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Topic Review
Neuroinflammation Receptors in Alzheimer’s Disease
Fibrillar aggregates and soluble oligomers of both Amyloid-β peptides (Aβs) and hyperphosphorylated Tau proteins (p-Tau-es), as well as a chronic neuroinflammation are the main drivers causing progressive neuronal losses and dementia in Alzheimer's disease (AD). However, the underlying pathogenetic mechanisms are still much disputed. Several endogenous neurotoxic ligands, including Aβs, and/or p-Tau-es activate innate immunity-related danger-sensing/pattern recognition receptors (PPRs) thereby advancing AD's neuroinflammation and progression. The major PRR families involved include scavenger, Toll-like, NOD-like, AIM2-like, RIG-like, and CLEC-2 receptors, plus the calcium-sensing receptor (CaSR). This quite intricate picture stresses the need to identify the pathogenetically topmost Aβ-activated PRR, whose signaling would trigger AD's three main drivers and their intra-brain spread. In theory, the candidate might belong to any PRR family. However, results of preclinical studies using in vitro nontumorigenic human cortical neurons and astrocytes and in vivo AD-model animals have started converging on the CaSR as the pathogenetically upmost PRR candidate. In fact, the CaSR binds both Ca2+ and Aβs and promotes the spread of both  Ca2+ dyshomeostasis and AD's three main drivers, causing a progressive neurons' death. Since CaSR's negative allosteric modulators block all these effects, CaSR's candidacy for topmost pathogenetic PRR has assumed a growing therapeutic potential worth clinical testing.
  • 1.3K
  • 10 Jan 2021
Topic Review
Mimicking the Mammalian Plasma Membrane
Cell membranes are very complex biological systems including a large variety of lipids and proteins. Therefore, they are difficult to extract and directly investigate with biophysical methods.
  • 1.3K
  • 02 Mar 2021
Topic Review
Glycosphingolipid Antigens and Human Diseases
Glycosphingolipids (GSLs) are composed of a mono-, di-, or oligosaccharide and a ceramide and function as constituents of cell membranes. Various molecular species of GSLs have been identified in mammalian cells due to differences in the structures of oligosaccharides. The oligosaccharide structure can vary depending on cell lineage, differentiation stage, and pathology; this property can be used as a cell identification marker. 
  • 1.3K
  • 18 Apr 2021
Topic Review
Immune Endocannabinoid System
Because of the immunoregulatory properties of cannabinoids, the endocannabinoid system (ECS) may have an important role in shaping the tumor microenvironment (TME). Members of the ECS, an entity that consists of cannabinoid receptors, endocannabinoids and their synthesizing/degrading enzymes, have been associated with both tumor growth and rejection. Immune cells express cannabinoid receptors and produce endocannabinoids, thereby forming an “immune endocannabinoid system”. Although in vitro effects of exogenous cannabinoids on immune cells are well described, the role of the ECS in the TME, and hence in tumor development and immunotherapy, is still elusive.
  • 1.3K
  • 15 Dec 2020
Topic Review
Nrf2 in Wound Healing Process
Wound healing involves a series of cellular events in damaged cells and tissues initiated with hemostasis and finally culminating with the formation of a fibrin clot. However, delay in the normal wound healing process during pathological conditions due to reactive oxygen species, inflammation and immune suppression at the wound site represents a medical challenge. So far, many therapeutic strategies have been developed to improve cellular homeostasis and chronic wounds in order to accelerate wound repair. In this context, the role of Nuclear factor erythroid 2-related factor 2 (Nrf2) during the wound healing process has been a stimulating research topic for therapeutic perspectives. Nrf2 is the main regulator of intracellular redox homeostasis. It increases cytoprotective gene expression and the antioxidant capacity of mammalian cells. It has been reported that some bioactive compounds attenuate cellular stress and thus accelerate cell proliferation, neovascularization and repair of damaged tissues by promoting Nrf2 activation.
  • 1.3K
  • 23 Jun 2021
Topic Review
Long Non-Coding RNA Epigenetics
Long noncoding RNAs exceeding a length of 200 nucleotides play an important role in ensuring cell functions and proper organism development by interacting with cellular compounds such as miRNA, mRNA, DNA and proteins. However, there is an additional level of lncRNA regulation, called lncRNA epigenetics, in gene expression control.
  • 1.3K
  • 25 Jun 2021
Topic Review
Genetic Effects on Plant Immunity
An immune system is a protective mechanism that shields plants from environmental stresses. This primary function is to maintain optimal circumstances for the growth and development of plant tissues while avoiding harm from biotic and abiotic stress factors. Plants subjected to various stressors initiate stress signaling cascades that affect multiple gene expressions and induce adaptation. These signaling pathways are coordinated by transcription factors, non-coding RNAs, RNA-binding proteins, and protein-protein interaction networks.
  • 1.3K
  • 22 Nov 2022
Topic Review
Thrombospondin-1 CD47 Signalling
Recent advances provide evidence that the cellular signalling pathway comprising the ligand-receptor duo of thrombospondin-1 (TSP1) and CD47 is involved in mediating a range of diseases affecting renal, vascular, and metabolic function, as well as cancer. In several instances, research has barely progressed past pre-clinical animal models of disease and early phase 1 clinical trials, while for cancers, anti-CD47 therapy has emerged from phase 2 clinical trials in humans as a crucial adjuvant therapeutic agent. This has important implications for interventions that seek to capitalize on targeting this pathway in diseases where TSP1 and/or CD47 play a role. Despite substantial progress made in our understanding of this pathway in malignant and cardiovascular disease, knowledge and translational gaps remain regarding the role of this pathway in kidney and metabolic diseases, limiting identification of putative drug targets and development of effective treatments. This review considers recent advances reported in the field of TSP1-CD47 signalling, focusing on several aspects including enzymatic production, receptor function, interacting partners, localization of signalling, matrix-cellular and cell-to-cell cross talk. The potential impact that these newly described mechanisms have on health, with a particular focus on renal and metabolic disease, is also discussed.
  • 1.3K
  • 02 Jul 2021
Topic Review
Approaches to Microsample Collections
Although the application of microsamples in metabolic phenotyping exists, it is still in its infancy, with whole blood being overwhelmingly the primary biofluid collected through the collection method of dried blood spots. 
  • 1.3K
  • 19 Jul 2022
Topic Review
The Neuroprotective Effect of Hydrogen Sulfide
Hydrogen sulfide (H2S) is a gaseous signaling molecule that performs various cellular functions in normal and pathological conditions. H2S has great neuroprotective potential. H2S reduces oxidative stress, lipid peroxidation, and neuroinflammation; inhibits processes associated with apoptosis, autophagy, ferroptosis and pyroptosis; prevents the destruction of the blood-brain barrier; increases the expression of neurotrophic factors; and models the activity of Ca2+ channels in neurotrauma. In addition, H2S activates neuroprotective signaling pathways in psychiatric and neurodegenerative diseases. However, high levels of H2S can cause cytotoxic effects. Thus, the development of H2S-associated neuroprotectors seems to be especially relevant.
  • 1.3K
  • 14 Jul 2023
Topic Review
Flavonoids in Cardiovascular Diseases
Flavonoids are metabolites of plants and fungus. Flavonoid research has been paid special attention to in recent times after the observation of their beneficial effects on the cardiovascular system. These favorable effects are exerted by flavonoids mainly due to their antioxidant properties, which result from the ability to decrease the oxidation of low-density lipoproteins, thus improving the lipid profiles. The other positive effect exerted on the cardiovascular system is the ability of flavonoids to produce vasodilation and regulate the apoptotic processes in the endothelium. Researchers suggested that these effects, including their anti-inflammatory function, are consequences of flavonoids’ potent antioxidant properties, but recent studies have shown multiple signaling pathways linked to them, thus suggesting that there are more mechanisms involved in the beneficial effect of the flavonoids on the human body. This review aims to present the latest data on the classification of these substances, their main mechanisms of action in the human body, and the beneficial effects on the physiological and pathological status of the cardiovascular system. 
  • 1.3K
  • 10 Oct 2020
Topic Review
Resveratrol in Human Male Fertility
Resveratrol (RSV) (3,4′,5 trihydroxystilbene) is a natural, non-flavonoid polyphenol widely present in the Mediterranean diet and, particularly, in grapes, peanuts, berries, and red wine.
  • 1.3K
  • 13 May 2021
Topic Review
Indicaxanthin Bioactivity in Health and Disease
Indicaxanthin is a dietary, highly bioavailable phytochemical from cactus pear fruit, with nutraceutical potential. Studies in healthy, transformed cells and whole organisms suggest health-promoting activities, particularly in counteracting inflammation and regulating mechanisms that control cell growth and longevity. In vitro evidence to date does not provide a unified picture of the molecular mechanisms mediating the action of Indicaxanthin; rather different mechanisms have emerged in relation to different stimuli and conditions in both healthy and transformed cells. Many of the activities appear to be geared toward restoring cellular redox homeostasis, correcting dysfunction generated by oxidative stress, and modulating signaling pathways that control vital processes in healthy cells; other activities, apparently independent of cellular redox balance, have also been observed.
  • 1.3K
  • 28 Dec 2022
Topic Review
Glaucoma Pathophysiology
Glaucoma is a progressive neurodegenerative disease that represents the major cause of irreversible blindness.
  • 1.2K
  • 31 May 2021
Topic Review
Filippi’s Glands and Silk Moths Cocoon Construction
Filippi’s glands (FGs), formerly also called Lyonet’s glands, are accessory secretory structures of the labial (silk) glands of lepidopteran caterpillars, which were implicated to play an important role in the maturation of the silk material and the construction of the cocoon.
  • 1.2K
  • 24 Dec 2021
Topic Review
Ceramide Transport Protein CERT and Its Inhibitors
Lipid transfer proteins (LTPs) are recognized as key players in the inter-organelle trafficking of lipids and are rapidly gaining attention as a novel molecular target for medicinal products. In mammalian cells, ceramide is newly synthesized in the endoplasmic reticulum (ER) and converted to sphingomyelin in the trans-Golgi regions. The ceramide transport protein CERT, a typical LTP, mediates the ER-to-Golgi transport of ceramide at an ER-distal Golgi membrane contact zone. A potent inhibitor of CERT, named (1R,3S)-HPA-12, was found by coincidence among ceramide analogs. Since then, various ceramide-resembling compounds have been found to act as CERT inhibitors. Nevertheless, the inevitable issue remains that natural ligand-mimetic compounds might directly bind both to the desired target and to various undesired targets that share the same natural ligand. To resolve this issue, a ceramide-unrelated compound named E16A, or (1S,2R)-HPCB-5, that potently inhibits the function of CERT has been developed, employing a series of in silico docking simulations, efficient chemical synthesis, quantitative affinity analysis, protein–ligand co-crystallography, and various in vivo assays. (1R,3S)-HPA-12 and E16A together provide a robust tool to discriminate on-target effects on CERT from off-target effects. 
  • 1.2K
  • 14 Mar 2022
Topic Review
Metabolic Reprogramming in Tumor Endothelial Cells
The dynamic crosstalk between the different components of the tumor microenvironment is critical to determine cancer progression, metastatic dissemination, tumor immunity, and therapeutic responses. Angiogenesis is critical for tumor growth, and abnormal blood vessels contribute to hypoxia and acidosis in the tumor microenvironment. In this hostile environment, cancer and stromal cells have the ability to alter their metabolism in order to support the high energetic demands and favor rapid tumor proliferation. 
  • 1.2K
  • 12 Oct 2022
Topic Review
Role of Hexokinases in Metabolic Reprogramming
The role of hexokinases in metabolic reprogramming in cancer is multifaceted and pivotal for the altered metabolic phenotype observed in cancer cells. Hexokinases, a group of enzymes responsible for catalyzing the first step of glycolysis, play a critical role in regulating glucose metabolism in cancer cells. In cancer, hexokinases are upregulated and exhibit distinct isoform preferences. Hexokinases facilitate the Warburg effect, a hallmark metabolic alteration in cancer cells characterized by increased glycolysis and decreased oxidative phosphorylation by promoting high glucose consumption and ATP production. Furthermore, hexokinases also participate in other metabolic pathways, such as the pentose phosphate pathway and mitochondrial metabolism, contributing to the rewiring of cancer cell metabolism. The overexpression of hexokinases in cancer cells supports the high bioenergetic and biosynthetic demands of rapidly proliferating cells and confers survival advantages by modulating cellular redox status and apoptosis. The dysregulation of hexokinases in cancer cells presents a promising target for cancer therapy. Understanding their role in metabolic reprogramming provides crucial insights into cancer metabolism and potential therapeutic strategies.
  • 1.2K
  • 14 Apr 2023
Topic Review
Agaricales Mushroom Lignin Peroxidase
Lignin biodegradation has been extensively studied in white-rot fungi, which largely belong to order Polyporales. Among the enzymes that wood-rotting polypores secrete, lignin peroxidases (LiPs) have been labeled as the most efficient. A recent thorough study of 52 Agaricomycetes genomes has revealed the high presence of putative ligninolytic peroxidases in fungi belonging to the order Agaricales. These include the first LiP outside the order Polyporales, identified in the genome of the mushroom Agrocybe pediades (ApeLiP) as a case of parallel and convergent evolution of LiPs between Agaricales and Polyporales.
  • 1.2K
  • 17 Sep 2021
Topic Review
Caseinolytic Protease Protease Families
Bacterial proteases participate in the proteolytic elimination of misfolded or aggregated proteins, carried out by members of the AAA+ protein superfamily such as Hsp100/Clp (heat shock protein-100/caseinolytic protease), Lon, and FtsH. It is estimated that the Clp and Lon families perform around 80% of cellular proteolysis in bacteria. The HSP100/Clp family of ATPases plays crucial roles in the folding, assembly, and degradation of proteins during normal growth and, mainly, under stress-inducing conditions. This family is formed by several ATPase chaperones and the peptidase ClpP (caseinolytic protease proteolytic subunit).
  • 1.2K
  • 18 Jan 2023
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