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Topic Review
Amyloidosis
Amyloidosis is a term referring to a group of various protein-misfolding diseases wherein normally soluble proteins form aggregates as insoluble amyloid fibrils. How, or whether, amyloid fibrils contribute to tissue damage in amyloidosis has been the topic of debate. In vitro studies have demonstrated the appearance of small globular oligomeric species during the incubation of amyloid beta peptide (Aβ).
  • 1.1K
  • 30 Aug 2021
Topic Review Video
Crosstalk between Apoptosis and Autophagy
Research in biomedical sciences has changed dramatically over the past fifty years. There is no doubt that the discovery of apoptosis and autophagy as two highly synchronized and regulated mechanisms in cellular homeostasis are among the most important discoveries in these decades. Along with the advancement in molecular biology, identifying the genetic players in apoptosis and autophagy has shed light on our understanding of their function in physiological and pathological conditions. Apoptosis and autophagy play essential roles in human health, and their malfunction leads to many diseases, including cancer, neurodegenerative disease, and autoimmune disorders. These mechanisms are highly regulated, and there is complex crosstalk between them.
  • 1.1K
  • 29 Mar 2022
Topic Review
Efferocytosis and Biological Barriers
Similar to previous pandemics, COVID-19 has been succeeded by well-documented post-infectious sequelae, including chronic fatigue, cough, shortness of breath, myalgia, and concentration difficulties. Dysfunctional efferocytosis has been associated with biological barrier disruption, inflammatory bowel disease (IBD), and a constellation of symptoms reminiscent of long COVID and other fatiguing illnesses.
  • 1.1K
  • 15 Nov 2022
Topic Review
Yeast Cell Polarity
A bottom-up route towards predicting evolution relies on a deep understanding of the complex network that proteins form inside cells. In a rapidly expanding panorama of experimental possibilities, the most difficult question is how to conceptually approach the disentangling of such complex networks. These can exhibit varying degrees of hierarchy and modularity, which obfuscate protein functions that may prove pivotal for adaptation. Using the well-established polarity network in budding yeast as a case study, we organize current literature to highlight protein entrenchments inside polarity in five sub modules: timing, mating, bud-scar, reaction-diffusion and the actin pathway. 
  • 1.1K
  • 07 Dec 2020
Topic Review
Bromodomain Proteins in Cancer
This review provides an in depth analysis of the role of bromodomain-containing proteins in cancer development. As readers of acetylated lysine on nucleosomal histones, bromodomain proteins are poised to activate gene expression, and often promote cancer progression. We examined changes in gene expression patterns that are observed in bromodomain-containing proteins and associated with specific cancer types. We also mapped the protein–protein interaction network for the human bromodomain-containing proteins, discuss the cellular roles of these epigenetic regulators as part of nine different functional groups, and identify bromodomain-specific mechanisms in cancer development. Lastly, we summarize emerging strategies to target bromodomain proteins in cancer therapy, including those that may be essential for overcoming resistance. Overall, this review provides a timely discussion of the different mechanisms of bromodomain-containing proteins in cancer, and an updated assessment of their utility as a therapeutic target for a variety of cancer subtypes.
  • 1.1K
  • 07 Aug 2021
Topic Review
Basic Principles and Mechanisms of Photodynamic Therapy
Photodynamic therapy (PDT) is a therapeutic modality which uses visible light wavelengths, mainly in the red and near-infrared (NIR) regions, for the activation of photosensitizing molecules (PSs). The widespread diffusion of photodynamic therapy (PDT) as a clinical treatment for solid tumors is mainly limited by the patient’s adverse reaction (skin photosensitivity), insufficient light penetration in deeply seated neoplastic lesions, unfavorable photosensitizers (PSs) biodistribution, and photokilling efficiency due to PS aggregation in biological environments.
  • 1.1K
  • 21 Sep 2022
Topic Review
Two Faces of Vitamin C: AA vs. DHA
Historically, vitamin C has been associated with many regulatory processes that involve specific signaling pathways. Among the most studied signaling pathways are those involved in the regulation of aging, differentiation, neurotransmission, proliferation, and cell death processes in cancer. This wide variety of regulatory effects is due to the fact that vitamin C has a dual mechanism of action. The reduced form of vitamin C (ascorbic acid, AA) is an essential micronutrient of small size; it is soluble in water and has two dissociable protons with pKa values of 4.2 and 11.8. At physiological pH, its reduced form predominates as the monovalent ascorbate anion (AA); when it loses the second proton, it is oxidized to dehydroascorbic acid (DHA).
  • 1.1K
  • 14 Jun 2022
Topic Review
Polyploidy and Ploidy Alterations in Hepatocytes
Polyploidy, a condition in which more than two sets of chromosomes are present in a cell, is a characteristic feature of hepatocytes. A significant number of hepatocytes physiologically undergo polyploidization at a young age. Polyploidization of hepatocytes is enhanced with age and in a diseased liver. It is worth noting that polyploid hepatocytes can proliferate, in marked contrast to other types of polyploid cells, such as megakaryocytes and cardiac myocytes. Polyploid hepatocytes divide to maintain normal liver homeostasis and play a role in the regeneration of the damaged liver. Furthermore, polyploid hepatocytes have been shown to dynamically reduce ploidy during liver regeneration. Although it is still unclear why hepatocytes undergo polyploidization, accumulating evidence has revealed that alterations in the ploidy in hepatocytes are involved in the pathophysiology of liver cirrhosis and carcinogenesis. 
  • 1.1K
  • 28 Sep 2022
Topic Review
Hallmarks of Aging in Macrophages
The skin is our largest organ and the outermost protective barrier. Its aging reflects both intrinsic and extrinsic processes resulting from the constant insults it is exposed to. Aging in the skin is accompanied by specific epigenetic modifications, accumulation of senescent cells, reduced cellular proliferation/tissue renewal, altered extracellular matrix, and a proinflammatory environment favoring undesirable conditions, including disease onset. Macrophages (Mφ) are the most abundant immune cell type in the skin and comprise a group of heterogeneous and plastic cells that are key for skin homeostasis and host defense. However, they have also been implicated in orchestrating chronic inflammation during aging. Since Mφ are related to innate and adaptive immunity, it is possible that age-modified skin Mφ promote adaptive immunity exacerbation and exhaustion, favoring the emergence of proinflammatory pathologies, such as skin cancer.
  • 1.1K
  • 10 Jun 2021
Topic Review
MRNA-Enhanced Cell Therapy
mRNA has emerged as an important biomolecule in the global call for the development of therapies during the COVID-19 pandemic. Synthetic in vitro-transcribed (IVT) mRNA can be engineered to mimic naturally occurring mRNA and can be used as a tool to target “undruggable” diseases. Recent advancement in the field of RNA therapeutics have addressed the challenges inherent to this drug molecule and this approach is now being applied to several therapeutic modalities, from cancer immunotherapy to vaccine development.
  • 1.1K
  • 03 Feb 2021
Topic Review
Breakdown of Filamentous Myofibrils
Protein degradation maintains cellular integrity by regulating virtually all biological pro- cesses, whereas impaired proteolysis perturbs protein quality control, and often leads to human disease. Two major proteolytic systems are responsible for protein breakdown in all cells: autophagy, which facilitates the loss of organelles, protein aggregates, and cell surface proteins; and the ubiquitin-proteasome system (UPS), which promotes degradation of mainly soluble proteins. Recent findings indicate that more complex protein structures, such as filamentous assemblies, which are not acces- sible to the catalytic core of the proteasome in vitro, can be efficiently degraded by this proteolytic machinery in systemic catabolic states in vivo. Mechanisms that loosen the filamentous structure seem to be activated first, hence increasing the accessibility of protein constituents to the UPS. In this review, we will discuss the mechanisms underlying the disassembly and loss of the intricate insoluble filamentous myofibrils, which are responsible for muscle contraction, and whose degradation by the UPS causes weakness and disability in aging and disease. Several lines of evidence indicate that myofibril breakdown occurs in a strictly ordered and controlled manner, and the function of AAA-ATPases is crucial for their disassembly and loss.
  • 1.1K
  • 30 Apr 2021
Topic Review
TGF-β in Skin Chronic Wounds
Chronic wounds are characterized for their incapacity to heal within an expected time frame. Potential mechanisms driving this impairment are poorly understood and current hypotheses point to the development of an unbalanced milieu of growth factor and cytokines. Among them, TGF-β is considered to promote the broadest spectrum of effects. Although it is known to contribute to healthy skin homeostasis, the highly context-dependent nature of TGF-β signaling restricts the understanding of its roles in healing and wound chronification. Historically, low TGF-β levels have been suggested as a pattern in chronic wounds. However, a revision of the available evidence in humans indicates that this could constitute a questionable argument. Thus, in chronic wounds, divergences regarding skin tissue compartments seem to be characterized by elevated TGF-β levels only in the epidermis. 
  • 1.1K
  • 13 May 2021
Topic Review
TCTP, Cell Biology and Disease
Translationally controlled tumour protein (TCTP) is multifunctional protein expressed in essentially all eukaryotic organisms. It is a cytoprotective protein that is involved in many basic biological processes, such as cellular stress responses, growth and development. Dysregulation of TCTP occurs in various disease processes, and recently the participation of TCTP in several cancer-promoting pathways has been unveiled. Understanding the core biological functions of TCTP, the mechanisms underlying its cellular regulation and its participation in disease processes is essential for the design of effective anti-cancer strategies that may involve targeting of TCTP.  To provide a current overview of the knowledge in this area, we published a review article in Cells, which represents a detailed compilation of the recent progress in this field . Here, we give a brief overview on the core findings that are reported in this article.
  • 1.1K
  • 27 Oct 2020
Topic Review
Platelet Concentrates
Platelet concentrates (PCs) typically refer to a group of materials produced from autologous blood designed to improve tissue regeneration.
  • 1.1K
  • 19 Feb 2021
Topic Review
Fibroblast Activation in Injured Heart
Fibrosis is characterized by the excessive accumulation of extra cellular matrix (ECM) components. It is a physiological response to pathological stimuli that helps to confine injuries. However, the prolonged activation of this process results in adverse tissue remodeling, which can ultimately affect the structure and function of organs (adverse remodeling).
  • 1.1K
  • 29 Mar 2022
Topic Review
Inflammaging of Hematopoietic Stem Cells
Hematopoietic stem cells (HSCs) sustain the lifelong production of all blood cell lineages. The functioning of aged HSCs is impaired, including a declined repopulation capacity and myeloid and platelet-restricted differentiation. Both cell-intrinsic and microenvironmental extrinsic factors contribute to HSC aging. Recent studies highlight the emerging role of inflammation in contributing to HSC aging. 
  • 1.1K
  • 13 Sep 2021
Topic Review
The Guanyl Radical
Guanyl radical or neutral guanine radical G(-H)• results from the loss of a H-atom or an electron/proton (e–/H+) couple from the guanine structures (G). Guanyl radical G(-H)• exists in two tautomeric forms and its role in single- and double-stranded oligonucleotides, in DNA and G-quadruplex, attracted considerable attention since directly connected to the damage of genetic material and its biological consequences. The emerging picture is still incomplete and extrapolation of its chemistry from nucleosides to more complex environment like DNA can be misleading.
  • 1.1K
  • 20 Jul 2021
Topic Review
SUMOylation
SUMOylation is a dynamic and essential Post-Translation Modification (PTM) consisting on the conjugation of Small Ubiquitin-like Modifiers (SUMOs) to an acceptor lysine of a substrate protein. SUMOylation predominantly regulates nuclear processes and its dysregulation is associated to diseases including cancer. SUMOs share a similar three-dimensional structure with other Ubiquitin-Like Modifiers (UBLs). However, SUMOs differ due to their flexible N-terminus, which also contains the site for SUMO chain formation. All eukaryotes express at least one SUMO paralogue. Five SUMO family members have been identified in humans (SUMO1, SUMO2, SUMO3, SUMO4, and SUMO5. However, SUMO1, SUMO2, and SUMO3 are the main family members where they are commonly classified as SUMO1 and SUMO2/3 because of the high similarity between mature SUMO2 and SUMO3. All SUMO paralogues are similar in structure but differ in expression levels. SUMO2 is the most abundant family member in mammalian cells. Studies in mice show that the knockout of SUMO2 is embryonic lethal, while SUMO1 and SUMO3 knockout mice were associated to mild phenotypes, possibly because SUMO2 might compensate the loss of either SUMO1 or SUMO3. Similarly to ubiquitination, SUMO is conjugated in a in a 3-step enzymatic cascade that involves a dimeric E1 activating enzyme (SAE1 and SAE2), an E2 conjugating enzyme (Ubc9), and several SUMO E3 enzymes.
  • 1.1K
  • 28 Mar 2022
Topic Review
Alternative Splicing in Cancer and Immune Cells
Splicing is a phenomenon enabling the excision of introns from pre-mRNA to give rise to mature mRNA. All the 20,000 genes of the human genome are concerned by this mechanism. Nevertheless, it is estimated that the proteome is composed of more than 100,000 proteins. How to go from 20,000 genes to more than 100,000 proteins? Alternative splicing (AS) is in charge of this diversity of proteins. AS which is found in most of the cells of an organism, participates in normal cells and in particular in immune cells, in the regulation of cellular behavior. In cancer, AS is highly dysregulated and involved in almost all of the hallmarks that characterize tumor cells.
  • 1.1K
  • 06 Apr 2022
Topic Review
Anticancer Effects of R-Loops
R-loops are three-stranded DNA/RNA hybrids that form by the annealing of the mRNA transcript to its coding template while displacing the non-coding strand. While R-loop formation regulates physiological genomic and mitochondrial transcription and DNA damage response, imbalanced R-loop formation can be a threat to the genomic integrity of the cell. As such, R-loop formation is a double-edged sword in cancer progression, and perturbed R-loop homeostasis is observed across various malignancies. 
  • 1.1K
  • 10 May 2023
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