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Topic Review
Lynch-like Syndrome
Lynch-like syndrome (LLS) is defined as colorectal cancer cases with microsatellite instability (MSI) and loss of expression of MLH1, MSH2, MSH6, or PMS2 by immunohistochemistry (IHC) in the absence of a germline mutation in these genes that cannot be explained by BRAF mutation or MLH1 hypermethylation.
  • 724
  • 11 Mar 2022
Topic Review
Vitamin B12 Biochemistry and (Patho)-Physiology
Vitamin B12 (B12) is an essential cofactor for two enzymes in human metabolism: methylmalonyl-CoA mutase (catalyzing the conversion of methylmalonyl-CoA to succinyl-CoA), and methionine synthase (catalyzing the synthesis of methionine from homocysteine). While an inherited defect of methylmalonyl-CoA mutase causes methylmalonic aciduria, severe acquired B12 deficiency, mostly due to reduced uptake of B12, causes classical pernicious anemia. It may also cause neurological symptoms, most commonly sensory, but also motoric or painful neuropathy, symptoms that are also common in DPN.
  • 725
  • 07 Jun 2023
Topic Review
IDA in Celiac Disease
The iron absorption process develops mainly in the proximal duodenum. This portion of the intestine is typically destroyed in celiac disease (CD), resulting in a reduction in absorption of iron and subsequent iron deficiency anemia (IDA). In fact, the most frequent extra-intestinal manifestation (EIM) of CD is IDA, with a prevalence between 12 and 82% (in relation with the various reports) in patients with new CD diagnosis. The primary treatment of CD is the gluten-free diet (GFD), which is associated with adequate management of IDA, if present. Iron replacement treatment historically has been based on oral products containing ferrous sulphate (FS). However, the absorption of FS is limited in patients with active CD and unpredictable in patients on a GFD. Furthermore, a poor tolerability of this kind of ferrous is particularly frequent in patients with CD or with other inflammatory bowel diseases. Normalization from anemic state typically occurs after at least 6 months of GFD, but the process can take up to 2 years for iron stores to replenish.
  • 724
  • 03 Jun 2021
Topic Review
Role of NADPH Oxidases in Pathologies
Nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidases, NOX), were discovered in immune cells, such as neutrophils and macrophages, in the 1970s. Upon phagocytosis of pathogens, the enzymatic complex is activated and triggers O2− production in an “oxidative burst” that acts to kill pathogens. Over time, enzymes with a similar function located in various tissues have been identified and subsequently grouped into the NOX family of enzymes. The mitochondrial electron transport chain was soon demonstrated as another source of O2− due to a “leaky” electron transport system, its O2− scavenged by superoxide dismutase (SOD) into H2O2.
  • 724
  • 29 Jun 2022
Topic Review
Thiamine in Hypoxic-Ischemic Encephalopathy
Because therapeutic hypothermia and thiamine may both act on the latent period of HIE damage, a synergistic effect of these therapeutic strategies is likely. Thiamine treatment may be especially important in mild hypoxic-ischemic encephalopathy (HIE) and in areas of the world where there is limited access to expensive hypothermia equipment.
  • 724
  • 31 Dec 2021
Topic Review
TKS4 and TKS5 Scaffold Proteins
Scaffold proteins are typically thought of as multi-domain “bridging molecules.” They serve as crucial regulators of key signaling events by simultaneously binding multiple participants involved in specific signaling pathways. In the case of epidermal growth factor (EGF)-epidermal growth factor receptor (EGFR) binding, the activated EGFR contacts cytosolic SRC tyrosine-kinase, which then becomes activated. This process leads to the phosphorylation of SRC-substrates, including the tyrosine kinase substrates (TKS) scaffold proteins. The TKS proteins serve as a platform for the recruitment of key players in EGFR signal transduction, promoting cell spreading and migration. The TKS4 and the TKS5 scaffold proteins are tyrosine kinase substrates with four or five SH3 domains, respectively. Their structural features allow them to recruit and bind a variety of signaling proteins and to anchor them to the cytoplasmic surface of the cell membrane. TKS4 and TKS5 had been recognized for their involvement in cellular motility, reactive oxygen species-dependent processes, and embryonic development. Furthermore, TKS4 has also been implicated in the regulation of homeostasis of mature adipose and bone tissue.
  • 723
  • 19 Jan 2021
Topic Review
The Health Effects Effects of Colorful Bioactive Pigments
Inadequate intake of fruits and vegetables (FV) is a leading modifiable dietary risk factor for mortality and contributes to the increasing burden of both communicable and non-communicable diseases. Despite the unequivocal health benefits of eating FV, 78% of adults worldwide do not consume the daily recommended servings, leading to a ‘phytonutrient gap’. Naturally occurring and pigmented phytonutrients (herein referred to as bioactive pigments) give FV their vibrant colors and correspond to one or more phytonutrient categories; e.g., red corresponds to lycopene, yellow to alpha-carotene, orange to beta-carotene, green to chlorophyll, purple and blue to anthocyanins, and white to flavones.
  • 723
  • 19 Jul 2022
Topic Review
Antivirals on the Cardiovascular Conditions
The COVID-19 pandemic has resulted in a complex clinical challenge, caused by a novel coronavirus, partially similar to previously known coronaviruses but with a different pattern of contagiousness, complications, and mortality. Safety profiles of antivirals are largely questioned and addressed by health agencies, in consideration of COVID-19 cardiac and pro-thrombotic complications generally experienced by predisposed subjects.
  • 723
  • 25 Feb 2022
Topic Review
Lactoferrin in Ocular Diseases
Besides the well-known antibacterial effect of lactoferrin, novel interest has been rising towards its potential application in the field of dry eye and viral infections. A growing body of evidence supports the antimicrobial efficacy of lactoferrin, which is not limited to its iron-chelating properties but also depends on its capability to directly interact with pathogen particles while playing immunomodulatory effects. Nowadays, lactoferrin antiviral activity is of special interest, since lactoferrin-based eye drops could be adopted to treat/prevent the new severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, which has conjunctivitis among its possible clinical manifestations. In the future, further data from randomized controlled studies are desirable to confirm the efficacy of lactoferrin in the wide range of ocular conditions where it can be used.
  • 723
  • 14 Oct 2020
Topic Review
Timeline of Tuberculosis
This is a timeline of tuberculosis, describing especially major discoveries, advances in treatment and major organizations.
  • 723
  • 23 Nov 2022
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