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2024 May
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia Microglia and Dendritic Cells as a Source of IL-6 in a Mouse Model of Multiple Sclerosis https://pubmed.ncbi.nlm.nih.gov/38880650/
..whereas the dendritic cell-derived IL-6, in addition to being critically involved in the balance of regulatory T cells and TH17 cells, may stimulate production of cytokines associated with pathogenic functions of T cells.
Results
The mean age was 35 years and 88% were women. Mean temperature was 56.9 °F, relative humidity 67.3%, and fine particulate matter 7.3 μg/m3. Higher relative humidity was associated with higher odds of migraine headache, but the association was only observed in warm season (April–September). Higher levels of daily maximum 8-hour ozone and daily maximum 8-hour carbon monoxide appeared to be associated with higher odds of migraine headache onset in cold season (October–March).
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MS
2024 Jun 14 Migraine Risk in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder: A Nationwide Cohort Study in South Korea https://pubmed.ncbi.nlm.nih.gov/38880093/
Conclusion: The study results revealed an increased risk of migraines in patients with MS but not in patients with NMSOD compared with matched controls.
Re: Tropospheric ozone
Posted: Fri Jun 21, 2024 11:19 am
by Petr75
O3
2024 Mar 5
Eye Institute & Affiliated Xiamen Eye Center, School of Pharmaceutical Sciences & School of Medicine, Xiamen University, Xiamen, Fujian, China Ozone exposure affects corneal epithelial fate by promoting mtDNA leakage and cGAS/STING activation https://pubmed.ncbi.nlm.nih.gov/38101018/
This study revealed the role of mtDNA leakage-mediated cGAS/STING activation in corneal squamous epithelial metaplasia caused by ozone exposure...
2024 Jun 7
Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany STING orchestrates the neuronal inflammatory stress response in multiple sclerosis https://pubmed.ncbi.nlm.nih.gov/38878778/
Inflammation-induced neurodegeneration is a defining feature of multiple sclerosis (MS), yet the underlying mechanisms remain unclear. By dissecting the neuronal inflammatory stress response, we discovered that neurons in MS and its mouse model induce the stimulator of interferon genes (STING)...
hort-term exposure to particles with aerodynamic diameters less than 2.5 μm (PM2.5) and ozone (O3) are important risk factors for human health...
Re: Tropospheric ozone
Posted: Sat Jun 22, 2024 11:12 pm
by Petr75
2024 Jul
School of Mathematics and Physics, Xi'an Jiaotong-Liverpool University, China; Department of Biostatistics, University of Washington, 1410 Northeast Campus Parkway, Seattle, USA Spatiotemporal joint analysis of PM2.5 and Ozone in California with INLA approach https://pubmed.ncbi.nlm.nih.gov/38880600/
Abstract
The substantial threat of concurrent air pollutants to public health is increasingly severe under climate change. To identify the common drivers and extent of spatiotemporal similarity of PM2.5 and ozone (O3), this paper proposed a log Gaussian-Gumbel Bayesian hierarchical model allowing for sharing a stochastic partial differential equation and autoregressive model of order one (SPDE-AR(1)) spatiotemporal interaction structure. The proposed model, implemented by the approach of integrated nested Laplace approximation (INLA), outperforms in terms of estimation accuracy and prediction capacity for its increased parsimony and reduced uncertainty, especially for the shared O3 sub-model...
Conclusion: Ozone exposure seems to induce metabolic disorders and NAD+ depletion through excessive PARP1 activation in SCNs.
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MS
2009
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Ohio, USA The importance of NAD in multiple sclerosis https://pubmed.ncbi.nlm.nih.gov/19149604/
.. A comprehensive review of immunomodulatory control of NAD biosynthesis and degradation in MS pathogenesis is presented.
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Poly (ADP-ribose) polymerase 1 (PARP1) plays a fundamental role in DNA repair and gene expression. Excessive PARP1 hyperactivation, however, has been associated with cell death. PARP1 and/or its activity are dysregulated in the immune and central nervous system of multiple sclerosis (MS) patients and animal models...
Re: Tropospheric ozone
Posted: Fri Jun 28, 2024 3:09 pm
by NHE
Petr75 wrote: ↑Fri Jun 28, 2024 11:54 am
2009
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Ohio, USA The importance of NAD in multiple sclerosis https://pubmed.ncbi.nlm.nih.gov/19149604/
.. A comprehensive review of immunomodulatory control of NAD biosynthesis and degradation in MS pathogenesis is presented.
I suspect ATP depletion plays a critical role in disability progression.
The full abstract:
The etiology of multiple sclerosis (MS) is unknown but it manifests as a chronic inflammatory demyelinating disease in the central nervous system (CNS). During chronic CNS inflammation, nicotinamide adenine dinucleotide (NAD) concentrations are altered by (T helper) Th1-derived cytokines through the coordinated induction of both indoleamine 2,3-dioxygenase (IDO) and the ADP cyclase CD38 in pathogenic microglia and lymphocytes. While IDO activation may keep auto-reactive T cells in check, hyper-activation of IDO can leave neuronal CNS cells starving for extracellular sources of NAD. Existing data indicate that glia may serve critical functions as an essential supplier of NAD to neurons during times of stress. Administration of pharmacological doses of non-tryptophan NAD precursors ameliorates pathogenesis in animal models of MS. Animal models of MS involve artificially stimulated autoimmune attack of myelin by experimental autoimmune encephalomyelitis (EAE) or by viral-mediated demyelination using Thieler's murine encephalomyelitis virus (TMEV). The Wld(S) mouse dramatically resists razor axotomy mediated axonal degeneration. This resistance is due to increased efficiency of NAD biosynthesis that delays stress-induced depletion of axonal NAD and ATP. Although the Wld(S) genotype protects against EAE pathogenesis, TMEV-mediated pathogenesis is exacerbated. In this review, we contrast the role of NAD in EAE versus TMEV demyelinating pathogenesis to increase our understanding of the pharmacotherapeutic potential of NAD signal transduction pathways. We speculate on the importance of increased SIRT1 activity in both PARP-1 inhibition and the potentially integral role of neuronal CD200 interactions through glial CD200R with induction of IDO in MS pathogenesis. A comprehensive review of immunomodulatory control of NAD biosynthesis and degradation in MS pathogenesis is presented. Distinctive pharmacological approaches designed for NAD-complementation or targeting NAD-centric proteins (SIRT1, SIRT2, PARP-1, GPR109a, and CD38) are outlined towards determining which approach may work best in the context of clinical application.
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I suspect ATP depletion plays a critical role in disability progression. (NHE)
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ATP - also my opinion (Petr)
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Ozone is a highly reactive environmental pollutant with well-recognized adverse effects on lung health. Bronchial
hyperresponsiveness (BHR) is one consequence of ozone exposure, particularly for individuals with underlying lung
disease. Our data demonstrated that ozone induced substantial ATP release from human airway epithelia in vitro and into
the airways of mice in vivo and that ATP served as a potent inducer of mast cell degranulation and BHR, acting through
P2X7 receptors on mast cells. Both mast cell–deficient and P2X7 receptor–deficient (P2X7–/–) mice demonstrated
markedly attenuated BHR to ozone. Reconstitution of mast cell–deficient mice with WT mast cells and P2X7–/– mast cells
restored ozone-induced BHR. Despite equal numbers of mast cells in reconstituted mouse lungs, mice reconstituted with
P2X7–/– mast cells demonstrated significantly less robust BHR than mice reconstituted with WT mast cells. These results
support a model where P2X7 on mast cells and other cell types contribute to ozone-induced BHR
2024 Jun 19 Exposure to O3 and NO2 on the interfacial chemistry of the pulmonary surfactant and the mechanism of lung oxidative damage https://pubmed.ncbi.nlm.nih.gov/38906186/
Abstract
Exposure to ozone (O3) and nitrogen dioxide (NO2) are related to pulmonary dysfunctions and various lung diseases, but the underlying biochemical mechanisms remain uncertain. Herein, the effect of inhalable oxidizing gas pollutants on the pulmonary surfactant (PS, extracted from porcine lungs), a mixture of active lipids and proteins that plays an important role in maintaining normal respiratory mechanics..
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Abstract
Respiratory dysfunction frequently occurs in patients with advanced multiple sclerosis (MS), and may manifest as acute or chronic respiratory failure, disordered control of breathing, respiratory muscle weakness, sleep disordered breathing, or neurogenic pulmonary edema.
2024 Jun 3 Polymorphisms in the Dopaminergic Receptor D3 Gene Correlate with Disease Progression Rate in Relapsing-Remitting Multiple Sclerosis Patients https://pubmed.ncbi.nlm.nih.gov/38927672/
Background: Multiple sclerosis (MS) is a common chronic autoimmune disease of the central nervous system. In MS, disability progresses unpredictably. Dopamine (DA) is a modulator of immune functions, and compelling evidence supports its involvement in both pathogenesis and treatment of MS. ..
..Ozone exposure, compared to air exposure increased BAL cathepsin S levels
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MS
2024 Jun 24
Neurological Private Practice, Bialystok, Poland 20S constitutive proteasome, 20S immunoproteasome, and cathepsin S are high-sensitivity and independent markers of immunological activity in relapsing-remitting type of multiple sclerosis https://pubmed.ncbi.nlm.nih.gov/38923513/
..Plasma 20S constitutive proteasome, 20S immunoproteasome, and cathepsin S concentrations were significantly higher in RRMS patients compared to the control group.
Abstract
Tropospheric ozone [O3] is a secondary air pollutant formed from the photochemical oxidation of volatile organic compounds in the presence of nitrogen oxides, and it is one of the most damaging air pollutants to crops. O3 entry into the plant generates reactive oxygen species leading to cellular damage and oxidative stress, leading to decreased primary production and yield. Increased O3 exposure has also been shown to have secondary impacts on plants by altering the incidence and response to plant pathogens.
2024 May
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia Microglia and Dendritic Cells as a Source of IL-6 in a Mouse Model of Multiple Sclerosis https://pubmed.ncbi.nlm.nih.gov/38880650/
..whereas the dendritic cell-derived IL-6, in addition to being critically involved in the balance of regulatory T cells and TH17 cells, may stimulate production of cytokines associated with pathogenic functions of T cells.
2024 Jun 19
Servei de Neurologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, Spain IL-6 Inhibition as a Therapeutic Target in Aged Experimental Autoimmune Encephalomyelitis https://pubmed.ncbi.nlm.nih.gov/38928437/