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Ameloblastoma (AB) is the most common benign odontogenic tumor. In this study, we investigated the expression and distribution of acetylated α-tubulin and αTAT1 in AB specimens. We analyzed tubulin acetylation caused by αTAT1 activation in a human AB cell line, AM-1. Results of the histopathological and in vitro studies clarified that TAK1 was phosphorylated by TGF-β stimulation, then, induced tubulin acetylation via αTAT1 activation, which subsequently activated the migration and invasion of AB cells.
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.
The expression and functional levels of TRPC3, a nonselective cation channel, and NCX1, a Na+/Ca2+ exchanger, are increased in the bladders of rats with partial bladder outlet obstruction-induced detrusor overactivity. The synergistic effects of TRPC3 and NCX1 significantly increase the concentration of Ca2+i in smooth muscle cells, which induces bladder hyperactivity in this animal model of overactive bladder. TRPC3 and NCX1 may be new therapeutic targets for detrusor overactivity.
An osteosarcoma-specific exosomal gene signature was developed using an orthotopic. xenograft model with a species-differentiating bioinformatics pipeline. The gene signature was validated in the serum of dogs with osteosarcoma, where it was able to detect minimal residual disease, and was therefore associated with prognosis following treatment.
A novel assay quantifies depolarization of synaptosomes from Alzheimer’s cortex, and the authors show that tau released from these samples is unphosphorylated and C-terminal-truncated. Most tau is exosomal, and free-floating tau did not seed aggregation. Seeding activity was lower in tauopathy than AD, and strongly related to amyloid level.
Nonalcoholic fatty liver disease is the most common cause of chronic liver disease globally and a risk factor for hepatocellular carcinoma. The study highlights the role of miR-155 in nonalcoholic steatohepatitis. miR-155-deficient mice displayed overall protection from diet-induced steatohepatitis and fibrosis. Therapeutic inhibition of miR-155 might be effective approach for treatment of nonalcoholic steatohepatitis.
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.
The authors present a robust diagnostic algorithm based on digital pathology and image analysis that quantifies intratumoral and stromal CD8+ T-cell densities in the tumor center and invasive margin compartment in metastatic melanoma. Spatial CD8+ T-cell densities are translated into the clinically relevant immune diagnostic categories “inflamed”, “excluded”, and “desert”. Their approach also allows efficient immune phenotyping of metastatic lesions, on biopsy material or even in the absence of material from the invasive margin.
The authors demonstrate in vitro CRISPR/CAS9-mediated editing of the canine adenovirus type 2 (CAV2) genome to successfully insert a red fluorescent protein reporter construct and to replace E3 gene sequences with a single domain antibody in the CAV2 genome. This work provides a significantly improved and efficient method for targeted editing of adenoviruses to generate altered and potentially therapeutic viral genomes in the shortest possible time.
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.
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.
The authors found that size selection magnetic beads could remove long RNA transcripts from total RNA with simplistic operation. After long transcript removal, microRNA could be concentrated and efficiently reverse-transcribed by stem-loop-6N primer. Touchdown qPCR improved microRNA quantification with lower CT values and better detection efficiency. Finally, they incorporated these observations and created a new protocol named long transcripts minus touchdown qPCR for screening and quantifying microRNAs.
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.
This study determined that circN4BP2L2 acts as an oncogene that promotes tumor growth and metastasis of colorectal cancer (CRC) by regulating the miR-340-5p/CXCR4 axis. The authors reveal a novel mechanism for the ceRNA regulatory network in CRC progression and identify a potential therapeutic target for CRC treatment.
The authors show that curcumin suppresses the proliferation and migration of acute myeloid leukemia (AML) cells. Curcumin also blocks cell cycle progression and sensitizes AML cells to Adriamycin by regulating the HOTAIR/miR-20a-5p/WT1 axis. These findings suggest a potential role of curcumin and HOTAIR in AML treatment.
As an extracellular proton sensor, ASCIC1a can be activated by acidification to promote the proliferation of synovial fibroblasts in rheumatoid arthritis via ERK/MAPK signaling. This effect is abolished by the specific ASIC1a inhibitor psalmotoxin-1 or ASIC1a-silencing
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.
The authors sought to determine whether the infectivity of sporadic Creutzfeldt–Jakob disease prion strains through peripheral routes is different from that from intracranial infection. They found that among the strains, V2 is the most infectious through peripheral routes. Thus, preventive measures against transmission of this strain will be important for the eradication of iatrogenic transmission of Creutzfeldt–Jakob disease.
Active learning (AL) model is a framework designed for single-cell RNA sequence (scRNA-seq) clustering. This model requires that the researchers label a small number of cells selected by a sample selection algorithm. The labeled cells are then used for the supervision of the clustering, to significantly boost the clustering performance of scRNA-seq.