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Topic Review
Neutrophils during Arboviral Infections
Arboviruses are known to cause large-scale epidemics in many parts of the world. These arthropod-borne viruses are a large group consisting of viruses from a wide range of families. The ability of their vector to enhance viral pathogenesis and transmission makes the development of treatments against these viruses challenging. Neutrophils are generally the first leukocytes to be recruited to a site of infection, playing a major role in regulating inflammation and, as a result, viral replication and dissemination. However, the underlying mechanisms through which neutrophils control the progression of inflammation and disease remain to be fully understood. In this review, we highlight the major findings from recent years regarding the role of neutrophils during arboviral infections. We discuss the complex nature of neutrophils in mediating not only protection, but also augmenting disease pathology. Better understanding of neutrophil pathways involved in effective protection against arboviral infections can help identify potential targets for therapeutics. 
  • 1.2K
  • 05 Jul 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
MafA Regulation in β-Cells
β-cells are insulin-producing cells in the pancreas that maintain euglycemic conditions. Pancreatic β-cell maturity and function are regulated by a variety of transcription factors that enable the adequate expression of the cellular machinery involved in nutrient sensing and commensurate insulin secretion. One of the key factors in this regulation is MAF bZIP transcription factor A (MafA). MafA expression is decreased in type 2 diabetes, contributing to β-cell dysfunction and disease progression. The molecular biology underlying MafA is complex, with numerous transcriptional and post-translational regulatory nodes. 
  • 1.2K
  • 21 Apr 2022
Topic Review
Vascular Smooth Muscle Cells Biomechanics
Cardiovascular diseases are one of the leading causes of global death in developing countries. More than 80% of cardiovascular disease-associated mortality is attributable to atherosclerosis, a chronic inflammatory disease of the vessel wall. During the development of atherosclerosis and other cardiovascular diseases, vascular smooth muscle cells (SMCs) continuously shift from a contractile state towards other phenotypes that differ substantially from differentiated SMCs.
  • 1.2K
  • 22 Sep 2021
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
Autoimmune Diseases in Epidermolysis Bullosa
Gene therapy serves as a promising therapy in the pipeline for treatment of epidermolysis bullosa (EB). However, with great promise, the risk of autoimmunity must be considered. While EB is a group of inherited blistering disorders caused by mutations in various skin proteins, autoimmune blistering diseases (AIBD) have a similar clinical phenotype and are caused by autoantibodies targeting skin antigens. Often, AIBD and EB have the same protein targeted through antibody or mutation, respectively. Moreover, EB patients are also reported to carry anti-skin antibodies of questionable pathogenicity. It has been speculated that activation of autoimmunity is both a consequence and cause of further skin deterioration in EB due to a state of chronic inflammation.
  • 1.2K
  • 11 Oct 2021
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
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
TGFβ Signaling
Transforming growth factor β (TGFβ) is a secreted growth and differentiation factor that influences vital cellular processes like proliferation, adhesion, motility, and apoptosis.
  • 1.2K
  • 25 Jan 2021
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
Cell Immortalization
Somatic human cells can divide a finite number of times, a phenomenon known as the Hayflick limit. It is based on the progressive erosion of the telomeric ends each time the cell completes a replicative cycle. Given this problem, researchers need cell lines that do not enter the senescence phase after a certain number of divisions. In this way, more lasting studies can be carried out over time and avoid the tedious work involved in performing cell passes to fresh media. However, some cells have a high replicative potential, such as embryonic stem cells and cancer cells. To accomplish this, these cells express the enzyme telomerase or activate the mechanisms of alternative telomere elongation, which favors the maintenance of the length of their stable telomeres. Researchers have been able to develop cell immortalization technology by studying the cellular and molecular bases of both mechanisms and the genes involved in the control of the cell cycle. Through it, cells with infinite replicative capacity are obtained. To obtain them, viral oncogenes/oncoproteins, myc genes, ectopic expression of telomerase, and the manipulation of genes that regulate the cell cycle, such as p53 and Rb, have been used.
  • 1.2K
  • 05 May 2023
Topic Review
TXA2 Signaling in Cancer
Several processes involved in cancer development, such as cell growth, migration, and angiogenesis, are regulated by the arachidonic acid derivative thromboxane A2 (TXA2). Higher levels of circulating TXA2 are observed in patients with multiple cancers, and this is accompanied by overexpression of TXA2 synthase (TBXAS1, TXA2S) and/or TXA2 receptors (TBXA2R, TP). Overexpression of TXA2S or TP in tumor cells is generally associated with poor prognosis, reduced survival, and metastatic disease. However, the role of TXA2 signaling in the stroma during oncogenesis has been underappreciated. TXA2 signaling regulates the tumor microenvironment by modulating angiogenic potential, tumor ECM stiffness, and host immune response. 
  • 1.2K
  • 26 Oct 2022
Topic Review
Alveolar Epithelial Cells in Pulmonary Fibrosis
An important contributor to the development of idiopathic pulmonary fibrosis (IPF) is the alteration of the intracellular homeostasis of alveolar epithelial cells, which are mainly composed of alveolar type I epithelial cells (AT1), alveolar type II epithelial cells (AT2), as well as abnormal basaloid cells, resulting in aberrant epithelial repair, myofibroblast activation, and increased extracellular matrix deposition to form lung fibrosis
  • 1.2K
  • 27 Feb 2023
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
Topic Review
Lysosomes in Maintaining Stem Cell Quiescence
Lysosomes are a critical component of the inner membrane system and are involved in various cellular biological processes, including macromolecular degradation, antigen presentation, intracellular pathogen destruction, plasma membrane repair, exosome release, cell adhesion/migration, and apoptosis. Lysosomes are a critical regulator of cellular metabolism, cancer, metastasis, and resistance to anticancer therapy. Additionally, lysosomal activities play a crucial role in acute myeloid leukemia (AML) development and progression, as well as maintaining the hematopoietic stem cells (HSCs) pool. It has been shown that AML cells undergo metabolic alterations due to chemotherapy or targeted treatment.
  • 1.2K
  • 31 Mar 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
3D Modeling of Epithelial Tumors
The current statistics on cancer show that 90% of all human cancers originate from epithelial cells. Breast and prostate cancer are examples of common tumors of epithelial origin that would benefit from improved drug treatment strategies. About 90% of preclinically approved drugs fail in clinical trials, partially due to the use of too simplified in vitro models and a lack of mimicking the tumor microenvironment in drug efficacy testing. This entry focuses on the epithelial cancers, followed by experimental models designed to recapitulate the epithelial tumor structure and microenvironment. A specific focus is to put on novel technologies for cell culture of spheroids, organoids, and 3D-printed tissue-like models, utilizing biomaterials of natural or synthetic origins, and how the models could be utilized for nanotechnology-based drug delivery in the future.
  • 1.2K
  • 24 Jun 2021
Topic Review
Phosphatidylinositol Binding Clathrin-Assembly Protein and Alzheimer’s Disease
Genome-wide association studies (GWAS) have identified the PICALM (Phosphatidylinositol binding clathrin-assembly protein) gene as the most significant genetic susceptibility locus after APOE and BIN1. PICALM is a clathrin-adaptor protein that plays a critical role in clathrin-mediated endocytosis and autophagy.
  • 1.2K
  • 22 Dec 2022
Topic Review
Targeting Ferroptosis against Ischemia/Reperfusion Cardiac Injury
Ischemic heart disease is a leading cause of death worldwide. Primarily, ischemia causes decreased oxygen supply, resulting in damage of the cardiac tissue. Naturally, reoxygenation has been recognized as the treatment of choice to recover blood flow through primary percutaneous coronary intervention. This treatment is the gold standard therapy to restore blood flow, but paradoxically it can also induce tissue injury. A number of different studies in animal models of acute myocardial infarction (AMI) suggest that ischemia-reperfusion injury (IRI) accounts for up to 50% of the final myocardial infarct size. Oxidative stress plays a critical role in the pathological process. Iron is an essential mineral required for a variety of vital biological functions but also has potentially toxic effects. A detrimental process induced by free iron is ferroptosis, a non-apoptotic type of programmed cell death. Accordingly, efforts to prevent ferroptosis in pathological settings have focused on the use of radical trapping antioxidants (RTAs), such as liproxstatin-1 (Lip-1). Hence, it is necessary to develop novel strategies to prevent cardiac IRI, thus improving the clinical outcome in patients with ischemic heart disease. 
  • 1.2K
  • 05 May 2022
Topic Review
Osteoporosis Treatments
A healthy and active lifestyle is vital for the proper maintenance of all body tissues, including bone. Several studies have highlighted the importance of physical exercise to improve the quality of life of patients with osteoporosis. Diet also plays a fundamental role in bone health. Calcium supplementation is able to decrease the rate of bone mineral density loss in women, presenting even better results in combination with vitamin D. Lately, isoflavones has gain interest as a treatment in osteoporosis but their effectiveness still remains unclear. Therefore, pharmacological therapies have been developed to counteract bone fragility based on molecular targets. Therapies for osteoporosis are focus on restoring the normal balance between bone resorption and bone formation. Bone anti-resorptive therapies focus on the inhibition or reduction of bone resorption process, these are; estrogens, selective estrogen receptor modulators (SERMs), bisphosphonates and monoclonal antibodies. On the other hand, bone formation agents target anabolic pathways to stimulate the osteoblastic activity. This include Teriparatide, a recombinant human parathyroid hormone (PTH), and Romosozumab; an anti-sclerostin monoclonal antibody with dual effect.  It increases bone formation and, to a lesser extent, it reduces bone resorption (or bone loss) which translates into a decrease in the risk of fracture. In summary, currently used osteoporosis therapies are not fully effective in all patients and present considerable side effects that seriously compromise their long-term use. Thus, the development of new therapeutic strategies for osteoporosis is necessary in an increasingly aging world population. In this context, cell-based therapeutic strategies based on mesenchymal stem cells are positioning as encouraging possibilities to address osteoporosis.
  • 1.2K
  • 27 Oct 2020
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