-
Journal of Neuroinflammation May 2024Autoimmune uveitis is a leading cause of severe vision loss, and animal models provide unique opportunities for studying its pathogenesis and therapeutic strategies....
Autoimmune uveitis is a leading cause of severe vision loss, and animal models provide unique opportunities for studying its pathogenesis and therapeutic strategies. Here we employ scRNA-seq, RNA-seq and various molecular and cellular approaches to characterize mouse models of classical experimental autoimmune uveitis (EAU), revealing that EAU causes broad retinal neuron degeneration and marker downregulation, and that Müller glia may act as antigen-presenting cells. Moreover, EAU immune response is primarily driven by Th1 cells, and results in dramatic upregulation of CC chemokines, especially CCL5, in the EAU retina. Accordingly, overexpression of CCR5, a CCL5 receptor, in mesenchymal stem cells (MSCs) enhances their homing capacity and improves their immunomodulatory outcomes in preventing EAU, by reducing infiltrating T cells and activated microglia and suppressing Nlrp3 inflammasome activation. Taken together, our data not only provide valuable insights into the molecular characteristics of EAU but also open an avenue for innovative MSC-based therapy.
Topics: Animals; Mice; Mesenchymal Stem Cells; Uveitis; Receptors, CCR5; Mice, Inbred C57BL; Single-Cell Analysis; Autoimmune Diseases; Gene Expression Profiling; Disease Models, Animal; Female; Single-Cell Gene Expression Analysis
PubMed: 38802924
DOI: 10.1186/s12974-024-03134-3 -
Turk Patoloji Dergisi May 2024Bronchial involvement in pulmonary actinomycosis is rare and has been reported in the literature rarely. However, these reports describe endobronchial actinomycosis...
Bronchial involvement in pulmonary actinomycosis is rare and has been reported in the literature rarely. However, these reports describe endobronchial actinomycosis secondary to foreign body aspiration (for example, a fish bone). Our case did not have any history or clinical evidence suggesting foreign body aspiration, which makes it even more rare. A 55-year-old woman presented with complaints of on and off haemoptysis and cough for three weeks. In view of the haemoptysis and consolidation seen on imaging, a bronchoalveolar lavage was done and sent for cytological assessment. Few atypical cells with nuclear hyperchromasia and prominent nucleoli were noted. In view of the persistent haemoptysis, worsening symptoms, and non-resolution of the consolidation despite antibiotics, and the finding of atypical cells, segmental resection was done. A final diagnosis of bronchiectatic actinomycosis with osseous metaplasia was given. The patient was started on prolonged antibiotics with good response and recovery. Other risk factors associated with pulmonary actinomycosis include alcoholism, diabetes, haematological diseases, human immunodeficiency viral infection, use of immunosuppressants, and rarely chronic lung diseases, such as bronchiectasis. Our case had this rare association of bronchiectasis with bronchial actinomycosis. Bronchiectatic actinomycosis is a rare infection and it can mimic several lung disorders like unresolving pneumonia, pulmonary tuberculosis, foreign body, and even lung tumours. The pathologists and clinicians should be aware of this entity and thus help in the early diagnosis and better management of patients with this disease.
PubMed: 38801125
DOI: 10.5146/tjpath.2024.13407 -
Frontiers in Cellular Neuroscience 2024[This retracts the article DOI: 10.3389/fncel.2024.1338129.].
[This retracts the article DOI: 10.3389/fncel.2024.1338129.].
PubMed: 38799984
DOI: 10.3389/fncel.2024.1425339 -
Journal of Clinical Biochemistry and... May 2024Photoreceptor degeneration decreases light sensitivity and leads to vision loss and various retinal diseases. Neurotrophin-3, originating from Müller glial cells in the...
Photoreceptor degeneration decreases light sensitivity and leads to vision loss and various retinal diseases. Neurotrophin-3, originating from Müller glial cells in the retina, plays a key role in protecting photoreceptors from damage induced by light or hypoxia. This neuroprotective approach is important because there are no established methods to regenerate lost photoreceptors. Dietary supplements are one of the useful methods for improving eye health. () Jack, which is native to the tropical forest of Malaysia and other Southeast Asian countries, exhibits several medicinal properties. In the present study, we demonstrated that the water extract of roots enhanced neurotrophin-3 gene expression in primary rat Müller cells. Using a stepwise bioassay-guided fractionation and purification of root extracts, we isolated the active compound underlying neurotrophin-3 gene-enhancing activities. Mass spectrometry and nuclear magnetic resonance spectral data identified the compound as eurycomanone. This study provides evidence for the efficacy of and eurycomanone in enhancing neurotrophin-3 expression in Müller cells . Although the biological significance of this effect and its underlying mechanism remain to be elucidated, this study suggests that may be promising for improving eye health and must be further investigated.
PubMed: 38799139
DOI: 10.3164/jcbn.23-73 -
International Journal of Molecular... May 2024Osteosarcoma is a type of bone cancer that primarily affects children and young adults. The overall 5-year survival rate for localized osteosarcoma is 70-75%, but it is...
Osteosarcoma is a type of bone cancer that primarily affects children and young adults. The overall 5-year survival rate for localized osteosarcoma is 70-75%, but it is only 20-30% for patients with relapsed or metastatic tumors. To investigate potential glycan-targeting structures for immunotherapy, we stained primary osteosarcomas with recombinant C-type lectin CD301 (MGL, CLEC10A) and observed moderate to strong staining on 26% of the tumors. NK92 cells expressing a CD301-CAR recognized and eliminated osteosarcoma cells in vitro. Cytotoxic activity assays correlated with degranulation and cytokine release assays. Combination with an inhibitory antibody against the immune checkpoint TIGIT (T-cell immunoreceptor with lg and ITIM domains) showed promising additional effects. Overall, this study showed, for the first time, the expression of CD301 ligands in osteosarcoma tissue and demonstrated their use as potential target structures for lectin-based immunotherapy.
Topics: Osteosarcoma; Humans; Bone Neoplasms; Immunotherapy; Lectins, C-Type; Polysaccharides; Receptors, Chimeric Antigen; Cell Line, Tumor; Female; Male; Child; Adolescent; Receptors, Immunologic
PubMed: 38791381
DOI: 10.3390/ijms25105344 -
International Journal of Molecular... May 2024The src homology 2 domain-containing inositol 5-phosphatases SHIP1 and SHIP2 are two proteins involved in intracellular signaling pathways and have been linked to the... (Review)
Review
The src homology 2 domain-containing inositol 5-phosphatases SHIP1 and SHIP2 are two proteins involved in intracellular signaling pathways and have been linked to the pathogenesis of several diseases. Both protein paralogs are well known for their involvement in the formation of various kinds of cancer. SHIP1, which is expressed predominantly in hematopoietic cells, has been implicated as a tumor suppressor in leukemogenesis especially in myeloid leukemia, whereas SHIP2, which is expressed ubiquitously, has been implicated as an oncogene in a wider variety of cancer types and is suggested to be involved in the process of metastasis of carcinoma cells. However, there are numerous other diseases, such as inflammatory diseases as well as allergic responses, Alzheimer's disease, and stroke, in which SHIP1 can play a role. Moreover, SHIP2 overexpression was shown to correlate with opsismodysplasia and Alzheimer's disease, as well as metabolic diseases. The SHIP1-inhibitor 3-α-aminocholestane (3AC), and SHIP1-activators, such as AQX-435 and AQX-1125, and SHIP2-inhibitors, such as K161 and AS1949490, have been developed and partly tested in clinical trials, which indicates the importance of the SHIP-paralogs as possible targets in the therapy of those diseases. The aim of this article is to provide an overview of the current knowledge about the involvement of SHIP proteins in the pathogenesis of cancer and other human diseases and to create awareness that SHIP1 and SHIP2 are more than just tumor suppressors and oncogenes.
Topics: Humans; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; Neoplasms; Animals; src Homology Domains; Signal Transduction; Inositol Polyphosphate 5-Phosphatases
PubMed: 38791291
DOI: 10.3390/ijms25105254 -
Cell Death Discovery May 2024Damage to the ribosome or an imbalance in protein biosynthesis can lead to some human diseases, such as diabetic retinopathy (DR) and other eye diseases. Here, we...
Damage to the ribosome or an imbalance in protein biosynthesis can lead to some human diseases, such as diabetic retinopathy (DR) and other eye diseases. Here, we reported that the kri1l gene was responsible for retinal development. The kri1l gene encodes an essential component of the rRNA small subunit processome. The retinal structure was disrupted in kri1l mutants, which resulted in small eyes. The boundaries of each layer of cells in the retina were blurred, and each layer of cells was narrowed and decreased. The photoreceptor cells and Müller glia cells almost disappeared in kri1l mutants. The lack of photoreceptor cells caused a fear of light response. The development of the retina started without abnormalities, and the abnormalities began two days after fertilization. In the kri1l mutant, retinal cell differentiation was defective, resulting in the disappearance of cone cells and Müller cells. The proliferation of retinal cells was increased, while apoptosis was also enhanced in kri1l mutants. γ-H2AX upregulation indicated the accumulation of DNA damage, which resulted in cell cycle arrest and apoptosis. The kri1l mutation reduced the expression of some opsin genes and key retinal genes, which are also essential for retinal development.
PubMed: 38789412
DOI: 10.1038/s41420-024-02022-2 -
Nature Communications May 2024Histone deacetylases (HDACs) play a crucial role in transcriptional regulation and are implicated in various diseases, including cancer. They are involved in histone...
Histone deacetylases (HDACs) play a crucial role in transcriptional regulation and are implicated in various diseases, including cancer. They are involved in histone tail deacetylation and canonically linked to transcriptional repression. Previous studies suggested that HDAC recruitment to cell-cycle gene promoters via the retinoblastoma (RB) protein or the DREAM complex through SIN3B is essential for G1/S and G2/M gene repression during cell-cycle arrest and exit. Here we investigate the interplay among DREAM, RB, SIN3 proteins, and HDACs in the context of cell-cycle gene repression. Knockout of SIN3B does not globally derepress cell-cycle genes in non-proliferating HCT116 and C2C12 cells. Loss of SIN3A/B moderately upregulates several cell-cycle genes in HCT116 cells but does so independently of DREAM/RB. HDAC inhibition does not induce general upregulation of RB/DREAM target genes in arrested transformed or non-transformed cells. Our findings suggest that E2F:RB and DREAM complexes can repress cell-cycle genes without relying on HDAC activity.
Topics: Humans; Histone Deacetylases; HCT116 Cells; Repressor Proteins; E2F Transcription Factors; Retinoblastoma Protein; Mice; Animals; Sin3 Histone Deacetylase and Corepressor Complex; Kv Channel-Interacting Proteins; Cell Cycle; Promoter Regions, Genetic; Gene Expression Regulation; Genes, cdc
PubMed: 38789411
DOI: 10.1038/s41467-024-48724-0 -
Cells May 2024Vision starts in retinal photoreceptors when specialized proteins (opsins) sense photons via their covalently bonded vitamin A derivative 11cis retinaldehyde...
Vision starts in retinal photoreceptors when specialized proteins (opsins) sense photons via their covalently bonded vitamin A derivative 11cis retinaldehyde (11cis-RAL). The reaction of non-enzymatic aldehydes with amino groups lacks specificity, and the reaction products may trigger cell damage. However, the reduced synthesis of 11cis-RAL results in photoreceptor demise and suggests the need for careful control over 11cis-RAL handling by retinal cells. This perspective focuses on retinoid(s) synthesis, their control in the adult retina, and their role during retina development. It also explores the potential importance of 9cis vitamin A derivatives in regulating retinoid synthesis and their impact on photoreceptor development and survival. Additionally, recent advancements suggesting the pivotal nature of retinoid synthesis regulation for cone cell viability are discussed.
Topics: Animals; Humans; Retina; Retinal Diseases; Retinaldehyde; Retinoids; Vitamin A
PubMed: 38786093
DOI: 10.3390/cells13100871 -
Cells May 2024Monocytes, as well as downstream macrophages and dendritic cells, are essential players in the immune system, fulfilling key roles in homeostasis as well as in...
Monocytes, as well as downstream macrophages and dendritic cells, are essential players in the immune system, fulfilling key roles in homeostasis as well as in inflammatory conditions. Conventionally, driven by studies on reporter models, mouse monocytes are categorized into a classical and a non-classical subset based on their inversely correlated surface expression of Ly6C/CCR2 and CX3CR1. Here, we aimed to challenge this concept by antibody staining and reporter mouse models. Therefore, we took advantage of and reporter mice, in which the respective gene was replaced by a fluorescent reporter protein gene. We analyzed the expression of CX3CR1 and CCR2 by flow cytometry using several validated fluorochrome-coupled antibodies and compared them with the reporter gene signal in these reporter mouse strains. Although we were able to validate the specificity of the fluorochrome-coupled flow cytometry antibodies, mouse Ly6C classical and Ly6C non-classical monocytes showed no differences in CX3CR1 expression levels in the peripheral blood and spleen when stained with these antibodies. On the contrary, in reporter mice, we were able to reproduce the inverse correlation of the CX3CR1 reporter gene signal and Ly6C surface expression. Furthermore, differential CCR2 surface expression correlating with the expression of Ly6C was observed by antibody staining, but not in reporter mice. In conclusion, our data suggest that phenotyping strategies for mouse monocyte subsets should be carefully selected. In accordance with the literature, the suitability of CX3CR1 antibody staining is limited, whereas for CCR2, caution should be applied when using reporter mice.
Topics: Animals; Receptors, CCR2; Monocytes; CX3C Chemokine Receptor 1; Mice; Flow Cytometry; Antibodies; Genes, Reporter; Phenotype; Mice, Inbred C57BL; Mice, Transgenic; Green Fluorescent Proteins; Antigens, Ly
PubMed: 38786041
DOI: 10.3390/cells13100819