scholarly journals Anti-flavivirus Properties of Lipid-Lowering Drugs

2021 ◽  
Vol 12 ◽  
Author(s):  
Carlos Noe Farfan-Morales ◽  
Carlos Daniel Cordero-Rivera ◽  
José Manuel Reyes-Ruiz ◽  
Arianna M. Hurtado-Monzón ◽  
Juan Fidel Osuna-Ramos ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Antiviral Treatment ◽  
Lipid Lowering ◽  
Effective Vaccine ◽  
Human Pathogens ◽  
Lipid Lowering Drugs ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Replicative Cycle

Although Flaviviruses such as dengue (DENV) and zika (ZIKV) virus are important human pathogens, an effective vaccine or antiviral treatment against them is not available. Hence, the search for new strategies to control flavivirus infections is essential. Several studies have shown that the host lipid metabolism could be an antiviral target because cholesterol and other lipids are required during the replicative cycle of different Flaviviridae family members. FDA-approved drugs with hypolipidemic effects could be an alternative for treating flavivirus infections. However, a better understanding of the regulation between host lipid metabolism and signaling pathways triggered during these infections is required. The metabolic pathways related to lipid metabolism modified during DENV and ZIKV infection are analyzed in this review. Additionally, the role of lipid-lowering drugs as safe host-targeted antivirals is discussed.

scholarly journals Regulation of Oligodendrocyte Functions: Targeting Lipid Metabolism and Extracellular Matrix for Myelin Repair

2020 ◽  
Vol 9 (2) ◽  
pp. 470 ◽  
Author(s):  
Davide Marangon ◽  
Marta Boccazzi ◽  
Davide Lecca ◽  
Marta Fumagalli
Keyword(s):  
Extracellular Matrix ◽  
Lipid Metabolism ◽  
Plasma Membranes ◽  
Neurological Diseases ◽  
Membrane Composition ◽  
Myelin Repair ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Extracellular Environment

Myelin is an essential structure that protects axons, provides metabolic support to neurons and allows fast nerve transmission. Several neurological diseases, such as multiple sclerosis, are characterized by myelin damage, which is responsible of severe functional impairment. Myelin repair requires the timely recruitment of adult oligodendrocyte precursor cells (OPCs) at the lesion sites, their differentiation and maturation into myelinating oligodendrocytes. As a consequence, OPCs undergo profound changes in their morphology, functions, and interactions with other cells and extracellular environment, thus requiring the reorganization of both their lipid metabolism and their membrane composition, which is substantially different compared to other plasma membranes. Despite the growing knowledge in oligodendroglia biology and in the mechanisms involved in OPC-mediated regeneration, the identification of strategies to promote remyelination still remains a challenge. Here, we describe how altered lipid metabolism in oligodendrocytes influences the pathogenesis of demyelination, and we show that several FDA-approved drugs with a previously unknown remyelination potential do act on cholesterol and lipid biosynthetic pathways. Since the interplay between myelin lipids and axons is strictly coordinated by the extracellular matrix (ECM), we also discuss the role of different ECM components, and report the last findings on new ECM-modifiers able to foster endogenous remyelination.

scholarly journals Adrenergic-Angiogenic Crosstalk in Head and Neck Cancer: Mechanisms and Therapeutic Implications

2021 ◽  
Vol 2 ◽  
Author(s):  
Vui King Vincent-Chong ◽  
Mukund Seshadri
Keyword(s):  
Head And Neck ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Therapeutic Implications ◽  
Multiple Components ◽  
Aggressive Tumors ◽  
Approved Drugs ◽  
Neural Signaling ◽  
Fda Approved Drugs

Head and neck squamous cell carcinomas (HNSCC) are loco-regionally aggressive tumors that often lead to debilitating changes in appearance, speech, swallowing and respiratory function in patients. It is therefore critical to develop novel targeted treatment strategies that can effectively target multiple components within the tumor microenvironment. In this regard, there has been an increased recognition of the role of neural signaling networks as mediators of disease progression in HNSCC. Here, we summarize the current knowledge on the mechanisms of adrenergic signaling in HNSCC specifically focusing on neurovascular crosstalk and the potential of targeting the adrenergic-angiogenic axis through repurposing of FDA-approved drugs against HNSCC.

166 TLR-4-Regulated Cerebrospinal Fluid Hypersecretion in Post-Hemorrhagic Hydrocephalus

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 242-242 ◽  
Author(s):  
Jason K Karimy ◽  
Jinwei Zhang ◽  
David B Kurland ◽  
Brianna Carusillo Theriault ◽  
Daniel Duran ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Fold Increase ◽  
Pharmacological Intervention ◽  
Antisense Oligodeoxynucleotide ◽  
Genetic Ablation ◽  
Csf Shunting ◽  
Approved Drugs ◽  
Molecular Patterns ◽  
Fda Approved Drugs

Abstract INTRODUCTION Intraventricular hemorrhage (IVH) frequently causes post-hemorrhagic hydrocephalus (PHH) as a result of impaired cerebrospinal fluid (CSF) homeostasis. The most common treatment for PHH is surgical CSF shunting, a procedure fraught with complications. Historically, it is thought that PHH results from impaired reabsorption of CSF, however, little consideration has been given to the role of CSF hypersecretion. Recently, toll-like receptor-4 (TLR-4) has been implicated in the CNS by detecting “alarmins”, including IVH-derived metabolites, via recognition of damage-associated molecular patterns. We speculate that IVH triggers TLR-4-dependent inflammation at the choroid plexus epithelia (CPE), leading to CSF hypersecretion contributing to the development of PHH. METHODS In an established rat model of IVH, we assessed the rate of CSF secretion, CPE inflammation and the effect of genetic and pharmacological intervention on the development of PHH. We developed and implemented a novel surgical method in rats to measure the rate of CSF secretion. TLR-4 knockout rats, antisense oligodeoxynucleotide-mediated gene knockdown, and intracerebroventricular delivery of FDA-approved drugs were used to assess the role of specific inflammatory and ion transport targets on CSF secretion rate and ventriculomegaly following IVH. Immunoblot and immunohistochemistry were used to detect and quantify inflammatory markers. RESULTS >We show IVH triggers TLR4-NFkB-mediated inflammation at the CPE that is associated with a striking ∼3-fold increase in CSF secretion sufficient to cause PHH. CSF hypersecretion is dependent on the NFkB-regulated kinase SPAK, which interacts with and phosphorylates the bumetanide-sensitive NKCC1 at the CPE apical membrane. Genetic ablation of TLR-4 or SPAK, and pharmacology antagonizing TLR-4-NFkB signaling or the SPAK-NKCC1 complex normalizes CSF secretion rates and ventriculomegaly after IVH. CONCLUSION These data uncover a previously unrecognized role for CSF hypersecretion in the pathogenesis of PHH, and reveal a novel TLR-4-dependent regulatory pathway of CSF secretion that can be targeted with repurposed, FDA-approved drugs for the non-surgical treatment of PHH.

scholarly journals The Role of the ACE2/MasR Axis in Ischemic Stroke: New Insights for Therapy

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1667
Author(s):  
Mansoureh Barzegar ◽  
Karen Y. Stokes ◽  
Oleg Chernyshev ◽  
Roger E. Kelley ◽  
Jonathan S. Alexander
Keyword(s):  
Ischemic Stroke ◽  
Time Window ◽  
Renin Angiotensin System ◽  
Experimental Stroke ◽  
Stroke Treatment ◽  
Angiotensin Converting Enzyme 2 ◽  
Thrombolytic Agents ◽  
Approved Drugs ◽  
Fda Approved Drugs

Ischemic stroke remains the leading cause of neurologically based morbidity and mortality. Current stroke treatment is limited to two classes of FDA-approved drugs: thrombolytic agents (tissue plasminogen activator (tPA)) and antithrombotic agents (aspirin and heparin), which have a narrow time-window (<4.5 h) for administration after onset of stroke symptoms. While thrombolytic agents restore perfusion, they carry serious risks for hemorrhage, and do not influence damage responses during reperfusion. Consequently, stroke therapies that can suppress deleterious effects of ischemic injury are desperately needed. Angiotensin converting enzyme-2 (ACE2) has been recently suggested to beneficially influence experimental stroke outcomes by converting the vasoconstrictor Ang II into the vasodilator Ang 1–7. In this review, we extensively discuss the protective functions of ACE2-Ang (1–7)-MasR axis of renin angiotensin system (RAS) in ischemic stroke.

In Silico Identification of Active Phytochemicals against COVID-19 by Targeting the SARS-CoV-2 Spike Glycoprotein Through Molecular Docking: A Drug Repurposing Approach

2021 ◽  
Vol 8 (2) ◽  
pp. 72-87
Author(s):  
Rathan Kumar
Keyword(s):  
Molecular Docking ◽  
Antiviral Treatment ◽  
Drug Repurposing ◽  
Modern Human ◽  
Binding Affinities ◽  
In Silico Identification ◽  
Adme Properties ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Natural Inhibitors

The spread of coronavirus disease (COVID-19) has become one of the most significant pandemics in modern human history, affecting more than 70 million people worldwide. Currently, only a few fda-approved drugs have suggested fighting the infection, in the absence of a specific antiviral treatment. Thus, repurposing the presently available drugs or using plant-based bioactive compounds can be the fastest possible solution. In this study, the computational methodology of molecular docking techniques was performed to screen and identify the viable potent inhibitors against the SARS-CoV-2 spike protein from a library of 200 active phytochemicals, based on their highest binding affinity towards the target protein. Later, the binding affinities of these phytochemicals were compared with that of the fda-approved drug fluvoxamine, which is currently in use against the mild COVID-19 patients. Out of these, 86 phytochemicals that exhibited better binding energy of value ≤-7.00kcal/mol, is selected for adme (absorption, distribution, metabolism, and excretion) analysis and drug likeliness studies to check the feasibility of these compounds. Wherein, 79 out of 86 phytochemicals showed a better theoretical affinity with sufficiently bearable adme properties. Thus, they can be the lead molecule for further investigation and validation processes towards developing natural inhibitors against the SARS-CoV-2 virus.

Differential associations between lipid-lowering drugs, statins and fibrates, and venous thromboembolism: Role of drug induced homocysteinemia?

2008 ◽  
Vol 122 (3) ◽  
pp. 314-319 ◽  
Author(s):  
Karine Lacut ◽  
Grégoire Le Gal ◽  
Jean-Hervé Abalain ◽  
Dominique Mottier ◽  
Emmanuel Oger
Keyword(s):  
Venous Thromboembolism ◽  
Lipid Lowering ◽  
Drug Induced ◽  
Lipid Lowering Drugs

scholarly journals EXPERT CONSENSUS. ROLE OF COMBINATION LIPID-LOWERING THERAPY (SIMVASTATIN/EZETIMIBE 20/10 MG) IN THE CORRECTION OF LIPID METABOLISM DISTURBANCES IN PATIENTS WITH CHRONIC KIDNEY DISEASE

2013 ◽  
Vol 12 (4) ◽  
pp. 75-78
Author(s):  
A. Catapano ◽  
E. V. Shlyakhto ◽  
A. I. Martynov ◽  
R. G. Oganov ◽  
V. V. Kukharchuk ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Lipid Metabolism ◽  
Kidney Disease ◽  
Expert Consensus ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy

Expert Consensus. Role of combination lipid-lowering therapy (simvastatin/ezetimibe 20/10 mg) in the correction of lipid metabolism disturbances in patients with chronic kidney disease.

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