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Topic Review
Canonical Hypoxia Signaling
The oxygen-sensing system is a complicated and elaborate system containing large molecular components, including hypoxia-inducible factors (HIFs) as the central regulator of oxygen homeostasis, prolyl hydroxylases (PHDs), Von Hippel-Lindau protein (pVHL) as the modulator of ubiquitin-mediated proteolysis, and the co-factors and downstream targets as functional contributors. It should be recognized that the PHDs-HIF-pVHL axis remains the best-characterized and central signaling in the oxygen sensing pathway, although novel mechanisms continue to be illuminated. In this entry, we summarize the current knowledge about canonical hypoxia signaling, including the function of HIF transcription factors, prolyl hydroxylation of HIFs, and pVHL.
  • 980
  • 02 Nov 2020
Topic Review
5-Hydroxytryptamine and Gut
Serotonin, also known as 5-hydroxytryptamine (5-HT), is a metabolite of tryptophan and is reported to modulate the development and neurogenesis of the enteric nervous system, gut motility, secretion, inflammation, sensation, and epithelial development. Approximately 95% of 5-HT in the body is synthesized and secreted by enterochromaffin (EC) cells, the most common type of neuroendocrine cells in the gastrointestinal (GI) tract, through sensing signals from the intestinal lumen and the circulatory system. Gut microbiota, nutrients, and hormones are the main factors that play a vital role in regulating 5-HT secretion by EC cells. Apart from being an important neurotransmitter and a paracrine signaling molecule in the gut, gut-derived 5-HT was also shown to exert other biological functions (in autism and depression) far beyond the gut. Moreover, studies conducted on the regulation of 5-HT in the immune system demonstrated that 5-HT exerts anti-inflammatory and proinflammatory effects on the gut by binding to different receptors under intestinal inflammatory conditions. Understanding the regulatory mechanisms through which 5-HT participates in cell metabolism and physiology can provide potential therapeutic strategies for treating intestinal diseases. Herein, we review recent evidence to recapitulate the mechanisms of synthesis, secretion, regulation, and biofunction of 5-HT to improve the nutrition and health of humans.
  • 980
  • 17 Aug 2021
Topic Review
ITS2 Secondary Structure
The secondary structure of ribosomal internal transcribed spacer 2 (ITS2) 
  • 978
  • 22 Sep 2020
Topic Review
Human Pluripotent Stem Cell-derived Cardiomyocytes
Atrial fibrillation (AF) is a type of sustained arrhythmia in humans often characterized by devastating alterations to the cardiac conduction system as well as the structure of the atria. AF can lead to decreased cardiac function, heart failure, and other complications. Long non-coding RNAs (lncRNAs) have been shown to play important roles in the cardiovascular system, including AF; however, a large group of lncRNAs is not conserved between mouse and human. Furthermore, AF has complex networks showing variations in mechanisms in different species, making it challenging to utilize conventional animal models to investigate the functional roles and potential therapeutic benefits of lncRNAs for AF. Fortunately, pluripotent stem cell (PSC)-derived cardiomyocytes (CMs) offer a reliable platform to study lncRNA functions in AF because of certain electrophysiological and molecular similarities with native human CMs.
  • 977
  • 27 Oct 2020
Topic Review
Effect of Oral l-Carnitine Supplementation on Exercise Performance
l-Carnitine (l-C) and any of its forms (glycine-propionyl l-Carnitine (GPL-C) or l-Carnitine l-tartrate (l-CLT)) has been frequently recommended as a supplement to improve sports performance due to, among others, its role in fat metabolism and in maintaining the mitochondrial acetyl-CoA/CoA ratio. 
  • 976
  • 15 Dec 2021
Topic Review
Fragile X Syndrome(FXS)
Among the inherited causes of intellectual disability and autism, Fragile X syndrome (FXS) is the most frequent form, for which there is currently no cure. In most FXS patients, the FMR1 gene is epigenetically inactivated following the expansion over 200 triplets of a CGG repeat (FM: full mutation). FMR1 encodes the Fragile X Mental Retardation Protein (FMRP), which binds several mRNAs, mainly in the brain. When the FM becomes methylated at 10–12 weeks of gesta-tion, the FMR1 gene is transcriptionally silent.
  • 975
  • 04 Mar 2021
Topic Review
ATF5 Function in Regulating Cell Stress and Survival
Activating transcription factor 5 (ATF5) belongs to the activating transcription factor/cyclic adenosine monophosphate (cAMP) response element-binding protein family of basic region leucine zipper transcription factors. ATF5 plays an important role in cell stress regulation and is involved in cell differentiation and survival, as well as centrosome maintenance and development. 
  • 975
  • 27 Jul 2022
Topic Review
Tumor Endothelial Cell
Tumor progression relies on angiogenesis from established normal vasculature to form new tumor blood vessels. Tumor endothelial cells (TECs) in the tumor blood vessels maintain tumor vessel formation through continual angiogenesis. TECs are heterogeneous with a diverse cellular origin. Moreover, the various factors and conditions in the tumor microenvironment elicit specific characteristics in TECs differentiating them from endothelial cells in normal vessels. TECs are the main focus of antiangiogenesis strategies, and their unique features make tumor blood vessels good anti-cancer therapeutic targets.
  • 974
  • 28 Oct 2020
Topic Review
Ion Channels of Nociception
Acute pain plays the vital role protecting our health whereas chronic and pathological pain are debilitating conditions.  However molecular mechanisms of pain which are the keys for pain relief remain largely unaddressed. Nevertheless, new molecular actors with important roles in pain mechanisms are being characterized, such as the mechanosensitive Piezo ion channels. This study presents modern trends and promising advances in the field of molecular mechanisms of pain. 
  • 973
  • 24 Mar 2021
Topic Review
High-Value Bioactive Primary Metabolites of Microalgae
Microalgae is an aquatic microorganism with a plethora of diverse bioactive compounds including phenolics, carotenoids, vitamin B12 and peptides. Microalgal bioactive compounds have been shown to possess positive health effects such as antihypertensive, anti-obesity, antioxidative, anticancer and cardiovascular protection.
  • 973
  • 08 Jul 2023
Topic Review
BH3-Only Proteins Noxa and Puma in Apoptosis Regulation
Apoptosis is an evolutionarily conserved and tightly regulated cell death pathway. Physiological cell death is important for maintaining homeostasis and optimal biological conditions by continuous elimination of undesired or superfluous cells. The BH3-only pro-apoptotic members are strong inducers of apoptosis. The pro-apoptotic BH3-only protein Noxa activates multiple death pathways by inhibiting the anti-apoptotic B-cell lymphoma-2 (Bcl-2) family protein, Mcl-1, and other protein members leading to Bax and Bak activation and mitochondrial outer membrane permeabilization (MOMP). On the other hand, Puma is induced by p53-dependent and p53-independent apoptotic stimuli in several cancer cell lines. Moreover, this protein is involved in several physiological and pathological processes, such as immunity, cancer, and neurodegenerative diseases. Future heat shock research could disclose the effect of hyperthermia on both Noxa and BH3-only proteins. This suggests post-transcriptional mechanisms controlling the translation of both Puma and Noxa mRNA in heat-shocked cells. 
  • 972
  • 10 Mar 2022
Topic Review
The Non-Coding RNA Language
Complex organisms are associations of different cells that coexist and collaborate creating a living consortium, the holobiont. The relationships between the holobiont members are essential for a proper homeostasis of all the organisms and they are founded on the establishment of complex inter-connections between all the cells. Non-coding RNAs are transcriptional products of the genomic output with regulatory function and they can act as communication signals between cells, being involved either in homeostasis or dysbiosis of the holobiont. Eukaryotic and prokaryotic cells can transmit signals via non-coding RNAs using specific extracellular conveyors that will travel to reach the target cell and will be translated into a regulatory response by a dedicated molecular machinery. Within holobionts, non-coding RNA regulatory signaling is involved in symbiotic and pathogenic relationships among cells. This review analyzes the current knowledge about the role of non-coding RNAs in cell-to-cell communication, with a special focus in the signaling between cells in multi-organism consortia.
  • 971
  • 28 Oct 2020
Topic Review
Function and Components of Telomerase
Telomerase is the only known eukaryotic-specific enzyme with reverse transcriptase activity, which adds telomeric repeats at the ends of linear chromosomes. In this way, it counteracts telomere shortening and cellular replicative senescence. Telomerase consists of a catalytic protein subunit with reverse transcriptase activity (TERT), and an essential RNA component known as telomerase RNA component (TERC) that contains a template for the synthesis of telomeric DNA, as well as additional proteins (dyskerin, NHP2, NOP10 and GAR1 in vertebrates) that play crucial roles in its biogenesis, localization, and regulation. Beside its telomere-elongating activity, a growing number of studies have evidenced non-telomeric functions.
  • 970
  • 20 Dec 2022
Topic Review
The Role of Cytochromes P450 in Plants
Cytochromes P450 are ancient enzymes diffused in organisms belonging to all kingdoms of life, including viruses, with the largest number of P450 genes found in plants. The functional characterization of cytochromes P450 has been extensively investigated in mammals, where these enzymes are involved in the metabolism of drugs and in the detoxification of pollutants and toxic chemicals.
  • 968
  • 29 Mar 2023
Topic Review
Carrageenan
Carrageenan (CGN) is a sulfated galactose copolymer composed of alternating units of D-galactose and 3,6-anhydro-galactose joined by α-1,3 and β-1,4-glycosidic linkages.
  • 965
  • 23 Sep 2020
Topic Review
Aging Stress Response
Aging induces several stress response pathways to counterbalance detrimental changes associated with this process. These pathways include nutrient signaling, proteostasis, mitochondrial quality control and DNA damage response. At the cellular level, these pathways are controlled by evolutionarily conserved signaling molecules, such as 5'AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), insulin/insulin-like growth factor 1 (IGF-1) and sirtuins, including SIRT1. Peroxisome proliferation-activated receptor coactivator 1 alpha (PGC-1α), encoded by the PPARGC1A gene, playing an important role in antioxidant defense and mitochondrial biogenesis, may interact with these molecules influencing lifespan and general fitness. Perturbation in the aging stress response may lead to aging-related disorders, including age-related macular degeneration (AMD), the main reason for vision loss in the elderly. This is supported by studies showing an important role of disturbances in mitochondrial metabolism, DDR and autophagy in AMD pathogenesis. In addition, disturbed expression of PGC-1α was shown to associate with AMD. Therefore, the aging stress response may be critical for AMD pathogenesis, and further studies are needed to precisely determine mechanisms underlying its role in AMD.
  • 965
  • 28 Sep 2021
Topic Review
Toll-Like receptors in glomeluronephritis
TLR receptors are a classic example of pattern recognition receptors (PRRs). Signals received by these receptors by recruiting specific molecules lead to activation of the transcription factors NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and IRF (interferon regulatory factor) and affect various elements of the host’s innate immune response . TLR mechanisms are based on the ability to recognize twofold signals. The first one is based on the detection of pathogen-associated molecular patterns (PAMPs), while the second reads molecules related to damage to the body’s own cells (DAMPs; danger-associated molecular patterns). One of the major challenges faced by modern nephrology is the identification of biomarkers associated with histopathological patterns or defined pathogenic mechanisms that may assist in the non-invasive diagnosis of kidney disease, particularly glomerulopathy. The identification of such molecules may allow prognostic subgroups to be established based on the type of disease, thereby predicting response to treatment or disease relapse. Advances in understanding the pathogenesis of diseases, such as membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, IgA (immunoglobulin A) nephropathy, and diabetic nephropathy, along with the progressive development and standardization of plasma and urine proteomics techniques, have facilitated the identification of an increasing number of molecules that may be useful for these purposes. 
  • 960
  • 23 Sep 2020
Topic Review
Small Molecule Deubiquitinase Enzymes Inhibitors
Ubiquitination is reversed by the activity of deubiquitinase enzymes (DUBs). About 100 human DUBs are known, and they are divided into seven major families: the cysteine proteases of the USP (ubiquitin-specific proteases), UCH (ubiquitin C-terminal hydrolases), OTU (ovarian tumor), MJD (Machado-Joseph domain-containing proteases), MINDY (motif interacting with the Ub-containing novel DUB family), and ZUFSP (zinc finger with the UFM1-specific peptidase domain protein) families and the Zn-dependent metalloproteases of the JAMM (JAB1/MPN/MOV34 domain-associated) family. DUBs play a role in seemingly every biological process and are central to many human pathologies, thus rendering them very desirable and challenging therapeutic targets. Despite significant drug discovery efforts, only approximately 15 chemical probe-quality small molecule inhibitors have been reported, hitting just 6 of about 100 known DUBs.
  • 960
  • 18 May 2022
Topic Review
Serum lipidomics in Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a highly debilitating chronic inflammatory autoimmune disease most prevalent in women. The true etiology of this disease is complex, multifactorial, and is yet to be completely elucidated. Changes in the lipid profile at a molecular level in RA are still poorly understood. Studies on the variation of lipid profile in RA using lipidomics showed that fatty acid and phospholipid profile, especially in phosphatidylcholine and phosphatidylethanolamine, are affected in this disease. These promising results could lead to the discovery of new diagnostic lipid biomarkers for early diagnosis of RA and targets for personalized medicine.
  • 958
  • 15 Jan 2021
Topic Review
Heme Oxgenase-1 in cytoprotection
Heme oxygenase catalyzes the rate-limiting step in heme degradation in order to generate biliverdin, carbon monoxide (CO), and iron. The inducible form of the enzyme, heme oxygenase-1 (HO-1), exerts a central role in cellular protection. The substrate, heme, is a potent pro-oxidant that can accelerate inflammatory injury and promote cell death. HO-1 has been implicated as a key mediator of inflammatory cell and tissue injury, as validated in preclinical models of acute lung injury and sepsis. A large body of work has also implicated HO-1 as a cytoprotective molecule against various forms of cell death, including necrosis, apoptosis and newly recognized regulated cell death (RCD) programs such as necroptosis, pyroptosis, and ferroptosis. While the antiapoptotic potential of HO-1 and its reaction product CO in apoptosis regulation has been extensively characterized, relatively fewer studies have explored the regulatory role of HO-1 in other forms of necrotic and inflammatory RCD (i.e., pyroptosis, necroptosis and ferroptosis). HO-1 may provide anti-inflammatory protection in necroptosis or pyroptosis. In contrast, in ferroptosis, HO-1 may play a pro-death role via enhancing iron release. HO-1 has also been implicated in co-regulation of autophagy, a cellular homeostatic program for catabolic recycling of proteins and organelles. While autophagy is primarily associated with cell survival, its occurrence can coincide with RCD programs. 
  • 958
  • 28 Apr 2021
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