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Topic Review
Anticoagulatory and Procoagulatory Effects of Cannabinoids
Abnormal blood coagulation or coagulopathy is a common manifestation of many pathological conditions. It occurs when there is an imbalance between the activities of the coagulation system and the fibrinolytic system, leading to excessive or impaired intravascular blood clot formation, which can disturb blood flow causing ischemia or hemorrhage in the affected tissues. A growing body of evidence has demonstrated blood coagulation abnormalities in association with cannabinoid use, suggesting the involvement of the endogenous cannabinoid system (ECS) in modulating blood coagulation. However, the evidence in the literature has been controversial on whether cannabinoids promote or inhibit blood coagulation. 
  • 779
  • 25 Jul 2022
Topic Review
New treatment strategies for β-thalassemia
Beta-thalassemia (β-thalassemia) is an autosomal recessive inherited disease characterized by decreased production of the β-globin chains of hemoglobin (Hb) A. The normal structure of HbA is two α- and two β-globin chains. Individuals with β-thalassemia are either homozygous or double heterozygotes for mutations in the β-globin gene.
  • 764
  • 13 Jul 2021
Topic Review
JAK2 in Myeloproliferative Neoplasms
The discovery of the activating V617F mutation in Janus kinase 2 (JAK2) has been decisive for the understanding of myeloproliferative neoplasms (MPN). Activated JAK2 signaling by JAK2, CALR, and MPL mutations has become a focus for the development of targeted therapies for patients with MPN. JAK2 inhibitors now represent a standard of clinical care for certain forms of MPN and offer important benefits for MPN patients. However, several key aspects remain unsolved regarding the targeted therapy of MPN with JAK2 inhibitors, such as reducing the MPN clone and how to avoid or overcome a loss of response. The current knowledge on the structure and signaling of JAK2 as central elements of MPN pathogenesis and feature benefits and limitations of therapeutic JAK2 targeting in MPN were summarized.
  • 737
  • 01 Mar 2022
Topic Review
Telomerase Reverse Transcriptase in Leukemia
Telomerase reverse transcriptase (TERT) has been established to possess diagnostic value in leukemia as most adult cells do not express high levels of telomerase. Indeed, studies have shown that prognosis is not favorable in patients who have leukemias expressing high levels of telomerase. Recent research has indicated that targeting of this gene is able to control the survival of malignant cells and therefore offers a potential treatment for TERT-dependent leukemias. 
  • 735
  • 04 Aug 2021
Topic Review
Diffuse Large B-Cell Lymphoma and Its Tumor Microenvironment
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. It is a clinically and morphologically heterogeneous entity that has continued to resist complete subtyping. Molecular subtyping efforts emerged in earnest with the advent of gene expression profiling (GEP). This molecular subtyping approach has continued to evolve simultaneously with others including immunohistochemistry and more modern genomic approaches. The veritable explosion of genomic data availability and evolving computational methodologies have provided additional avenues, by which further understanding and subclassification of DBLCLs is possible.
  • 700
  • 23 May 2022
Topic Review
Interleukin-7 Signaling in Lymphoid Malignancies
The cytokine interleukin-7 (IL-7) and its receptor are critical for lymphocyte development and homeostasis. The loss of IL-7 signaling causes severe combined immunodeficiency, whereas gain-of-function of the pathway contributes to malignant transformation. It has become increasingly clear that in lymphoid malignancies, especially in T-cell leukemia, many components of the IL-7 signaling pathway carry genetic alterations leading to increased signaling. Moreover, the majority of leukemic cells express the wild type IL-7 receptor and remain dependent on IL-7 signaling for survival, cell cycle progression and proliferation. In this review, we discuss the role of deregulated IL-7-induced JAK-STAT signaling in lymphoid malignancies of T- and B-cell origin.
  • 698
  • 18 May 2021
Topic Review
Hematopoiesis
Hematopoiesis is a stepwise process through which hematopoietic stem cells (HSCs) differentiate to progenitor cells that demonstrate a restricted potential and eventually further differentiate to form all mature blood and immune cells. 
  • 693
  • 07 Sep 2021
Topic Review
The Identity of Thrombosis
Since “two-path unifying theory” of hemostasis was published, it has been confirmed that hemostasis is blood clotting mechanism forming “hemostatic plug” in bleeding from external and internal bodily injury, and is also thrombosis promoting mechanism in intravascular injury by producing “thrombus”.
  • 691
  • 10 Nov 2022
Topic Review
Phosphatidylserine
Cancer is among the leading causes of death worldwide. In recent years, many cancer-associated biomarkers have been identified that are used for cancer diagnosis, prognosis, screening, and early detection, as well as for predicting and monitoring carcinogenesis and therapeutic effectiveness. Phosphatidylserine (PS) is a negatively charged phospholipid which is predominantly located in the inner leaflet of the cell membrane. In many cancer cells, PS externalizes to the outer cell membrane, a process regulated by calcium-dependent flippases and scramblases. Saposin C coupled with dioleoylphosphatidylserine (SapC-DOPS) nanovesicle (BXQ-350) and bavituximab, (Tarvacin, human–mouse chimeric monoclonal antibodies) are cell surface PS-targeting drugs being tested in clinical trial for treating a variety of cancers. Additionally, a number of other PS-selective agents have been used to trigger cytotoxicity in tumor-associated endothelial cells or cancer cells in pre-clinical studies.
  • 682
  • 25 May 2022
Topic Review
Genesis of Endotheliopathy
Endotheliopathy, according to the “two-activation theory of the endothelium”, is triggered by the activated complement system in critical illnesses, such as sepsis, diabetes and polytrauma, leading to two distinctly different molecular dysfunctions: (1) the activation of the inflammatory pathway due to the release of inflammatory cytokines, such as interleukins, interferons and tumor necrosis factors, and (2) the activation of the microthrombotic pathway due to the exocytosis of hemostatic factors, including ultra-large von Willebrand factor (ULVWF) multimers and FVIII. These lead to inflammation and microthrombogenesis. The former produces inflammatory diseases, and the latter produces endotheliopathy-associated vascular microthrombotic disease (EA-VMTD), which orchestrates not only TTP-like syndrome characterized by the triad of consumptive thrombocytopenia, microangiopathic hemolytic anemia and multiorgan dysfunction syndrome, but also many other endotheliopathic syndromes. The diagnostic features of EA-VMTD are well established now and therapeutic strategies are being formulated. 
  • 672
  • 11 Oct 2022
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