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Topic Review
Factor V Leiden
Factor V Leiden (rs6025 or F5 p.R506Q) is a variant (mutated form) of human factor V (one of several substances that helps blood clot), which causes an increase in blood clotting (hypercoagulability). Due to this mutation, protein C, an anticoagulant protein that normally inhibits the pro-clotting activity of factor V, is not able to bind normally to factor V, leading to a hypercoagulable state, i.e., an increased tendency for the patient to form abnormal and potentially harmful blood clots. Factor V Leiden is the most common hereditary hypercoagulability (prone to clotting) disorder amongst ethnic Europeans. It is named after the Dutch city of Leiden, where it was first identified in 1994 by Rogier Maria Bertina under the direction of (and in the laboratory of) Pieter Hendrick Reitsma. Despite the increased risk of venous thromboembolisms, people with one copy of this gene have not been found to have shorter lives than the general population.
  • 1.8K
  • 07 Nov 2022
Topic Review
Hyperinsulinaemia-Osteofragilitas
Bone fragility leading to increased risk of low energy (fragility) fractures that is independent of bone mineral density, occurring in individuals with detected and undetected hyperinsulinaemia. Patients with type 2 diabetes mellitus (T2DM) and/or cardiovascular disease (CVD), conditions of hyperinsulinaemia, have lower levels of osteocalcin and bone remodelling, and increased rates of fragility fractures. Unlike osteoporosis with lower bone mineral density (BMD), T2DM bone fragility “hyperinsulinaemia-osteofragilitas” phenotype presents with normal to increased BMD. Hyperinsulinaemia and insulin resistance positively associate with increased BMD and fragility fractures.  Hyperinsulinaemia enforces glucose fuelling, which decreases NAD+-dependent antioxidant activity. This increases reactive oxygen species and mitochondrial fission, and decreases oxidative phosphorylation high-energy production capacity, required for osteoblasto/cytogenesis. Osteocytes directly mineralise and resorb bone, and inhibit mineralisation of their lacunocanalicular space via pyrophosphate. Hyperinsulinaemia decreases vitamin D availability via adipocyte sequestration, reducing dendrite connectivity, and compromising osteocyte viability. Decreased bone remodelling and micropetrosis ensues. Trapped/entombed magnesium within micropetrosis fossilisation spaces propagates magnesium deficiency (MgD), potentiating hyperinsulinaemia and decreases vitamin D transport. Vitamin D deficiency reduces osteocalcin synthesis and favours osteocyte apoptosis.  Carbohydrate restriction/fasting/ketosis increases beta-oxidation, ketolysis, NAD+-dependent antioxidant activity, osteocyte viability and osteocalcin, and decreases excess insulin exposure. Osteocalcin is required for hydroxyapatite alignment, conferring bone structural integrity, decreasing fracture risk and improving metabolic/endocrine homeodynamics. Patients presenting with fracture and normal BMD should be investigated for T2DM and hyperinsulinaemia.
  • 1.8K
  • 09 Oct 2021
Topic Review
Transport through the Blood–Brain Barrier
The blood–brain barrier (BBB) is a complex structure present in mammalian organisms and is responsible for maintaining the parameters of the internal environment of the central nervous system (CNS).
  • 1.8K
  • 12 May 2023
Topic Review
Extracellular Vesicles Mediated Regulation
Small noncoding RNAs (sRNA) appear to play a key role in extracellular vesicle (EV)-mediated information transfer. Within the vesicular envelope, RNAs are well protected from degradation and can be shuttled between individuals from one and the same species and beyond. Various communication routes have been discovered such as mother-infant-interaction via breast milk, diverse host-pathogen-relations, and dietary uptake of food derived EVs, proving that EV-mediated inter-kingdom regulation is more than a random event.
  • 1.8K
  • 23 Oct 2020
Topic Review
Isolation and Purification of EVs
Extracellular vesicles are sacs that are secreted by almost all types of cells and are responsible for intracellular communication. They inherit their content and characteristics from their donor cells. Pathological and physiological characteristics of donor cells are reflected in the appearance of specific nucleotide and proteins (on the EV surface or in their content).
  • 1.8K
  • 11 Jan 2022
Topic Review
Appendage Regeneration in Vertebrates
Appendage regeneration in vertebrates means the ability to regenerate amputated or injured tissues and organs, which is a fascinating property shared by several invertebrates and, interestingly, some vertebrates.
  • 1.8K
  • 01 Jun 2021
Topic Review
Structure, Expression Regulation, and Subcellular Localization of USP16
Ubiquitin-specific peptidase 16 (USP16) is a deubiquitinase that plays a role in the regulation of gene expression, cell cycle progression, and various other functions. It was originally identified as the major deubiquitinase for histone H2A and has since been found to deubiquitinate a range of other substrates, including proteins from both the cytoplasm and nucleus. USP16 is phosphorylated when cells enter mitosis and dephosphorylated during the metaphase/anaphase transition. While much of USP16 is localized in the cytoplasm, separating the enzyme from its substrates is considered an important regulatory mechanism. Some of the functions that USP16 has been linked to include DNA damage repair, immune disease, tumorigenesis, protein synthesis, coronary artery health, and male infertility. The strong connection to immune response and the fact that multiple oncogene products are substrates of USP16 suggests that USP16 may be a potential therapeutic target for the treatment of certain human diseases.
  • 1.8K
  • 06 Apr 2023
Topic Review
Breast cancer cell growth/motility is influenced by metal compounds
Triple-negative breast cancer (TNBC) is a  highly "aggressive" malignant neoplasm with limited treatment options due to the lack of expression of estrogen and progesterone receptors and HER2/neu. In search of novel molecules displaying anti-TNBC activities, the TNBC cell line MDA-MB231 was exposed to cadmium chloride and/or manganese chloride, and a biological characterization of the effect observed was performed. The data obtained demonstrate a cytotoxic effect exerted by cadmium chloride with drastic changes affecting gene expressions and production of reactive oxygen species. Conversely, manganese chloride was effective in increasing cell number and promoting cell invasive ability.  Such effect was reverted by coexposure with cadmium chloride. Thus, metal compounds appear to be able to modulate the biological behavior of TNBC cells, although addressing them to different fates. The data obtained suggest that high environmental pollution with manganese chloride might increase the risk of breast tumorigenesis. On the other hand, the restraining modulatory property of cadmium chloride looks promising and deserves a more detailed mechanistic study aimed to the identification of possible molecular targets instrumental in inhibiting the expansion of malignant breast cancer.
  • 1.8K
  • 30 Oct 2020
Topic Review
Organoids and Aging
The biology of aging is focused on the identification of novel pathways that regulate the underlying processes of aging to develop interventions aimed at delaying the onset and progression of chronic diseases to extend lifespan. However, the research on the aging field has been conducted mainly in animal models, yeast, Caenorhabditis elegans, and cell cultures. Thus, it is unclear to what extent this knowledge is transferable to humans since they might not reflect the complexity of aging in people. An organoid culture is an in vitro 3D cell-culture technology that reproduces the physiological and cellular composition of the tissues and/or organs. This technology is being used in the cancer field to predict the response of a patient-derived tumor to a certain drug or treatment serving as patient stratification and drug-guidance approaches. Modeling aging with patient-derived organoids has a tremendous potential as a preclinical model tool to discover new biomarkers of aging, to predict adverse outcomes during aging, and to design personalized approaches for the prevention and treatment of aging-related diseases and geriatric syndromes. This could represent a novel approach to study chronological and/or biological aging, paving the way to personalized interventions targeting the biology of aging.
  • 1.8K
  • 19 Oct 2021
Topic Review
The Extracellular Matrix in Cancer
As the core component of all organs, the extracellular matrix (ECM) is an interlocking macromolecular meshwork of proteins, glycoproteins, and proteoglycans that provides mechanical support to cells and tissues. In cancer, the ECM can be remodelled in response to environmental cues, and it controls a plethora of cellular functions, including metabolism, cell polarity, migration, and proliferation, to sustain and support oncogenesis. The biophysical and biochemical properties of the ECM, such as its structural arrangement and being a reservoir for bioactive molecules, control several intra- and intercellular signalling pathways and induce cytoskeletal changes that alter cell shapes, behaviour, and viability.
  • 1.8K
  • 18 Apr 2023
Topic Review Video
Blood-Spinal Cord Barrier
The blood-spinal cord barrier (BSCB) has been long thought of as a functional equivalent to the blood-brain barrier (BBB), restricting blood flow into the spinal cord. The spinal cord is supported by various disc tissues that provide agility and has different local immune responses compared to the brain. Though physiologically, structural components of the BSCB and BBB share many similarities, the clinical landscape significantly differs. 
  • 1.8K
  • 14 Jan 2022
Topic Review
Cardiac Connexins
Connexins are a family of transmembrane proteins that play a key role in cardiac physiology. Gap junctional channels put into contact the cytoplasms of connected cardiomyocytes, allowing the existence of electrical coupling. However, in addition to this fundamental role, connexins are also involved in cardiomyocyte death and survival. Thus, chemical coupling through gap junctions plays a key role in the spreading of injury between connected cells. Moreover, in addition to their involvement in cell-to-cell communication, mounting evidence indicates that connexins have additional gap junction-independent functions. Opening of unopposed hemichannels, located at the lateral surface of cardiomyocytes, may compromise cell homeostasis and may be involved in ischemia/reperfusion injury. In addition, connexins located at non-canonical cell structures, including mitochondria and the nucleus, have been demonstrated to be involved in cardioprotection and in regulation of cell growth and differentiation.
  • 1.8K
  • 13 May 2021
Topic Review
Aurora Kinase B in Cancer
Aurora kinase B (AURKB) is a mitotic serine/threonine protein kinase that belongs to the aurora kinase family along with aurora kinase A (AURKA) and aurora kinase C (AURKC). AURKB is a member of the chromosomal passenger protein complex and plays a role in cell cycle progression.
  • 1.8K
  • 23 Jun 2021
Topic Review
Gain of Function Mutant p53 in Cancer
The tumor suppressor p53, encoded by the TP53 gene and known as “the guardian of the genome”, performs a variety of functions in cancer prevention.
  • 1.8K
  • 17 Nov 2022
Topic Review
ClpP
The mitochondrial protease called ClpP plays a central role in mitochondrial protein quality control. ClpP agonists have emerged as a novel class of mitochondria-targeting drugs. Hyperactivating ClpP induces uncontrolled, but selective, degradation of ClpP substrates and disrupts mitochondrial functions, leading to growth inhibition of breast cancer cells, without adverse effect in non-malignant cells. 
  • 1.8K
  • 03 Apr 2023
Topic Review
Selenoproteins
Selenium is a vital trace element present as selenocysteine (Sec) in proteins that are, thus, known as selenoproteins. Humans have 25 selenoproteins, most of which are functionally characterized as oxidoreductases, where the Sec residue plays a catalytic role in redox regulation and antioxidant activity. Glutathione peroxidase plays a pivotal role in scavenging and inactivating hydrogen and lipid peroxides, whereas thioredoxin reductase reduces oxidized thioredoxins as well as non-disulfide substrates, such as lipid hydroperoxides and hydrogen peroxide. Selenoprotein R protects the cell against oxidative damage by reducing methionine-R-sulfoxide back to methionine. Selenoprotein O regulates redox homeostasis with catalytic activity of protein AMPylation. Moreover, endoplasmic reticulum (ER) membrane selenoproteins (SelI, K, N, S, and Sel15) are involved in ER membrane stress regulation. Selenoproteins containing the CXXU motif (SelH, M, T, V, and W) are putative oxidoreductases that participate in various cellular processes depending on redox regulation.
  • 1.8K
  • 03 Jun 2021
Topic Review
Molecular Mechanism of Autophagy
Autophagy (self-eating) is a multifaceted and evolutionarily preserved sequence of actions that is activated in response to dysfunctional organelles and aggregated protein to sustain cellular homeostasis.
  • 1.8K
  • 02 Mar 2021
Topic Review
IL-7 and IL-7R in Cancer
Interleukin-7 (IL-7) is a multipotent cytokine that maintains the homeostasis of the immune system. IL-7 plays a vital role in T-cell development, proliferation, and differentiation, as well as in B cell maturation through the activation of the IL-7 receptor (IL-7R). IL-7 is closely associated with tumor development and has been used in cancer clinical research and therapy.
  • 1.8K
  • 21 Sep 2022
Topic Review
CCL2
Factors secreted from adipose tissue may induce and/or maintain a local and systemic low-grade activation of the innate immune system. Attraction of macrophages into adipose tissue and altered crosstalk between macrophages, adipocytes, and other cells of adipose tissue are symptoms of metabolic inflammation. Among several secreted factors attracting immune cells to adipose tissue, chemotactic C-C motif chemokine ligand 2 (CCL2) (also described as monocyte chemoattractant protein-1 (MCP-1)) has been shown to play a crucial role in adipose tissue macrophage infiltration. 
  • 1.8K
  • 28 Sep 2021
Topic Review
WNT Signaling
The WNT signaling pathway is an evolutionarily conserved signal transduction pathway that regulates a wide range of cellular functions during development and adulthood. It controls multiple aspects of development, including cell proliferation, cell fate determination, apoptosis, cell migration and cell polarity during development and stem cell maintenance in adults. Inappropriate activation of the WNT pathway is also a major factor in human oncogenesis.
  • 1.8K
  • 11 Mar 2022
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