scholarly journals Editorial – Disc Biology Special Issue

2022 ◽  
Vol 43 ◽  
pp. 1-3
Author(s):  
A Vernengo ◽  
◽  
Z Li ◽  
S Grad
Keyword(s):  
Intervertebral Disc ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Therapeutic Intervention ◽  
Load Distribution ◽  
Special Issue ◽  
Preclinical Models ◽  
Spinal Flexibility ◽  
Health And Disease ◽  
Multiple Signaling

The intervertebral disc (IVD) has long been known as a mechanical structure responsible for spinal flexibility and load distribution, while its dysfunction is a frequent source of pain and disability. In recent years, multiple signaling pathways contributing to the regulation of the IVD homeostasis in health and disease have been discovered. At the same time, crosstalk of the IVD with adjacent tissues, immune cells, nerve cells and systemic mediators has been identified as an essential mechanism of degeneration and repair. Such discoveries open the door for the design of new therapeutic and diagnostic targets. This Disc Biology Special Issue provides an abstract of cutting-edge findings in terms of tissue regulation, therapeutic intervention and preclinical models, which will help to improve the management of IVD disorders.

scholarly journals A homogeneous bioluminescent immunoassay to probe cellular signaling pathway regulation

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Byounghoon Hwang ◽  
Laurie Engel ◽  
Said A. Goueli ◽  
Hicham Zegzouti
Keyword(s):  
Signaling Pathways ◽  
High Throughput Screening ◽  
Cellular Signaling ◽  
Cell Behavior ◽  
Cell Type ◽  
Cellular Signaling Pathway ◽  
Health And Disease ◽  
Endogenous Substrate ◽  
Pathway Regulation ◽  
Multiple Signaling

AbstractMonitoring cellular signaling events can help better understand cell behavior in health and disease. Traditional immunoassays to study proteins involved in signaling can be tedious, require multiple steps, and are not easily adaptable to high throughput screening (HTS). Here, we describe a new immunoassay approach based on bioluminescent enzyme complementation. This immunoassay takes less than two hours to complete in a homogeneous “Add and Read” format and was successfully used to monitor multiple signaling pathways’ activation through specific nodes of phosphorylation (e.g pIκBα, pAKT, and pSTAT3). We also tested deactivation of these pathways with small and large molecule inhibitors and obtained the expected pharmacology. This approach does not require cell engineering. Therefore, the phosphorylation of an endogenous substrate is detected in any cell type. Our results demonstrate that this technology can be broadly adapted to streamline the analysis of signaling pathways of interest or the identification of pathway specific inhibitors.

Mast Cells as a Double-Edged Sword in Immunity: Their Function in Health and Disease. First of Two Parts

2020 ◽  
Vol 20 (5) ◽  
pp. 654-669
Author(s):  
Thea Magrone ◽  
Manrico Magrone ◽  
Emilio Jirillo
Keyword(s):  
Steady State ◽  
Mast Cells ◽  
Immune Cells ◽  
Food Antigens ◽  
Health And Disease ◽  
The Relationship

Mast cells (MCs) have recently been re-interpreted in the context of the immune scenario in the sense that their pro-allergic role is no longer exclusive. In fact, MCs even in steady state conditions maintain homeostatic functions, producing mediators and intensively cross-talking with other immune cells. Here, emphasis will be placed on the array of receptors expressed by MCs and the variety of cytokines they produce. Then, the bulk of data discussed will provide readers with a wealth of information on the dual ability of MCs not only to defend but also to offend the host. This double attitude of MCs relies on many variables, such as their subsets, tissues of residency and type of stimuli ranging from microbes to allergens and food antigens. Finally, the relationship between MCs with basophils and eosinophils will be discussed.

scholarly journals Disruption of Gap Junctional Communication by the Platelet-derived Growth Factor Is Mediated via Multiple Signaling Pathways

1999 ◽  
Vol 274 (15) ◽  
pp. 10489-10496 ◽  
Author(s):  
Mohammad Z. Hossain ◽  
Ajit B. Jagdale ◽  
Peng Ao ◽  
Andrius Kazlauskas ◽  
Alton L. Boynton
Keyword(s):  
Growth Factor ◽  
Signaling Pathways ◽  
Platelet Derived Growth Factor ◽  
Gap Junctional Communication ◽  
Junctional Communication ◽  
Gap Junctional ◽  
Multiple Signaling

scholarly journals Hypoxia-inducible Factor 2α: A Key Player in Tumorigenesis and Metastasis of Pheochromocytoma and Paraganglioma?

2021 ◽  
Author(s):  
Nicole Bechmann ◽  
Graeme Eisenhofer
Keyword(s):  
Extracellular Matrix ◽  
Signaling Pathways ◽  
Metastatic Disease ◽  
Therapeutic Intervention ◽  
Treatment Options ◽  
Hypoxia Inducible Factor ◽  
Germline Mutations ◽  
Driver Mutations ◽  
Mesenchymal Transition ◽  
Therapeutic Relevance

AbstractGermline or somatic driver mutations linked to specific phenotypic features are identified in approximately 70% of all catecholamine-producing pheochromocytomas and paragangliomas (PPGLs). Mutations leading to stabilization of hypoxia-inducible factor 2α (HIF2α) and downstream pseudohypoxic signaling are associated with a higher risk of metastatic disease. Patients with metastatic PPGLs have a variable prognosis and treatment options are limited. In most patients with PPGLs, germline mutations lead to the stabilization of HIF2α. Mutations in HIF2α itself are associated with adrenal pheochromocytomas and/or extra-adrenal paragangliomas and about 30% of these patients develop metastatic disease; nevertheless, the frequency of these specific mutations is low (1.6–6.2%). Generally, mutations that lead to stabilization of HIF2α result in distinct catecholamine phenotype through blockade of glucocorticoid-mediated induction of phenylethanolamine N-methyltransferase, leading to the formation of tumors that lack epinephrine. HIF2α, among other factors, also contributes importantly to the initiation of a motile and invasive phenotype. Specifically, the expression of HIF2α supports a neuroendocrine-to-mesenchymal transition and the associated invasion-metastasis cascade, which includes the formation of pseudopodia to facilitate penetration into adjacent vasculature. The HIF2α-mediated expression of adhesion and extracellular matrix genes also promotes the establishment of PPGL cells in distant tissues. The involvement of HIF2α in tumorigenesis and in multiple steps of invasion-metastasis cascade underscores the therapeutic relevance of targeting HIF2α signaling pathways in PPGLs. However, due to emerging resistance to current HIF2α inhibitors that target HIF2α binding to specific partners, alternative HIF2α signaling pathways and downstream actions should also be considered for therapeutic intervention.

scholarly journals From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2278
Author(s):  
Afshin Derakhshani ◽  
Zeinab Rostami ◽  
Hossein Safarpour ◽  
Mahdi Abdoli Shadbad ◽  
Niloufar Sadat Nourbakhsh ◽  
...  
Keyword(s):  
Single Cell ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cancer Development ◽  
Immune Checkpoints ◽  
Single Cell Sequencing ◽  
Increased Risk

Over the past decade, there have been remarkable advances in understanding the signaling pathways involved in cancer development. It is well-established that cancer is caused by the dysregulation of cellular pathways involved in proliferation, cell cycle, apoptosis, cell metabolism, migration, cell polarity, and differentiation. Besides, growing evidence indicates that extracellular matrix signaling, cell surface proteoglycans, and angiogenesis can contribute to cancer development. Given the genetic instability and vast intra-tumoral heterogeneity revealed by the single-cell sequencing of tumoral cells, the current approaches cannot eliminate the mutating cancer cells. Besides, the polyclonal expansion of tumor-infiltrated lymphocytes in response to tumoral neoantigens cannot elicit anti-tumoral immune responses due to the immunosuppressive tumor microenvironment. Nevertheless, the data from the single-cell sequencing of immune cells can provide valuable insights regarding the expression of inhibitory immune checkpoints/related signaling factors in immune cells, which can be used to select immune checkpoint inhibitors and adjust their dosage. Indeed, the integration of the data obtained from the single-cell sequencing of immune cells with immune checkpoint inhibitors can increase the response rate of immune checkpoint inhibitors, decrease the immune-related adverse events, and facilitate tumoral cell elimination. This study aims to review key pathways involved in tumor development and shed light on single-cell sequencing. It also intends to address the shortcomings of immune checkpoint inhibitors, i.e., their varied response rates among cancer patients and increased risk of autoimmunity development, via applying the data from the single-cell sequencing of immune cells.

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