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Topic Review
Molecular and Functional Properties of Acid-Sensing Ion Channels
Acid-sensing ion channels (ASICs) are voltage-independent H+-gated cation channels largely expressed in the nervous system of rodents and humans, and involved in pain sensing and associated pathologies. At least six isoforms (ASIC1a, 1b, 2a, 2b, 3 and 4) associate into homotrimers or heterotrimers to form functional channels with highly pH-dependent gating properties.
  • 1.7K
  • 25 Oct 2022
Topic Review
Vitamin D, Oxidative-Stress and Aging
Recent advances in vitamin D research indicate that this vitamin, a secosteroid hormone, has beneficial effects on several body systems other than the musculoskeletal system. Both 25 dihydroxy vitamin D [25(OH)2D] and its active hormonal form, 1,25-dihydroxyvitamin D [1,25(OH)2D] are essential for human physiological functions, including damping down inflammation and the excessive intracellular oxidative stresses. Vitamin D is one of the key controllers of systemic inflammation, oxidative stress and mitochondrial respiratory function, and thus, the aging process in humans. In turn, molecular and cellular actions form 1,25(OH)2D slow down oxidative stress, cell and tissue damage, and the aging process. On the other hand, hypovitaminosis D impairs mitochondrial functions, and enhances oxidative stress and systemic inflammation. The interaction of 1,25(OH)2D with its intracellular receptors modulates vitamin D–dependent gene transcription and activation of vitamin D-responsive elements, which triggers multiple second messenger systems. Thus, it is not surprising that hypovitaminosis D increases the incidence and severity of several age-related common diseases, such as metabolic disorders that are linked to oxidative stress. These include obesity, insulin resistance, type 2 diabetes, hypertension, pregnancy complications, memory disorders, osteoporosis, autoimmune diseases, certain cancers, and systemic inflammatory diseases. Vitamin D adequacy leads to less oxidative stress and improves mitochondrial and endocrine functions, reducing the risks of disorders, such as autoimmunity, infections, metabolic derangements, and impairment of DNA repair; all of this aids a healthy, graceful aging process. Vitamin D is also a potent anti-oxidant that facilitates balanced mitochondrial activities, preventing oxidative stress-related protein oxidation, lipid peroxidation, and DNA damage. New understandings of vitamin D-related advances in metabolomics, transcriptomics, epigenetics, in relation to its ability to control oxidative stress in conjunction with micronutrients, vitamins, and antioxidants, following normalization of serum 25(OH)D and tissue 1,25(OH)2D concentrations, likely to promise cost-effective better clinical outcomes in humans. 
  • 1.7K
  • 29 Oct 2020
Topic Review
Effects of Creatine Supplementation on Brain Function
Creatine, a nitrogenous organic compound derived from reactions involving the amino acids arginine, glycine, and methionine, is important for resynthesizing ATP, particularly during times of increased metabolic demand (e.g., sleep deprivation, mental health conditions, or neurological diseases). Creatine supplementation (and guanidinoacetic acid; GAA) has the ability to increase brain creatine content in humans. Furthermore, creatine has shown some promise for attenuating symptoms of concussion, mild traumatic brain injury and depression but its effect on neurodegenerative diseases appears to be lacking. 
  • 1.6K
  • 09 Jun 2022
Topic Review
Cadmium and Lead Exposure
This entry provides information relevant to public health policy regarding advisable exposure limits for cadmium (Cd) and lead (Pb) that have no biologic role in humans. All of their perceptible effects are toxic. These metals exist in virtually all foodstuffs. Foods which are frequently consumed in large quantities such as cereals, rice, potatoes and vegetables contribute the most to total intake of these metals. Because Cd and Pb exposure are highly prevalent, even a small increase in disease risk can result in a large number of people affected by a disease that is preventable. Public measures to minimize environmental pollution and the food-chain transfer of Cd and Pb are required to prevent Cd- and Pb- related ailments and mortality as are risk reduction measures that set a maximally permissible concentration of Cd and Pb in staple food to the lowest achievable levels.
  • 1.5K
  • 29 Oct 2020
Topic Review
Calcium Phosphate Nanocluster Complexes
Calcium phosphate nanocluster complexes comprise a core of amorphous calcium phosphate and a sequestering shell of intrinsically disordered phosphopeptides or phosphoproteins. Solutions containing the nanocluster complexes can be thermodynamically stable or metastable due to a tendency to form a precipitate enriched in calcium phosphate. Theoretical and biophysical studies with native and recombinant phosphopeptides have shown how the radius of the core and the stability of the solution depend on the concentration of the sequestering peptide, its affinity for the calcium phosphate and its concentration in relation to the concentration of the calcium phosphate. The thickness of the sequestering shell depends on the conformation of the peptide on the core surface. A sequestering peptide is a flexible sequence including one or more short linear motifs, each of which usually contains several phosphorylated and other acidic residues.  These are the main binding sites to the core so that a peptide with several binding motifs can forms loops and trains on the core surface. Calcium phosphate nanocluster complexes were first identified as substructures of casein micelles in milk and have been prepared as individual particles from peptides derived from caseins and osteopontin. Stable biofluids containing nanocluster complexes cannot cause soft tissues to become mineralized whereas stable or metastable biofluids containing nanocluster complexes can help to mineralize hard tissues.
  • 1.4K
  • 09 Nov 2020
Topic Review
B-Cell Lymphoma-Extra-Large
B-Cell Lymphoma-extra-large (BCL-xL) is involved in longevity and successful aging,which indicates a role for BCL-xL in cell survival pathway regulation. Beyond its well described role as an inhibitor of apoptosis by preventing cytochrome c release, BCL-xL has also been related, indirectly, to autophagy and senescence pathways. Although in these latter cases, BCL-xL has dual roles, either activating or inhibiting, depending on the cell type and the specific conditions. Taken together, all these findings suggest a precise mechanism of action for BCL-xL, able to regulate the crosstalk between apoptosis, autophagy, and senescence, thus promoting cell survival or cell death. All three pathways can be both beneficial or detrimental depending on the circumstances. Thus, targeting BCL-xL would in turn be a “double-edge sword” and therefore, additional studies are needed to better comprehend this dual and apparently contradictory role of BCL-XL in longevity.
  • 1.2K
  • 31 Jul 2020
Topic Review
EMT Program in Breast cancer
Notch signaling is a primitive signaling pathway having various roles in the normal origin and development of each multicellular organisms. Therefore, any aberration in the pathway will inevitably lead to deadly outcomes such as cancer. It has now been more than two decades since Notch was acknowledged as an oncogene in mouse mammary tumor virus-infected mice. Since that discovery, activated Notch signaling and consequent up-regulation of tumor-promoting Notch target genes have been observed in human breast cancer. Moreover, consistent over-expression of Notch ligands and receptors has been shown to correlate with poor prognosis in human breast cancer. Notch regulates a number of key processes during breast carcinogenesis, of which, one key phenomenon is epithelial–mesenchymal transition (EMT). EMT is a key process for large-scale cell movement during morphogenesis at the time of embryonic development. Cancer cells aided by transcription factors usurp this developmental program to execute the multi-step process of tumorigenesis and metastasis. In this review, we recapitulate recent progress in breast cancer research that has provided new perceptions into the molecular mechanisms behind Notch-mediated EMT regulation during breast tumorigenesis.
  • 1.2K
  • 29 Oct 2020
Topic Review
Characteristics of Vitamin E
Vitamin E is a fat-soluble organic micronutrient that helps to preserve human health. Its main function is likely that of a radical scavenger protecting biological membranes from lipid peroxidation. Vegetable oils, such as wheat germ, sunflower, corn germ, soybean, and rapeseed, are the primary dietary source of vitamin E for humans. It is also found in some nuts, fruits, and vegetables, such as almonds, avocados, spinach, and kale.
  • 1.2K
  • 16 Sep 2022
Topic Review
TRPV1
Intracellular calcium (Ca2+) concentration ([Ca2+]i) is a key determinant of cell fate and is implicated in carcinogenesis. Membrane ion channels are structures through which ions enter or exit the cell, depending on the driving forces. The opening of transient receptor potential vanilloid 1 (TRPV1) ligand-gated ion channels facilitates transmembrane Ca2+ and Na+ entry, which modifies the delicate balance between apoptotic and proliferative signaling pathways. Proliferation is upregulated through two mechanisms: (1) ATP binding to the G-protein-coupled receptor P2Y2, commencing a kinase signaling cascade that activates the serine-threonine kinase Akt, and (2) the transactivation of the epidermal growth factor receptor (EGFR), leading to a series of protein signals that activate the extracellular signal-regulated kinases (ERK) 1/2. The TRPV1-apoptosis pathway involves Ca2+ influx and efflux between the cytosol, mitochondria, and endoplasmic reticulum (ER), the release of apoptosis-inducing factor (AIF) and cytochrome c from the mitochondria, caspase activation, and DNA fragmentation and condensation. While proliferative mechanisms are typically upregulated in cancerous tissues, shifting the balance to favor apoptosis could support anti-cancer therapies. TRPV1, through [Ca2+]i signaling, influences cancer cell fate; therefore, the modulation of the TRPV1-enforced proliferation–apoptosis balance is a promising avenue in developing anti-cancer therapies and overcoming cancer drug resistance. 
  • 1.1K
  • 09 Nov 2020
Topic Review
Milk Exosomes
Milk contains various extracellular vesicles and non-vesicular structures: exosomes (with diameter 40-100 nm), vesicles of other size, fat globules (with diameter 4-6 mkm, containing milk fat globule membranes), and their aggregates. Due to the biocompatibility of milk exosomes, these vesicles have a wide potential as vehicles for oral delivery of therapeutically relevant molecules (drugs and therapeutic nucleic acids).
  • 1.1K
  • 21 Sep 2020
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