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Topic Review
Sphingosine 1-phosphate
The breakdown of the endothelial cell (EC) barrier contributes significantly to sepsis mortality. Sphingosine 1-phosphate (S1P) is one of the most effective EC barrier-stabilizing signaling molecules. Stabilization is mainly transduced via the S1P receptor type 1 (S1PR1). Here, we demonstrate that S1P was autonomously produced by ECs. S1P secretion was significantly higher in primary human umbilical vein endothelial cells (HUVEC) compared to the endothelial cell line EA.hy926. Constitutive barrier stability of HUVEC, but not EA.hy926, was significantly compromised by the S1PR1 antagonist W146 and by the anti-S1P antibody Sphingomab. HUVEC and EA.hy926 differed in the expression of the S1P-transporter Spns2, which allowed HUVEC, but not EA.hy926, to secrete S1P into the extracellular space. Spns2 deficient mice showed increased serum albumin leakage in bronchoalveolar lavage fluid (BALF). Lung ECs isolated from Spns2 deficient mice revealed increased leakage of fluorescein isothiocyanate (FITC) labeled dextran and decreased resistance in electric cell-substrate impedance sensing (ECIS) measurements. Spns2 was down-regulated in HUVEC after stimulation with pro-inflammatory cytokines and lipopolysaccharides (LPS), which contributed to destabilization of the EC barrier. Our work suggests a new mechanism for barrier integrity maintenance. Secretion of S1P by EC via Spns2 contributed to constitutive EC barrier maintenance, which was disrupted under inflammatory conditions via the down-regulation of the S1P-transporter Spns2.
  • 925
  • 30 Oct 2020
Topic Review
Cancer-Homing CAR-T Cells
Chimeric antigen receptor (CAR) therapy is based on patient blood-derived T cells and natural killer cells, which are engineered in vitro to recognize a target antigen in cancer cells. Most CAR-T recognize target antigens through immunoglobulin antigen-binding regions.
  • 925
  • 13 Jan 2022
Topic Review
EBV-Associated Diseases
Epstein-Barr virus (EBV), the representative of the Herpesviridae family, is a pathogen extensively distributed in the human population. One of its most characteristic features is the capability to establish latent infection in the host. The infected cells serve as a sanctuary for the dormant virus, and therefore their desensitization to apoptotic stimuli is part of the viral strategy for long-term survival. 
  • 925
  • 18 Jul 2022
Topic Review
Glycan-Binding Protein Scaffolds
Glycans—a broad term describing carbohydrates, including oligosaccharides and polysaccharides—are the third class of important biological macromolecules following nucleic acids and proteins. Glycans are found in all domains of life and in viruses. They can exist as free sugars, but are more commonly found as glycoconjugates, including proteoglycans, glycoproteins, and glycolipids. Glycans are involved in a wide variety of physiological functions and have implications in numerous infectious and non-infectious diseases, making them diagnostic and therapeutic targets. Additionally, glycans are targeted in various biotechnological and industrial applications. The broad applications of glycans have spurred interest in the development of glycan binding proteins (GBPs).GBPs include lectins, antibodies, pseudoenzymes, and carbohydrate-binding modules (CBMs). Lectins are non-immunoglobulin proteins containing at least one non-catalytic domain that exhibits reversible carbohydrate binding. CBMs are similar to lectins, but are small binding domains typically found in lectins or carbohydrate-active enzymes (CAZymes). CAZymes can be further classified into glycoside hydrolases, glycosyltransferases, polysaccharide lyases, and carbohydrate esterases—detailed information on these enzymes is available through the Carbohydrate Active Enzymes (CAZy) database.
  • 924
  • 28 Jan 2021
Topic Review
Endolysosomal TRPMLs
Lysosomes, the membrane-bound digestive cell organelles, are well-known for their catabolic function.
  • 924
  • 04 Feb 2021
Topic Review
Pullulan-Degrading Enzymes
Starch and pullulan degrading enzymes are essential industrial biocatalysts. Pullulan-degrading enzymes are grouped into pullulanases (types I and type II) and pullulan hydrolase (types I, II and III).
  • 924
  • 04 Mar 2022
Topic Review
Proanthocyanidins
PAs’ function as antioxidant, anti-inflammatory drugs, signal pathway regulators remain critical in many diseases.
  • 923
  • 14 Jan 2021
Topic Review
CNS Glial Cells FA Synthesis
The central nervous system (CNS) has an exceptionally high lipid content. The brain contains the highest diversity of lipids than any other organ. Fatty acids (FA) are essential monomeric components that define the structural diversity of lipids and determine their functional properties in the CNS. FAs and their metabolites are critical for brain homeostasis and influence many neural functions, including cell survival, neurogenesis and synaptogenesis. Glial cells are a highly heterogeneous population of cells and predominate the mammalian brain. Astrocytes, oligodendrocytes and microglia are the major types of glial cells in the CNS. Their main function is to sustain a homeostatic environment for neuronal circuits, providing not only structural or trophic support but also controlling neuronal function and plasticity. To do so, glial cells heavily rely on transient and temporal changes in the FA and lipid metabolism.
  • 923
  • 23 Aug 2021
Topic Review
Development of Rudimentary Structure of Mammary Gland
The mammary gland is a compound, branched tubuloalveolar structure and a major characteristic of mammals. The mammary gland has evolved from epidermal apocrine glands, the skin glands as an accessory reproductive organ to support postnatal survival of offspring by producing milk as a source of nutrition. The mammary gland development begins during embryogenesis as a rudimentary structure that grows into an elementary branched ductal tree and is embedded in one end of a larger mammary fat pad at birth. At the onset of ovarian function at puberty, the rudimentary ductal system undergoes dramatic morphogenetic change with ductal elongation and branching. During pregnancy, the alveolar differentiation and tertiary branching are completed, and during lactation, the mature milk-producing glands eventually develop. The early stages of mammary development are hormonal independent, whereas during puberty and pregnancy, mammary gland development is hormonal dependent. The mammary gland develops as a rudimentary structure from a thickening under the ventral skin during embryogenesis. This rudimentary structure grows into a rudimentary branched ductal tree embedded in one end of a larger mammary fat pad at birth. The embryonic development of the mammary gland is a series of several hormone-independent specialized events.
  • 923
  • 18 Apr 2022
Topic Review
Intracellular pH Regulation in Muscle
Here we talk about the effects of acidosis on insulin signaling and glucose uptake in skeletal muscle and whether correcting defects that maintain [pH]i within the muscle, such as carnosine, could alleviate insulin resistance improve insulin responses during metabolic syndrome.
  • 923
  • 22 Oct 2020
Topic Review
PI3K
The phosphoinositide 3-kinase (PI3K) is a family of kinases that play a key role in the biology of chronic lymphocytic leukemia (CLL).
  • 922
  • 19 Mar 2021
Topic Review
Mitochondrial Transporter Protein Families
Mitochondrial carriers facilitate the transfer of small molecules across the inner mitochondrial membrane (IMM) to support mitochondrial function and core cellular processes. In addition to the classical SLC25 (solute carrier family 25) mitochondrial carriers, the past decade has led to the discovery of additional protein families with numerous members that exhibit IMM localization and transporter-like properties. These include mitochondrial pyruvate carriers, sideroflexins, and mitochondrial cation/H+ exchangers. These transport proteins were linked to vital physiological functions and disease.
  • 922
  • 20 Jan 2021
Topic Review
Sea Slug Elysia crispata
Some species of sacoglossan sea slugs are able to steal chloroplasts from the algae they feed on and maintain them functional for several months, a process termed “kleptoplasty”. One of these photosynthetic slugs is Elysia crispata, found in coral reefs of the Gulf of Mexico. This sacoglossan inhabits different depths (0–25 m), being exposed to different food sources and contrasting light conditions.
  • 921
  • 19 Apr 2022
Topic Review
Polyphenols in the Mediterranean Diet
The Mediterranean diet varies by country and region, so it has a range of definitions. In general, however, it is high in vegetables, fruits, legumes (such as beans), nuts, cereals, fish and unsaturated fats (such as olive oil). It usually includes a low intake of meat and dairy foods. In particular, some plants are characteristic of the Mediterranean vegetation; some have been present for thousands of years, such as olive trees, walnuts, oregano, pomegranates, onions and others including various citrus species. Polyphenols have a typical molecular structure with one or more aromatic rings, and one or more double bonds are present in the molecule. This structure guarantees an antioxidant action for all classes, as there is delocalization of the free radical itself, with consequent antioxidant activity.
  • 921
  • 31 May 2022
Topic Review
MRNA Export in Cancer
Export of mRNAs from the nucleus to the cytoplasm is a key regulatory step in the expression of proteins. mRNAs are transported through the nuclear pore complex (NPC) in association with key co-factors.  Export of selected subsets of mRNAs permits targeted elevation of specific protein expression. Indeed, there are different export pathways depending on the mRNA underpinning this selectivity.  Export of mRNAs can respond to a variety of cellular stimuli making it a dynamic means to respond to extracellular stimuli. mRNA export can be dysregulated in, and contribute to, human diseases including cancer and neurodegeneration. This entry focuses on its role in cancer.
  • 920
  • 08 Jan 2021
Topic Review
CeRNA Networks in Neurodegenerative Diseases
Protein aggregation is classically considered the main cause of neuronal death in neurodegenerative diseases (NDDs). However, increasing evidence suggests that alteration of RNA metabolism is a key factor in the etiopathogenesis of these complex disorders. Non-coding RNAs are the major contributor to the human transcriptome and are particularly abundant in the central nervous system, where they have been proposed to be involved in the onset and development of NDDs. Interestingly, some ncRNAs (such as lncRNAs, circRNAs and pseudogenes) share a common functionality in their ability to regulate gene expression by modulating miRNAs in a phenomenon known as the competing endogenous RNA mechanism. Moreover, ncRNAs are found in body fluids where their presence and concentration could serve as potential non-invasive biomarkers of NDDs.
  • 920
  • 17 Feb 2021
Topic Review
The Effects of Diets on the “Gut–Brain” Pathways
With depression becoming increasingly prevalent, being closely associated with stress, and many patients exhibiting resistance to current treatments, depression pathophysiology requires further elucidation. Recent research has shown complex bidirectional links between the brain and the gut, and the gut microbiota and the influence of diet is beginning to provide new clues to the complex nature of this disorder. It is well known that diet is a key modulator of gut microbial composition. In humans, good quality plant-based diets such as the Mediterranean diet have been shown to reduce pathogenic bacteria in the gut, increase Bifidobacterium and Clostridium, as well as lower the risk of depression, while poorer quality diets such as the Western diet have been shown to reduce Lactobacillus in the gut, reduce overall gut microbial diversity and have been associated with increased depression risk. Evaluating the effects of diets on the brain-to-gut and gut-to-brain mechanisms in animal models of stress and depression may aid in the elucidation of the pathophysiology of depression and may provide novel therapeutic approaches. 
  • 920
  • 21 Feb 2022
Topic Review
Tyrosine Hydroxylase Phosphorylation
Tyrosine hydroxylase (TH) is the rate-limiting enzyme of dopamine biosynthesis. The phosphorylation of TH is strictly regulated.
  • 920
  • 06 Nov 2020
Topic Review
FTO Intronic SNP
Browning of white adipose tissue shifts adipocytes from energy storage white to energy expenditure beige types. The balance between the two adipocyte populations in white adipose tissue is highly determined by noncoding variants of the Fat mass and obesity-associated (FTO) locus which has the strongest association with obesity. The rs1421085 FTO risk allele results in a loss of ARID5B repression of IRX3 and IRX5 which promotes excess white adipocyte formation. Recent studies have revealed the presence of brown adipose tissues at several anatomical sites in humans including the deep-neck (DN).  We found that the characteristic gene expression profile and associated pathways of DN brown adipocytes were determined by partially overlapping effects of tissue site specific commitments of the stem cells, PPARγ stimulation and the FTO status of donors. The presence of FTO rs1421085 risk alleles had a strong influence, manifested during differentiation, on browning resulting in compromised expression of metabolic and mitochondrial genes as well as pathways which are decisive in thermogenesis.
  • 919
  • 30 Oct 2020
Topic Review
Adipokines, Myokines, and Hepatokines
Adipose, skeletal, and hepatic muscle tissues are the main endocrine organs that produce adipokines, myokines, and hepatokines. These biomarkers can be harmful or beneficial to an organism and still perform crosstalk, acting through the endocrine, paracrine, and autocrine pathways. Far beyond understanding the actions of each biomarker alone, it is important to underline that these cytokines act together in the body, resulting in a complex network of actions in different tissues, which may have beneficial or non-beneficial effects on the genesis of various physiological disorders and their respective outcomes, such as type 2 diabetes mellitus (DM2), obesity, metabolic syndrome, and cardiovascular diseases (CVD). Overweight individuals secrete more pro-inflammatory adipokines than those of a healthy weight, leading to an impaired immune response and greater susceptibility to inflammatory and infectious diseases. Myostatin is elevated in pro-inflammatory environments, sharing space with pro-inflammatory organokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), resistin, and chemerin. Fibroblast growth factor FGF21 acts as a beta-oxidation regulator and decreases lipogenesis in the liver. The crosstalk mentioned above can interfere with homeostatic disorders and can play a role as a potential therapeutic target that can assist in the methods of diagnosing metabolic syndrome and CVD.
  • 919
  • 25 Mar 2021
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