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NPJ Parkinson's Disease Sep 2023
PubMed: 37704671
DOI: 10.1038/s41531-023-00560-7 -
Biological Trace Element Research Dec 2023The pathophysiology of coronavirus disease-19 (COVID-19) is characterized by worsened inflammation because of weakened immunity, causing the infiltration of immune... (Review)
Review
The pathophysiology of coronavirus disease-19 (COVID-19) is characterized by worsened inflammation because of weakened immunity, causing the infiltration of immune cells, followed by necrosis. Consequently, these pathophysiological changes may lead to a life-threatening decline in perfusion due to hyperplasia of the lungs, instigating severe pneumonia, and causing fatalities. Additionally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause mortality due to viral septic shock, resulting from unrestrained and backfiring immune reactions to the pathogen. Sepsis can cause premature organ failure in COVID-19 patients, as well. Notably, vitamin D and its derivatives and minerals, such as zinc and magnesium, have been reported to improve the immune system against respiratory illnesses. This comprehensive review aims to provide updated mechanistic details of vitamin D and zinc as immunomodulators. Additionally, this review also focuses on their role in respiratory illnesses, while specifically delineating the plausibility of employing them as a preventive and therapeutic agent against current and future pandemics from an immunological perspective. Furthermore, this comprehensive review will attract the attention of health professionals, nutritionists, pharmaceuticals, and scientific communities, as it encourages the use of such micronutrients for therapeutic purposes, as well as promoting their health benefits for a healthy lifestyle and wellbeing.
Topics: Humans; COVID-19; Vitamin D; SARS-CoV-2; Zinc; Vitamins; Pharmaceutical Preparations
PubMed: 36890344
DOI: 10.1007/s12011-023-03620-4 -
Epilepsy Research Dec 2023The lack of preventive and disease modifying therapies for temporal lobe epilepsy (TLE) is a major unmet medical need. Search for such therapies utilize mouse models and...
The lack of preventive and disease modifying therapies for temporal lobe epilepsy (TLE) is a major unmet medical need. Search for such therapies utilize mouse models and require detection of seizures in electroencephalography (EEG) recordings. The labor-intensive nature of reviewing EEGs spanning many weeks underscores the need for a method of automated detection. Here we report a simple automated method of detecting seizures in long term EEG recordings from electrodes implanted in the hippocampus in animal models of TLE. We utilize a 2-pronged approach that relies on the increase in power within the gamma band range (20-50hz) during the seizure followed by suppression of activity following the seizure (post-ictal suppression [PIS]). We demonstrate the utility of this method for detecting seizures in hippocampal and amygdala EEG recordings from multiple models of TLE.
Topics: Animals; Mice; Epilepsy, Temporal Lobe; Seizures; Electroencephalography; Hippocampus; Amygdala; Disease Models, Animal
PubMed: 38000152
DOI: 10.1016/j.eplepsyres.2023.107256 -
Research in Veterinary Science Nov 2023Marek's disease (MD) is a severe infectious and immunosuppressive neoplastic condition that significantly impacts the global poultry industry. Investigating the role of...
Marek's disease (MD) is a severe infectious and immunosuppressive neoplastic condition that significantly impacts the global poultry industry. Investigating the role of non-coding RNA in pathogenic mechanisms of MD virus (MDV) offers valuable insights for the effective prevention and management of MD. A higher expression of the novel lncRNA-9802 can be found in spleen tissues of MDV-infected chickens from our prior research, and there is a potential association between lncRNA-9802 and cell proliferation. In this study, we further demonstrated that over-expression of lncRNA-9802 could promote the proliferation of DF-1 cells. It has been established that lncRNA-9802 mediated its effects by binding to miR-1646, and further modulated the expression of the Bax and Bcl-2 genes. Deciphering the role of the recently discovered MD-associated lncRNA-9802/miR-1646 axis provides valuable theoretical basis for decoding the molecular mechanisms underlying MDV pathogenesis.
Topics: Animals; bcl-2-Associated X Protein; Cell Proliferation; Chickens; Herpesvirus 2, Gallid; Marek Disease; MicroRNAs; RNA, Long Noncoding; Signal Transduction
PubMed: 37837750
DOI: 10.1016/j.rvsc.2023.105047 -
Frontiers in Immunology 2023Infectious Bursal Disease Virus (IBDV) causes immunosuppression in chickens. While B-cell destruction is the main cause of humoral immunosuppression, bursal T cells from...
CD4TGFβ cells infiltrated the bursa of Fabricius following IBDV infection, and correlated with a delayed viral clearance, but did not correlate with disease severity, or immunosuppression.
INTRODUCTION
Infectious Bursal Disease Virus (IBDV) causes immunosuppression in chickens. While B-cell destruction is the main cause of humoral immunosuppression, bursal T cells from IBDV-infected birds have been reported to inhibit the mitogenic response of splenocytes, indicating that some T cell subsets in the infected bursa have immunomodulatory activities. CD4CD25TGFβ cells have been recently described in chickens that have immunoregulatory properties and play a role in the pathogenesis of Marek's Disease Virus.
METHODS
To evaluate if CD4CD25TGFβ cells infiltrated the bursa of Fabricius (BF) following IBDV infection, and influenced the outcome of infection, birds were inoculated at either 2 days or 2 weeks of age with vaccine strain (228E), classic field strain (F52/70), or PBS (mock), and bursal cell populations were quantified by flow cytometry.
RESULTS
Both 228E and F52/70 led to atrophy of the BF, a significant reduction of Bu1-B cells, and a significant increase in CD4 and CD8α T cells in the BF, but only F52/70 caused suppression of immune responses to a test antigen in younger birds, and clinical signs in older birds. Virus was cleared from the BF more rapidly in younger birds than older birds. An infiltration of CD4CD25T cells into the BF, and elevated expression of bursal TGFβ-1 mRNA was observed at all time points following infection, irrespective of the strain or age of the birds, but CD4TGFβcells and CD4CD25TGFβ cells only appeared in the BF at 28 dpi in younger birds. In older birds, CD4TGFβ cells and CD4CD25TGFβ cells were present at earlier time points, from 7dpi following 228E infection, and from 14 and 28 dpi following F52/70 infection, respectively.
DISCUSSION
Our data suggest that an earlier infiltration of CD4TGFβ cells into the BF correlated with a delayed clearance of virus. However, the influx of CD4TGFβ cells and CD4CD25TGFβ into the BF did not correlate with increased pathogenicity, or immunosuppression.
Topics: Animals; Bursa of Fabricius; Chickens; Immunosuppression Therapy; Infectious bursal disease virus; Transforming Growth Factor beta
PubMed: 37744374
DOI: 10.3389/fimmu.2023.1197746 -
Journal of Neuroinflammation Feb 2024Traumatic encephalopathy syndrome (TES) is defined as the clinical manifestation of the neuropathological entity chronic traumatic encephalopathy (CTE). A core feature...
BACKGROUND
Traumatic encephalopathy syndrome (TES) is defined as the clinical manifestation of the neuropathological entity chronic traumatic encephalopathy (CTE). A core feature of TES is neurobehavioral dysregulation (NBD), a neuropsychiatric syndrome in repetitive head impact (RHI)-exposed individuals, characterized by a poor regulation of emotions/behavior. To discover biological correlates for NBD, we investigated the association between biomarkers of inflammation (interleukin (IL)-1β, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α) in cerebrospinal fluid (CSF) and NBD symptoms in former American football players and unexposed individuals.
METHODS
Our cohort consisted of former American football players, with (n = 104) or without (n = 76) NBD diagnosis, as well as asymptomatic unexposed individuals (n = 55) from the DIAGNOSE CTE Research Project. Specific measures for NBD were derived (i.e., explosivity, emotional dyscontrol, impulsivity, affective lability, and a total NBD score) from a factor analysis of multiple self-report neuropsychiatric measures. Analyses of covariance tested differences in biomarker concentrations between the three groups. Within former football players, multivariable linear regression models assessed relationships among log-transformed inflammatory biomarkers, proxies for RHI exposure (total years of football, cumulative head impact index), and NBD factor scores, adjusted for relevant confounding variables. Sensitivity analyses tested (1) differences in age subgroups (< 60, ≥ 60 years); (2) whether associations could be identified with plasma inflammatory biomarkers; (3) associations between neurodegeneration and NBD, using plasma neurofilament light (NfL) chain protein; and (4) associations between biomarkers and cognitive performance to explore broader clinical symptoms related to TES.
RESULTS
CSF IL-6 was higher in former American football players with NBD diagnosis compared to players without NBD. Furthermore, elevated levels of CSF IL-6 were significantly associated with higher emotional dyscontrol, affective lability, impulsivity, and total NBD scores. In older football players, plasma NfL was associated with higher emotional dyscontrol and impulsivity, but also with worse executive function and processing speed. Proxies for RHI exposure were not significantly associated with biomarker concentrations.
CONCLUSION
Specific NBD symptoms in former American football players may result from multiple factors, including neuroinflammation and neurodegeneration. Future studies need to unravel the exact link between NBD and RHI exposure, including the role of other pathophysiological pathways.
Topics: Humans; Aged; Middle Aged; Chronic Traumatic Encephalopathy; Football; Interleukin-6; Brain Injuries, Traumatic; Biomarkers
PubMed: 38336728
DOI: 10.1186/s12974-024-03034-6 -
Virology Feb 2024Marek's disease is a contagious proliferative disease of chickens caused by an alphaherpesvirus called Marek's disease virus. A bivalent mRNA vaccine encoding MDV's...
Marek's disease is a contagious proliferative disease of chickens caused by an alphaherpesvirus called Marek's disease virus. A bivalent mRNA vaccine encoding MDV's glycoprotein-B and phosphoprotein-38 antigens was synthesized and encapsulated in lipid nanoparticles. Tumor incidence, lesion score, organ weight indices, MDV genome load and cytokine expression were used to evaluate protection and immunostimulatory effects of the tested mRNA vaccine after two challenge trials. Results from the first trial showed decreased tumor incidence and a reduction in average lesion scores in chickens that received the booster dose. The second trial demonstrated that vaccination with the higher dose of the vaccine (10 μg) significantly decreased tumor incidence, average lesion scores, bursal atrophy, and MDV load in feather tips when compared to the controls. Changes in expression of type I and II interferons suggested a possible role for these cytokines in initiation and maintenance of the vaccine-originated immune responses.
Topics: Animals; Marek Disease; Chickens; mRNA Vaccines; Herpesvirus 2, Gallid; Neoplasms
PubMed: 38134535
DOI: 10.1016/j.virol.2023.109970 -
Journal of Interventional Cardiac... Oct 2023Adoption and outcomes for conduction system pacing (CSP), which includes His bundle pacing (HBP) or left bundle branch area pacing (LBBAP), in real-world settings are...
BACKGROUND
Adoption and outcomes for conduction system pacing (CSP), which includes His bundle pacing (HBP) or left bundle branch area pacing (LBBAP), in real-world settings are incompletely understood. We sought to describe real-world adoption of CSP lead implantation and subsequent outcomes.
METHODS
We performed an online cross-sectional survey on the implantation and outcomes associated with CSP, between November 15, 2020, and February 15, 2021. We described survey responses and reported HBP and LBBAP outcomes for bradycardia pacing and cardiac resynchronization CRT indications, separately.
RESULTS
The analysis cohort included 140 institutions, located on 5 continents, who contributed data to the worldwide survey on CSP. Of these, 127 institutions (90.7%) reported experience implanting CSP leads. CSP and overall device implantation volumes were reported by 84 institutions. In 2019, the median proportion of device implants with CSP, HBP, and/or LBBAP leads attempted were 4.4% (interquartile range [IQR], 1.9-12.5%; range, 0.4-100%), 3.3% (IQR, 1.3-7.1%; range, 0.2-87.0%), and 2.5% (IQR, 0.5-24.0%; range, 0.1-55.6%), respectively. For bradycardia pacing indications, HBP leads, as compared to LBBAP leads, had higher reported implant threshold (median [IQR]: 1.5 V [1.3-2.0 V] vs 0.8 V [0.6-1.0 V], p = 0.0008) and lower ventricular sensing (median [IQR]: 4.0 mV [3.0-5.0 mV] vs. 10.0 mV [7.0-12.0 mV], p < 0.0001).
CONCLUSION
In conclusion, CSP lead implantation has been broadly adopted but has yet to become the default approach at most surveyed institutions. As the indications and data for CSP continue to evolve, strategies to educate and promote CSP lead implantation at institutions without CSP lead implantation experience would be necessary.
Topics: Humans; Bundle of His; Bradycardia; Cross-Sectional Studies; Heart Conduction System; Cardiac Conduction System Disease; Electrocardiography; Cardiac Pacing, Artificial; Treatment Outcome
PubMed: 36607529
DOI: 10.1007/s10840-022-01417-4 -
Journal of Nuclear Medicine : Official... Jun 2024We used a new data-driven methodology to identify a set of reference regions that enhanced the quantification of the SUV ratio of the second-generation tau tracer...
We used a new data-driven methodology to identify a set of reference regions that enhanced the quantification of the SUV ratio of the second-generation tau tracer 2-(2-([F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c']dipyridine ([F]PI-2620) in a group of patients clinically diagnosed with 4-repeat tauopathy, specifically progressive supranuclear palsy or cortical basal syndrome. The study found that SUV ratios calculated using the identified reference regions (i.e., fusiform gyrus and crus-cerebellum) were significantly associated with symptom severity and disease duration. This establishes, for the first time to our knowledge, the suitability of [F]PI-2620 for tracking disease progression in this 4-repeat disease population. This is an important step toward increased clinical utility, such as patient stratification and monitoring in disease-modifying treatment trials. Additionally, the applied methodology successfully optimized reference regions for automated detection of brain imaging tracers. This approach may also hold value for other brain imaging tracers.
Topics: Humans; Positron-Emission Tomography; tau Proteins; Male; Female; Middle Aged; Aged; Phenotype; Pyridines; Tauopathies; Radiopharmaceuticals
PubMed: 38575191
DOI: 10.2967/jnumed.123.265930 -
Immunologic Research Dec 2023The effects of specific cytokines produced by T cell subsets (such as Th1, Th2, and newly discovered Th17, Treg, Tfh, or Th22) are diverse, depending on interactions...
The effects of specific cytokines produced by T cell subsets (such as Th1, Th2, and newly discovered Th17, Treg, Tfh, or Th22) are diverse, depending on interactions with other cytokines, distinct signaling pathways, phase of the disease, or etiological factor. The immunity equilibrium of the immune cells, such as the Th1/Th2, the Th17/Treg, and the Th17/Th1 balance is necessary for the maintenance of the immune homeostasis. If the balance of the T cells subsets is damaged, the autoimmune response becomes enhanced which leads to autoimmune diseases. Indeed, both the Th1/Th2 and the Th17/Treg dichotomies are involved in the pathomechanism of autoimmune diseases. The aim of the study was to determine the cytokines of Th17 lymphocytes as well as the factors modulating their activity in patients with pernicious anemia. The magnetic bead-based immunoassays used (Bio-Plex) allow simultaneous detection of multiple immune mediators from one serum sample. In our study, we showed that patients suffering from pernicious anemia develop the Th1/Th2 imbalance with a quantitative advantage of cytokines participating in Th1-related immune response, the Th17/Treg imbalance with a quantitative advantage of cytokines participating in Treg-related response, as well as the Th17/Th1 imbalance with a quantitative predominance of cytokines participating in Th1-related immune response. Our study results indicate that T lymphocytes and their specific cytokines play an role in the course of pernicious anemia. The observed changes may indicate the immune response to pernicious anemia or be an element of the pernicious anemia pathomechanism.
Topics: Humans; Cytokines; Anemia, Pernicious; T-Lymphocytes, Regulatory; Th17 Cells; Autoimmune Diseases; Th1 Cells; Th2 Cells
PubMed: 37269464
DOI: 10.1007/s12026-023-09399-9