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Journal of the Neurological Sciences Jul 2023To assess marked central canal T2-hyperintensity in patients with myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) myelitis compared to myelitis...
OBJECTIVE
To assess marked central canal T2-hyperintensity in patients with myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) myelitis compared to myelitis patients with aquaporin-4-antibody-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD) and multiple sclerosis (MS).
MATERIAL/METHODS
Two blinded raters evaluated spinal cord magnetic resonance imaging (MRIs) of myelitis patients with MOGAD (n = 63), AQP4 + NMOSD (n = 37), and MS (n = 26), assessing for marked central canal T2-hyperintensity and its evolution. If there were conflicting results, a third neurologist assessed the MRI.
RESULTS
Marked central canal T2-hyperintensity was more frequent in patients with MOGAD (18/63[29%]) than MS (1/26[4%]; p = 0.01) myelitis but did not differ from AQP4 + NMOSD (13/37[35%]; p = 0.49). Marked central canal T2-hyperintensity had completely resolved on follow-up axial MRI for most MOGAD (12/14[86%]) and AQP4 + NMOSD (10/10[100%]; p = 0.49) patients.
CONCLUSIONS
Marked central canal T2-hyperintensity is a common transient radiologic accompaniment of MOGAD and AQP4 + NMOSD myelitis, but not MS myelitis.
Topics: Myelin-Oligodendrocyte Glycoprotein; Myelitis, Transverse; Magnetic Resonance Imaging; Autoantibodies; Multiple Sclerosis; Diagnosis, Differential; Humans; Male; Female; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Spinal Canal; Spinal Cord
PubMed: 37201267
DOI: 10.1016/j.jns.2023.120687 -
Applied Radiation and Isotopes :... Jul 2023Some scientific discoveries are well known only to a core group of researchers working on technical subjects. Nevertheless, they open new research directions, allow...
Some scientific discoveries are well known only to a core group of researchers working on technical subjects. Nevertheless, they open new research directions, allow existing knowledge to be viewed in entirely new and useful ways, or provide a way to make something that was hard or impossible to make before. Carbon-11 methyl triflate ([C]MeOTf) is one such advance, facilitating the synthesis of many carbon-11 radio tracers and broadening the range of applications of carbon-11 radiochemistry. The year 2022 marked the 30th anniversary of the original paper in Applied Radiation and Isotopes introducing a simple synthesis of [C]MeOTf from carbon-11 methyl iodide ([C]MeI) and it also marked the end of the fruitful career and life of the researcher who developed it, Douglas Jewett. It seems fitting to say a few words on how it came to be and how it has helped advance carbon-11 radiochemistry.
PubMed: 37087867
DOI: 10.1016/j.apradiso.2023.110812 -
Cureus Nov 2022Rhabdomyolysis is a pathological condition presenting with symptoms of localized or generalized myalgia and weakness, associated with an increase in serum creatine...
Rhabdomyolysis is a pathological condition presenting with symptoms of localized or generalized myalgia and weakness, associated with an increase in serum creatine kinase level and, often leading to myoglobinuria and acute kidney injury. It has a wide range of etiologies. Immune-mediated necrotizing myopathy (IMNM) is a rare type of inflammatory myopathy, that leads to rhabdomyolysis, and it is divided into three different subtypes: anti-3-hydroxy-3-methylglutaryl-coA reductase (anti-HMGCR, anti-signal recognition particle (anti-SRP), and seronegative. There are slight differences in incidence, age of onset, clinical course, and prognosis between these subtypes. We describe the case of a 67-year-old female with myalgias and weakness of the thighs for six weeks. Laboratory findings showed marked rhabdomyolysis and severe acute kidney injury. The workup led to the diagnosis of seronegative immune-mediated necrotizing myopathy (IMNM) and treatment with corticosteroid and methotrexate was introduced, which led to marked clinical improvement.
PubMed: 36540529
DOI: 10.7759/cureus.31519 -
EMBO Reports Mar 2024The correct establishment of DNA methylation patterns is vital for mammalian development and is achieved by the de novo DNA methyltransferases DNMT3A and DNMT3B. DNMT3B...
The correct establishment of DNA methylation patterns is vital for mammalian development and is achieved by the de novo DNA methyltransferases DNMT3A and DNMT3B. DNMT3B localises to H3K36me3 at actively transcribing gene bodies via its PWWP domain. It also functions at heterochromatin through an unknown recruitment mechanism. Here, we find that knockout of DNMT3B causes loss of methylation predominantly at H3K9me3-marked heterochromatin and that DNMT3B PWWP domain mutations or deletion result in striking increases of methylation in H3K9me3-marked heterochromatin. Removal of the N-terminal region of DNMT3B affects its ability to methylate H3K9me3-marked regions. This region of DNMT3B directly interacts with HP1α and facilitates the bridging of DNMT3B with H3K9me3-marked nucleosomes in vitro. Our results suggest that DNMT3B is recruited to H3K9me3-marked heterochromatin in a PWWP-independent manner that is facilitated by the protein's N-terminal region through an interaction with a key heterochromatin protein. More generally, we suggest that DNMT3B plays a role in DNA methylation homeostasis at heterochromatin, a process which is disrupted in cancer, aging and Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome.
Topics: Animals; DNA Methylation; Heterochromatin; DNA (Cytosine-5-)-Methyltransferases; DNA Methyltransferase 3A; Mutation; Mammals; Primary Immunodeficiency Diseases; Face
PubMed: 38291337
DOI: 10.1038/s44319-024-00061-5 -
Experimental Eye Research Dec 2023Progressive loss of retinal ganglion cells (RGCs) caused by retinal ischemia-reperfusion (IR) injury can lead to irreversible vision impairment, with neuroinflammatory...
Progressive loss of retinal ganglion cells (RGCs) caused by retinal ischemia-reperfusion (IR) injury can lead to irreversible vision impairment, with neuroinflammatory responses playing an important role in this process. COG1410, a mimetic peptide of apolipoprotein E, has demonstrated protective potential in the central nervous system, but its effects on retinal IR injury remain unexplored. In this study, we established a mouse model of retinal IR injury to investigate the effects of COG1410 on retinal microglia and RGCs. We observed CD16/32-marked and CD206-marked microglia and RGCs using immunofluorescence staining, detected the expression of inflammatory factors by PCR, and evaluated retinal apoptosis with TUNEL staining. We further investigated the potential mechanism by detecting the expression of key proteins via Western blot. The results reveal that COG1410 decreased the number of CD16/32-marked microglia and increased the number of CD206-marked microglia, alleviated the expression of IL-1β and TNF-α, and reduced the loss of RGCs by inhibiting the mitochondrial-related apoptotic pathway. COG1410 was found to increase the expression of ERK1/2 and Nr4a1 but decrease the expression of NF-κB. The expression of TREM2 showed an increasing trend after COG1410 administration, but it was not statistically significant. In conclusion, COG1410 regulates microglial states and protects RGCs in retinal IR injury, showing promising potential for the treatment of eye diseases.
Topics: Mice; Animals; Retinal Ganglion Cells; Microglia; Retina; Reperfusion Injury
PubMed: 37839665
DOI: 10.1016/j.exer.2023.109678 -
Advances in Experimental Medicine and... 2020Most types of cells in the body have no or very limited capacity of catabolizing cholesterol, so cholesterol efflux is essential for cholesterol homeostasis. There are... (Review)
Review
Most types of cells in the body have no or very limited capacity of catabolizing cholesterol, so cholesterol efflux is essential for cholesterol homeostasis. There are multiple mechanisms responsible for cellular cholesterol efflux. Among them, the active efflux pathways are mediated primarily by the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1. ABCA1 is essential for cholesterol and phospholipid efflux to apolipoprotein A-I and high density lipoprotein (HDL) biogenesis. ABCG1 promotes cholesterol efflux primarily to HDL particles. Atherosclerotic cardiovascular disease is a chronic inflammatory disease characterized by marked macrophage foam cell accumulation in atherosclerotic plaques and associated pro-inflammatory responses in lesional cells. Findings from both animal and human studies indicate a critical role of disturbed cholesterol homeostasis in pro-inflammatory responses in these cells, particularly in lesional macrophages. ABCA1 and ABCG1 are highly expressed in macrophages, particularly in response to cholesterol accumulation, and are essential in maintenance of cholesterol homeostasis. Functional deficiency of ABCA1 and ABCG1 in macrophage markedly increases atherogenesis, with exacerbated inflammatory responses. ABCA1 and ABCG1 also play a critical role in control of hematopoietic stem and progenitor cell (HSPC) proliferation and extramedullary hematopoiesis. Hematopoietic ABCA1 and ABCG1 deficiencies cause marked HSPC expansion and extramedullary hematopoiesis, particularly in hypercholesterolemia, and lead to marked monocytosis and neutrophilia with exacerbated pro-inflammatory responses. All these contribute to atherosclerosis. In this chapter, we describe these findings and discuss the current understanding of the underlying mechanisms. We also discuss other ABC transporters such as ABCG4, which also promotes cholesterol efflux to HDL and controls megakaryocyte proliferation and platelet biogenesis. By this pathway, ABCG4 also modulates atherogenesis. Therapeutic approaches targeting the pathways and mechanisms described also are discussed.
Topics: ATP-Binding Cassette Transporters; Animals; Cardiovascular Diseases; Cholesterol; Foam Cells; Humans; Lipoproteins
PubMed: 32705595
DOI: 10.1007/978-981-15-6082-8_6 -
Scientific Reports Aug 2023Automated text recognition techniques have made significant advancements; however, certain tasks still present challenges. This study is motivated by the need to...
Automated text recognition techniques have made significant advancements; however, certain tasks still present challenges. This study is motivated by the need to automatically recognize hand-marked text on construction defect tags among millions of photographs. To address this challenge, we investigated three methods for automating hand-marked semantic text recognition (HMSTR)-a modified scene text recognition-based (STR) approach, a two-step HMSTR approach, and a lumped approach. The STR approach involves locating marked text using an object detection model and recognizing it using a competition-winning STR model. Similarly, the two-step HMSTR approach first localizes the marked text and then recognizes the semantic text using an image classification model. By contrast, the lumped approach performs both localization and identification of marked semantic text in a single step using object detection. Among these approaches, the two-step HMSTR approach achieved the highest F1 score (0.92) for recognizing circled text, followed by the STR approach (0.87) and the lumped approach (0.78). To validate the generalizability of the two-step HMSTR approach, subsequent experiments were conducted using check-marked text, resulting in an F1 score of 0.88. Although the proposed methods have been tested specifically with tags, they can be extended to recognize marked text in reports or books.
PubMed: 37648714
DOI: 10.1038/s41598-023-41489-4 -
International Journal of Molecular... Jun 2022MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. An aberrant regulation of gene expression by...
MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. An aberrant regulation of gene expression by miRNAs is associated with numerous diseases, including cancer. MiRNAs expression can be influenced by various stimuli, among which hypoxia; however, the effects of different types of continuous hypoxia (moderate or marked) on miRNAs are still poorly studied. Lately, some hypoxia-inducible miRNAs (HRMs, hypoxia-regulated miRNAs) have been identified. These HRMs are often activated in different types of cancers, suggesting their role in tumorigenesis. The aim of this study was to evaluate changes in miRNAs expression both in moderate continuous hypoxia and marked continuous hypoxia to better understand the possible relationship between hypoxia, miRNAs, and colorectal cancer. We used RT-PCR to detect the miRNAs expression in colorectal cancer cell lines in conditions of moderate and marked continuous hypoxia. The expression of miRNAs was analyzed using a two-way ANOVA test to compare the differential expression of miRNAs among groups. The levels of almost all analyzed miRNAs (miR-21, miR-23b, miR-26a, miR-27b, and miR-145) were greater in moderate hypoxia versus marked hypoxia, except for miR-23b and miR-21. This study identified a series of miRNAs involved in the response to different types of continuous hypoxia (moderate and marked), highlighting that they play a role in the development of cancer. To date, there are no other studies that demonstrate how these two types of continuous hypoxia could be able to activate different molecular pathways that lead to a different expression of specific miRNAs involved in tumorigenesis.
Topics: Carcinogenesis; Cell Transformation, Neoplastic; Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Hypoxia; MicroRNAs
PubMed: 35682972
DOI: 10.3390/ijms23116294 -
Three-axis classification of mouse lung mesenchymal cells reveals two populations of myofibroblasts.Development (Cambridge, England) Mar 2022The mesenchyme consists of heterogeneous cell populations that support neighboring structures and are integral to intercellular signaling, but are poorly defined...
The mesenchyme consists of heterogeneous cell populations that support neighboring structures and are integral to intercellular signaling, but are poorly defined morphologically and molecularly. Leveraging single-cell RNA-sequencing, 3D imaging and lineage tracing, we classify the mouse lung mesenchyme into three proximal-distal axes that are associated with the endothelium, epithelium and interstitium, respectively. From proximal to distal: the vascular axis includes vascular smooth muscle cells and pericytes that transition as arterioles and venules ramify into capillaries; the epithelial axis includes airway smooth muscle cells and two populations of myofibroblasts - ductal myofibroblasts, surrounding alveolar ducts and marked by CDH4, HHIP and LGR6, which persist post-alveologenesis, and alveolar myofibroblasts, surrounding alveoli and marked by high expression of PDGFRA, which undergo developmental apoptosis; and the interstitial axis, residing between the epithelial and vascular trees and sharing the marker MEOX2, includes fibroblasts in the bronchovascular bundle and the alveolar interstitium, which are marked by IL33/DNER/PI16 and Wnt2, respectively. Single-cell imaging reveals a distinct morphology of mesenchymal cell populations. This classification provides a conceptual and experimental framework applicable to other organs.
Topics: Animals; Lung; Mesenchymal Stem Cells; Mesoderm; Mice; Myofibroblasts; Pulmonary Alveoli
PubMed: 35302583
DOI: 10.1242/dev.200081