The utility of serum glucose potassium ratio as a predictive factor for haemorrhagic transformation, stroke recurrence, and mortality among ischemic stroke patients

Saudi Pharmaceutical Journal, Journal Year: 2024, Volume and Issue: 32(6), P. 102082 - 102082

Published: April 22, 2024

Glucose-Potassium Ratio (GPR) has emerged as a biomarker in several pathophysiological conditions. However, the association between GPR and long-term outcomes stroke patients not been investigated. Our study evaluated applicability of baseline predictive prognostic tool for clinical ischemic patients. The multicenter retrospective cohort included acute-subacute adult who had their serum levels measured. Eligible were categorized into two sub-cohorts based on (<1.67 vs. ≥ 1.67). primary outcome was incidence 30-day hemorrhagic transformation, while recurrence, all-cause mortality within twelve months, considered secondary. Among 4083 screened, 1047 current study. In comparison with < 1.67 group, significantly higher ratio months (aHR 2.07 [95 % CI 1.21–3.75] p = 0.01), transformation but failed to reach statistical significance 1.60 0.95–2.79], 0.08). Overall, is an independent predictor acute subacute stroke. Further studies are necessary validate these findings.

Language: Английский

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The Role of Smoking and Nicotine in the Transmission and Pathogenesis of COVID-19

Journal of Pharmacology and Experimental Therapeutics, Journal Year: 2020, Volume and Issue: 375(3), P. 498 - 509

Published: Oct. 8, 2020

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 virus, is turning out to be one of most devastating global pandemics in history humankind. There a shortage effective therapeutic strategies or preventative vaccines for this date. A rigorous investigation needed identifying and developing more COVID-19. Angiotensin-converting enzyme (ACE2), crucial factor COVID-19 pathogenesis, has been identified as potential target treatment. Smoking vaping are risk factors that also shown upregulate ACE2 expression. In review, we have discussed pathobiology lungs brain role transmission disease. Furthermore, possible interactions between nicotine/smoking brain, which could aggravate COVID-19, resulting poor outcome. SIGNIFICANCE STATEMENT: This review addresses present pandemic (COVID-19) with respect its brain. It focuses on negative impact tobacco nicotine exposure outcomes interaction angiotensin-converting receptor. adds time-sensitive critically important growing knowledge about factors, transmission, pathobiology, prognosis

Language: Английский

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The Missing Enzymes: A Call to Update Pharmacological Profiling Practices for Better Drug Safety Assessment

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Pharmacological profiling is critical for the development of safe drugs. With increasing awareness its significance and attempts to share best practices, here we aimed understand how pharmacological implemented reported in primary literature by analyzing representation nonkinase enzymes selectivity screens. This aspect has been overlooked previous publications, despite constituting a significant portion targets currently marketed Our analysis shows that while industry recommendations improved have widely adopted, remain largely underrepresented: about quarter studies did not include enzymes, on average, comprise only 11% all We discuss possible reasons this shortcoming provide examples missing from current conclude with notion screens should be expanded more improve drug safety.

Language: Английский

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Decoding mechanisms and protein markers in lung-brain axis

Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)

Published: May 19, 2025

The lung-brain axis represents a complex bidirectional communication network that is pivotal in the crosstalk between respiratory and neurological functions. This review summarizes current understanding of mechanisms protein markers mediate effects lung diseases on brain health. In this review, we explore linking injury to neurocognitive impairments, focusing neural pathways, immune regulation inflammatory responses, microorganism hypoxemia. Specifically, highlight role vagus nerve modulating central nervous system response pulmonary stimuli; Additionally, regulatory function underscored, with evidence suggesting lung-derived mediators can traverse blood-brain barrier, induce neuroinflammation cognitive decline; Furthermore, discuss potential microbiota influence through microbial translocation activation; Finally, impact hypoxemia examined, findings indicating it exacerbate cerebral via oxidative stress impaired perfusion. Moreover, analyze how conditions, such as pneumonia, ALI/ARDS, asthma, contribute dysfunction. Prolonged mechanical ventilation also impairment. Conversely, (e.g., stroke, traumatic injury) lead acute complications. addition, TLR4, ACE2, A-SAA, HMGB1, TREM2 are crucial correlate disease severity. We emerging therapeutic strategies targeting axis, including immunomodulation microbiome engineering. Overall, interplay for developing integrated treatment improving patient outcomes. Further research needed elucidate molecular foster interdisciplinary collaboration.

Language: Английский

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Motor deficit in the mouse ferric chloride-induced distal middle cerebral artery occlusion model of stroke

Behavioural Brain Research, Journal Year: 2019, Volume and Issue: 380, P. 112418 - 112418

Published: Dec. 5, 2019

Language: Английский

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Between two storms, vasoactive peptides or bradykinin underlie severity of COVID‐19?

Physiological Reports, Journal Year: 2021, Volume and Issue: 9(5)

Published: March 1, 2021

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to be a world-wide pandemic with overwhelming socioeconomic impact. Since inflammation is one of the major causes COVID-19 complications, associated molecular mechanisms have been focus many studies better understand this and develop improved treatments for patients contracting SARS-CoV-2. Among these, strong emphasis has placed on pro-inflammatory cytokines, associating severity so-called "cytokine storm." More recently, peptide bradykinin, its dysregulated signaling or "bradykinin storm," emerged as primary mechanism explain COVID-19-related complications. Unfortunately, important development may not fully capture main players that underlie severity. To end, in focused review, several lines evidence are provided suggest addition two closely related vasoactive peptides, substance P neurotensin, also likely drive microvascular permeability inflammation, responsible pathology. Furthermore, based published experimental observations, it postulated ACE neprilysin, peptidase neurolysin (Nln) contribute accumulation progression disease. In conclusion, proposed "vasoactive storm" simultaneous inhibition all three peptidergic systems could therapeutically more advantageous rather than modulation any single alone.

Language: Английский

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Delayed atomoxetine or fluoxetine treatment coupled with limited voluntary running promotes motor recovery in mice after ischemic stroke

Neural Regeneration Research, Journal Year: 2020, Volume and Issue: 16(7), P. 1244 - 1244

Published: Dec. 17, 2020

Currently, there is an unmet need for treatments promoting post-stroke functional recovery. The aim of this study was to evaluate and compare the dose-dependent effect delayed atomoxetine or fluoxetine therapy (starting on day 5), coupled with limited physical exercise (2 hours daily voluntary wheel running; days 9 42), motor recovery adult male mice after photothrombotic stroke. These drugs are selective norepinephrine serotonin reuptake inhibitors indicated disorders unrelated predetermined primary end-point function measured in two tasks spontaneous behaviors grid-walking cylinder tests. Additionally, we quantified running distance speed throughout study, number parvalbumin-positive neurons medial agranular cortex infarct volumes. Both sensorimotor tests revealed that neither nor a drug treatment alone significantly facilitated However, combination either promoted restoration by 42 post-stroke, being more potent drug. This accompanied significant decrease inhibitory interneurons ipsilateral recovering function, while volumes were comparable among experimental groups. If further validated larger studies, our observations suggest add-on limited, structured rehabilitation could offer therapeutic modality stroke survivors who have difficulty engage early, high-intensity physiotherapy. Furthermore, light recently completed Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) Efficacy Fluoxetine-a randomisEd Controlled Trial Stroke (EFFECTS) trials, call newly designed studies where pharmacotherapy evaluated rather than alone. approved Texas Tech University Health Sciences Center Institutional Animal Care Use Committee (protocol # 16019).

Language: Английский

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Neurolysin substrates bradykinin, neurotensin and substance P enhance brain microvascular permeability in a human in vitro model

Journal of Neuroendocrinology, Journal Year: 2021, Volume and Issue: 33(2)

Published: Jan. 28, 2021

Abstract Increased brain microvascular permeability and disruption of blood‐brain barrier (BBB) function are among hallmarks several acute neurodegenerative disorders, including stroke. Numerous studies suggest the involvement bradykinin (BK), neurotensin (NT) substance P (SP) in BBB impairment oedema formation after stroke; however, there is paucity data regard to direct effects these peptides on endothelial cells (BMECs) BBB. The present study aimed evaluate BK, NT SP an vitro model based human induced pluripotent stem cell (iPSC)‐derived BMECs. Our indicate that all three increase a concentration‐dependent manner formed from two different iPSC lines (CTR90F CTR65M) widely used hCMEC/D3 combination at sub‐effective concentration also resulted increased iPSC‐derived indicating potentiation their action. Furthermore, we observed abrogation with pretreatment pharmacological blockers targeting specific receptors. Additional mechanistic short‐term not mediated through alteration tight‐junction proteins claudin‐5 occludin, but likely involve redistribution F‐actin secretion vascular growth factor. This first experimental document response action model. In addition, our confirms expected well‐documented, effect adds well‐recognised actions BK Lastly, demonstrate peptidase neurolysin can neutralise BBB, suggesting potential therapeutic implications.

Language: Английский

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The role of peptidase neurolysin in neuroprotection and neural repair after stroke

Neural Regeneration Research, Journal Year: 2020, Volume and Issue: 16(1), P. 21 - 21

Published: Aug. 10, 2020

Current experimental stroke research has evolved to focus on detailed understanding of the brain's self-protective and restorative mechanisms, harness this knowledge for development new therapies. In context, role peptidases neuropeptides is growing interest. focused review, peptidase neurolysin (Nln) its extracellular peptide substrates are briefly discussed in relation pathophysiology ischemic stroke. Upregulation Nln following viewed as a compensatory cerebroprotective mechanism acute phase stroke, because main inactivated by neuro/cerebrotoxic (bradykinin, substance P, neurotensin, angiotensin II, hemopressin), whereas peptides generated neuro/cerebroprotective (angiotensin-(1–7), Leu-/Met-enkephalins). This notion confirmed studies documenting aggravation outcomes mice after inhibition dramatic improvement overexpressing brain. The (sub)chronic less clear it likely, that does not have major neural repair mechanisms. because, uniform modulating neurorestorative mechanisms one direction, some appearing enhancing/stimulating potential, others doing opposite. Future focusing should determine potential target therapy, unique ability modulate multiple neuropeptide systems critically involved brain injury likely advantageous over modulation pathogenic pathway pharmacotherapy.

Language: Английский

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Delayed Exercise-induced Upregulation of Angiogenic Proteins and Recovery of Motor Function after Photothrombotic Stroke in Mice

Neuroscience, Journal Year: 2021, Volume and Issue: 461, P. 57 - 71

Published: March 2, 2021

Language: Английский

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