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Topic Review
Extracellular Vesicles in CKD
Over the last few years, preclinical and clinical studies have emphasized the role of extracellular vesicles (EVs) in human diseases. These particles are delimited by a lipid bilayer and are released by almost all cell types and in all organisms. EVs appear to have biological effects in various pathophysiological situations and especially in renal disease. In human organs, EVs can interact with cells and prompt the release of many different molecules, such as proteins, lipids and nucleic acids, that, in turn, regulate various cell signaling pathways. Moreover, EVs are present in the urine and the blood and therefore can be used as potential diagnostic biomarkers in human diseases, such as chronic kidney disease (CKD, also known as chronic renal failure).
  • 1.2K
  • 29 Apr 2021
Topic Review
Secretory Immunoglobulin A Immunity in COPD
Chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis (CF) are distinct respiratory diseases that share features such as the obstruction of small airways and disease flare-ups that are called exacerbations and are often caused by infections. Along the airway epithelium, immunoglobulin (Ig) A contributes to first line mucosal protection against inhaled particles and pathogens. Dimeric IgA produced by mucosal plasma cells is transported towards the apical pole of airway epithelial cells by the polymeric Ig receptor (pIgR), where it is released as secretory IgA. Secretory IgA mediates immune exclusion and promotes the clearance of pathogens from the airway surface by inhibiting their adherence to the epithelium. 
  • 1.2K
  • 27 Jul 2022
Topic Review
Navigating the ERK1/2 MAPK Cascade
The RAS-ERK pathway is a fundamental signaling cascade crucial for many biological processes including proliferation, cell cycle control, growth, and survival; common across all cell types. Notably, ERK1/2 are implicated in specific processes in a context-dependent manner as in stem cells and pancreatic β-cells. Alterations in the different components of this cascade result in dysregulation of the effector kinases ERK1/2 which communicate with hundreds of substrates. Aberrant activation of the pathway contributes to a range of disorders, including cancer.
  • 1.2K
  • 25 Oct 2023
Topic Review
LOCs/OOCs for Biomedical Applications
Lab-on-a-chip (LOC) and organ-on-a-chip (OOC) devices are highly versatile platforms that enable miniaturization and advanced controlled laboratory functions (i.e., microfluidics, advanced optical or electrical recordings, high-throughput screening). The manufacturing advancements of LOCs/OOCs for biomedical applications and their current limitations are briefly discussed. Multiple studies have exploited the advantages of mimicking organs or tissues on a chip. Among these, we focused our attention on the brain-on-a-chip, blood–brain barrier (BBB)-on-a-chip, and neurovascular unit (NVU)-on-a-chip applications.
  • 1.2K
  • 14 Jul 2021
Topic Review
New Frontiers in Peripheral Nerve Regeneration
The peripheral nervous system (PNS) exhibits a limited capacity for functional and morphological repair and regeneration. Peripheral nerve recovery is a multistep process with a complex molecular and cellular regulatory circuitry. Severe injury of peripheral nerves often results in a loss of motor, sensory, and autonomic functions of innervated organs and tissues, therefore calling for novel treatment strategies to ensure effective regeneration.
  • 1.2K
  • 24 Dec 2021
Topic Review
Mechanosensitive Ion Channels
Mechanosensitive ion channels mediate the neuronal sensation of mechanical signals such as sound, touch, and pain.
  • 1.2K
  • 21 Oct 2021
Topic Review
Cofilin Signaling
Three ADF/cofilin family members are expressed in mammals: ADF, cofilin-1, and cofilin-2. The first member ADF (also known as destrin), encoded by the gene DSTN in humans, was initially identified in the chick brain. Cofilin was discovered as an actin-interacting protein in the porcine brain. Later, Ono et al. identified two mammalian variants of cofilin, non-muscle type (also known as cofilin-1 and n-cofilin) and muscle type (also known as cofilin-2 and m-cofilin). In humans, cofilin-1 and cofilin-2 are encoded by the genes CFL1 and CFL2, respectively. Different isoforms of ADF/cofilin have qualitatively similar but quantitatively different effects on actin dynamics. To be noted, both ADF and cofilin show cooperative binding with actin filaments. Interestingly, cofilin-1 comprises almost 90% of the total ADF/cofilin family in CNS. Cofilin can bind to both G-actin and F-actin, exhibiting stronger affinities for the ADP-bound actins than the ATP- or ADP-Pi-bound forms. Cofilin binding to F-actin induces actin subunit rotation, enhances Pi release along the filament, and promotes filament severing in a concentration-dependent manner.
  • 1.2K
  • 28 Oct 2021
Topic Review
Role of SLC7A11 in Cancer Metabolism
Solute carrier family 7 member 11 (SLC7A11) is a cell transmembrane protein composing the light chain of system xc−, transporting extracellular cystine into cells for cysteine production and glutathione (GSH) biosynthesis. SLC7A11 is a critical gateway for redox homeostasis by maintaining the cellular levels of GSH that counter cellular oxidative stress and suppress ferroptosis. SLC7A11 is overexpressed in various human cancers and regulates tumor development, proliferation, metastasis, microenvironment, and treatment resistance.
  • 1.2K
  • 08 Jan 2023
Topic Review
The RUNX Family Promote Genomic Instability
The RUNX family of transcription factors, including RUNX1, RUNX2, and RUNX3, are key regulators of development and can function as either tumor suppressors or oncogenes in cancer. Emerging evidence suggests that the dysregulation of RUNX genes can promote genomic instability in both leukemia and solid cancers by impairing DNA repair mechanisms. RUNX proteins control the cellular response to DNA damage by regulating the p53, Fanconi anemia, and oxidative stress repair pathways through transcriptional or non-transcriptional mechanisms. 
  • 1.2K
  • 04 May 2023
Topic Review
Telomeres
To survive and reproduce, living organisms must maintain homeostasis both in unchallenged (normal) and challenged (stressful) contexts. This requires the evolution of powerful stress response mechanisms adapted to a particular ecosystem and to regular environmental fluctuations. Thus, these mechanisms may be very diverse within the tree of life. The pioneering work of Miroslav Radman on the stress response in bacteria demonstrated the rapid and adaptive value of changing mutation rates for rapid evolution (the mutator effect). In other words, to facilitate the survival of a species, whether it be to respond to a replication blockade or to a stressful environment, it is better to rapidly evolve by generating more mutations, some being possibly lethal, than to die immediately. We believe that this principle applies to the complex dynamics of telomeres in eukaryotes, which become altered in response to stress.
  • 1.2K
  • 02 Jun 2021
Topic Review
MTOR Signalling
In the liver, mTORC1, which consists of mTOR, mammalian lethal with Sec13 protein 8 (mLST8), Dishevelled, Egl-10 and Pleckstrin domain-containing mTOR-interacting protein (Deptor), regulatory-associated protein of mTOR (Raptor) and proline-rich protein kinase B (Akt) substrate (Pras40), is critical for controlling metabolic processes. 
  • 1.2K
  • 27 Oct 2020
Topic Review
Myeloma Cell Death
Multiple myeloma (MM) is a neoplastic disease of plasma cells, characterized by a complex array of clinical manifestations. Despite extensive efforts and progress in the care of MM patients, the disease is still fatal because of de novo or acquired resistance of malignant cells to standard chemotherapies. In turn, new therapies and/or combination therapies are urgently needed. Reactive oxygen species (ROS) are unstable and highly reactive chemical molecules, able to alter the main structural components of cells, such as proteins and lipids, and thus, modifying cell fates. ROS levels are tightly controlled in normal cells both for their production and degradation. In turn, an unbalance of the redox status might be exploited to induce cell death. This is indeed the case for myeloma cells even those that are resistant, opening new perspectives for refractory or relapsed MM patients. 
  • 1.2K
  • 15 Jun 2021
Topic Review
Lipids in Macrophages of Different Tissue Location
Lipid metabolism is the major intracellular mechanism driving a variety of cellular functions such as energy storage, hormone regulation and cell division. Lipids, being a primary component of the cell membrane, play a pivotal role in the survival of macrophages. Lipids are crucial for a variety of macrophage functions including phagocytosis, energy balance and ageing. Lipid-loaded macrophages have recently been emerging as a hallmark for several diseases.
  • 1.2K
  • 12 Jan 2023
Topic Review
Applications for Colon Organoid Models in Cancer
Organoids are 3D organ-like structures grown from stem cells in vitro that mimic the organ or disease from which they are derived. Due to their stem cell origin, organoids contain a heterogeneous population of cells reflecting the diversity of cell types seen in vivo. Similarly, tumour organoids reflect intratumoural heterogeneity in a way that traditional 2D cell culture and cell lines do not, and, therefore, they show greater promise as a more relevant model for effective disease modelling and drug testing. Tumour organoids arise from cancer stem cells, which contribute to many of the greatest challenges to cancer treatment, including therapy resistance, tumour recurrence, and metastasis. Organoids show promise as relevant in vitro models with a range of applications from drug testing to modelling disease progression.
  • 1.2K
  • 30 Jan 2023
Topic Review
Skeletal Muscle Extracellular Matrix
The skeletal muscle provides movement and support to the skeleton, controls body temperature, and regulates the glucose level within the body. This is the core tissue of insulin-mediated glucose uptake via glucose transporter type 4 (GLUT4). The extracellular matrix (ECM) provides a scaffold for cells, controlling biological processes, and providing structural as well as mechanical support to surrounding cells. Disruption of ECM homeostasis results in several pathological conditions. Various ECM components are typically found to be augmented in the skeletal muscle of obese and/or diabetic humans. A better understanding of the importance of skeletal muscle ECM remodeling, integrin signaling, and other factors that regulate insulin activity may help in the development of novel therapeutics for managing diabetes and other metabolic disorders.
  • 1.2K
  • 09 Sep 2021
Topic Review
Current Methodologies for Visualizing ATP in Living Cells
Measuring total ATP levels within cellular compartmental pools in real-time presents a newer and more innovative approach to qualitatively analyzing ATP. Although this method is not precisely quantitative, it can be helpful in determining changes in ATP concentrations in one region of a cell compared to another in a variety of disease states. The overall goal of these assays and imaging methodologies are to evaluate and visualize dynamic ATP trends, such as usage and depletion, between cells and their sub-compartments. However, semi-quantitative evaluation of the relative ATP signal is feasible. The currently developed technologies that utilize this approach to ATP quantification are mainly genetically encoded biosensors. In conjunction with a fluorescent or bioluminescent protein, most of these biosensors harness the folding capabilities of the ϵ subunit of the bacterial ATP synthase subunit. The bacterial ATP synthase protein comprises a β-barrel domain located at the N terminus and an α-helical domain with two α-helices located at the C terminus. Upon ATP binding, the two α-helices interact and refine their conformational structure of the ϵ subunit, leading to fluorescent/bioluminescent illumination, indicating that ATP is present. Overall, this subunit adopts two different conformations: open (ATP-free) or closed (ATP-bound). The uses and applicability of this technology are limitless. 
  • 1.2K
  • 24 Jun 2022
Topic Review
Natural Killer Cells: Tumor Surveillance and Signaling
Natural killer (NK) cells play a pivotal role in cancer immunotherapy due to their innate ability to detect and kill tumorigenic cells. The decision to kill is determined by the expression of a myriad of activating and inhibitory receptors on the NK cell surface. Cell-to-cell engagement results in either self-tolerance or a cytotoxic response, governed by a fine balance between the signaling cascades downstream of the activating and inhibitory receptors. 
  • 1.2K
  • 04 Jul 2022
Topic Review
Natural Polyphenols as SERCA Activators
Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) is a key protein responsible for transporting Ca2+ ions from the cytosol into the lumen of the sarco/endoplasmic reticulum (SR/ER), thus maintaining Ca2+ homeostasis within cells. Accumulating evidence suggests that impaired SERCA function is associated with disruption of intracellular Ca2+ homeostasis and induction of ER stress, leading to different chronic pathological conditions. Therefore, appropriate strategies to control Ca2+ homeostasis via modulation of either SERCA pump activity/expression or relevant signaling pathways may represent a useful approach to combat pathological states associated with ER stress. Natural dietary polyphenolic compounds, such as resveratrol, gingerol, ellagic acid, luteolin, or green tea polyphenols, with a number of health-promoting properties, have been described either to increase SERCA activity/expression directly or to affect Ca2+ signaling pathways.
  • 1.2K
  • 24 Aug 2022
Topic Review
Trichomonas vaginalis
In Trichomonas, the hydrogenosome, a double membrane-bounded organelle that produces ATP, also can be a good target. Other structures include mitosomes, ribosomes, and proteasomes. Metronidazole is the most frequent compound used to kill many anaerobic organisms, including Giardia and Trichomonas. It enters the cell by passive diffusion and needs to find a highly reductive environment to be reduced to the nitro radicals to be active. However, it provokes several side effects, and some strains present metronidazole resistance. Therefore, to improve the quality of the chemotherapy against parasitic protozoa is important to invest in the development of highly specific compounds that interfere with key steps of essential metabolic pathways or in the functional macromolecular complexes which are most often associated with cell structures and organelles. 
  • 1.2K
  • 15 Nov 2022
Topic Review
JNK Pathway in CNS Pathologies
The c-Jun N-terminal kinase (JNK) signalling pathway is a conserved response to a wide range of internal and external cellular stress signals.
  • 1.2K
  • 19 Apr 2021
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