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Topic Review
Alveolar Regeneration in COVID-19 Patients: Network Perspective
Lung alveolar regeneration to repair the damaged tissue and restoration of normal tissue function could be achieved by transplantation of progenitor or stem cells and exosome-mediated delivery of therapeutic agents, including miRNAs. Not only as a biomarker of COVID-19but also as therapeutic agents, miRNAs have proven to play a crucial role in lung damage and repair. miRNAs can either be regulated locally in the lungsor transported to the damaged site by extracellular vehicles (EVs) secreted by stem cells to induce tissue regeneration by decreasing inflammation and apoptosis, stimulating surfactant production, regulating gene expression of junction proteins to repair microvascular permeability, and reducing fibrosis.
  • 1.1K
  • 03 Nov 2021
Topic Review
Targeting KRAS in Pancreatic Ductal Adenocarcinoma
Pancreatic cancer is one of the most intractable malignant tumors worldwide, and is known for its refractory and poor prognosis. Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. KRAS is the most commonly mutated oncogene in PDAC. It has been considered the “untargetable” oncogene for decades until the emergence of G12C inhibitors, which put an end to this dilemma by covalent binding to the switch-II pocket of the G12C mutant protein. However, G12C inhibitors showed remarkable efficacy against non-small-cell lung cancer (NSCLC), while the G12C mutation is rare in PDAC. Based on the successful experience of G12C inhibitors, targeting KRAS G12D/V, which forms the majority of KRAS mutations in PDAC, is gradually being regarded as a potential therapy.
  • 1.1K
  • 01 Nov 2022
Topic Review
Apelinergic System in Pregnancy
The apelinergic system is a highly conserved pleiotropic system. It comprises the apelin receptor apelin peptide jejunum (APJ) and its two peptide ligands, Elabela/Toddler (ELA) and apelin, which have different spatiotemporal localizations. This system has been implicated in the regulation of the adipoinsular axis, in cardiovascular and central nervous systems, in carcinogenesis, and in pregnancy in humans. During pregnancy, the apelinergic system is essential for embryo cardiogenesis and vasculogenesis and for placental development and function. It may also play a role in the initiation of labor. The apelinergic system seems to be involved in the development of placenta-related pregnancy complications, such as preeclampsia (PE) and intrauterine growth restriction, but an improvement in PE-like symptoms and birth weight has been described in murine models after the exogenous administration of apelin or ELA.
  • 1.1K
  • 08 May 2023
Topic Review
Polyploidy Events in Grasses
Polyploidy events have long been recognized as the primary driving force behind the survival of the vast majority of plant lineages, playing critical roles in crop evolution, speciation, and domestication. The fascinating modern genomics era has revealed that the genomes of all flowering plants have been polyploidized multiple times. To help safeguard the future of the global food supply in the face of climate change, a thorough understanding of polyploid genomes is critical, especially for the improvement of members of the grass family, Poaceae, which includes the world’s big three cereals—rice, wheat, and maize—as well as some potential underutilized ancient grasses (such as teff) that are less well known or studied. 
  • 1.1K
  • 23 Jun 2022
Topic Review
Frataxin–Scaffold Interaction in Fe–S Cluster
Iron–sulfur clusters are essential to almost every life form and utilized for their unique structural and redox-targeted activities within cells during many cellular pathways. Proteins central to the eukaryotic ISC cluster assembly complex include the cysteine desulfurase, a cysteine desulfurase accessory protein, the acyl carrier protein, the scaffold protein and frataxin (in humans, NFS1, ISD11, ACP, ISCU and FXN, respectively). Recent molecular details of this complex (labeled NIAUF from the first letter from each ISC protein outlined earlier), which exists as a dimeric pentamer, have provided real structural insight into how these partner proteins arrange themselves around the cysteine desulfurase, the core dimer of the (NIAUF)2 complex.
  • 1.1K
  • 15 Jun 2021
Topic Review
Chronic Effects of Fluoxetine on Danio rerio
Fluoxetine is an antidepressant widely used to treat depressive and anxiety states. Due to its mode of action in the central nervous system (selective serotonin reuptake inhibitor (SSRI)), it becomes toxic to non-target organisms, leading to alterations detrimental to its survival.
  • 1.1K
  • 06 Apr 2022
Topic Review
ORP5 and ORP8
Oxysterol binding related proteins 5 and 8 (ORP5 and ORP8) are two close homologs of the larger oxysterol binding protein (OSBP) family of sterol sensors and lipid transfer proteins (LTP). Early studies indicated these transmembrane proteins, anchored to the endoplasmic reticulum (ER), bound and sensed cholesterol and oxysterols. They were identified as important for diverse cellular functions including sterol homeostasis, vesicular trafficking, proliferation and migration. In addition, they were implicated in lipid-related diseases such as atherosclerosis and diabetes, but also cancer, although their mechanisms of action remained poorly understood. Then, alongside the increasing recognition that membrane contact sites (MCS) serve as hubs for non-vesicular lipid transfer, added to their structural similarity to other LTPs, came discoveries showing that ORP5 and 8 were in fact phospholipid transfer proteins that rather sense and exchange phosphatidylserine (PS) for phosphoinositides, including phosphatidylinositol-4-phosphate (PI(4)P) and potentially phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2). Evidence now points to their action at MCS between the ER and various organelles including the plasma membrane, lysosomes, mitochondria, and lipid droplets. Dissecting exactly how this unexpected phospholipid transfer function connects with sterol regulation in health or disease remains a challenge for future studies.
  • 1.1K
  • 15 Jul 2021
Topic Review
Automated Stuttering Classification
Speech disfluency, particularly stuttering, can have a significant impact on effective communication. Stuttering is a speech disorder characterized by repetitions, prolongations, and blocks in the flow of speech, which can result in communication difficulties, social isolation, and low self-esteem. Stuttering can also lead to negative reactions from listeners, such as impatience or frustration, which can further exacerbate communication difficulties.
  • 1.1K
  • 07 Oct 2023
Topic Review
Glia Dysfunction in Major Mental Diseases
Microglia exert multiple functional roles and contribute to the building of the neuronal circuit through synaptic pruning and stripping during development; they participate in surveillance by secreting neurotrophic factors that react against infectious agents or toxic elements and engage in phagocytic debris clearance, including the removal of dying neurons. The role of glia dysfunction, particularly Bergmann Glia in glutamate removal, is well described in autism.
  • 1.1K
  • 03 May 2023
Topic Review
Ubiquitylation and ISGylation
Ubiquitylation and ISGylation are protein post-translational modifications (PTMs) and two of the main events involved in the activation of pattern recognition receptor (PRRs) signals allowing the host defense response to viruses.
  • 1.1K
  • 21 Feb 2022
Topic Review
Peripheral Events in the Pathophysiology of PTNP
The ICOP (International Classification of Orofacial Pain), 1ST edition describes post-traumatic trigeminal neuropathic pain (PTNP) as “a unilateral or bilateral facial or oral pain following and caused by trauma to the trigeminal nerve(s), with other symptoms and/or clinical signs of trigeminal nerve dysfunction, and persisting or recurring for more than 3 months”. A cascade of events in the peripheral and central nervous system function is involved in the pathophysiology of pain following nerve injuries. Central and peripheral processes occur in tandem and may often be co-dependent. Due to the complexity of central mechanisms, only peripheral events contributing to the pathophysiology have been reviewed herein.
  • 1.1K
  • 15 Dec 2022
Topic Review
Limbic System in Tinnitus
Tinnitus is originally derived from the Latin verb tinnire, which means “to ring”. Tinnitus, a complex disorder, is a result of sentient cognizance of a sound in the absence of an external auditory stimulus. It is reported in children, adults, and older populations. Patients suffering from tinnitus often present with hearing loss, anxiety, depression, and sleep disruption in addition to a hissing and ringing in the ear. Surgical interventions and many other forms of treatment have been only partially effective due to heterogeneity in tinnitus patients and a lack of understanding of the mechanisms of tinnitus. 
  • 1.1K
  • 25 Jun 2023
Topic Review
Paclitaxel and Breast Cancer
Paclitaxel (PTX), the most widely used anticancer drug, is applied for the treatment of various types of malignant diseases. Mechanisms of PTX action represent several ways in which PTX affects cellular processes resulting in programmed cell death. PTX is frequently used as the first-line treatment drug in breast cancer (BC). Unfortunately, the resistance of BC to PTX treatment is a great obstacle in clinical applications and one of the major causes of death associated with treatment failure. Factors contributing to PTX resistance, such as ABC transporters, microRNAs (miRNAs), or mutations in certain genes, along with side effects of PTX including peripheral neuropathy or hypersensitivity associated with the vehicle used to overcome its poor solubility, are responsible for intensive research concerning the use of PTX in preclinical and clinical studies. Novelties such as albumin-bound PTX (nab-PTX) demonstrate a progressive approach leading to higher efficiency and decreased risk of side effects after drug administration. Moreover, PTX nanoparticles for targeted treatment of BC promise a stable and efficient therapeutic intervention.
  • 1.1K
  • 05 Aug 2021
Topic Review
NF-κB and Human Cancer
Transcription factor NF-κB has been extensively studied for its varied roles in cancer since its initial characterization as a potent retroviral oncogene several decades ago. It is now clear that NF-κB plays a major role in a large variety of human cancers, including especially ones of immune cell origin. NF-κB is generally constitutively or aberrantly activated in human cancers where it is involved.
  • 1.1K
  • 25 Dec 2021
Topic Review
Elderly Tinnitus and Neuropsychological Dysfunction
Tinnitus is a common and disabling symptom often associated with hearing loss. While clinical practice frequently shows that a certain degree of psychological discomfort often characterizes tinnitus suffers, it has been recently suggested in adults as a determining factor for cognitive decline affecting attention and memory domains. 
  • 1.1K
  • 18 Jun 2021
Topic Review
LAIR1
Leukocyte-associated immunoglobulin (Ig)-like receptor 1 (LAIR1, CD305) belongs to the family of immune-inhibitory receptors and is widely expressed on hematopoietic mature cells, particularly on immune cells. Four different types of ligands of LAIR1 have been described, including collagens, suggesting a potential immune-regulatory function on the extracellular matrix. By modulating cytokine secretion and cellular functions, LAIR1 displays distinct patterns of expression among NK cell and T/B lymphocyte subsets during their differentiation and cellular activation and plays a major negative immunoregulatory role. Beyond its implications in physiology, the activity of LAIR1 can be inappropriately involved in various autoimmune or inflammatory disorders and has been implicated in cancer physiopathology, including hematological neoplasms. Its action as an inhibitory receptor can result in the dysregulation of immune cellular responses and in immune escape within the tumor microenvironment. 
  • 1.1K
  • 28 Dec 2022
Topic Review
Annexins and Membrane Repair Dysfunctions
Muscular dystrophies constitute a group of genetic disorders that cause weakness and progressive loss of skeletal muscle mass. Among them, Miyoshi muscular dystrophy 1 (MMD1), limb girdle muscular dystrophy type R2 (LGMDR2/2B), and LGMDR12 (2L) are characterized by mutation in gene encoding key membrane-repair protein, which leads to severe dysfunctions in sarcolemma repair. Cell membrane disruption is a physiological event induced by mechanical stress, such as muscle contraction and stretching. Like many eukaryotic cells, muscle fibers possess a protein machinery ensuring fast resealing of damaged plasma membrane. Members of the annexins A (ANXA) family belong to this protein machinery. ANXA are small soluble proteins, twelve in number in humans, which share the property of binding to membranes exposing negatively-charged phospholipids in the presence of calcium (Ca2+). Many ANXA have been reported to participate in membrane repair of varied cell types and species, including human skeletal muscle cells in which they may play a collective role in protection and repair of the sarcolemma. Here, we discuss the participation of ANXA in membrane repair of healthy skeletal muscle cells and how dysregulation of ANXA expression may impact the clinical severity of muscular dystrophies.
  • 1.1K
  • 31 May 2021
Topic Review
The Mutant p53 Secretome
p53 suppresses tumorigenesis by activating a plethora of effector pathways. While most of these operate primarily inside of cells to limit proliferation and survival of incipient cancer cells, many extend to the extracellular space. In particular, p53 controls expression and secretion of numerous extracellular factors that are either soluble or contained within extracellular vesicles such as exosomes. As part of the cellular secretome, they execute key roles in cell-cell communication and extracellular matrix remodeling. Mutations in the p53-encoding TP53 gene are the most frequent genetic alterations in cancer cells, and therefore, have profound impact on the composition of the tumor cell secretome.
  • 1.1K
  • 10 Jun 2021
Topic Review
Indole and Indole-Related Compounds by the Intestinal Microbiota
The intestinal microbiota metabolic activity towards the available substrates generates myriad bacterial metabolites that may accumulate in the luminal fluid. Indole and indole-related compounds are, first, involved in intestinal microbial community communication, regulating important aspects of bacterial physiology. These molecules are also known to be active on the intestinal mucosa, exerting overall beneficial effects in different experimental situations, notably in inflammatory situations. After absorption, indole is partly metabolized in the liver into the co-metabolite indoxyl sulfate.
  • 1.1K
  • 20 May 2022
Topic Review
Flavonoids in Breast Cancer
Breast cancer (BC) remains the second most common cause of cancer-related deaths in women in the US, despite advances in detection and treatment. In addition, breast cancer survivors often struggle with long-term treatment related comorbidities. Identifying novel therapies that are effective while minimizing toxicity is critical in curtailing this disease. Flavonoids, a subclass of plant polyphenols, are emerging as promising treatment options for the prevention and treatment of breast cancer. Recent evidence suggests that in addition to anti-oxidant properties, flavonoids can directly interact with proteins, making them ideal small molecules for the modulation of enzymes, transcription factors and cell surface receptors. Of particular interest is the ability of flavonoids to modulate the tumor associated macrophage function. However, clinical applications of flavonoids in cancer trials are limited. Epidemiological and smaller clinical studies have been largely hypothesis generating. Future research should aim at addressing known challenges with a broader use of preclinical models and investigating enhanced dose-delivery systems that can overcome limited bioavailability of dietary flavonoids. 
  • 1.1K
  • 03 Sep 2021
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