neurons, glial and endothelial cells donated b AD patients, when compared to controls. Discussion(s): IFITM3 and FYN were found as interactors within biological networks overlapping between AD and SARS-CoV-2 infection. Within the context of SARS-CoV-2 induced tau aggregation and interactions between tau and Ab1-42, the FYN - IFITM3 regulome may outline an important innate immunity element responsive to viral infection and IFN-I signaling in both AD and COVID-19.Copyright © 2021 The Authors
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Objective: As part of Epilepsy Connections' role in providing support to people affected by epilepsy, we aim to raise awareness of epilepsy at a community/grassroots level, with particular focus on: (1) school communities through our Schools Project/Seizure-Smart Schools;and (2) providing fun activities for families affected by childhood epilepsies (FACE). We recognise that for young people with epilepsy (YPE) to live their lives to the full, their needs go much further than the clinical involvement of their healthcare teams. Our objectives were (1) To promote knowledge of epilepsy, seizures and how to help when a seizure happens'so that YPE can go about their lives, confident that the people around them are informed and respectful;and (2) to provide fun activities for YPE and their families. Method(s): (1) Age-appropriate playground-based activities (message games, story time/roleplay/drama, arts and crafts, using hands-on brain/neuron models) for nursery/primary classes, and workshops for secondary/college students/school staff;(2) large-scale public events (virtual festivals and face-to-face) in collaboration with the Glasgow Science Centre, and EPNA Congress in Glasgow;(3) bespoke, supported days out for individual families;(4) Three residential trips to Ardentinny Outdoor Education Centre since September 2021, for families new to us and those already accessing our services. Result(s): (1) Engagement with thousands of participants;(2) YPE and families took part in fun, adventurous outdoors activities (canoeing, gorge walking, climbing, abseiling, forest and beach walks), got together for meals, informal peer support and family disco! Conclusion(s): Families value having breaks and activities in a supportive, inclusive and bespoke way. We re-modelled how we provide our activities within school communities and with FACE, to reflect COVID-19 protective measures. Nonetheless, the ongoing impact of COVID-19 restricts opportunities to engage.
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In December 2019, the novel coronavirus strain SARS-CoV-2 caused an outbreak that quickly spread worldwide and led to the COVID-19 pandemic. COVID-19, the severe infectious disease caused by SARS-CoV-2, often presents with symptoms including fever, cough, and mental confusion and can cause the acute respiratory inflammatory disorder. Additionally, viral infection with SARS-CoV-2 is associated with mental health, neuronal degeneration, and psychiatric complications. With infection by the virus, cytokines are released by immune cells, causing acute systemic inflammation affecting the lungs. Lung damage can occur, resulting in hypoxia, brain damage, and mental health dysfunction. In addition, a cascade of inflammatory cytokines, including IL-1, IL-6, and TNF, are released, a phenomenon termed the "cytokine storm" that causes serious pathological damage to tissues and organs and mental health. This exaggerated production of cytokines leads to lymphopenia and disrupts the balance of Treg and Th17 cells, weakening the immune system. The elderly population is particularly at risk for damage associated with the "cytokine storm", which can affect neurological functions or result in death. Copyright © by BIOLIFE.
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Introduction: The world's population has been exposed to traumatic events and high levels of stress due to the ongoing COVID-19 outbreak. Stress is known currently as a universal experience, but the concept was first defined in 1936 by Hans Selye. It has been shown that stress is associated with impairments in neuroplasticity (e.g. neuronal atrophy and synaptic loss in the hippocampus, prefrontal cortex) and has a crucial role in almost all mental disorders. Objective(s): In this paper we aim to highlight the recent theoretical and experimental advances in neuroscience regarding stress induced neuroplasticity. Method(s): We analyzed scientific literature written in English and published between 2019-2021. We used the electronic portal PubMed-NCBI. Result(s): In the last few years, molecular and cellular studies on animal models of stress related and stress-induced psychopathologies revealed alterations in gene expression, micro ARNs expression, as well as in intracellular signaling pathways that mediate the stress induced adaptations. These findings have led to new theories regarding depression and anxiety in the molecular neurobiology field. It has been shown that stress reduces BDNF expression inducing neuronal atrophy in various brain areas. Contrastingly, other studies have demonstrated that chronic antidepressant treatment increases BDNF expression. Furthermore, a crucial role has been assigned to miRNAs in the development of chronic stressinduced depression-like behavior and neuroplasticity. Conclusion(s): We hope that this paper will increase interest in the field of stress induced cellular and molecular changes. More research needs to be pursued in order to achieve a deeper understanding of the pathophysiology of stress-induced mental disorders.
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Taste is one of the fundamental senses that allow us to distinguish nutritious food substances from toxic ones. However, the ability to taste decreases with age or can be lost due to some diseases such as COVID- 19, drugs, and disturbances in the molecular activities in taste homeostasis and renewal. Previous studies have shown the potential role of the Hedgehog signaling pathway in taste papillae homeostasis Therefore, inhibition or stimulation of the Hedgehog pathway can be explored to address taste disturbances. This study investigated photobiomodulation effects on the Hedgehog signaling pathway after inhibition with Vismodegib of taste receptor and geniculate ganglion neuronal cells in vitro and in vivo. Laser treatment performed at 630 and 850 nm, with varying energies of 30, 60, and 120J resulted in the modulation of Hedgehog signaling proteins and genes. Photobiomodulation offers a noninvasive approach with deep penetration in tissue to restore taste by promoting tastebud regeneration and stimulating desensitized afferent nerves.
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Background: Despite similar motor recovery of limbs in research, clinically the lower limb is observed to demonstrate greater recovery than the upper limb (UL). Understanding the relation between the post-stroke rehabilitation experience in the hospital environment and neuroplasticity and motor recovery of the UL may provide insight into how to optimize the hospital and promote recovery. Aim(s): This feasibility study aimed to collect cross-sectional data from inpatients who were clinically receiving UL motor training within a rehabilitation hospital to determine the feasibility of our protocol as well as describe the factors and potential associations between motor performance and therapy participation, fatigue, stress and sleep. Method(s): Inpatients were recruited across two rehabilitation wards;inclusion criteria were broad (stroke diagnosis and clinically identified UL motor impairment). Therapy session duration and frequencies were recorded prior to assessing sleep quality and amount over one night (Actiwatch, Phillips Respironics, USA)). Participants rated their perceived fatigue (Fatigue Severity Scale-FSS) and sleep quality (Leeds Sleep Evaluation Questionnaire-LSEQ), and overnight nursing documentation of sleep was extracted from the medical record. Motor performance was assessed via the box and block test. All data were collected across a 24h period. Result(s): N=14 participants participated (age 71+/-11y) at a mean+/-SD 32+/-23 days post-stroke and 22+/-21 days since admission to rehabilitation. Participants received motor training 10+/-3 times per week, and sessions were 51+/-18min in length. Mean+/-SD sleep duration was 9.5+/-1.9h with 1.1+/-0.7h awake-time during the night. All participants reported fatigue, with mean FSS (37+/-16), and identified issues with respect to getting to sleep as well as quality of sleep on the LSEQ. All data were feasible to collect, however COVID restrictions and bed-numbers influenced recruitment rate. Conclusion(s): Findings provide key feasibility data to better understand targetable factors to optimise the post-stroke rehabilitation experience, neuroplasticity and UL motor recovery after stroke.