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Topic Review
Mast Cell Functions
Mast cells (MCs) are well-known as key effector cells of type I allergic reactions, commonly named anaphylactic responses.
  • 1.3K
  • 02 Feb 2021
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
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. 
  • 1.3K
  • 02 Jun 2021
Topic Review
Lipid Metabolism in Glioblastoma
Glioblastoma (GBM) is the most lethal primary brain tumor. With limited therapeutic options, novel therapies are desperately needed. Recent studies have shown that GBM acquires large amounts of lipids for rapid growth through activation of sterol regulatory element-binding protein 1 (SREBP-1), a master transcription factor that regulates fatty acid and cholesterol synthesis, and cholesterol uptake. Interestingly, GBM cells divert substantial quantities of lipids into lipid droplets (LDs), a specific storage organelle for neutral lipids, to prevent lipotoxicity by increasing the expression of diacylglycerol acyltransferase 1 (DGAT1) and sterol-O-acyltransferase 1 (SOAT1), which convert excess fatty acids and cholesterol to triacylglycerol and cholesteryl esters, respectively. 
  • 1.3K
  • 16 Aug 2022
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
The Importance of Organoids for One Health
One Health describes the importance of considering humans, animals, and the environment in health research. One Health and the 3R concept, i.e., the replacement, reduction, and refinement of animal experimentation, shape today’s research more and more. The development of organoids from many different organs and animals led to the development of highly sophisticated model systems trying to replace animal experiments. Organoids may be used for disease modelling in various ways elucidating the manifold host–pathogen interactions. 
  • 1.3K
  • 28 Sep 2022
Topic Review
Alternative Lengthening of Telomeres and Cancer Treatment
Telomeres are non-coding short repeat sequences (TTAGGG in vertebrates) which in combination with shelterin proteins protect the ends of linear chromosomes from degradation, recombination, and end fusions. Human telomeres range from 5–15 kb in length. Human Alternative Lengthening of Telomeres (ALT) cancers are often present as mesenchymal or epithelial origin in subsets of osteosarcomas, liposarcomas, glioblastomas, or astrocytomas.
  • 1.3K
  • 06 Apr 2023
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
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
Tregs in IBD
Inflammatory bowel disease (IBD) is a complex inflammatory chronic and pathological condition that includes Crohn’s disease (CD) and Ulcerative colitis (UC). CD primarily affects the small and large intestine whereas the prime targets for UC are colon and rectum. Immune sentinel subsets of CD4+ T cells such as Th (T helper cells)-1, Th2, Th17, and regulatory T cells (Tregs) play a crucial role in the pathogenesis of IBD. Immunological balance between effector Th cells and Trges is essential for maintaining immune-homeostasis. Immunoregulatory Trges are characterized by the expression of transcription factor Forkhead box P3 (Foxp3), and surface marker CD25, and are functionally immunosuppressive & important for immune tolerance. Therapeutic arrangement based on Tregs is important to address the systemic inflammatory and autoimmune diseases such as IBD and rheumatoid arthritis.
  • 1.3K
  • 11 Aug 2021
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
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
Vasculogenic Mimicry in Breast Cancer
In solid tumors, vasculogenic mimicry (VM) is the formation of vascular structures by cancer cells, allowing to generate a channel-network able to transport blood and tumor cells. While angiogenesis is undertaken by endothelial cells, VM is assumed by cancer cells. Besides the participation of VM in tumor neovascularization, the clinical relevance of this process resides in its ability to favor metastasis and to drive resistance to antiangiogenic therapy. VM occurs in many tumor types, including breast cancer, where it has been associated with a more malignant phenotype, such as triple-negative and HER2-positive tumors. The latter may be explained by known drivers of VM, like hypoxia, TGFB, TWIST1, EPHA2, VEGF, matrix metalloproteinases, and other tumor microenvironment-derived factors, which altogether induce the transformation of tumor cells to a mesenchymal phenotype with a high expression rate of stemness markers.
  • 1.3K
  • 29 Mar 2022
Topic Review
Amyloid Precursor Protein
Amyloid precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. Its primary function is not known, though it has been implicated as a regulator of synapse formation, neural plasticity, antimicrobial activity , and iron export. APP is best known as the precursor molecule whose proteolysis generates amyloid beta (Aβ), a polypeptide containing 37 to 49 amino acid residues, whose amyloid fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients.
  • 1.3K
  • 25 Nov 2022
Topic Review
Corneal Confocal Microscopy Imaging
In vivo corneal confocal microscopy (IVCM) is a non-invasive ophthalmic imaging technique that provides images of the cornea at the cellular level. The observation of the corneal cells, both normal and inflammatory, and the possibility of quantification of the corneal nerve density with manual or automated tools, makes IVCM have a significant potential to improve the diagnosis and prognosis in several systemic and corneal conditions.
  • 1.3K
  • 04 Jan 2023
Topic Review
Fibronectin in Osteoarthritis
Fibronectin is a component of the extracellular matrix essential to its assembly, which also regulates some cellular functions. However, cleavage of fibronectin in pathological conditions releases fibronectin fragments with pro-inflammatory and degradative properties. During the development of osteoarthritis, tissue proteolysis and injury induce extracellular matrix degradation, generating fibronectin fragments that promote inflammation and degradation by the induction of cytokine and proteinase expressions.
  • 1.3K
  • 02 Dec 2021
Topic Review
Filaggrin in Atopic Dermatitis
The discovery in 2006 that loss-of-function mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris and can predispose to atopic dermatitis (AD) galvanized the dermatology research community and shed new light on a skin protein that was first identified in 1981. However, although outstanding work has uncovered several key functions of filaggrin in epidermal homeostasis, a comprehensive understanding of how filaggrin deficiency contributes to AD is still incomplete, including details of the upstream factors that lead to the reduced amounts of filaggrin, regardless of genotype.
  • 1.3K
  • 16 May 2022
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
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
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