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Topic Review
Synthetic Vulnerabilities in the KRAS Pathway
Mutations in Kristen Rat Sarcoma viral oncogene (KRAS) are among the most frequent gain-of-function genetic alterations in human cancer. Most KRAS-driven cancers depend on its sustained expression and signaling. Despite spectacular recent success in the development of inhibitors targeting specific KRAS alleles, the discovery and utilization of effective directed therapies for KRAS-mutant cancers remains a major unmet need.
  • 388
  • 24 Jun 2022
Topic Review
Current Methodologies for Visualizing ATP in Living Cells
Measuring total ATP levels within cellular compartmental pools in real-time presents a newer and more innovative approach to qualitatively analyzing ATP. Although this method is not precisely quantitative, it can be helpful in determining changes in ATP concentrations in one region of a cell compared to another in a variety of disease states. The overall goal of these assays and imaging methodologies are to evaluate and visualize dynamic ATP trends, such as usage and depletion, between cells and their sub-compartments. However, semi-quantitative evaluation of the relative ATP signal is feasible. The currently developed technologies that utilize this approach to ATP quantification are mainly genetically encoded biosensors. In conjunction with a fluorescent or bioluminescent protein, most of these biosensors harness the folding capabilities of the ϵ subunit of the bacterial ATP synthase subunit. The bacterial ATP synthase protein comprises a β-barrel domain located at the N terminus and an α-helical domain with two α-helices located at the C terminus. Upon ATP binding, the two α-helices interact and refine their conformational structure of the ϵ subunit, leading to fluorescent/bioluminescent illumination, indicating that ATP is present. Overall, this subunit adopts two different conformations: open (ATP-free) or closed (ATP-bound). The uses and applicability of this technology are limitless. 
  • 569
  • 24 Jun 2022
Topic Review
Therapeutic Approaches of Radioresistance in NSCLC
Survival in unresectable locally advanced stage non-small cell lung cancer (NSCLC) patients remains poor despite chemoradiotherapy. Adjuvant immunotherapy improved survival for these patients but it is still far from curing most of the patients with only a 57% survival remaining at 3 years. This poor survival is due to the resistance to chemoradiotherapy, local relapses, and distant relapses. Several biological mechanisms have been found to be involved in the chemoradioresistance such as cancer stem cells, cancer mutation status, or the immune system. New drugs to overcome this radioresistance in NSCLCs have been investigated such as radiosensitizer treatments or immunotherapies. Different modalities of radiotherapy have also been investigated to improve efficacity such as dose escalation or proton irradiations.
  • 325
  • 24 Jun 2022
Topic Review
Unexpected Role of MPO-Oxidized LDLs in Atherosclerosis
Inflammation and its resolution are the result of the balance between pro-inflammatory and pro-resolving factors, such as specialized pro-resolving mediators (SPMs). This balance is crucial for plaque evolution in atherosclerosis, a chronic inflammatory disease. Myeloperoxidase (MPO) has been related to oxidative stress and atherosclerosis, and MPO-oxidized low-density lipoproteins (Mox-LDLs) have specific characteristics and effects. They participate in foam cell formation and cause specific reactions when interacting with macrophages and endothelial cells. They also increase the production of intracellular reactive oxygen species (ROS) in macrophages and the resulting antioxidant response. Mox-LDLs also drive macrophage polarization. Mox-LDLs are known to be pro-inflammatory particles. However, in the presence of Mox-LDLs, endothelial cells produce resolvin D1 (RvD1), a SPM. SPMs are involved in the resolution of inflammation by stimulating efferocytosis and by reducing the adhesion and recruitment of neutrophils and monocytes. RvD1 also induces the synthesis of other SPMs. In vitro, Mox-LDLs have a dual effect by promoting RvD1 release and inducing a more anti-inflammatory phenotype macrophage, thereby having a mixed effect on inflammation.
  • 406
  • 23 Jun 2022
Topic Review
Growth and Division of Peroxisomes
The identification and molecular characterization of peroxisomal division proteins, microscopic observations and the analysis of patient fibroblasts have contributed to a refined growth and division model for peroxisomes. In mammalian cells, peroxisome formation by membrane growth and division represents a multi-step process involving the remodelling of the peroxisomal membrane, membrane expansion/elongation (growth), membrane constriction and final scission (fission). Peroxisomal growth and division results in the formation of new peroxisomes (multiplication/proliferation), which import matrix and membrane proteins to maintain functionality.
  • 276
  • 23 Jun 2022
Topic Review
Histone Demethylase JMJD2D
Histone demethylase JMJD2D is a multifunctional epigenetic factor coordinating androgen receptor activation, DNA damage repair, DNA replication, cell cycle regulation, and inflammation modulation. JMJD2D is also a well-established epigenetic facilitator in the progression of multiple malignant tumors, especially in colorectal cancer (CRC) and hepatocellular cancer (HCC).
  • 555
  • 22 Jun 2022
Topic Review
Botulinum Toxin Type A
Botulinum neurotoxin A (BoNT-A) which is generally known as anti-contraction of muscles has been reported as a successful treatment in various types of chronic ulcers.
  • 459
  • 22 Jun 2022
Topic Review
Plant Meiosis
Meiosis is an essential cell-division process for ensuring genetic diversity across generations. Meiotic recombination ensures the accuracy of genetic interchange between homolous chromosomes and segregation of parental alleles. Programmed DNA double-strand breaks (DSBs), catalyzed by the evolutionarily conserved topoisomerase VIA (a subunit of the archaeal type II DNA topoisomerase)-like enzyme Spo11 and several other factors, is a distinctive feature of meiotic recombination initiation.
  • 293
  • 22 Jun 2022
Topic Review
Spleen Reparative Regeneration
The spleen is the largest lymphoid unpaired parenchymal organ of the abdominal cavity found in all vertebrates. Spleen is able to regenerate, though not necessarily to the initial volume. The recovery lasts one month and preserves the architecture, albeit with an increase in the relative volume of lymphoid follicles. The renovated tissues, however, exhibit skewed functional profiles; notably, the decreased production of antibodies and the low cytotoxic activity of T cells, consistent with the decline of T-dependent zones and prolonged reduction in T cell numbers. Autotransplantations of splenic material are of particular clinical interest, as the procedure can possibly mitigate the development of post-splenectomy syndrome. Under these conditions, regeneration lasts 1-2 months, depending on the species. The transplants effectively destroy senescent erythrocytes, assist in microbial clearance, and produce antibodies, thus averting sepsis and bacterial pneumonia. Meanwhile, cellular sources of splenic recovery in such models remain obscure, as well as the time required for T and B cell number re-constitution.
  • 754
  • 21 Jun 2022
Topic Review
Changes in Homeostasis of the Dermal Extracellular Matrix
Skin aging is a multi-factorial process that affects nearly every aspect of skin biology and function. With age, an impairment of structures, quality characteristics, and functions of the dermal extracellular matrix (ECM) occurs in the skin, which leads to disrupted functioning of dermal fibroblasts (DFs), the main cells supporting morphofunctional organization of the skin. The DF functioning directly depends on the state of the surrounding collagen matrix (CM). The intact collagen matrix ensures proper adhesion and mechanical tension in DFs, which allows these cells to maintain collagen homeostasis while ECM correctly regulates cellular processes. When the integrity of CM is destroyed, mechanotransduction is disrupted, which is accompanied by impairment of DF functioning and destruction of collagen homeostasis, thereby contributing to the progression of aging processes in skin tissues. 
  • 718
  • 21 Jun 2022
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