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Topic Review
Chromogranin A -Derived Peptides as Inflammatory Modulator Molecules
Chromogranin A (CgA) is a glyco-phosphoprotein discovered for the first time in the adrenal medulla but also produced in several cells. CgA can generate different derived antimicrobial peptides (AMPs) influencing numerous physiological processes. CgA-derived peptides modulate inflammation and represent an example of endogenous Multifunctional AMPs (MF-AMPs).
  • 988
  • 21 Oct 2022
Topic Review
WD40 Repeat
The WD40 repeat (also known as the WD or beta-transducin repeat) is a short structural motif of approximately 40 amino acids, often terminating in a tryptophan-aspartic acid (W-D) dipeptide. Tandem copies of these repeats typically fold together to form a type of circular solenoid protein domain called the WD40 domain.
  • 988
  • 23 Nov 2022
Topic Review
Exercise-Boosted Mitochondrial Remodeling in Parkinson’s Disease
Parkinson’s disease (PD) is a movement disorder characterized by the progressive degeneration of dopaminergic neurons resulting in dopamine deficiency in the striatum. Given the estimated escalation in the number of people with PD, interventions aimed at minimizing morbidity and improving quality of life are crucial. Mitochondrial dysfunction and oxidative stress are intrinsic factors related to PD pathogenesis. Accumulating evidence suggests that patients with PD might benefit from various forms of exercise in diverse ways, from general health improvements to disease-specific effects and, potentially, disease-modifying effects.
  • 988
  • 23 Dec 2022
Topic Review
Seminal Microbiome on Human Fertility
Certain clusters of bacteria have been associated with fertility and health, while the outgrowth of several species is potentially correlated with infertility indicators. This constitutes a compelling reason for outlining the external elements that may induce changes in the seminal microbiome composition, like lifestyle factors, gut microbiota, pathologies, prebiotics, and probiotics.
  • 988
  • 15 Mar 2024
Topic Review
Calcium Sources to Somatic Release of Serotonin
The soma, dendrites and axon of neurons may display calcium-dependent release of transmitters and peptides. Such release is named extrasynaptic for occurring in absence of synaptic structures. Emphasis is given to the somatic release of serotonin by the classical leech Retzius neuron, which has allowed detailed studies on the fine steps from excitation to exocytosis. Trains of action potentials induce transmembrane calcium entry through L-type channels. For action potential frequencies above 5 Hz, summation of calcium transients on individual action potentials activates the second calcium source: ryanodine receptors produce calcium-induced calcium release. The resulting calcium tsunami activates mitochondrial ATP synthesis to fuel transport of vesicles to the plasma membrane. Serotonin that is released maintains a large-scale exocytosis by activating the third calcium source: serotonin autoreceptors coupled to phospholipase C promote IP3 production. Activated IP3 receptors in peripheral endoplasmic reticulum release calcium that promotes vesicle fusion. The Swiss-clock workings of the machinery for somatic exocytosis has a striking disadvantage. The essential calcium-releasing endoplasmic reticulum near the plasma membrane hinders the vesicle transport, drastically reducing the thermodynamic efficiency of the ATP expenses and elevating the energy cost of release. 
  • 987
  • 09 Feb 2022
Topic Review
Mesenchymal Stromal Cell Aging
Mesenchymal stem/stromal cells (MSCs) are a reservoir for tissue homeostasis and repair that age during organismal aging. Beside the fundamental in vivo role of MSCs, they have also emerged in the last years as extremely promising therapeutic agents for a wide variety of clinical conditions. MSC use frequently requires in vitro expansion, thus exposing cells to replicative senescence. Aging of MSCs (both in vivo and in vitro) can affect not only their replicative potential, but also their properties, like immunomodulation and secretory profile, thus possibly compromising their therapeutic effect. It is therefore of critical importance to unveil the underlying mechanisms of MSC senescence and to define shared methods to assess MSC aging status.
  • 985
  • 16 Jun 2021
Topic Review
Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma
Cancer-associated fibroblasts (CAFs) are key components of the pancreatic tumor microenvironment, maintaining the extracellular matrix, while also being involved in intricate crosstalk with cancer cells and infiltrating immunocytes. Therefore, they are potential targets for developing therapeutic strategies against pancreatic ductal adenocarcinoma (PDAC). However, studies have demonstrated significant heterogeneity in CAFs with respect to their origins, spatial distribution, and functional phenotypes within the PDAC tumor microenvironment. Therefore, it is imperative to understand and delineate this heterogeneity prior to targeting CAFs for PDAC therapy. 
  • 985
  • 07 Feb 2022
Topic Review
Preclinical and Clinical Endeavors Targeting Mitochondria
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons, for which current treatment options are limited. Recent studies have shed light on the role of mitochondria in ALS pathogenesis, making them an attractive therapeutic intervention target.
  • 985
  • 26 Feb 2024
Topic Review
Th17 Response in COVID-19
COVID-19 is an acute infectious disease of the respiratory system caused by infection with the SARS-CoV-2 virus (Severe Acute Respiratory Syndrome Coronavirus 2). Transmission of SARS-CoV-2 infections occurs through droplets and contaminated objects. A rapid and well-coordinated immune system response is the first line of defense in a viral infection. However, a disturbed and over-activated immune response may be counterproductive, causing damage to the body. Severely ill patients hospitalised with COVID-19 exhibit increased levels of many cytokines, including Interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, IL-10, IL-17, granulocyte colony stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor (TNF). Increasing evidence suggests that Th17 cells play an important role in the pathogenesis of COVID-19, not only by activating cytokine cascade but also by inducing Th2 responses, inhibiting Th1 differentiation and suppressing Treg cells.
  • 985
  • 25 Jun 2021
Topic Review
Extracellular Vesicles in Epigenetic Regulation
Extracellular vesicles (EVs) are complex phospholipidic structures actively released by cells. EVs are recognized as powerful means of intercellular communication since they contain many signaling molecules (including lipids, proteins, and nucleic acids).
  • 984
  • 14 Dec 2020
Topic Review
Asbestos and Intrahepatic Cholangiocarcinoma
The link between asbestos exposure and the onset of thoracic malignancies is well established. However epidemiological studies have provided evidences that asbestos may be also involved in the development of gastrointestinal tumors, including intrahepatic cholangiocarcinoma (ICC). In line with this observation, asbestos fibers have been detected in the liver of patients with ICC. Although the exact mechanism still remains unknown, the presence of asbestos fibers in the liver could be explained in the light of their translocation pathway following ingestion/inhalation. In the liver, thin and long asbestos fibers could remain trapped in the smaller bile ducts, particularly in the stem cell niche of the canals of Hering, and exerting their carcinogenic effect for a long time, thus inducing hepatic stem/progenitor cells (HpSCs) malignant transformation. In this scenario, chronic liver damage induced by asbestos fibers over the years could be seen as a classic model of stem cell-derived carcinogenesis, where HpSC malignant transformation represents the first step of this process. This phenomenon could explain the recent epidemiological findings, where asbestos exposure seems mainly involved in ICC, rather than extrahepatic cholangiocarcinoma, development.
  • 984
  • 04 Jun 2021
Topic Review
In Vitro Human Cancer Models for Biomedical Applications
Cancer is one of the leading causes of death worldwide, and its incidence is steadily increasing. Although years of research have been conducted on cancer treatment, clinical treatment options for cancers are still limited. Animal cancer models have been widely used for studies of cancer therapeutics, but these models have been associated with many concerns, including inaccuracy in the representation of human cancers, high cost and ethical issues. Therefore, in vitro human cancer models are being developed quickly to fulfill the increasing demand for more relevant models in order to get a better knowledge of human cancers and to find novel treatments.
  • 984
  • 19 May 2022
Topic Review
Three Members of the Synuclein Family
Synucleins are a family of small aggregation-prone proteins consisting of three members, alpha, beta and gamma-synuclein. Alpha-synuclein is the most investigated member of the family due to its involvement in neurodegenerative diseases called synucleinopatjies. Synucleins easily change their conformation and may be converted to toxic aggregates. They are in the focus of attention of biochemists, molecular and cellular biologists who try to reveal their normal functions and role  in diseaases.  
  • 983
  • 03 Jan 2023
Topic Review
Autophagy in Multiple Myeloma
Multiple myeloma (MM) is the second most prevalent hematologic malignancy. One of the significant obstacles in treating most MM patients is drug resistance, especially for individuals who have experienced relapses or developed resistance to such cutting-edge treatments. One of the critical processes in developing drug resistance in MM is autophagic activity, an intracellular self-digestive process. In multiple myeloma, it has been shown that High mobility group box protein 1 (HMGB1)-dependent autophagy can contribute to drug resistance.
  • 982
  • 10 Apr 2023
Topic Review
Mitochondrial Unfolded Protein Response for Therapy
The mitochondrial unfolded protein response (UPRmt) is a mechanism aimed to preserve or repair damaged mitochondria. UPRmt is responsible for maintaining mitochondrial proteostasis via mitochondrial activation of a transcriptional program in the nuclear DNA. This compensation system can be divided into three main pathways: activation of (1) chaperones, which boost refolding of misfolded proteins to restore them to their functional conformation and assist the folding of newly synthesized proteins; (2) proteases that are able to degrade aberrant proteins or aggregates; and (3) an antioxidant system that palliates ROS overproduction. Although human UPRmt is not fully understood, it is gaining relevance in a variety of physiological processes on top of its canonical function, such as ageing, oxidative stress resistance, hematopoietic stem cell maintenance, glycolysis, antibacterial immunity, coenzyme Q biosynthesis, and mitochondrial fission. Loss of mitochondrial proteostasis is the main UPRmt inducer. Accumulation of damaged proteins exceeding the protein-processing capacity of the chaperones and proteases in mitochondria would activate UPRmt, for instance. Additionally, factors interfering with mitochondrial function promote UPRmt induction. Examples of these are the inhibition of complex I by rotenone, bacterial toxins, knockdown of quality control proteins, or generation of excess ROS by paraquat.
  • 980
  • 22 Jul 2022
Topic Review
Core PCP Proteins in Coordinating Cilia Orientation
As exemplified by the unidirectionally beating cilia of multi-ciliated cells, various epithelial cells polarize not only along the apical-basal axis (inside–outside axis) of epithelial tissues, but also on the plane of epithelial tissues. The latter cell polarity, which is perpendicular to the apical–basal axis, is referred to as planar cell polarity (PCP). Pioneering research using the wings of Drosophila melanogaster identified a group of proteins, core PCP proteins, that orchestrate the establishment of PCP.
  • 980
  • 21 Nov 2022
Topic Review
Aberrant Stress Granule Dynamics
Stress granules are membrane-less organelles formed through the process of liquid–liquid phase separation (LLPS) under certain stress conditions, such as oxidative stress and heat shock, among others.
  • 978
  • 12 Oct 2021
Topic Review
Chronic Inflammation in Cancer Cachexia
Cachexia, a type of metabolic syndrome linked to the disease, is associated with a dysregulation of metabolic pathways. Cancer Cachexia is a subtle condition that reduces patients’ quality of life by impairing their response to therapy and survival. Inflammatory mediators that may play a role in the pathogenesis of neoplastic cachexia, for example, overlap with those that may play a role in the pathogenesis of obesity. Cachexia is a complication of cancer-related malnutrition associated with catabolic/hypermetabolic changes.
  • 977
  • 05 May 2022
Topic Review
Hematopoietic Stem Cells and Metabolic Program
Hematopoietic stem cells (HSCs) in bone marrow continuously supply a large number of blood cells throughout life in collaboration with hematopoietic progenitor cells (HPCs). HSCs and HPCs are thought to regulate and utilize intracellular metabolic programs to obtain metabolites, such as adenosine triphosphate (ATP), which is necessary for various cellular functions. The metabolic programs of tissue stem/progenitor cells and their underlying molecular mechanisms have been elucidated using a variety of metabolic analysis methods.
  • 977
  • 05 Jan 2023
Topic Review
Cell Mechanics in Embryoid Bodies
Embryoid bodies (EBs) resemble self-organizing aggregates of pluripotent stem cells that recapitulate some aspects of early embryogenesis. Within few days, the cells undergo a transition from rather homogeneous epithelial-like pluripotent stem cell colonies into a three-dimensional organization of various cell types with multifaceted cell–cell interactions and lumen formation—a process associated with repetitive epithelial-mesenchymal transitions. In the last few years, culture methods have further evolved to better control EB size, growth, cellular composition, and organization—e.g., by the addition of morphogens or different extracellular matrix molecules. There is a growing perception that the mechanical properties, cell mechanics, and cell signaling during EB development are also influenced by physical cues to better guide lineage specification; substrate elasticity and topography are relevant, as well as shear stress and mechanical strain. Epithelial structures outside and inside EBs support the integrity of the cell aggregates and counteract mechanical stress. Furthermore, hydrogels can be used to better control the organization and lineage-specific differentiation of EBs. In this review, we summarize how EB formation is accompanied by a variety of biomechanical parameters that need to be considered for the directed and reproducible self-organization of early cell fate decisions.
  • 976
  • 08 Oct 2021
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