ABSTRACT
Giant cell arteritis (GCA) is a chronic granulomatous vasculitis of medium and large arteries leading to cranial and extracranial manifestations. Temporal artery biopsy is considered the gold standard; however, its sensitivity is low at 47%. We report a unique case of Bing-Neel Syndrome (BNS) presenting as biopsy-proven GCA. BNS is a rare complication (1%) of Waldenstrom Macroglobulinemia (WM), which results from infiltration of lymph plasmacytoid cells and plasma cells into the central nervous system. A 77-year-old female with a past medical history of glaucoma, hypertension, diabetes, and chronic ocular ischemic syndrome in her right eye presented with progressive left eye vision loss for 5 days. Fundoscopic examination was notable for pseudophakic pseudopallor but no optic disc edema. Intraocular pressure was >40 and normalized after acetazolamide. The patient was started on pulse dose steroids by her neuro-ophthalmologist. She was discharged home on 60 mg of prednisone. At follow up with her neuro-ophthalmologist, new dot blot hemorrhages in the left eye were noted and she was readmitted for pulse dose of intravenous methylprednisolone. Temporal artery biopsy was consistent with GCA spectrum. Work up revealed paraproteinemia and subsequent bone marrow biopsy demonstrated WM. The patient was treated for her WM and her ophthalmic complications stabilized.
ABSTRACT
The vertebrate retina is a tractable system for studying control of cell neurogenesis and cell fate specification. During embryonic development, retinal neurogenesis is under strict temporal regulation, with cell types generated in fixed but overlapping temporal intervals. The temporal sequence and relative numbers of retinal cell types generated during development are robust and show minimal experience-dependent variation. In many cold-blooded vertebrates, acute retinal injury induces a different form of neurogenesis, where Müller glia reprogram into retinal progenitor-like cells that selectively regenerate retinal neurons lost to injury. The extent to which the molecular mechanisms controlling developmental and injury-induced neurogenesis resemble one another has long been unclear. However, a recent study in zebrafish has shed new light on this question, using single-cell multiomic analysis to show that selective loss of different retinal cell types induces the formation of fate-restricted Müller glia-derived progenitors that differ both from one another and from progenitors in developing retina. Here, we discuss the broader implications of these findings, and their possible therapeutic relevance.
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Many tissue-specific adult stem cell lineages maintain a balance between proliferation and differentiation. Here, we study how the H3K4me3 methyltransferase Set1 regulates early-stage male germ cells in Drosophila. Early-stage germline-specific knockdown of Set1 results in temporally progressive defects, arising as germ cell loss and developing into overpopulated early-stage germ cells. These germline defects also impact the niche architecture and cyst stem cell lineage non-cell-autonomously. Additionally, wild-type Set1, but not the catalytically inactive Set1, rescues the Set1 knockdown phenotypes, highlighting the functional importance of the methyltransferase activity of Set1. Further, RNA-sequencing experiments reveal key signaling pathway components, such as the JAK-STAT pathway gene Stat92E and the BMP pathway gene Mad, which are upregulated upon Set1 knockdown. Genetic interaction assays support the functional relationships between Set1 and JAK-STAT or BMP pathways, as both Stat92E and Mad mutations suppress the Set1 knockdown phenotypes. These findings enhance our understanding of the balance between proliferation and differentiation in an adult stem cell lineage. The phenotype of germ cell loss followed by over-proliferation when inhibiting a histone methyltransferase also raises concerns about using their inhibitors in cancer therapy.
Subject(s)
Cell Differentiation , Drosophila Proteins , Drosophila melanogaster , Germ Cells , Histone-Lysine N-Methyltransferase , Signal Transduction , Animals , Male , Cell Differentiation/genetics , Drosophila Proteins/metabolism , Drosophila Proteins/genetics , Signal Transduction/genetics , Histone-Lysine N-Methyltransferase/metabolism , Histone-Lysine N-Methyltransferase/genetics , Germ Cells/metabolism , Germ Cells/cytology , Drosophila melanogaster/metabolism , Drosophila melanogaster/genetics , Stem Cells/metabolism , Stem Cells/cytology , STAT Transcription Factors/metabolism , STAT Transcription Factors/genetics , Janus Kinases/metabolism , Janus Kinases/genetics , Cell Proliferation/genetics , Cell Lineage/genetics , Gene Expression Regulation, DevelopmentalABSTRACT
Many genes are known to regulate retinal regeneration after widespread tissue damage. Conversely, genes controlling regeneration after limited cell loss, as per degenerative diseases, are undefined. As stem/progenitor cell responses scale to injury levels, understanding how the extent and specificity of cell loss impact regenerative processes is important. Here, transgenic zebrafish enabling selective retinal ganglion cell (RGC) ablation were used to identify genes that regulate RGC regeneration. A single cell multiomics-informed screen of 100 genes identified seven knockouts that inhibited and 11 that promoted RGC regeneration. Surprisingly, 35 out of 36 genes known and/or implicated as being required for regeneration after widespread retinal damage were not required for RGC regeneration. The loss of seven even enhanced regeneration kinetics, including the proneural factors neurog1, olig2 and ascl1a. Mechanistic analyses revealed that ascl1a disruption increased the propensity of progenitor cells to produce RGCs, i.e. increased 'fate bias'. These data demonstrate plasticity in the mechanism through which Müller glia convert to a stem-like state and context specificity in how genes function during regeneration. Increased understanding of how the regeneration of disease-relevant cell types is specifically controlled will support the development of disease-tailored regenerative therapeutics.
Subject(s)
Animals, Genetically Modified , Retinal Ganglion Cells , Zebrafish Proteins , Zebrafish , Animals , Zebrafish/genetics , Retinal Ganglion Cells/metabolism , Retinal Ganglion Cells/cytology , Retinal Ganglion Cells/physiology , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism , Nerve Regeneration/genetics , Nerve Regeneration/physiology , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , CRISPR-Cas Systems/genetics , Regeneration/genetics , Regeneration/physiology , Retina/metabolism , Retina/cytology , Stem Cells/metabolism , Stem Cells/cytology , Transcription FactorsABSTRACT
Terahertz scattering scanning near-field optical microscopy is a robust spectral detection technique with a nanoscale resolution. However, there are still major challenges in investigating the heterogeneity of cell membrane components in individual cells. Here, we present a novel and comprehensive analytical approach for detecting and investigating heterogeneity in cell membrane components at the single-cell level. In comparison to the resolution of the topographical atomic force microscopy image, the spatial resolution of the terahertz near-field amplitude image is 3 times that of the former. This ultrafine resolution enables the compositional distribution in the cell membrane, such as the distribution of extracellular vesicles, to be finely characterized. Furthermore, via extraction of the near-field absorption images at specific frequencies, the visualization and compositional difference analysis of cell membrane components can be presented in detail. These findings have significant implications for the intuitive and visual analysis of cell development and disease evolutionary pathways.
Subject(s)
Cell Membrane , Single-Cell Analysis , Single-Cell Analysis/methods , Cell Membrane/chemistry , Humans , Terahertz Imaging/methods , Microscopy, Atomic Force/methods , Extracellular Vesicles/chemistryABSTRACT
Key Clinical Message: Unlike most cases, the lesions were localized to the dorsum of the hand, lacked pruritus (itching), and did not exhibit "sperm-like blood vessels," which are typically pathognomonic to classical MF. Abstract: The study presents a rare case involving a 44-year-old woman who developed a skin condition on the base of her left thumb. Initially misdiagnosed as pigmented purpura, the need for further investigation arose to determine the nature of the condition accurately. The medical evaluation encompassed a comprehensive analysis of the patient's skin ailment. A series of diagnostic examinations were conducted to ascertain the underlying cause. Although routine blood tests yielded unremarkable results, the distinct characteristics of the rash prompted a more thorough investigation. Subsequent assessment revealed that the skin condition was not pigmented purpura, as initially presumed, but rather a manifestation of cutaneous T-cell lymphoma (CTCL) known as mycosis fungoides (MF). MF is an infrequent lymphoma predominantly affecting individuals aged 45-65, exhibiting a male-to-female sex ratio of 2:1. The annual incidence of MF ranges from 0.3 to 0.96 cases per 100,000 individuals. The woman's skin exhibited discrete patches adorned with colored dots, progressively thickening and pigmentation. Notably, the absence of pruritus did not dispel suspicion. This case underscores the significance of accurately diagnosing uncommon dermatological disorders to facilitate appropriate medical intervention. The unique appearance of the rash and its distinctive features, despite normal blood results, enabled the identification of MF. The patient's treatment encompassed a combination of steroids and narrowband UV therapy. Vigilance, continued research, and heightened awareness are paramount for early intervention and improved patient outcomes. Such efforts contribute to an enhanced understanding of the complexities of this condition.
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Objective: Bendamustine was approved for treating chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Despite its therapeutic benefits, the long-term safety of bendamustine in a large population remains inadequately understood. This study evaluates the adverse events (AEs) associated with bendamustine, using a real-world pharmacovigilance database to support its clinical application. Methods: We conducted a post-marketing risk analysis to assess the association between bendamustine and its AEs. Data were extracted from the US FDA's Adverse Event Reporting System (FAERS), covering the period from January 2017 to September 2023. The characteristics of bendamustine-associated AEs and the onset time were further analyzed. Statistical analysis was performed using MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2016, and Minitab 21.0. Results: 9,461,874 reports were collected from the FAERS database, 9,131 identified bendamustine as the "primary suspected" drug. We identified 331 significant disproportionality preferred terms (PTs). Common AEs included pyrexia, neutropenia, infusion site reaction, progressive multifocal leukoencephalopathy (PML), injection site vasculitis, and pneumonia-all documented on bendamustine's label. Notably, 16 unexpected and significant AEs were discovered, including hypogammaglobulinemia, which is concerning due to its potential to increase infection susceptibility following bendamustine treatment. Other significant findings were anaphylactic reactions, PML, and cutaneous malignancies, suggesting updates to the drug's label may be necessary. Physicians should monitor for neurological and skin changes in patients and discontinue treatment if PML is suspected. Moreover, the median onset time for bendamustine-associated AEs was 13 days, with an interquartile range [IQR] of 0-59 days, predominantly occurring on the first day post-initiation. The ß of bendamustine-related AEs suggested risk reduction over time. Conclusion: Our study uncovered some potential pharmacovigilance signals for bendamustine, providing important insights for its safe and effective clinical use.
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PURPOSE: To evaluate changes in retinal microvascular density and choroidal vascularity in patients with retinoblastoma (RB) after intra-arterial chemotherapy (IAC). DESIGN: Retrospective clinical cohort study. METHODS: This study included 12 unilateral RB eyes treated with IAC (RB tumor), 12 contralateral normal eyes (RB fellow), and 12 healthy controls. The macular retinal thickness and retinal microvascular structure, including the foveal avascular zone (FAZ) area, macular and peripapillary superficial vessel density (SVD), and deep vessel density (DVD), were measured by optical coherence tomography angiography (OCTA). The choroidal thickness (ChT) and choroidal vascularity, including total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI), were measured by spectral-domain optical coherence tomography (SD-OCT). A comparison among the 3 groups was conducted, and the correlations among the parameters were analyzed. RESULTS: Among the 3 cohorts, the foveal retinal thickness, SVD, DVD, ChT, TCA, LA, SA, and CVI were significantly lower in RB tumor compared to RB fellow and the control eyes (all P < .01). There were no significant differences in the parameters between the contralateral and control eyes. The correlation analyses indicated a significant negative correlation between the total melphalan dose and foveal and parafoveal DVD, ChT, and LA. CONCLUSIONS: The retinal microvascular density and choroidal vascularity were lower in unilateral RB treated with IAC, and seemed to be related to the total melphalan dose. There were no measurable changes in the contralateral eyes.
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Previous studies of neuronal survival have primarily focused on identifying intrinsic mechanisms controlling the process. This study explored how intercellular communication contributes to retinal ganglion cell (RGC) survival following optic nerve crush based on single-cell RNA-seq analysis. We observed transcriptomic changes in retinal cells in response to the injury, with astrocytes and Müller glia having the most interactions with RGCs. By comparing RGC subclasses characterized by distinct resilience to cell death, we found that the high-survival RGCs tend to have more ligand-receptor interactions with neighboring cells. We identified 47 interactions stronger in high-survival RGCs, likely mediating neuroprotective effects. We validated one identified target, the µ-opioid receptor (Oprm1), to be neuroprotective in three retinal injury models. Although the endogenous Oprm1 is preferentially expressed in intrinsically photosensitive RGCs, its neuroprotective effect can be transferred to other subclasses by pan-RGC overexpression of Oprm1. Lastly, manipulating the Oprm1 activity improved visual functions in mice.
Subject(s)
Neuroprotective Agents , Optic Nerve Injuries , Animals , Mice , Cell Communication , Cell Death , Cell Survival , Neuroprotective Agents/pharmacology , Neuroprotective Agents/metabolism , Optic Nerve/metabolism , Optic Nerve Injuries/metabolism , Retinal Ganglion Cells/physiologyABSTRACT
AIMS: To describe the clinical features, multimodal imaging, treatments and natural course of acute spontaneous vortex vein occlusion. METHODS: Clinical data were collected on nine patients with acute vortex vein occlusion. The symptoms and signs, multimodal imaging, treatments and follow-up results were summarised. RESULTS: Six patients (66.7%) were men and three (33.3%) were women. The mean age was 47.8±15.4 years. Patients were initially misdiagnosed as having choroidal tumour (66.7%), scleritis (22.2%) and peripheral exudative haemorrhagic chorioretinopathy (11.1%). The related clinical characteristics included choroidal pseudo-tumour (100%), anterior segment injection (88.9%), acute ocular pain (77.8%), transient blurred vision (66.7%) and subsequent scleral icterus (66.7%). Six patients (66.7%) experienced a definite Valsalva manoeuvre prior to the onset. In acute phase, ultrasonography showed a low-to-medium reflective lesion without inside blood flow signal (mean thickness, 2.7±0.6 mm). Swept-source optical coherence tomography angiography (SS-OCTA) demonstrated the dilated vortex veins and ampulla with suprachoroidal haemorrhage and exudation. Indocyanine green angiography (ICGA) demonstrated choroidal circulation abnormalities in the affected quadrant. MRI showed a well-defined mass with enhancement. The main treatment was medical observation (44.5%). The choroidal pseudo-tumour spontaneously resolved with a mean course of 4.1±1.9 weeks. CONCLUSIONS: Acute vortex vein occlusion is a rare condition and initial misdiagnosis is not uncommon. It is mainly identified as an evanescent choroidal pseudo-tumour with acute pain, red eye and blurred vision. Widefield ICGA and SS-OCTA can offer valuable diagnostic clues. Medical observation may be a treatment option.
ABSTRACT
Many cell types come from tissue-specific adult stem cells that maintain the balance between proliferation and differentiation. Here, we study how the H3K4me3 methyltransferase, Set1, regulates early-stage male germ cell proliferation and differentiation in Drosophila. Early-stage germline-specific knockdown of set1 results in a temporally progressed defects, arising as germ cell loss and developing to overpopulated early-stage germ cells. These germline defects also impact the niche architecture and cyst stem cell lineage in a non-cell-autonomous manner. Additionally, wild-type Set1, but not the catalytically inactive Set1, could rescue the set1 knockdown phenotypes, highlighting the functional importance of the methyl-transferase activity of the Set1 enzyme. Further, RNA-seq experiments reveal key signaling pathway components, such as the JAK-STAT pathway gene stat92E and the BMP pathway gene mad, that are upregulated upon set1 knockdown. Genetic interaction assays support the functional relationships between set1 and JAK-STAT or BMP pathways, as mutations of both the stat92E and mad genes suppress the set1 knockdown phenotypes. These findings enhance our understanding of the balance between proliferation and differentiation in an adult stem cell lineage. The germ cell loss followed by over-proliferation phenotypes when inhibiting a histone methyl-transferase raise concerns about using their inhibitors in cancer therapy.
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BACKGROUND: Stroke presentation secondary to a cardiac myxoma thromboembolism is rare in the pediatric population. Because of such rarity, the reported cases in the literature are primarily case reports. Additionally, general pediatric stroke management lacks evidence-based guidelines because of its low incidence and lack of clinical trials. In pediatric strokes identified from a cardiac myxoma, the incidence favors boys with the classical presentation of unilateral weakness and aphasia. We present a pediatric patient who presented with strokelike symptoms secondary to an intracranial embolus from a previously undiagnosed cardiac myxoma. METHODS: We performed a systematic review by searching PubMed, Google Scholar, Web of Science, and Embase databases for cases of pediatric myxoma causing stroke (n = 2431) and identified 19 reported uses of surgical management in treating pediatric patients who present with stroke symptoms secondary to a cardiac myxoma thromboembolism. RESULTS: The most common imaging modality was magnetic resonance imaging in 42% of cases, computed tomography in 36.8%, followed by computed tomography angiography in 31.6% of cases. Of these 19 children treated with procedures, 36.8% of pediatric patients aged between 4 and 14 years underwent neurosurgery (n = 7). CONCLUSIONS: We describe an urgent mechanical thrombectomy and share preoperative and postoperative images and pathology slides confirming a stroke from myxoma origin. We provide added insight in the safe use of mechanical thrombectomy as treatment for pediatric strokes secondary to a thromboembolism.
Subject(s)
Heart Neoplasms , Intracranial Embolism , Myxoma , Stroke , Thrombectomy , Humans , Myxoma/complications , Myxoma/surgery , Myxoma/diagnostic imaging , Heart Neoplasms/complications , Heart Neoplasms/surgery , Heart Neoplasms/diagnostic imaging , Thrombectomy/methods , Child , Stroke/etiology , Stroke/surgery , Stroke/diagnostic imaging , Intracranial Embolism/etiology , Intracranial Embolism/surgery , Intracranial Embolism/diagnostic imaging , Male , Adolescent , Child, Preschool , FemaleABSTRACT
Schlemm's canal (SC) is central in intraocular pressure regulation but requires much characterization. It has distinct inner and outer walls, each composed of Schlemm's canal endothelial cells (SECs) with different morphologies and functions. Recent transcriptomic studies of the anterior segment added important knowledge, but were limited in power by SEC numbers or did not focus on SC. To gain a more comprehensive understanding of SC biology, we performed bulk RNA sequencing on C57BL/6J SC, blood vessel, and lymphatic endothelial cells from limbal tissue (~4500 SECs). We also analyzed mouse limbal tissues by single-cell and single-nucleus RNA sequencing (C57BL/6J and 129/Sj strains), successfully sequencing 903 individual SECs. Together, these datasets confirm that SC has molecular characteristics of both blood and lymphatic endothelia with a lymphatic phenotype predominating. SECs are enriched in pathways that regulate cell-cell junction formation pointing to the importance of junctions in determining SC fluid permeability. Importantly, and for the first time, our analyses characterize 3 molecular classes of SECs, molecularly distinguishing inner wall from outer wall SECs and discovering two inner wall cell states that likely result from local environmental differences. Further, and based on ligand and receptor expression patterns, we document key interactions between SECs and cells of the adjacent trabecular meshwork (TM) drainage tissue. Also, we present cell type expression for a collection of human glaucoma genes. These data provide a new molecular foundation that will enable the functional dissection of key homeostatic processes mediated by SECs as well as the development of new glaucoma therapeutics.
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Early postnatal brain development involves complex interactions among maturing neurons and glial cells that drive tissue organization. We previously analyzed gene expression in tissue from the mouse medial nucleus of the trapezoid body (MNTB) during the first postnatal week to study changes that surround rapid growth of the large calyx of Held (CH) nerve terminal. Here, we present genes that show significant changes in gene expression level during the second postnatal week, a developmental timeframe that brackets the onset of airborne sound stimulation and the early stages of myelination. Gene Ontology analysis revealed that many of these genes are related to the myelination process. Further investigation of these genes using a previously published cell type-specific bulk RNA-Seq data set in cortex and our own single-cell RNA-Seq data set in the MNTB revealed enrichment of these genes in the oligodendrocyte lineage (OL) cells. Combining the postnatal day (P)6-P14 microarray gene expression data with the previously published P0-P6 data provided fine temporal resolution to investigate the initiation and subsequent waves of gene expression related to OL cell maturation and the process of myelination. Many genes showed increasing expression levels between P2 and P6 in patterns that reflect OL cell maturation. Correspondingly, the first myelin proteins were detected by P4. Using a complementary, developmental series of electron microscopy 3D image volumes, we analyzed the temporal progression of axon wrapping and myelination in the MNTB. By employing a combination of established ultrastructural criteria to classify reconstructed early postnatal glial cells in the 3D volumes, we demonstrated for the first time that astrocytes within the mouse MNTB extensively wrap the axons of the growing CH terminal prior to OL cell wrapping and compaction of myelin. Our data revealed significant expression of several myelin genes and enrichment of multiple genes associated with lipid metabolism in astrocytes, which may subserve axon wrapping in addition to myelin formation. The transition from axon wrapping by astrocytes to OL cells occurs rapidly between P4 and P9 and identifies a potential new role of astrocytes in priming calyceal axons for subsequent myelination.
Subject(s)
Astrocytes , Myelin Sheath , Animals , Mice , Axons/ultrastructure , Oligodendroglia/physiology , Brain Stem/physiologyABSTRACT
Current treatments for neurodegenerative diseases and neural injuries face major challenges, primarily due to the diminished regenerative capacity of neurons in the mammalian CNS as they mature. Here, we investigated the role of Ezh2, a histone methyltransferase, in regulating mammalian axon regeneration. We found that Ezh2 declined in the mouse nervous system during maturation but was upregulated in adult dorsal root ganglion neurons following peripheral nerve injury to facilitate spontaneous axon regeneration. In addition, overexpression of Ezh2 in retinal ganglion cells in the CNS promoted optic nerve regeneration via both histone methylation-dependent and -independent mechanisms. Further investigation revealed that Ezh2 fostered axon regeneration by orchestrating the transcriptional silencing of genes governing synaptic function and those inhibiting axon regeneration, while concurrently activating various factors that support axon regeneration. Notably, we demonstrated that GABA transporter 2, encoded by Slc6a13, acted downstream of Ezh2 to control axon regeneration. Overall, our study underscores the potential of modulating chromatin accessibility as a promising strategy for promoting CNS axon regeneration.
Subject(s)
Axons , Optic Nerve Injuries , Animals , Mice , Axons/metabolism , Ganglia, Spinal/metabolism , Mammals , Nerve Regeneration/genetics , Optic Nerve Injuries/genetics , Optic Nerve Injuries/metabolism , Retinal Ganglion Cells/metabolismABSTRACT
AIMS: To describe the clinical features, imaging characteristics, histopathology, treatment and outcomes of intraocular medulloepithelioma. METHODS: Medical records of 11 patients with clinically or histopathologically confirmed medulloepithelioma were retrieved and reviewed. Clinical features, diagnostic challenges, imaging characteristics, management, histopathology and prognosis were assessed. RESULTS: The median age of the patients at initial diagnosis was 4 years, with the most common manifestations being leukocoria (five eyes), loss of vision (four eyes), ocular pain (one eye) and ophthalmic screening (one eye). The clinical signs include a grey-white ciliary body lesion, cataract or lens subluxation, secondary glaucoma and evident cysts. The ultrasound biomicroscopy (UBM) imaging most commonly displays ciliary body mass with intratumoural cysts (nine eyes). Three patients underwent surgery for cataract or glaucoma while the tumours were incidentally found. Two of the three patients managed by eye preserve treatments eventually required enucleation because of local tumour recurrence or phthisis. One patient treated with intra-arterial chemotherapy and cryotherapy had successful tumour regression and globe salvage. CONCLUSIONS: Initial misdiagnosis, delay in diagnosis and subsequent misdirected management is not uncommon in medulloepithelioma. The presence of multiple cysts in the tumour and retrolental neoplastic cyclitic membrane detected by UBM can offer certain information. Selective intra-arterial melphalan may prevent further tumour growth, but longer follow-up is necessary until treatment efficacy is fully evaluated.
Subject(s)
Cataract , Cysts , Glaucoma , Iris Diseases , Neuroectodermal Tumors, Primitive , Uveal Neoplasms , Humans , Child, Preschool , Ciliary Body/diagnostic imaging , Ciliary Body/pathology , Uveal Neoplasms/pathology , Neuroectodermal Tumors, Primitive/diagnostic imaging , Neuroectodermal Tumors, Primitive/therapy , Cataract/complications , Glaucoma/diagnosis , Glaucoma/therapy , Glaucoma/complicationsABSTRACT
Uveal melanoma (UM) is the most common intraocular malignant tumor in adults, with a lack of effective treatment for metastasis and a poor prognosis. Stimulator of interferon genes (STING, also known as TMEM173) plays an important role in tumor development by regulating cell proliferation, metastasis and other cellular processes. However, the function of STING in UM remains unclear and requires further investigation. The present study analyzed the expression status of STING to elucidate the mechanisms underlying UM. The correlation between STING and the prognosis of UM was evaluated based on UM RNAseq data and clinical information extracted from The Cancer Genome Atlas database. Quantification of STING in UM cell lines and tissues was performed using the Wes Separation protein immunoassay. The effects of STING on the proliferation, migration and invasion of UM cells were investigated using Cell Counting Kit8, Transwell and wound healing experiments. Survival analysis demonstrated that high levels of STING in UM tissues indicated a poor prognosis. The expression of STING in UM tissues was higher than that in the choroid membranes. Furthermore, it was found that downregulation of STING expression in UM cells suppressed migration and invasion, whereas overexpression of STING significantly promoted migration and invasion. Notably, STING had no significant effect on UM cell proliferation. It was also identified that STING positively upregulated the phosphorylation of p38 mitogenactivated protein kinase (p38MAPK) in UM cells, enhancing cell migration and invasion, which the p38MAPK inhibitor SB203580 reversed. Finally, the results of the present study demonstrated that high STING expression in UM indicates a poor prognosis. STING was revealed to promote the migration and invasion of UM cells through p38MAPK signaling.
Subject(s)
Melanoma , Uveal Neoplasms , Adult , Humans , Cell Line, Tumor , Melanoma/pathology , Uveal Neoplasms/genetics , Uveal Neoplasms/metabolism , Uveal Neoplasms/pathology , MAP Kinase Signaling System/genetics , Cell Proliferation/geneticsABSTRACT
Objective To investigate the distribution of serum allergens in children with respiratory allergic or infectious diseases,and then provide evidence for the prevention and treatment of children's respiratory allergic and infectious diseases.Methods The clinical data of 2 334 children aged 1 to 14 years old(median 5 years)visited Shengjing Hospital Affiliated to China Medical University from April 2019 to June 2022 were retrospectively analyzed.All the children were diagnosed with respiratory allergic or infectious diseases.The Phadia 250 automatic fluorescence enzyme immunoassay system and its supporting detection reagents were used to detect serum sIgE to allergens and statistical analysis was conducted using the GraphPad Prism 8.0 software.Results The positive rates of sIgE to allergens in children with respiratory allergic diseases(n=1 151)and respiratory infectious diseases(n=1 183)were 75.85%and 47.68%,respectively.The main allergen in the children with asthma was a mixture of dust mites(44.18%),followed by a mixture of fungi(40.64%).The main allergens in the children with allergic rhinitis were a mixture of dust mites and weed pollen,both accounting for 52.51%.The common allergen of respiratory infectious diseases was mold mixture(27.81%),followed by a mixture of dust mites(24.77%).The main allergen in children under 7 years old was a mixture of fungi(33.31%).As age increased,the positive rates of allergens in different combinations increased.The positive rates of serum sIgE to dust mite mixture,dander mixture,and weed pollen mixture in children aged≥7 years old were significantly higher than those in children aged≤3 years old and 4-6 years old(P<0.000 1).The positive rate of serum sIgE to allergens in male patients(64.33%)was significantly higher than that in female patients(56.33%,χ2=14.29,P=0.000 2).Among various disease groups,the levels of sIgE to dust mite mixture and weed pollen mixture were distributed at levels 1-6,with the highest distribution rate at level 6 in allergic rhinitis.Each disease group was associated with one allergen or a combination of two allergens.As the number of allergen combinations increased,the positive rate of sIgE gradually de-creased.The tIgE levels in children with allergic rhinitis were significantly higher than those in children with asthma,upper respiratory tract infection,and lower respiratory tract infection(all P<0.005).Conclusion Dust mite mixture and mold mixture are common al-lergens in children with asthma,while weed pollen mixture and dust mite mixture are common allergens in children with allergic rhini-tis.As age increases,children become more and more allergic to dust mite,mold,dander,weeds,and pollen.
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BACKGROUND:Material biomechanics is the investigation of the mechanical microenvironment of biomaterials through a material science approach,which belongs to the frontier discipline of sustainable development. OBJECTIVE:To explore the current research hotspots and development trends of material biomechanics and provide theoretical references for subsequent research. METHODS:Based on CiteSpace bibliometric software,we generated keyword co-occurrence and clustering,emergent word detection,and other knowledge maps based on 3 182 material biomechanics literature in the Web of Science core database during 2012-2022 for visualization analysis. RESULTS AND CONCLUSION:The number of research articles on the biomechanics of materials has been increasing in the last decade,and the United States,China,and Germany are the top three countries in terms of the number of articles published,and the research is mainly concentrated on major universities and research institutions,with significant aggregation.Material biomechanics research mainly involves the disciplines of material science,biomedical engineering,and kinesiology.Finite element analysis,material properties,mechanical performance of biomaterials,and molecular biomechanics are the focus of scholars'attention and research.At present,the research in the field of material biomechanics focuses on the use of finite element analysis to calculate the mechanical response of different biomedical materials under different conditions of loading and mechanical properties for the prevention of sports diseases,surgical planning,and postoperative rehabilitation.The application of inorganic materials and the mode of transport of molecular signals may be the prospect of future research.
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OBJECTIVE To evaluate the global cancer-associated thromboembolism risk assessment tools based on evidence- based methods, and to provide methodological reference and evidence-based basis for constructing a specific tool in China. METHODS A comprehensive search was conducted on 6 databases, including CNKI, Wanfang data, VIP, CBM, PubMed, and Embase, as well as on the websites of NCCN, ASCO, ESMO and so on with a deadline of June 30, 2022. Furthermore, a supplementary search was conducted in January 2023. The essential characteristics and methodological quality of included risk assessment tools were described and analyzed qualitatively, focusing on comparing each assessment stratification ability. RESULTS Totally 14 risk assessment tools were included in the study, with a sample size of 208-18 956 cases and an average age distribution of 53.1-74.0 years. The applicable population included outpatient cancer student@sina.com patients, lymphoma patients, and multiple myeloma patients,etc. The common predictive factors were body mass index, venous thromboembolism history, and tumor site. All tools had undergone methodological validation, with 9 presented in a weighted scoring format. Only seven tools were used simultaneously for specificity, sensitivity, negative predictive value (NPV), positive predictive value (PPV) and area under the curve (AUC) or C statistical analysis. CONCLUSIONS The risk of bias in constructing existing tools is high, and the heterogeneity of tool validation results is significant. The overall methodological quality must be improved, and its risk stratification ability must also be investigated. There are still certain limitations in clinical practice in China.