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Topic Review
Altered Pathways in Fabry Disease
Fabry disease is a rare X-linked disease characterized by deficient expression and activity of alpha-galactosidase A (α-GalA) with consequent lysosomal accumulation of glycosphingolipid in various organs. Enzyme replacement therapy is the cornerstone of the treatment of all Fabry patients, although in the long-term it fails to completely halt the disease’s progression. This suggests on one hand that the adverse outcomes cannot be justified only by the lysosomal accumulation of glycosphingolipids and on the other that additional therapies targeted at specific secondary mechanisms might contribute to halt the progression of cardiac, cerebrovascular, and renal disease that occur in Fabry patients. 
  • 303
  • 15 Mar 2023
Topic Review
Alternate Causes for Pathogenesis of Exfoliation Glaucoma
Exfoliation glaucoma (XFG) is the most recognizable form of secondary open-angle glaucoma associated with a high risk of blindness. This disease is characterized by white flaky granular deposits in the anterior chamber that leads to the elevation of intraocular pressure (IOP) and subsequent glaucomatous optic nerve damage. Conventionally, XFG is known to respond poorly to medical therapy, and surgical intervention is the only management option in most cases.
  • 393
  • 11 Mar 2022
Topic Review
Alternative Emerging Therapies to Retinal Prostheses
Retinal prostheses show promise in restoring vision, but ongoing clinical trials and high costs limit their adoption. To explore alternatives for treating retinal diseases, we present an overview of cell-based and gene-based therapies. This entry aims to determine if retinal prostheses are losing favor as a therapeutic option. Cell-based therapies, particularly using pluripotent stem cells like induced pluripotent stem cells (iPSCs) and retinal progenitor cells (RPCs), hold promise for treating retinal diseases. iPSC-derived retinal pigment epithelium (RPE) cells show potential in delaying disease progression and restoring vision loss when the RPE layer is damaged. Additionally, bone marrow stem cells (BMSCs) release beneficial factors and have the ability to migrate towards lesion sites, although full differentiation into photoreceptors is not confirmed. Gene therapy also shows promise for treating retinal diseases caused by genetic mutations. Different approaches are used depending on the type of mutation (recessive or dominant). For example. viral vectors like AAV are commonly employed due to their efficient targeting and low immunogenicity. Optogenetics is a novel approach for treating inherited retinal diseases (IRDs) by introducing photosensitive proteins (opsins) to the degenerated retina. Opsins restore function and photosensitivity to remaining retinal cells. Clinical trials are underway, but more research is needed to understand opsin properties.
  • 247
  • 18 Sep 2023
Topic Review
Alternative RNA Splicing
Alternative splicing relies on the distinction between intronic and exonic sections of DNA within genes. The pre-processed mRNA transcript bears these same sections, which are recognized and spliced together by the spliceosome, a large complex of five small nuclear ribonucleoproteins (snRNPs) and proteins. Specific consensus sequences such as 5′ dinucleotide GU and 3′ dinucleotide AG in introns are critical to intron recognition.
  • 580
  • 15 Nov 2021
Topic Review
Alternative Splicing Events in Colorectal Cancer
Colorectal cancer is the second leading cause of cancer-related deaths worldwide. The incidence of this cancer continues to rise, especially in developing countries. Alternative splicing is a normal cellular process that results in the generation of proteins with different structures and functions from a single gene. Colorectal cancer can cause dysregulation of alternative splicing processes to promote its development and growth until it spreads. Dysregulated alternative splicing processes have been shown to promote cancer survival by producing proteins that activate genes known to promote cancer development or deactivate those that inhibit cancer development.
  • 154
  • 19 Sep 2023
Topic Review
Alternative Splicing in Myeloid Malignancies
Alternative RNA splicing (AS) is an essential physiologic function that diversifies the human proteome. AS also has a crucial role during cellular development. In fact, perturbations in RNA-splicing have been implicated in the development of several cancers, including myeloid malignancies. 
  • 642
  • 16 Dec 2021
Topic Review
Alternatives to Antibiotics
Infections caused by antibiotic-resistant bacteria (ARB) are one of the major global health challenges. In addition to developing new antibiotics to combat ARB, sensitizing ARB, or pursuing alternatives to existing antibiotics are promising options to counter antibiotic resistance.  Anti-ARB strategies include the following: (i) discovery of novel antibiotics by modification of existing antibiotics, screening of small-molecule libraries, or exploration of peculiar places; (ii) improvement in the efficacy of existing antibiotics through metabolic stimulation or by loading a novel, more efficient delivery systems; (iii) development of alternatives to conventional antibiotics such as bacteriophages and their encoded endolysins, anti-biofilm drugs, probiotics, nanomaterials, vaccines, and antibody therapies. 
  • 468
  • 12 Jan 2023
Topic Review
Alveolar Damage and Dysfunction in Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of interstitial lung diseases (ILDs), marked by an ongoing, chronic fibrotic process within the lung tissue. IPF leads to an irreversible deterioration of lung function, ultimately resulting in an increased mortality rate. 
  • 237
  • 30 Nov 2023
Topic Review
Alveolar Edema in COVID-19
The coronavirus disease 2019 (COVID-19) has spread over the world for more than one year. COVID-19 often develops life-threatening hypoxemia. Endothelial injury caused by the viral infection leads to intravascular coagulation and ventilation-perfusion mismatch, alveolar edema also plays a key role in the disease progression. Diffuse alveolar damage (DAD) is the histopathological pattern commonly described in COVID-19. Endothelial barrier disruption induces interstitial flooding via activation of the actin-myosin contractile apparatus. Then alveolar edema leads to hypoxia at the injured alveolar units. Hypoxia in turn inhibits edema fluid clearance, due in part to the disassembly of the keratin intermediate filament network, a fundamental element of the cellular cytoskeleton, therefore destructing the epithelial barrier. Therefore, a long-term hypoxia aggravates the disease by inducing more alveolar edema, which forms a vicious circle.
  • 571
  • 09 Aug 2021
Topic Review
Alveolar NLRP3 Inflammasome Regulators
Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is a successful intracellular pathogen that is responsible for the highest mortality rate among diseases caused by bacterial infections. During early interaction with the host innate cells, M. tuberculosis cell surface antigens interact with Toll like receptor 4 (TLR4) to activate the nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain-containing 3 (NLRP3) canonical, and non-canonical inflammasome pathways. NLRP3 inflammasome activation in the alveoli has been reported to contribute to the early inflammatory response that is needed for an effective anti-TB response through production of pro-inflammatory cytokines, including those of the Interleukin 1 (IL1) family. However, overstimulation of the alveolar NLRP3 inflammasomes can induce excessive inflammation that is pathological to the host. Several studies have explored the use of medicinal plants and/or their active derivatives to inhibit excessive stimulation of the inflammasomes and its associated factors, thus reducing immunopathological response in the host. This review describes the molecular mechanism of the NLRP3 inflammasome activation in the alveoli during M. tuberculosis infection. Furthermore, the mechanisms of inflammasome inhibition using medicinal plant and their derivatives will also be explored, thus offering a novel perspective on the alternative control strategies of M. tuberculosis-induced immunopathology. 
  • 506
  • 24 Nov 2021
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