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Topic Review
Neutrophil in Pancreatic Tumor Microenvironment
Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with a poor prognosis and low survival rates. PDAC is characterized by a fibroinflammatory tumor microenvironment enriched by abundant fibroblasts and a variety of immune cells, contributing to its aggressiveness. Neutrophils are essential infiltrating immune cells in the PDAC microenvironment. Recent studies have identified several cellular mechanisms by which neutrophils are recruited to tumor lesions and promote tumorigenesis. 
  • 1.3K
  • 29 Mar 2022
Topic Review
Diet in Stem and Cancer Stem Cells
Diet and lifestyle factors greatly affect health and susceptibility to diseases, including cancer. Stem cells’ functions, including their ability to divide asymmetrically, set the rules for tissue homeostasis, contribute to health maintenance, and represent the entry point of cancer occurrence. Stem cell properties result from the complex integration of intrinsic, extrinsic, and systemic factors. In this context, diet-induced metabolic changes can have a profound impact on stem cell fate determination, lineage specification and differentiation.
  • 1.3K
  • 01 Aug 2022
Topic Review
Calcium in Apoptosis and Cancer
Calcium (Ca2+) is a major second messenger in cells and is essential for the fate and survival of all higher organisms. Different Ca2+ channels, pumps, or exchangers regulate variations in the duration and levels of intracellular Ca2+, which may be transient or sustained. These changes are then decoded by an elaborate toolkit of Ca2+-sensors, which translate Ca2+ signal to intracellular operational cell machinery, thereby regulating numerous Ca2+-dependent physiological processes. Alterations to Ca2+ homoeostasis and signaling are often deleterious and are associated with certain pathological states, including cancer. Altered Ca2+ transmission has been implicated in a variety of processes fundamental for the uncontrolled proliferation and invasiveness of tumor cells and other processes important for cancer progression, such as the development of resistance to cancer therapies.
  • 1.3K
  • 22 Sep 2021
Topic Review
Cytokine-Induced Killer Cells
Cytokine-induced killer (CIK) cells are a cluster of heterogeneous cells uniting a T cell and natural killer cell‐like phenotype in their terminally differentiated CD3+CD56+ subset, and exert anti-tumor activity in a non-MHC restricted manner. CIK cells are expanded ex vivo with the sequential addition of multiple cytokines, including interferon‐γ, monoclonal antibodies against CD3 and interleukin‐2.
  • 1.3K
  • 29 Sep 2020
Topic Review
Connexins in Cancer
The expression, localization, and function of connexins, the protein subunits that comprise gap junctions, are often altered in cancer. In addition to cell–cell coupling through gap junction channels, connexins also form hemichannels that allow communication between the cell and the extracellular space and perform non-junctional intracellular activities. Historically, connexins have been considered tumor suppressors; however, they can also serve tumor-promoting functions in some contexts. Here, we review the literature surrounding connexins in cancer cells in terms of specific connexin functions and propose that connexins function upstream of most, if not all, of the hallmarks of cancer. The development of advanced connexin targeting approaches remains an opportunity for the field to further interrogate the role of connexins in cancer phenotypes, particularly through the use of in vivo models. More specific modulators of connexin function will both help elucidate the functions of connexins in cancer and advance connexin-specific therapies in the clinic.
  • 1.3K
  • 24 Dec 2020
Topic Review
Flavonoids as Modulators of Potassium Channels
Potassium channels are widely distributed integral proteins responsible for the effective and selective transport of K+ ions through the biological membranes. According to the existing structural and mechanistic differences, they are divided into several groups. All of them are considered important molecular drug targets due to their physiological roles, including the regulation of membrane potential or cell signaling. Among the pharmaceuticals of plant origin, which are potassium channel modulators, flavonoids appear as a powerful group of biologically active substances. It is caused by their well-documented anti-oxidative, anti-inflammatory, anti-mutagenic, anti-carcinogenic, and antidiabetic effects on human health.
  • 1.3K
  • 30 Jan 2023
Topic Review
Adipose Tissue and FoxO1
Forkhead box O class proteins (FoxOs) are expressed nearly in all tissues and are involved in different functions such as energy metabolism, redox homeostasis and differentiation. The plasticity of FoxOs is demonstrated by post-translational modifications that determine diverse levels of transcriptional regulations also controlled by their subcellular localization. Among the different members of the FoxO family, we focused on FoxO1 in adipose tissue, where it is abundantly expressed and is involved in differentiation and transdifferentiation processes. The capability of FoxO1 to respond differently in dependence of adipose tissue subtype underlines the specific involvement of the transcription factor in energy metabolism and the “browning” process of adipocytes. FoxO1 can localize to nuclear, cytoplasm, and mitochondrial compartments of adipocytes responding to different availability of nutrients and source of reactive oxygen species (ROS).
  • 1.3K
  • 02 Jun 2021
Topic Review
Pluripotency Factor Lin28
Lin28 is an RNA-binding protein that can function as a pluripotency factor and is enriched in stem and progenitor cells and embryonic tissues.  Lin28 can regulate protein synthesis by binding mRNAs to regulate their translation, and by governing microRNA production through binding let-7 family precursor microRNAs to block their processing to mature functional microRNAs.   Lin28 was first discovered in C.elegans and is highly evolutionarily-conserved across the animal kingdom.  In most vertebrates, including mammals, there are two Lin28 paralogs, termed Lin28A and Lin28B.   An appreciation for the complex interactions between the NF-κB transcription factor and the Lin28 RNA binding protein/let-7 microRNA pathways has grown substantially over the past decade.  In many biological settings, accumulated evidence has revealed that Lin28 can be upregulated from low basal levels in adult tissues following injury or in plastic responses. Both the NF-κB and Lin28/let-7 pathways are master regulators impacting cell survival, growth and proliferation, and an understanding of how interfaces between these pathways participate in governing pluripotency, progenitor differentiation, and neuroplastic responses remains an emerging area of research.
  • 1.3K
  • 05 Jan 2021
Topic Review
Role of SLC7A11 in Cancer Metabolism
Solute carrier family 7 member 11 (SLC7A11) is a cell transmembrane protein composing the light chain of system xc−, transporting extracellular cystine into cells for cysteine production and glutathione (GSH) biosynthesis. SLC7A11 is a critical gateway for redox homeostasis by maintaining the cellular levels of GSH that counter cellular oxidative stress and suppress ferroptosis. SLC7A11 is overexpressed in various human cancers and regulates tumor development, proliferation, metastasis, microenvironment, and treatment resistance.
  • 1.3K
  • 08 Jan 2023
Topic Review
Ccr4–Not Complex
This entry mainly gives an overview of the structure of the Ccr4-Not complex, its major components and their enzymatic activities. In the accompanying manuscript the biological roles of the complex is discussed in detail as well as clinical conditions associa
  • 1.3K
  • 17 Nov 2020
Topic Review
Cellular Protein Trafficking in Low-Temperature Response Pathway
Over the years, although substantial progress has been made in understanding low-temperature response mechanisms in plants, the research is more focused on aerial parts of the plants rather than on the root or whole plant, and more efforts have been made in identifying and testing the major regulators of this pathway preferably in the model organism rather than in crop plants. For the low-temperature stress response mechanism, ICE-CBF regulatory pathway turned out to be the solely established pathway, and historically most of the low-temperature research is focused on this single pathway instead of exploring other alternative regulators.
  • 1.3K
  • 24 Apr 2022
Topic Review
The Molecular Mechanisms of 4-N-[2-(4-Phenoxyphenyl)Ethyl]Quinazoline-4,6-Diamine Activity
Quinazoline derivatives are a large pool of natural and synthetic compounds. The first derivatives of quinazoline were synthesized at the end of the 19th century. one quinazoline derivative (4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine)—EVP4593 (also marked as QNZ) was originally synthesized in 2003 as a modulator of the nuclear factor kappa B (NF-κB) signal transduction pathway. Since that time, EVP4593 has been widely used as a blocker of NF-κB signaling (Sigma-Aldrich, cat #481417). Further it has been reported the ability of EVP4593 to affect store-operated calcium channels.
  • 1.3K
  • 21 Dec 2022
Topic Review
The origin cell of cancer
       Tumours may develop from stem cells as well as differentiated cells able to divide. Phenotypically, the two principal  types of cell of origin convert with the degree of genetic changes as the stem cell derived tumours stop earlier in the differentiation and the differentiated cells  gradually lose specific traits. However, the growth regulation of the cell of origin, which depends on its receptors conveying signals influencing proliferation, is essential in tumourigenesis since every cell division carries a small risk of mutation. Moreover, some normal cells have properties making them prone to develop into tumours as neuroendocrine cells which display low adherence as they occur spread by other cells, and also because they release signal substances affecting the vascular bed (for instance histamine).. Therefore, these cells may be the origin of tumours more malignant than apparent from their phenotype. Knowledge of the receptors of the cell of origin gives increased possibility to understand the tumourigenesis and also  improvement of prophylaxis and treatment of the tumours. Finally, spread of nearly normal tumour cells at an early phase gives a plausible explanation of quiescent tumor cell/dormant tumours.
  • 1.3K
  • 30 Oct 2020
Topic Review
NKG2D Natural Killer Cell Receptor
The functionality of NK cells is preserved by the set of activating and inhibitory receptors. Under normal conditions, the appropriate level of major histocompatibility complex (MHC) class I molecules is supervised by inhibitory receptors, which keep NK cells silenced. The “missing self” mechanism considers reduced levels of MHC I (Ia and Ib) molecules when NK cells become activated.
  • 1.3K
  • 02 Jul 2021
Topic Review
Mechanosensitive Ion Channels
Mechanosensitive ion channels mediate the neuronal sensation of mechanical signals such as sound, touch, and pain.
  • 1.3K
  • 21 Oct 2021
Topic Review
Mast Cells as a Therapeutic Target
Anaphylaxis is one of the most life-threatening and intensive allergic reactions. Unlike anaphylactoid reaction, it is an immunoglobulin E-mediated response. Its symptoms can occur in multiple organ systems, such as cutaneous, respiratory, cardiovascular, and others. Mast cells together with basophils are the first cells that are responding to IgE-mediated anaphylaxis. Mast cells (MCs) are the immune cells distributed throughout nearly all tissues, mainly in the skin, near blood vessels and lymph vessels, nerves, lungs, and the intestines. Although MCs are essential to the healthy immune response, their overactivity and pathological states can lead to numerous health hazards. The side effect of mast cell activity is usually caused by degranulation. It can be triggered by immunological factors, such as immunoglobulins, lymphocytes, or antigen–antibody complexes, and non-immune factors, such as radiation and pathogens. An intensive reaction of mast cells can even lead to anaphylaxis, one of the most life-threatening allergic reactions. What is more, mast cells play a role in the tumor microenvironment by modulating various events of tumor biology, such as cell proliferation and survival, angiogenesis, invasiveness, and metastasis. 
  • 1.3K
  • 04 May 2023
Topic Review
Cell Signaling Pathways and Radioresistance of Cancer Cells
Radiation eradicates cancer cells mainly by causing DNA damage. However, radiation also concomitantly activates multiple prosurvival signaling pathways, which include those mediated by ATM, ATR, AKT, ERK, and NF-κB that promote DNA damage checkpoint activation/DNA repair, autophagy induction, and/or inhibition of apoptosis. Furthermore, emerging data support the role of YAP signaling in promoting the intrinsic radioresistance of cancer cells, which occurs through its activation of the transcription of many essential genes that support cell survival, DNA repair, proliferation, and the stemness of cancer stem cells. Together, these signaling pathways protect cancer cells by reducing the magnitude of radiation-induced cytotoxicity and promoting radioresistance. 
  • 1.3K
  • 24 Mar 2022
Topic Review
High Mobility Group Box 1
The High Mobility Group Box 1 (HMGB1) is the most abundant nuclear nonhistone protein that is involved in transcription regulation. In addition, HMGB1 has previously been found as an extracellularly acting protein enhancing neurite outgrowth in cultured neurons. Although HMGB1 is widely expressed in the developing central nervous system of vertebrates and invertebrates, its function in the developing mouse brain is poorly understood. Here, we have analyzed developmental defects of the HMGB1 null mouse forebrain, and further examined our findings in ex vivo brain cell cultures. We find that HMGB1 is required for the proliferation and differentiation of neuronal stem cells/progenitor cells. Enhanced apoptosis is also found in the neuronal cells lacking HMGB1. Moreover, HMGB1 depletion disrupts Wnt/β-catenin signaling and the expression of transcription factors in the developing cortex, including Foxg1, Tbr2, Emx2, and Lhx6. Finally, HMGB1 null mice display aberrant expression of CXCL12/CXCR4 and reduced RAGE signaling. In conclusion, HMGB1 plays a critical role in mammalian neurogenesis and brain development.
  • 1.3K
  • 27 Oct 2020
Topic Review
Natural Polyphenols as SERCA Activators
Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) is a key protein responsible for transporting Ca2+ ions from the cytosol into the lumen of the sarco/endoplasmic reticulum (SR/ER), thus maintaining Ca2+ homeostasis within cells. Accumulating evidence suggests that impaired SERCA function is associated with disruption of intracellular Ca2+ homeostasis and induction of ER stress, leading to different chronic pathological conditions. Therefore, appropriate strategies to control Ca2+ homeostasis via modulation of either SERCA pump activity/expression or relevant signaling pathways may represent a useful approach to combat pathological states associated with ER stress. Natural dietary polyphenolic compounds, such as resveratrol, gingerol, ellagic acid, luteolin, or green tea polyphenols, with a number of health-promoting properties, have been described either to increase SERCA activity/expression directly or to affect Ca2+ signaling pathways.
  • 1.3K
  • 24 Aug 2022
Topic Review
Pannexin-1 Channels and Neuroinflammation
Neuroinflammation is a major component of central nervous system (CNS) injuries and neurological diseases, including Alzheimer’s disease, multiple sclerosis, neuropathic pain, and brain trauma. The activation of innate immune cells at the damage site causes the release of pro-inflammatory cytokines and chemokines, which alter the functionality of nearby tissues and might mediate the recruitment of leukocytes to the injury site. If this process persists or is exacerbated, it prevents the adequate resolution of the inflammation, and ultimately enhances secondary damage. Adenosine 5′ triphosphate (ATP) is among the molecules released that trigger an inflammatory response, and it serves as a chemotactic and endogenous danger signal. Extracellular ATP activates multiple purinergic receptors (P2X and P2Y) that have been shown to promote neuroinflammation in a variety of CNS diseases. Recent studies have shown that Pannexin-1 (Panx1) channels are the principal conduits of ATP release from dying cells and innate immune cells in the brain.
  • 1.3K
  • 25 May 2021
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