Volume 101 Issue 11, November 2021
Inside the USCAP Journals
Cellular senescence is a key mechanism of age-related vascular endothelial dysfunction. The authors explored the role of IL-17A on endothelial cell senescence and its associated signaling pathways. Their data reveals a previously unsuspected link between IL-17A and endothelial cell senescence, mediated by the NF-κB /p53/Rb signaling pathway.
LncRNA XIST shuttled by adipose tissue-derived mesenchymal stem cell-derived extracellular vesicles suppresses myocardial pyroptosis in atrial fibrillation by disrupting miR-214-3p-mediated Arl2 inhibition
This paper provides insights into a novel targeted therapy for atrial fibrillation. The authors show that extracellular vesicles derived from mouse adipose tissue-derived mesenchymal stem cells transfer the long non-coding RNA XIST into cardiomyocytes. XIST then suppresses NLRP3 inflammasome activation and myocardial pyroptosis by reducing miR-214-3p-mediated inhibition of the GTP-binding protein Arl2.
Fisetin, a natural flavanol, can localize to the nucleolus and decrease rRNA biogenesis. It preferentially targets tumorigenic cells and cells with cancer stem-like properties. In combination with the RNA Pol I inhibitor BMH-21, it synergistically inhibits pulmonary metastasis, making this combination an exciting potential therapeutic strategy.
Modulation of osteoclastogenesis through adrenomedullin receptors on osteoclast precursors: initiation of differentiation by asymmetric cell division
Adrenomedullin (ADM) significantly stimulates osteoclastogenesis only in the presence of calcitonin. Functional ADM receptor partly composed of osteoclast-specific cell surface Kat1 antigen was detected in cells in the osteoclast-lineage. Expression of ADM receptor was firstly detected in proliferating osteoclast progenitors performing asymmetric cell division and is then expressed in mononuclear osteoclast precursors. Specific regulation of ADM receptors expressed on mononuclear osteoclast precursors could provide an alternative way to modulate bone remodeling therapeutically.
Long non-coding RNA MALAT1 enhances angiogenesis during bone regeneration by regulating the miR-494/SP1 axis
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression is upregulated in MC3T3-E1 cells cultured in osteogenic medium. MALAT1 acts as a miR-494 sponge to activate specificity protein 1(SP1)/Toll-like receptor 2/bone morphogenetic protein 2 signaling axis. Knockdown of MALAT1 or overexpression of miR-494 inhibits osteogenic differentiation and angiogenesis. Overexpression of SP1 or inhibition of miR-494 reverses the regulatory of sh-MALAT1 on osteogenic differentiation and angiogenesis in MC3T3-E1.
P. aeruginosa dependent pneumonia decreased lysosomal proteins, transcription factor E3 (TFE3) and transcription factor EB (TFEB); and increased transcription repressor Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3). ZKSCAN3 knockout mice exhibited enhanced bacterial killing.
Bone morphogenetic protein induces bone invasion of melanoma by epithelial–mesenchymal transition via the Smad1/5 signaling pathway
Bone morphogenetic protein (BMP) induces epithelial–mesenchymal transition (EMT) both B16 mouse and A2058 human melanoma cell lines. The injection of B16 cells expressing constitutively activated ALK3 enhanced zygoma destruction compared with empty B16 cells, suggesting that the activation of BMP signaling enhances bone invasion by inducing EMT in melanoma cells.
Long noncoding RNA MIR22HG promotes Leydig cell apoptosis by acting as a competing endogenous RNA for microRNA-125a-5p that targets N-Myc downstream-regulated gene 2 in late-onset hypogonadism
Leydig cell apoptosis is responsible for the deficiency in serum testosterone in late-onset hypogonadism. This study reveals that lncRNA MIR22HG upregulates NDRG2 expression by targeting miR-125a-5p, thus promoting Leydig cell apoptosis in late-onset hypogonadism.
Activation of RSK2 upregulates SOX8 to promote methotrexate resistance in gestational trophoblastic neoplasia
Resistance to chemotherapy is frequently driven by aberrantly activated kinases. RSK2 was identified as a potential regulator of methotrexate resistance in gestational trophoblastic neoplastic cells. RSK2 activation promotes methotrexate resistance via upregulation of SOX8 and attenuation of reactive oxygen species. RSK2 inhibitors might therefore be useful to treat methotrexate-resistant gestational trophoblastic neoplasia.
A novel human endometrial epithelial cell line for modeling gynecological diseases and for drug screening
This study describes the characterization of a human endometrial epithelial cell line, hEM3. hEM3 is not transformed, can grow organoids, and does not harbor pathogenic mutations in genes involving DNA mismatch repair (MMR). hEM3 with ARID1A knockout has been generated for drug screening in an ARID1A-deficient and MMR-proficient context. In conclusion, hEM3 can be a model for studying endometrial pathogenesis.
Recombinant myelin oligodendrocyte glycoprotein quality modifies evolution of experimental autoimmune encephalitis in macaques
The authors describe quantitatively and qualitatively different forms of experimental autoimmune encephalitis (EAE) in cynomolgus macaques. They found that bacterial contaminants within recombinant human myelin oligodendrocyte glycoprotein seemed to aggravate disease evolution. They provide anatomopathological features of fulminant and progressive forms of EAE, allowing them to distinguish specific factors influencing the evolution of this model of autoimmune demyelinating disease.