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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
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
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
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
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
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 Interplay between Calcium and Reactive Oxygen Species
Mitochondria are key players in energy production, critical activity for the smooth functioning of energy-demanding organs such as the muscles, brain, and heart. Therefore, dysregulation or alterations in mitochondrial bioenergetics primarily perturb these organs. Within the cell, mitochondria are the major site of reactive oxygen species (ROS) production through the activity of different enzymes since it is one of the organelles with the major availability of oxygen.
  • 1.3K
  • 16 Feb 2023
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
Secretory Immunoglobulin A Immunity in COPD
Chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis (CF) are distinct respiratory diseases that share features such as the obstruction of small airways and disease flare-ups that are called exacerbations and are often caused by infections. Along the airway epithelium, immunoglobulin (Ig) A contributes to first line mucosal protection against inhaled particles and pathogens. Dimeric IgA produced by mucosal plasma cells is transported towards the apical pole of airway epithelial cells by the polymeric Ig receptor (pIgR), where it is released as secretory IgA. Secretory IgA mediates immune exclusion and promotes the clearance of pathogens from the airway surface by inhibiting their adherence to the epithelium. 
  • 1.3K
  • 27 Jul 2022
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
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
Carbocysteine’s Effects in Chronic Obstructive Pulmonary Disease Patients
Carbocysteine (R-2-amino-3[(carboxymethyl)thiol] propionic acid) is a biologically active dibasic amino acid. The carbocysteine molecule is characterized by the presence of a bound sulfhydrilic group. Carbocysteine can increase cilia beating in airway epithelial cells, thus improving the function of the mucociliary escalator and its function of removing harmful particles, viruses, and bacteria from the airway surface.
  • 1.3K
  • 01 Jul 2022
Topic Review
Heterochromatin Networks
Recent data point to the leading role of heterochromatin in genome maintenance, highlighting the attractions between heterochromatic regions as being central to phase separation of the active and inactive chromatin domains. The three main properties of heterochromatin—the position silencing effect on transcription, stickiness, and flexible rigidity are important for its network formation.
  • 1.3K
  • 07 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
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
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
Topic Review
Cell Therapies in Acute Kidney Injury
The incidence of renal disease is gradually increasing worldwide, and this condition has become a major public health problem because it is a trigger for many other chronic diseases. Cell therapies using multipotent mesenchymal stromal cells, hematopoietic stem cells, macrophages, and other cell types have been used to induce regeneration and provide a cure for acute and chronic kidney disease in experimental models. 
  • 1.3K
  • 18 Jan 2023
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
Cryptosporidium Parvum
Cryptosporidium parvum is a zoonotic intracellular protozoan responsible for the diarrheal illness cryptosporidiosis in humans and animals. Although a number of zoite surface proteins are known to be expressed during, and believed to be involved in, attachment and invasion of host cells, the molecular mechanisms by which C. parvum invades the host epithelial cells are not well understood. In the present study, we investigated the gene expression patterns, protein localization in developmental stages in culture, and in vitro neutralization characteristics of Cpgp40/15 and Cpgp40. Indirect immunoflfluorescence assay showed that Cpgp40/15 is associated with the parasitophorous vacuole membrane (PVM) during intracellular development. Both anti-gp40/15 and anti-gp40 antibodies demonstrated the ability to neutralize C. parvum infection in vitro. Further studies are needed to fully understand the specifific role and functional mechanism of Cpgp40/15 (or gp40/15 complex) in the invasion of the host or in the PVM and to determine the feasibility of gp40/15 as a vaccine candidate for cryptosporidiosis in vivo.
  • 1.3K
  • 29 Oct 2020
Topic Review
RNA-Binding Proteins Regulating
The majority of the genome is transcribed into pieces of non-(protein) coding RNA, among which long non-coding RNAs (lncRNAs) constitute a large group of particularly versatile molecules that govern basic cellular processes including transcription, splicing, RNA stability, and translation. The frequent deregulation of numerous lncRNAs in cancer is known to contribute to virtually all hallmarks of cancer. The post-transcriptional regulation of lncRNAs is mediated by RNA-binding proteins (RBPs). Interestingly, RBPs themselves are commonly deregulated in cancer and could thus constitute a major contribution to the deregulation of cancer-associated lncRNAs. Discussed here are four examples of well-known RBPs that regulate the transport or localization of cancer-associated lncRNAs and thereby impact the functionality of these lncRNAs. So far, out of the vast number of RBPs that exist, only a relatively small number has been found to specifically guide the transport or localization of cancer-related lncRNAs. In general, there is still a lack of knowledge about how lncRNAs are shuttled between or retained within different cellular compartments and future research will have to shed more light on these regulatory mechanisms.
  • 1.3K
  • 29 Oct 2020
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