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Topic Review
Role of Mitochondria in the Central Nervous System
Disruption of the synapses leads to a deterioration in the communication of nerve cells and decreased plasticity, which is associated with a loss of cognitive functions and neurodegeneration. Maintaining proper synaptic activity depends on the qualitative composition of mitochondria, because synaptic processes require sufficient energy supply and fine calcium regulation.
  • 941
  • 15 Mar 2023
Topic Review
Analyses of HCV Strains
Approximately 71 million people worldwide are infected with the hepatitis C virus (HCV). Injectable drug use represents the most common route of transmission in Europe and other developed countries. We studied the molecular characteristics of the HCV infection among mono-infected people who used drugs (PWUD) in Italy. Among 208 PWUD with anti-HCV antibodies, 101 (48.6%) were HCV RNA-positive, the majority (47%) were infected with the HCV genotype (Gt)1a, followed by Gt3a (34.9%), Gt4 (9.1%), Gt1b (4.5%), and Gt2 (4.5%). Bayesian phylogenetic analyses of clustered HCV NS5B sequences from 66 HCV-positive PWUDs with available plasma samples indicated age and neighborhood proximity as the most common characteristics between closely related HCV strains. Population dynamics, as measured by a coalescent Bayesian skyline analysis, revealed an increase in HCV Gt1a infections from the mid-1980s to mid-1990s. While HCV Gt3a infections were first detected in the 1980s, patient numbers with this genotype subtype remained relatively constant. For both Gt1a and Gt3a, Birth–Death Bayesian Skyline analyses produced higher reproduction numbers post 2014. For earlier time intervals, slow growths were observed for both Gt1a and Gt3a with reproduction numbers (Re) of approximately 1. The evolutionary rates for Gt1a and Gt3a were estimated as 2.23 × 10−4 and 3.85 × 10−4, respectively. 
  • 940
  • 05 Jul 2021
Topic Review
Direct and Indirect Myc Regulation by Mitotic Kinases
c-Myc and the other protein family members (i.e., N-Myc and L-Myc), collectively known as “Myc”, are ubiquitous basic helix–loop–helix–leucine zipper (bHLH-LZ) transcription factors that are critical for several cellular processes during cancer genesis and progression. The importance of kinases in Myc regulation goes beyond their ability to phosphorylate the protein. Some kinases can also indirectly affect Myc protein stability by inducing the degradation of the ubiquitin ligase (PLK1 and PKA). Additionally, some kinases physically interact with Myc, protecting it from proteasomal degradation, such as Aurora-A in neuroblastoma.
  • 940
  • 08 Mar 2023
Topic Review
Cellular Senescence in Lung Fibrosis
Cellular senescence, one of the hallmarks of aging, is defined as a cellular state of irreversibly arrested proliferation of aged or damaged cells.
  • 940
  • 09 Jul 2021
Topic Review
Caspase Inhibition Improves Electrotransfer Efficiency
Chimeric antigen receptor (CAR) T cell therapy has been approved to treat patients with various B cell-related tumors, including B-cell precursor acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), and high-grade B-cell lymphoma. T cell receptor (TCR) knockout is a critical step in producing universal CAR T cells. A promising approach to achieving the knockout is to deliver the CRISPR/Cas9 system into T cells using electrotransfer technology.
  • 938
  • 27 Sep 2020
Topic Review
Single-Cell RNA Sequencing in Lymphatic Endothelial Cells
Lymphatic endothelial cells (LECs) line the lymphatic vasculature and play a central role in the immune response. LECs have abilities to regulate immune transport, to promote immune cell survival, and to cross present antigens to dendritic cells. Single-cell RNA sequencing (scRNA) technology has accelerated new discoveries in the field of lymphatic vascular biology. 
  • 938
  • 19 Nov 2021
Topic Review
Cellular Differentiation
Across embryonic development to late adulthood, highly regulated cellular differentiation is imperative for proper development and growth, as well as for the maintenance of specialized tissues throughout life. In general, this crucial cellular process underlies organogenesis and tissue regeneration, and its dysregulation or pathological dysfunction may accelerate aging and/or the onset of disease. Furthermore, the effects of cannabinoids on cellular differentiation are seen across a broad variety of tissues, including many peripheral tissues such as muscle, bone, and blood.
  • 938
  • 04 Jul 2023
Topic Review
Neuropeptide B
Neuropeptide B (NPB) is a peptide hormone that was initially described in 2002. In humans, the biological effects of NPB depend on the activation of two G protein-coupled receptors, NPBWR1 (GPR7) and NPBWR2 (GPR8), and, in rodents, NPBWR1. NPB and its receptors are expressed in the central nervous system (CNS) and in peripheral tissues. NPB is also present in the circulation. In the CNS, NPB modulates appetite, reproduction, pain, anxiety, and emotions. In the peripheral tissues, NPB controls secretion of adrenal hormones, pancreatic beta cells, and various functions of adipose tissue. Experimental downregulation of either NPB or NPBWR1 leads to adiposity. 
  • 937
  • 29 Jul 2021
Topic Review
Roles of Non-Coding RNA in Alzheimer’s Disease Pathophysiology
Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that is accompanied by deficits in memory and cognitive functions. The disease is pathologically characterised by the accumulation and aggregation of an extracellular peptide referred to as amyloid-β (Aβ) in the form of amyloid plaques and the intracellular aggregation of a hyperphosphorelated protein tau in the form of neurofibrillary tangles (NFTs) that cause neuroinflammation, synaptic dysfunction, and oxidative stress. The search for pathomechanisms leading to disease onset and progression has identified many key players that include genetic, epigenetic, behavioural, and environmental factors, which lend support to the fact that this is a multi-faceted disease where failure in various systems contributes to disease onset and progression. Although the vast majority of individuals present with the sporadic (non-genetic) form of the disease, dysfunctions in numerous protein-coding and non-coding genes have been implicated in mechanisms contributing to the disease.
  • 937
  • 25 Aug 2023
Topic Review
Recent Advances in Glioma Cancer Treatment
Gliomas are the brain’s most frequent and deadly tumors, accounting for roughly 30% of all brain malignancies. Glioblastoma (GBM) is characterized by changes in cell metabolism, including an increased Warburg effect, dysfunctional oxidative phosphorylation (OXPHOS), disrupted lipids metabolism, and other metabolic changes. Targeting epigenetic variables, immunotherapy, gene therapy, and different vaccine- and peptide-based treatments are some innovative approaches to improve anti-glioma treatment efficacy. Following the identification of lymphatics in the central nervous system, immunotherapy offers a potential method with the potency to permeate the blood-brain barrier.
  • 935
  • 06 Sep 2022
Topic Review
Non-Catalytic Tyrosine-Phosphorylated Receptors
Non-catalytic tyrosine-phosphorylated receptors (NTRs), also called immunoreceptors or Src-family kinase-dependent receptors, are a group of cell surface receptors expressed by leukocytes that are important for cell migration and the recognition of abnormal cells or structures and the initiation of an immune response. These transmembrane receptors are not grouped into the NTR family based on sequence homology, but because they share a conserved signalling pathway utilizing the same signalling motifs. A signaling cascade is initiated when the receptors bind their respective ligand resulting in cell activation. For that tyrosine residues in the cytoplasmic tail of the receptors have to be phosphorylated, hence the receptors are referred to as tyrosine-phosphorylated receptors. They are called non-catalytic receptors, as the receptors have no intrinsic tyrosine kinase activity and cannot phosphorylate their own tyrosine residues. Phosphorylation is mediated by additionally recruited kinases. A prominent member of this receptor family is the T-cell receptor.
  • 935
  • 28 Nov 2022
Topic Review
Cell Receptors for Collagen
Collagen, an extracellular protein, covers the entire human body and has several important biological functions in normal physiology. Collagen possibly binds with at least six different groups of receptors in biological cells. These are integrins, DDR, Glycoprotein VI, Osteoclast-associated receptor (OSCAR), LAIR-1, and uPARAP/Endo180.
  • 934
  • 10 Mar 2022
Topic Review
HDL Cholesterol Efflux Capacity
Over the years, the relationship between high-density lipoprotein (HDL) and atherosclerosis, initially highlighted by the Framingham study, has been revealed to be extremely complex, due to the multiple HDL functions involved in atheroprotection. Among them, HDL cholesterol efflux capacity (CEC), the ability of HDL to promote cell cholesterol efflux from cells, has emerged as a better predictor of cardiovascular (CV) risk compared to merely plasma HDL-cholesterol (HDL-C) levels. HDL CEC is impaired in many genetic and pathological conditions associated to high CV risk such as dyslipidemia, chronic kidney disease, diabetes, inflammatory and autoimmune diseases, endocrine disorders, etc. 
  • 934
  • 19 Mar 2021
Topic Review
Ink4a/Arf Expression in Pancreatic Progenitor
The identification of the molecular mechanisms controlling early cell fate decisions in mammals is of paramount importance as the ability to determine specific lineage differentiation represents a significant opportunity for new therapies. Pancreatic Progenitor Cells (PPCs) constitute a regenerative reserve essential for the maintenance and regeneration of the pancreas. Besides, PPCs represent an excellent model for understanding pathological pancreatic cellular remodelling. Given the lack of valid markers of early endoderm, the identification of new ones is of fundamental importance. Both products of the Ink4a/Arf locus, in addition to being critical cell-cycle regulators, appear to be involved in several disease pathologies. Moreover, the locus’ expression is epigenetically regulated in ES reprogramming processes, thus constituting the ideal candidates to modulate PPCs homeostasis. 
  • 933
  • 22 Sep 2021
Topic Review
Immune System's Role in Liver Biology and Metabolism
The liver is a remarkable organ, which coordinates a multitude of critical functions, whilst retaining the ability to dramatically remodel and regenerate damaged tissue. The liver is composed of four lobes which are subdivided into lobule structures. These are hexagonal in appearance, with each corner displaying the portal triad that consists of the portal vein, bile duct and hepatic artery. Although the liver is an exceptionally regenerative organ, chronic damage may result in scar tissue formation. This does not only have consequences for organ function but is also a major barrier for liver tissue remodeling and regeneration.
  • 933
  • 12 Jun 2023
Topic Review
Immunomodulatory Effects of Histone Deacetylase 6 Inhibitors
Patients diagnosed with metastatic uveal melanoma (MUM) have a poor survival prognosis. Unfortunately for this rare disease, there is no known cure and suitable therapeutic options are limited. Histone deacetylase 6 inhibitors (HDAC6i) are currently in clinical trials for other cancers and show potential beneficial effects against tumor cell survival in vitro and in vivo. In MUM cells, HDAC6i show an anti-proliferative effect in vitro and in preclinical zebrafish xenograft models. 
  • 932
  • 05 Sep 2022
Topic Review
CD34 Stem Cell Therapy
Ischemia with non-obstructive coronary arteries (INOCA) is an increasingly recognized disease, with a prevalence of 3 to 4 million individuals, and is associated with a higher risk of morbidity, mortality, and a worse quality of life. Persistent angina in many patients with INOCA is due to coronary microvascular dysfunction (CMD), which can be difficult to diagnose and treat. A coronary flow reserve <2.5 is used to diagnose endothelial-independent CMD. Antianginal treatments are often ineffective in endothelial-independent CMD and thus novel treatment modalities are currently being studied for safety and efficacy. CD34+ cell therapy is a promising treatment option for these patients, as it has been shown to promote vascular repair and enhance angiogenesis in the microvasculature. 
  • 932
  • 11 May 2021
Topic Review
Aptamer-Based Probes for Cancer Diagnostics and Treatment
Aptamers are single-stranded DNA or RNA oligomers that have the ability to generate unique and diverse tertiary structures that bind to cognate molecules with high specificity. In recent years, aptamer researches have witnessed a huge surge, owing to its unique properties, such as high specificity and binding affinity, low immunogenicity and toxicity, and simplicity of synthesis with negligible batch-to-batch variation. Aptamers may bind to targets, such as various cancer biomarkers, making them applicable for a wide range of cancer diagnosis and treatment. In cancer diagnostic applications, aptamers are used as molecular probes instead of antibodies.
  • 932
  • 08 Dec 2022
Topic Review
Respiratory Epithelial Cells against Fungal Infections
The respiratory epithelium is highly complex, and its composition varies along the conducting airways and alveoli. In addition to their primary function in maintaining the respiratory barrier and lung homeostasis for gas exchange, epithelial cells interact with inhaled pathogens, which can manipulate cell signaling pathways, promoting adhesion to these cells or hosting tissue invasion. Moreover, pathogens (or their products) can induce the secretion of chemokines and cytokines by epithelial cells, and in this way, these host cells communicate with the immune system, modulating host defenses and inflammatory outcomes.
  • 929
  • 31 May 2022
Topic Review
Antibodies and Pentraxins
Macrophages play a key role in induction of inflammatory responses. These inflammatory responses are mostly considered to be instigated by activation of pattern recognition receptors (PRRs) or cytokine receptors. However, recently it has become clear that also antibodies and pentraxins, which can both activate Fc receptors (FcRs), induce very powerful inflammatory responses by macrophages that can even be an order of magnitude greater than PRRs. While the physiological function of this antibody-dependent inflammation (ADI) is to counteract infections, undesired activation or over-activation of this mechanism will lead to pathology, as observed in a variety of disorders, including viral infections such as COVID-19, chronic inflammatory disorders such as Crohn’s disease, and autoimmune diseases such as rheumatoid arthritis.
  • 925
  • 04 Jun 2021
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