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Topic Review
Antibodies and Pentraxins
Macrophages play a key role in induction of inflammatory responses. These inflammatory responses are mostly considered to be instigated by activation of pattern recognition receptors (PRRs) or cytokine receptors. However, recently it has become clear that also antibodies and pentraxins, which can both activate Fc receptors (FcRs), induce very powerful inflammatory responses by macrophages that can even be an order of magnitude greater than PRRs. While the physiological function of this antibody-dependent inflammation (ADI) is to counteract infections, undesired activation or over-activation of this mechanism will lead to pathology, as observed in a variety of disorders, including viral infections such as COVID-19, chronic inflammatory disorders such as Crohn’s disease, and autoimmune diseases such as rheumatoid arthritis.
  • 505
  • 04 Jun 2021
Topic Review
Asbestos and Intrahepatic Cholangiocarcinoma
The link between asbestos exposure and the onset of thoracic malignancies is well established. However epidemiological studies have provided evidences that asbestos may be also involved in the development of gastrointestinal tumors, including intrahepatic cholangiocarcinoma (ICC). In line with this observation, asbestos fibers have been detected in the liver of patients with ICC. Although the exact mechanism still remains unknown, the presence of asbestos fibers in the liver could be explained in the light of their translocation pathway following ingestion/inhalation. In the liver, thin and long asbestos fibers could remain trapped in the smaller bile ducts, particularly in the stem cell niche of the canals of Hering, and exerting their carcinogenic effect for a long time, thus inducing hepatic stem/progenitor cells (HpSCs) malignant transformation. In this scenario, chronic liver damage induced by asbestos fibers over the years could be seen as a classic model of stem cell-derived carcinogenesis, where HpSC malignant transformation represents the first step of this process. This phenomenon could explain the recent epidemiological findings, where asbestos exposure seems mainly involved in ICC, rather than extrahepatic cholangiocarcinoma, development.
  • 620
  • 04 Jun 2021
Topic Review
Selenoproteins
Selenium is a vital trace element present as selenocysteine (Sec) in proteins that are, thus, known as selenoproteins. Humans have 25 selenoproteins, most of which are functionally characterized as oxidoreductases, where the Sec residue plays a catalytic role in redox regulation and antioxidant activity. Glutathione peroxidase plays a pivotal role in scavenging and inactivating hydrogen and lipid peroxides, whereas thioredoxin reductase reduces oxidized thioredoxins as well as non-disulfide substrates, such as lipid hydroperoxides and hydrogen peroxide. Selenoprotein R protects the cell against oxidative damage by reducing methionine-R-sulfoxide back to methionine. Selenoprotein O regulates redox homeostasis with catalytic activity of protein AMPylation. Moreover, endoplasmic reticulum (ER) membrane selenoproteins (SelI, K, N, S, and Sel15) are involved in ER membrane stress regulation. Selenoproteins containing the CXXU motif (SelH, M, T, V, and W) are putative oxidoreductases that participate in various cellular processes depending on redox regulation.
  • 1.1K
  • 03 Jun 2021
Topic Review
Temozolomide Use in IDH-Mutant Gliomas
In this entry, we discuss the use of the alkylating agent temozolomide (TMZ) in the treatment of IDH-mutant gliomas. We describe the challenges associated with TMZ in clinical (drug resistance and tumor recurrence) and preclinical settings (variabilities associated with in vitro models) in treating IDH-mutant glioma.
  • 713
  • 03 Jun 2021
Topic Review
PPARs in Cancer Stromal Cells
Most anticancer therapies target malignant cancer cells while largely ignoring the surrounding noncancer cell components of the tumor or TME. The TME or tumor stroma comprises nonmalignant host cellular and acellular components, including, but not limited to, fibroblasts, immune cells, endothelial cells, fat cells, and noncellular components of the tumor niche such as the basement membrane and ECM. Although most normal host cells in the stroma possess certain tumor-suppressing abilities, the stroma will change during malignancy, causing the tumor stromal cells to confer pro- or anti-tumor properties in a context- and cell type-dependent manner. Over the past decades, the role of the TME in determining every aspect of cancer progression and the efficacy of treatment has become evident. The functions of PPARs in these stromal cells are increasingly appreciated and have direct or indirect impacts on cancer progression.
  • 588
  • 03 Jun 2021
Topic Review
TRPC Channels in Cardiac Plasticity
The heart flexibly changes its structure in response to changing environments and oxygen/nutrition demands of the body. Increased and decreased mechanical loading induces hypertrophy and atrophy of cardiomyocytes, respectively. In physiological conditions, these structural changes of the heart are reversible. However, chronic stresses such as hypertension or cancer cachexia cause irreversible remodeling of the heart, leading to heart failure. Accumulating evidence indicates that calcium dyshomeostasis and aberrant reactive oxygen species production cause pathological heart remodeling. Canonical transient receptor potential (TRPC) is a nonselective cation channel subfamily whose multimodal activation or modulation of channel activity play important roles in a plethora of cellular physiology.
  • 539
  • 03 Jun 2021
Topic Review
Telomeres
To survive and reproduce, living organisms must maintain homeostasis both in unchallenged (normal) and challenged (stressful) contexts. This requires the evolution of powerful stress response mechanisms adapted to a particular ecosystem and to regular environmental fluctuations. Thus, these mechanisms may be very diverse within the tree of life. The pioneering work of Miroslav Radman on the stress response in bacteria demonstrated the rapid and adaptive value of changing mutation rates for rapid evolution (the mutator effect). In other words, to facilitate the survival of a species, whether it be to respond to a replication blockade or to a stressful environment, it is better to rapidly evolve by generating more mutations, some being possibly lethal, than to die immediately. We believe that this principle applies to the complex dynamics of telomeres in eukaryotes, which become altered in response to stress.
  • 757
  • 02 Jun 2021
Topic Review
Thymoquinone and COVID-19
Thymoquinone (TQ) is the most pharmacologically active ingredient in Nigella sativa seeds (black seeds); it is reported to have anticancer, anti-inflammatory and antioxidant effects in various settings.
  • 1.8K
  • 02 Jun 2021
Topic Review
MSC-Based Therapy in Osteoarthritis Treatment
Osteoarthritis (OA) is a chronic degenerative disorder of the joint and its prevalence and severity is increasing owing to ageing of the population. Osteoarthritis is characterized by the degradation of articular cartilage and remodeling of the underlying bone. Extracellular vesicles are naturally released by cells and they carry their origin cell information to be delivered to target cells. On the other hand, mesenchymal stem cells (MSCs) are highly proliferative and have a great potential in cartilage regeneration. 
  • 869
  • 02 Jun 2021
Topic Review
Rho GTPase Regulators
The Rho family GTPases are small G proteins that act as molecular switches shuttling between active and inactive forms. Rho GTPases are regulated by two classes of regulatory proteins, guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Rho GTPases transduce the upstream signals to downstream effectors, thus regulating diverse cellular processes, such as growth, migration, adhesion, and differentiation. In particular, Rho GTPases play essential roles in regulating neuronal morphology and function. Recent evidence suggests that dysfunction of Rho GTPase signaling contributes substantially to the pathogenesis of autism spectrum disorder (ASD). It has been found that 20 genes encoding Rho GTPase regulators and effectors are listed as ASD risk genes by Simons foundation autism research initiative (SFARI).
  • 449
  • 02 Jun 2021
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