Background: Given the growing acknowledgment of the detrimental effects of excessive myocardial fibrosis on pathological remodeling after myocardial ischemia-reperfusion injury (I/R), targeting the modulation of myocardial fibrosis may offer protective and therapeutic advantages. However, effective clinical interventions and therapies that target myocardial fibrosis remain limited. As a promising chimeric antigen receptor (CAR) cell therapy, whether CAR macrophages (CAR-Ms) can be used to treat I/R remains unclear.
View Article and Find Full Text PDFMicroplastic is an emerging pollutant and a technical fossil in Anthropocene sediments. Typhoon frequency and intensity have increased due to climate change, which has a major effect on the distribution patterns of microplastics. It is still unknown, though, how the topography of the peninsula affects the reconstruction of the distribution of microplastic in typhoons.
View Article and Find Full Text PDFLIN28A is important in somatic reprogramming and pluripotency regulation. Although previous studies addressed that LIN28A can repress let-7 microRNA maturation in the cytoplasm, few focused on its role within the nucleus. Here, we show that the nucleolus-localized LIN28A protein undergoes liquid-liquid phase separation (LLPS) in mouse embryonic stem cells (mESCs) and in vitro.
View Article and Find Full Text PDFChimeric antigen receptor (CAR) T cell therapies have successfully treated hematological malignancies. Macrophages have also gained attention as an immunotherapy owing to their immunomodulatory capacity and ability to infiltrate solid tumors and phagocytize tumor cells. The first-generation CD3ζ-based CAR-macrophages could phagocytose tumor cells in an antigen-dependent manner.
View Article and Find Full Text PDFThe Chimeric antigen receptor (CAR)-T cell therapy has made inroads in treating hematological malignancies. Nonetheless, there are still multiple hurdles in CAR-T cell therapy for solid tumors. Primary CAR-expressing macrophage cells (CAR-Ms) and induced pluripotent stem cells (iPSCs)-derived CAR-expressing macrophage cells (CAR-iMacs) have emerged as attractive alternatives in our quest for an efficient and inexpensive approach for tumor immune cell therapy.
View Article and Find Full Text PDFKidney Dis (Basel)
January 2022
Background: Cells of the immune system can inhibit tumor growth and progression; however, immune cells can also promote tumor cell growth, survival, and angiogenesis as a result of the immunosuppressive microenvironments. In the last decade, a growing number of new therapeutic strategies focused on reversing the immunosuppressive status of tumor microenvironments (TMEs), to reprogram the TME to be normal, and to further activate the antitumor functions of immune cells. Most of the "hot tumors" are encompassed with M2 macrophages promoting tumor growth, and the accumulation of M2 macrophages into tumor islets leads to poor prognosis in a wide variety of tumors.
View Article and Find Full Text PDFThe nucleolus is the organelle for ribosome biogenesis and sensing various types of stress. However, its role in regulating stem cell fate remains unclear. Here, we present evidence that nucleolar stress induced by interfering rRNA biogenesis can drive the 2-cell stage embryo-like (2C-like) program and induce an expanded 2C-like cell population in mouse embryonic stem (mES) cells.
View Article and Find Full Text PDFLIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development.
View Article and Find Full Text PDFBackground: Previous studies demonstrated the dependence of cancer on nerve. Recently, a growing number of studies reveal that cancer cells share the property and regulatory network with neural stem/progenitor cells. However, relationship between the property of neural stemness and cell tumorigenicity is unknown.
View Article and Find Full Text PDFThe Chimera antigen receptor (CAR)-T cell therapy has gained great success in the clinic. However, there are still major challenges for its wider applications in a variety of cancer types including lack of effectiveness due to the highly complex tumor microenvironment, and the forbiddingly high cost due to the personalized manufacturing procedures. In order to overcome these hurdles, numerous efforts have been spent focusing on optimizing Chimera antigen receptors, engineering and improving T cell capacity, exploiting features of subsets of T cell or NK cells, or making off-the-shelf universal cells.
View Article and Find Full Text PDFDespite progress in developing cell therapies, such as T cell or stem cell therapies to treat diseases, immunoincompatibility remains a major barrier to clinical application. Given the fact that a host's immune system may reject allogeneic transplanted cells, methods have been developed to genetically modify patients' primary cells. To advance beyond this time-consuming and costly approach, recent research efforts focus on generating universal pluripotent stem cells to benefit a broader spectrum of patients.
View Article and Find Full Text PDFMisexpression of chromatin modification factors and changed epigenetic modifications play crucial roles for tumorigenesis. Our previous studies demonstrated that inhibition of epigenetic modification enzymes EZH2, LSD1, DNMTs, and HDACs caused post-mitotic neuron-like differentiation in different cancer cells. However, how they regulate neuronal differentiation in cancer cells was unknown.
View Article and Find Full Text PDFCancer cells are immature cells resulting from cellular reprogramming by gene misregulation, and redifferentiation is expected to reduce malignancy. It is unclear, however, whether cancer cells can undergo terminal differentiation. Here, we show that inhibition of the epigenetic modification enzyme enhancer of zeste homolog 2 (EZH2), histone deacetylases 1 and 3 (HDAC1 and -3), lysine demethylase 1A (LSD1), or DNA methyltransferase 1 (DNMT1), which all promote cancer development and progression, leads to postmitotic neuron-like differentiation with loss of malignant features in distinct solid cancer cell lines.
View Article and Find Full Text PDFTcf7l1 (also known as Tcf3) is a bimodal transcription factor that plays essential roles in embryogenesis and embryonic and adult stem cells. On one hand, Tcf7l1 works as transcriptional repressor via the recruitment of Groucho-related transcriptional corepressors to repress the transcription of Wnt target genes, and, on the other hand, it activates Wnt target genes when Wnt-activated β-catenin interacts with it. However, how its activity is modulated is not well understood.
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