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Topic Review
Biography
Topic Review
IPSC-Based PDAC Models and Immunotherapies
Advances in the treatment of pancreatic ductal adenocarcinoma (PDAC) using neoadjuvant chemoradiotherapy, chemotherapy, and immunotherapy have had minimal impact on the overall survival of patients. A general lack of immunogenic features and a complex tumor microenvironment (TME) are likely culprits for therapy refractoriness in PDAC. Induced pluripotent stem cells (iPSCs) should be explored as a means to advance the treatment options for PDAC, by providing representative in vitro models of pancreatic cancer development. In addition, iPSCs could be used for tailor-made cellular immunotherapies or as a source of tumor-associated antigens in the context of vaccination.
511
29 Mar 2022
Topic Review
CAR T Cells
Cells are also used as a therapeutic tool. In this type of immunotherapy, the patient’s T cells are genetically engineered ex vivo to express a CAR that recognizes a specific antigen present on the surface of the tumor cells. After reinfusion of these cells in the patient’s circulation, the binding between the CAR T cells and the cancer cells induces a cytotoxic response. One example of this therapy currently being used in clinics is for the treatment of advanced B-cell lymphomas, resulting in complete remission in 30 to 40 % of the patients. Importantly, it needs to be emphasized that CAR T cells are used last in line as a therapeutic strategy to suppress tumor cells. This means that the T cells are often isolated from the patients after various treatments, including chemotherapy that can alter the metabolic phenotype of the T cells (mitochondrial damage and metabolic alterations). Therefore, metabolism is an important aspect in the conception and the anti-tumoral activity of a CAR T cell.
453
29 Mar 2022
Topic Review
Role of Immunoproteasome Subunits in Cancer
Cell-mediated immunity is driven by antigenic peptide presentation on major histocompatibility complex (MHC) molecules. Specialized proteasome complexes called immunoproteasomes process viral, bacterial, and tumor antigens for presentation on MHC class I molecules, which can induce CD8 T cells to mount effective immune responses. Immunoproteasomes are distinguished by three subunits that alter the catalytic activity of the proteasome and are inducible by inflammatory stimuli such as interferon-γ (IFN-γ). This inducible activity places them in central roles in cancer, autoimmunity, and inflammation.
603
29 Mar 2022
Topic Review
Cardiac Reprogramming
Direct reprogramming of fibroblasts into CM-like cells has emerged as an attractive strategy to generate induced CMs (iCMs) in heart regeneration. However, low conversion rate, poor purity, and the lack of precise conversion of iCMs are still present as significant challenges. In this review, we summarize the recent development in understanding the molecular mechanisms of cardiac reprogramming with various strategies to achieve more efficient iCMs. reprogramming. Specifically, we focus on the identified critical roles of transcriptional regulation, epigenetic modification, signaling pathways from the cellular microenvironment, and cell cycling regulation in cardiac reprogramming. We also discuss the progress in delivery system optimization and cardiac reprogramming in human cells related to preclinical applications. We anticipate that this will translate cardiac reprogramming-based heart therapy into clinical applications. In addition to optimizing the cardiogenesis related transcriptional regulation and signaling pathways, an important strategy is to modulate the pathological microenvironment associated with heart injury, including inflammation, pro-fibrotic signaling pathways, and the mechanical properties of the damaged myocardium. We are optimistic that cardiac reprogramming will provide a powerful therapy in heart regenerative medicine.
386
29 Mar 2022
Topic Review
Fibroblast Growth Factor 23
FGF23 is a bone-derived hormone that is essential for regulating vitamin D and phosphate homeostasis.
503
29 Mar 2022
Topic Review
Fibroblast Activation in Injured Heart
Fibrosis is characterized by the excessive accumulation of extra cellular matrix (ECM) components. It is a physiological response to pathological stimuli that helps to confine injuries. However, the prolonged activation of this process results in adverse tissue remodeling, which can ultimately affect the structure and function of organs (adverse remodeling).
589
29 Mar 2022
Topic Review
Vegetables on the Modulation of Platelet Function
Cardiovascular diseases (CVDs) are a primary cause of deaths worldwide. Thrombotic diseases, specifically stroke and coronary heart diseases, account for around 85% of CVDs-induced deaths. Platelets (small circulating blood cells) are responsible for the prevention of excessive bleeding upon vascular injury, through blood clotting (haemostasis). However, their unnecessary activation results in thrombotic diseases. Hence, it is critical to control platelet activation under pathological conditions. Regular diet has a strong relationship with the development of CVDs, and therefore reviewing their beneficial effects on the modulation of platelet function is essential. Here, a few important, regularly used vegetables and demonstrate their effects on the modulation of platelet activation are listed.
478
29 Mar 2022
Topic Review
Calebin A, a Compound of Turmeric
Calebin A (CA) is one of the active constituents of turmeric and has anti-inflammatory and antioxidant effects. Excessive inflammation and cell apoptosis are the main causes of tendinitis and tendinopathies. However, the role of CA in tendinitis is still unclear and needs to be studied in detail.
398
29 Mar 2022
Topic Review
Profiling Cancer Cells by Cell-SELEX
The identification of tumor cell-specific surface markers is a key step towards personalized cancer medicine, allowing early assessment and accurate diagnosis, and development of efficacious targeted therapies. What mainly limits the number of ideal clinical biomarkers is the high complexity and heterogeneity of several human cancers and still-limited methods for molecular profiling of specific cancer types. The cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) technology for the differential selection of oligonucleotide aptamers against a specific cancer-cell type has become the selection technique for the discovery of cell-surface markers. Indeed, it allows selection, at the same time, of a set of aptamers acting as highly efficacious recognition elements for functional surface signatures of target cells. Importantly, these aptamers may be used to identify cell-surface molecules whose role is still unexplored. This fulfills the great challenge of simultaneously targeting multiple proteins whose alterations, in concert, define the pathological state of the cell and are thus more informative for biomarker discovery than the alteration of a single protein.
308
29 Mar 2022
Topic Review
FAK Inhibition and Corneal Fibroblast Differentiation in vitro
Fibrosis is often known as a response of a tissue to injury, and since the three transforming growth factor-beta (TGF-β) isoforms (TGF-β1, -β2, and -β3) are the main regulators of cell migration, differentiation, proliferation, and gene expression, they were implicated in both reparative and fibrotic responses. All three TGF-β isoforms are homologues, sharing an extensive similarity in their amino acid sequences (80%), which may result in overlapping functions (i.e., SMAD-dependent signaling, modulating inflammatory responses); however, subtle differences in the sequences exist, thus potentially eliciting opposing effects. For example, several studies showed that TGF-β1 and -β2 are factors that drive the formation of fibrosis in corneal scarring models [8,9,10], whereas TGF-β3 was reported to downregulate fibrosis and promote scarless wound healing (healing without fibrosis).
480
29 Mar 2022
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