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.
  • 630
  • 16 May 2022
Topic Review
Two-Pore Channels and Ca2+ Homeostasis in Immune Cells
Two-pore channels (TPCs) are ligand-gated cation-selective ion channels that are preserved in plant and animal cells. In the latter, TPCs are located in membranes of acidic organelles, such as endosomes, lysosomes, and endolysosomes. Mast cells, along with basophil granulocytes, play an essential role in anaphylaxis and allergic reactions by releasing inflammatory mediators. Signaling in mast cells is mainly regulated via the release of Ca2+ from the endoplasmic reticulum as well as from acidic compartments, such as endolysosomes. For the crosstalk of these organelles TPCs seem essential. Allergic reactions and anaphylaxis were previously shown to be associated with the endolysosomal two-pore channel TPC1. The release of histamine, controlled by intracellular Ca2+ signals, was increased upon genetic or pharmacologic TPC1 inhibition. Conversely, stimulation of TPC channel activity by one of its endogenous ligands, namely nicotinic adenine dinucleotide phosphate (NAADP) or phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), were found to trigger the release of Ca2+ from the endolysosomes; thereby improving the effect of TPC1 on regulated mast cell degranulation. 
  • 367
  • 16 May 2022
Topic Review
Hippo in Gastric Cancer
The Hippo signalling pathway is one of the most crucial and complex ones in physiology, and there is no doubt that the regulatory mechanisms it possesses are various. The role of this signalisation process in tissue homeostasis makes it keen to lead to cancerous processes when dysregulated. 
  • 839
  • 16 May 2022
Topic Review
Generation of Liver Organoids
The liver represents the most important metabolic organ of the human body. It is evident that an imbalance of liver function can lead to several pathological conditions, known as liver failure. Orthotropic liver transplantation (OLT) is currently the most effective and established treatment for end-stage liver diseases and acute liver failure (ALF). Due to several limitations, stem-cell-based therapies are currently being developed as alternative solutions. Stem cells or progenitor cells derived from various sources have emerged as an alternative source of hepatic regeneration. Therefore, hematopoietic stem cells (HSCs), mesenchymal stromal cells (MSCs), endothelial progenitor cells (EPCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are also known to differentiate into hepatocyte-like cells (HPLCs) and liver progenitor cells (LPCs) that can be used in preclinical or clinical studies of liver disease. Furthermore, these cells have been shown to be effective in the development of liver organoids that can be used for disease modeling, drug testing and regenerative medicine.
  • 375
  • 13 May 2022
Topic Review
Muscarinic Receptors Associated with Cancer
Cancer has been considered the pathology of the century and factors such as the environment may play an important etiological role. The ability of muscarinic agonists to stimulate growth and muscarinic receptor antagonists to inhibit tumor growth has been demonstrated for breast, melanoma, lung, gastric, colon, pancreatic, ovarian, prostate, and brain cancer. 
  • 326
  • 13 May 2022
Topic Review
Single-Cell RNA Sequencing for Plant Research
In recent years, advances in single-cell RNA sequencing (scRNA-seq) technologies have continued to change views on biological systems by increasing the spatiotemporal resolution of analysis to single-cell resolution. Application of scRNA-seq to plants enables the comprehensive characterization of both common and rare cell types and cell states, uncovering new cell types and revealing how cell types relate to each other spatially and developmentally. The use of sequencing technologies in plants to analyze genetic variation and metabolic regulation has played a major role in enhancing understanding of plant developmental processes and response to stimuli. However, the traditional sequencing method only generates average cell data and incapable of analyzing large number of cells, therefore losing cell heterogeneity information. The technical reason behind this limitation is that the material or study sample used for traditional sequencing contains several cells that are mixed to obtain whole-genome sequence information of all cells. However, the plant developmental process includes several regulatory factors and significant heterogeneity between different cells, which require a technology that enables cell heterogeneity and the discovery of new marker genes.
  • 347
  • 11 May 2022
Topic Review
YAP/TAZ Activation in Head and Neck Cancer
The Hippo signaling pathway, originally discovered as a mechanism regulating tissue growth and organ size, transduces intracellular and extracellular signals to regulate the transcriptional co-activators YAP and TAZ. Alterations in the Hippo pathway resulting in persistent YAP and TAZ activation have emerged as major oncogenic drivers. The researchers' analysis of the human Head and neck squamous cell carcinoma (HNSCC) oncogenome revealed multiple genomic alterations impairing Hippo signaling and activating YAP and TAZ, which in turn contribute to HNSCC development. This includes mutations and deletions of the FAT1 gene (29%) and amplification of the WWTR1 (encoding TAZ, 14%) and YAP1 genes (8%), together representing one of the most genetically altered signaling mechanisms in this malignancy. 
  • 1.4K
  • 11 May 2022
Topic Review
Bile Acids in Alcohol-Associated Liver Disease
Alcohol-associated liver disease (ALD) is a spectrum of diseases, the onset and progression of which are due to chronic alcohol use. ALD ranges, by increasing severity, from hepatic steatosis to alcoholic hepatitis (AH) and alcohol-associated cirrhosis (AC), and in some cases, can lead to the development of hepatocellular carcinoma (HCC). ALD continues to be a significant health burden and is now the main cause of liver transplantations in the United States. ALD leads to biological, microbial, physical, metabolic, and inflammatory changes in patients that vary depending on disease severity. ALD deaths have been increasing in recent years and are projected to continue to increase. Current treatment centers focus on abstinence and symptom management, with little in the way of resolving disease progression. Due to the metabolic disruption and gut dysbiosis in ALD, bile acid (BA) signaling and metabolism are also notably affected and play a prominent role in disease progression in ALD, as well as other liver disease states, such as non-alcoholic fatty liver disease (NAFLD).
  • 517
  • 11 May 2022
Topic Review
Epigenetic Regulation/Dysregulation in Cancer Stem Cells
In cancer, several of post-translational modifications can undergo dysregulation, driving intratumoral heterogeneity and leading to tumor subpopulations with novel epigenetic regulation. These epigenetic regulations are carried out mainly by histone writers, erasers and readers.
  • 394
  • 10 May 2022
Topic Review
Chromosome Territories in Hematological Cancers
Chromosomes are organized in distinct nuclear areas designated as chromosome territories (CT). The structural formation of CT is a consequence of chromatin packaging and organization that ultimately affects cell function. Chromosome positioning can identify structural signatures of genomic organization, especially for diseases where changes in gene expression contribute to a given phenotype.  The term “chromosome territories” was first coined by Theodor Boveri (1909) in the 20th century. However, the idea of a territorial-like organization of chromosomes during interphase appeared as early as 1885, described by Carl Rabl, based on his experiments of cell division using Salamandra maculata. Rabl observed a polarized nuclear position of chromosomes at the beginning and at the end of mitosis, suggesting a preserved chromosome position during cell cycle phases.
  • 551
  • 10 May 2022
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