Pathophysiology of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: A Review

Journal of the American Heart Association, Journal Year: 2021, Volume and Issue: 10(15)

Published: July 30, 2021

Delayed cerebral ischemia is a major predictor of poor outcomes in patients who suffer subarachnoid hemorrhage. Treatment options are limited and often ineffective despite many years investigation clinical trials. Modern advances basic science have produced much more complex, multifactorial framework which delayed better understood novel treatments can be developed. Leveraging this knowledge to improve outcomes, however, depends on holistic understanding the disease process. We conducted review literature analyze current state into with emphasis themes that emerged over past decades. Specifically, we discuss microcirculatory dysfunction, glymphatic impairment, inflammation, neuroelectric disruption as pathological factors addition canonical focus vasospasm. This intends give clinicians researchers summary foundations pathophysiology while also underscoring interactions interdependencies between factors. Through overview, highlight translational studies potential future therapeutic opportunities.

Language: Английский

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Inflammation mechanism and anti-inflammatory therapy of dry eye

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Feb. 14, 2024

Dry eye is a widespread chronic inflammatory disease that causes fatigue, tingling, burning, and other symptoms. attributed to rheumatic diseases, diabetes, hormone disorders, contact lenses, which activate pathways: mitogen-activated protein kinases (MAPK) nuclear factor-B (NF-κB), promote macrophage cell T activation, inflammation factors. Clinicians use combination of anti-inflammatory drugs manage different symptoms dry eye; some these are being developed. This review introduces the mechanisms involved We also elucidate drug mechanism detection limits.

Language: Английский

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Receptor-mediated targeted drug delivery systems for treatment of inflammatory bowel disease: Opportunities and emerging strategies

Acta Pharmaceutica Sinica B, Journal Year: 2020, Volume and Issue: 11(9), P. 2798 - 2818

Published: Nov. 7, 2020

Inflammatory bowel disease (IBD) is a chronic intestinal with painful clinical manifestations and high risks of cancerization. With no curative therapy for IBD at present, the development effective therapeutics highly advocated. Drug delivery systems have been extensively studied to transmit inflamed colon sites through enhanced permeability retention (EPR) effect caused by inflammation. However, drug still could not achieve concentration value that merely utilized on EPR display better therapeutic efficacy in region because nontargeted release. Substantial researches shown some specific receptors cell adhesion molecules expresses surface colonic endothelial and/or immune cells when occurs, ligand-modified targeting such can specifically deliver into obtain great effects. This review introduces overexpressed retrospects functionalized related ligands. Finally, challenges future directions this field are presented advance receptor-mediated targeted IBD.

Language: Английский

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Mitochondrial permeability transition pore is involved in oxidative burst and NETosis of human neutrophils

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2020, Volume and Issue: 1866(5), P. 165664 - 165664

Published: Jan. 8, 2020

Language: Английский

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Clinical characteristics and outcomes among hospitalized adults with severe COVID-19 admitted to a tertiary medical center and receiving antiviral, antimalarials, glucocorticoids, or immunomodulation with tocilizumab or cyclosporine: A retrospective observational study (COQUIMA cohort)

EClinicalMedicine, Journal Year: 2020, Volume and Issue: 28, P. 100591 - 100591

Published: Oct. 15, 2020

Language: Английский

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Impact of novel microbial secondary metabolites on the pharma industry

Applied Microbiology and Biotechnology, Journal Year: 2022, Volume and Issue: 106(5-6), P. 1855 - 1878

Published: Feb. 21, 2022

Microorganisms are remarkable producers of a wide diversity natural products that significantly improve human health and well-being. Currently, these comprise half all the pharmaceuticals on market. After discovery penicillin by Alexander Fleming 85 years ago, search for study antibiotics began to gain relevance as drugs. Since then, have played valuable role in treating infectious diseases saved many lives. New molecules with anticancer, hypocholesterolemic, immunosuppressive activity now been introduced treat other relevant diseases. Smaller biotechnology companies academic laboratories generate novel secondary metabolites big pharmaceutical no longer develop. The purpose this review is illustrate some recent developments show potential modern technologies like metagenomics genome mining offer development new molecules, different functions therapeutic alternatives needed overcome current severe problems, such SARS-CoV-2 pandemic, antibiotic resistance, emerging • Novel treatment infections caused bacteria, fungi, viruses. Second wave efforts microbial origin against related variants. Microbial drugs used clinical practice hypocholesterolemic agents, immunosuppressants, anticancer therapy.

Language: Английский

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Mitochondrial dysfunction in sepsis: mechanisms and therapeutic perspectives

Critical Care, Journal Year: 2024, Volume and Issue: 28(1)

Published: Sept. 3, 2024

Sepsis is a severe medical condition characterized by systemic inflammatory response, often culminating in multiple organ dysfunction and high mortality rates. In recent years, there has been growing recognition of the pivotal role played mitochondrial damage driving progression sepsis. Various factors contribute to impairment during sepsis, encompassing mechanisms such as reactive nitrogen/oxygen species generation, mitophagy inhibition, dynamics change, membrane permeabilization. Damaged mitochondria actively participate shaping milieu triggering key signaling pathways, including those mediated Toll-like receptors, NOD-like cyclic GMP-AMP synthase. Consequently, surge interest developing therapeutic strategies targeting mitigate septic pathogenesis. This review aims delve into intricate underpinning sepsis its significant impact on immune dysregulation. Moreover, we spotlight promising mitochondria-targeted interventions that have demonstrated efficacy preclinical models.

Language: Английский

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Toward a pathophysiology inspired treatment of VEXAS syndrome

Seminars in Hematology, Journal Year: 2021, Volume and Issue: 58(4), P. 239 - 246

Published: Oct. 1, 2021

Language: Английский

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Cyclosporine A loaded brain targeting nanoparticle to treat cerebral ischemia/reperfusion injury in mice

Journal of Nanobiotechnology, Journal Year: 2022, Volume and Issue: 20(1)

Published: June 3, 2022

Ischemic stroke is one of the main causes death and disability in world. The treatment for ischemic to restore blood perfusion as soon possible. However, when brain tissue re-perfused by blood, mitochondrial permeability transition pore (mPTP) neuron microglia excessively opened, resulting apoptosis nerve inflammation. This aggravates injury. Cyclosporine A (CsA) inhibits over-opening mPTP, subsequently reducing release ROS cerebral ischemia/reperfusion injured microglia. CsA insoluble water present high concentrations lymphatic tissue. Herein, infarction targeted nanoparticle (CsA@HFn) was developed treat injury.CsA@HFn efficiently penetrated blood-brain barrier (BBB) selectively accumulated area, inhibiting opening mPTP production neuron. reduced damage BBB. Consequently, CsA@HFn significantly infarct area. Moreover, inhibited recruitment astrocytes region polarized into M2 type microglia, which alleviated inflammation.CsA@HFn showed a significant therapeutic effect on injury alleviating neuron, inflammation BBB has great potential stroke.

Language: Английский

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Cyclosporine A Inhibits Viral Infection and Release as Well as Cytokine Production in Lung Cells by Three SARS-CoV-2 Variants

Microbiology Spectrum, Journal Year: 2022, Volume and Issue: 10(1)

Published: Jan. 5, 2022

In December 2019, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started spreading worldwide causing the disease 2019 (COVID-19) pandemic. The hyperactivation of immune system has been proposed to account for severity and death in COVID-19 patients. Despite several approaches having tested, no therapeutic protocol approved. Given that Cyclosporine A (CsA) is well-known exert strong antiviral activity on viral strains an anti-inflammatory role different organs with relevant benefits diverse pathological contexts, we tested its effects SARS-CoV-2 infection lung cells. We found treatment CsA either before or after CaLu3 cells by three variants: (i) reduces expression both RNA proteins infected cells; (ii) decreases number progeny virions released (iii) dampens virus-triggered synthesis cytokines (including IL-6, IL-8, IL1α TNF-α) are involved cytokine storm Altogether, these data provide rationale repositioning IMPORTANCE most recently identified member betacoronavirus genus responsible Repurposing available drugs "quick dirty" approach try reduce mortality symptoms affected patients initially, can still represent undeniable valuable face as continuous appearance rapid diffusion more "aggressive"/transmissible variants, capable eluding antibody neutralization, challenges effectiveness some anti-SARS-CoV-2 vaccines. Here, known drug, (CsA), it release from upon exposure variants. Knock down main intracellular target CsA, Cyclophilin A, does not phenocopy drug inhibition infection. findings shed light cellular mechanisms treat

Language: Английский

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