Publications by authors named "Christopher Sobey"

Article Synopsis
  • Hypertension is a significant risk factor for both stroke and cognitive decline, but its specific impact on cognitive impairment after a stroke is still uncertain.
  • In a study with C57BL/6J mice, researchers induced hypertension and then conducted strokes to assess cognitive outcomes using the Barnes maze and analyzed the brain's transcriptomic profile through RNA sequencing.
  • Results indicated that hypertensive mice experienced worse cognitive performance and more brain injury compared to normotensive mice after a stroke, with over 1500 genes linked to neuroinflammation being differentially expressed.
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Introduction: Marginal zone and follicular B cells are known to contribute to the development of angiotensin II-induced hypertension in mice, but the effector function(s) mediating this effect (e.g., antigen presentation, antibody secretion and/or cytokine production) are unknown.

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Single-cell technologies such as flow cytometry and single-cell RNA sequencing have allowed for comprehensive characterization of the kidney cellulome. However, there is a disparity in the various protocols for preparing kidney single-cell suspensions. We aimed to address this limitation by characterizing kidney cellular heterogeneity using three previously published single-cell preparation protocols.

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Aortic diseases such as atherosclerosis, aortic aneurysms, and aortic stiffening are significant complications that can have significant impact on end-stage cardiovascular disease. With limited pharmacological therapeutic strategies that target the structural changes in the aorta, surgical intervention remains the only option for some patients with these diseases. Although there have been significant contributions to our understanding of the cellular architecture of the diseased aorta, particularly in the context of atherosclerosis, furthering our insight into the cellular drivers of disease is required.

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Article Synopsis
  • Vascular inflammation and fibrosis are key issues in hypertension that can lead to heart disease and cognitive decline, but current treatments focus more on symptoms than underlying tissue damage.
  • A study on male mice showed that angiotensin II increased blood pressure and vascular damage, while injected amnion epithelial cells reduced these harmful effects and helped prevent cognitive impairment.
  • These results indicate that amnion epithelial cells may be a promising new therapy for addressing both vascular issues and cognitive decline in people with hypertension.
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The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.

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Stroke is a major cause of morbidity worldwide; yet, there is a lack of treatment options to address post-stroke cognitive and motor impairment, thus there is an urgency for developing neuroprotective and restorative therapies. Much of our fundamental understanding of stroke pathology has been derived from animal models. The photothrombotic model of ischemic stroke is commonly used to study cellular and molecular mechanisms of neurodegeneration, test functional/cognitive outcomes, identify important biomarkers, and assess the effectiveness of novel therapies.

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Obesity and vascular dysfunction are independent and sexually dimorphic risk factors for cardiovascular disease. A high fat diet (HFD) is often used to model obesity in mice, but the sex-specific effects of this diet on aortic inflammation and function are unclear. Therefore, we characterized the aortic immune cell profile and function in 6-week-old male and female C57BL/6 mice fed a normal chow diet (NCD) or HFD for 10 weeks.

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Intermittent fasting (IF) has been shown to reduce cardiovascular risk factors in both animals and humans, and can protect the heart against ischemic injury in models of myocardial infarction. However, the underlying molecular mechanisms behind these effects remain unclear. To shed light on the molecular and cellular adaptations of the heart to IF, we conducted comprehensive system-wide analyses of the proteome, phosphoproteome, and transcriptome, followed by functional analysis.

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Background: Chronic pelvic pain is a burdensome condition that involves multiple medical sub-specialties and is often difficult to treat. Sacral stimulation for functional bladder disease has been well established, but little large-scale evidence exists regarding utilization of other neuromodulation techniques to treat chronic pelvic pain. Emerging evidence does suggest that neuromodulation is a promising treatment, and we aim to characterize the use and efficacy of such techniques for treating chronic pelvic pain syndromes.

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Atherosclerosis is characterized by the narrowing of the arterial lumen due to subendothelial lipid accumulation, with hypercholesterolemia being a major risk factor. Despite the recent advances in effective lipid-lowering therapies, atherosclerosis remains the leading cause of mortality globally, highlighting the need for additional therapeutic strategies. Accumulating evidence suggests that the sympathetic nervous system plays an important role in atherosclerosis.

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Inflammation is a hallmark mechanism of ischemic stroke-induced brain injury. Recent studies have shown that an intracellular multimeric protein complex known as an inflammasome is a key factor for inducing an inflammatory response, and apoptotic and pyroptotic cell death in ischemic stroke. Inflammasome assembly leads to the activation of pro-inflammatory caspases, and the maturation and secretion of pro-inflammatory cytokines IL-1β and IL-18.

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A spinal cord stimulator is an important long-term treatment modality for refractory chronic pain of multiple etiologies. Hardware-related complications remain known adverse events associated with this intervention. Understanding the risk factors for development of such complications is important for optimizing the efficacy and longevity of spinal cord stimulators.

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The association between constipation and cardiovascular risk is unclear. This population-level matched cohort study compared the association of constipation with hypertension and incident cardiovascular events in 541,172 hospitalized patients aged ≥ 60 years. For each constipation admission, one exact age-matched non-constipated admission was randomly selected from all hospitalizations within 2 weeks to form the comparison cohort.

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Background: Thrombolytic agents such as tissue plasminogen activator (tPA) are the only drug class approved to treat ischemic stroke and are usually administered within 4.5 h. However, only ~20% of ischemic stroke patients are eligible to receive the therapy.

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Introduction: Depletion of mature B cells affords protection against experimental hypertension. However, whether B cell-mediated hypertension is dependent on differentiation into antibody-secreting cells (ASCs) remains unclear. Using the proteasome inhibitor, bortezomib, the present study tested the effect of ASC reduction on angiotensin II-induced hypertension.

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Vascular cognitive impairment (VCI) describes a wide spectrum of cognitive deficits related to cerebrovascular diseases. Although the loss of blood flow to cortical regions critically involved in cognitive processes must feature as the main driver of VCI, the underlying mechanisms and interactions with related disease processes remain to be fully elucidated. Recent clinical studies of cerebral blood flow measurements have supported the role of chronic cerebral hypoperfusion (CCH) as a major driver of the vascular pathology and clinical manifestations of VCI.

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Background: We proposed a Phase I dose escalation trial to assess the safety of allogeneic human amniotic epithelial cells (hAECs) in stroke patients with a view to informing the design for a Phase II trial.

Methods: The design is based on 3 + 3 dose escalation design with additional components for measuring MR signal of efficacy as well as the effect of hAECs (2-8 × 10/kg, i.v.

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Obesity is a major global health concern, with prevalence rates rapidly rising due to increased availability of highly processed foods rich in fats and/or sugars and technological advances promoting more sedentary behaviour. There is increasing evidence to suggest that obesity predisposes individuals to developing cognitive impairment and dementia. However, the relationship between the brain and the peripheral metabolic state is complex, and many of the underlying mechanisms of cognitive impairment in obesity are yet to be fully elucidated.

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Ca/calmodulin-dependent protein kinase II alpha (CaMKIIα) is a major contributor to physiological and pathological glutamate-mediated Ca signals, and its involvement in various critical cellular pathways demands specific pharmacological strategies. We recently presented γ-hydroxybutyrate (GHB) ligands as the first small molecules selectively targeting and stabilizing the CaMKIIα hub domain. Here, we report that the cyclic GHB analogue 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA), improves sensorimotor function after experimental stroke in mice when administered at a clinically relevant time and in combination with alteplase.

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We investigated the association of dietary intake of major types of fatty acids with heart disease mortality in a general adult cohort with or without a prior diagnosis of myocardial infarction (MI). This cohort study included US adults who attended the National Health and Nutrition Examination Surveys from 1988 to 2014. Heart disease mortality was ascertained by linkage to the National Death Index records through 31 December 2015.

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