scholarly journals Elevated microglial oxidative phosphorylation and phagocytosis stimulate post-stroke brain remodeling and cognitive function recovery in mice

2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Shanshan Song ◽  
Lauren Yu ◽  
Md Nabiul Hasan ◽  
Satya S. Paruchuri ◽  
Steven J. Mullett ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Oxidative Phosphorylation ◽  
Aerobic Glycolysis ◽  
Tricarboxylic Acid Cycle ◽  
Post Stroke ◽  
Pathway Activation ◽  
Function Recovery ◽  
Underlying Mechanisms ◽  
New Research ◽  
Upregulated Genes

AbstractNew research shows that disease-associated microglia in neurodegenerative brains present features of elevated phagocytosis, lysosomal functions, and lipid metabolism, which benefit brain repair. The underlying mechanisms remain poorly understood. Intracellular pH (pHi) is important for regulating aerobic glycolysis in microglia, where Na/H exchanger (NHE1) is a key pH regulator by extruding H+ in exchange of Na+ influx. We report here that post-stroke Cx3cr1-CreER+/−;Nhe1flox/flox (Nhe1 cKO) brains displayed stimulation of microglial transcriptomes of rate-limiting enzyme genes for glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. The other upregulated genes included genes for phagocytosis and LXR/RXR pathway activation as well as the disease-associated microglia hallmark genes (Apoe, Trem2, Spp1). The cKO microglia exhibited increased oxidative phosphorylation capacity, and higher phagocytic activity, which likely played a role in enhanced synaptic stripping and remodeling, oligodendrogenesis, and remyelination. This study reveals that genetic blockade of microglial NHE1 stimulated oxidative phosphorylation immunometabolism, and boosted phagocytosis function which is associated with tissue remodeling and post-stroke cognitive function recovery.

scholarly journals Effects of Oxygen on Virulence Traits of Streptococcus mutans

2007 ◽  
Vol 189 (23) ◽  
pp. 8519-8527 ◽  
Author(s):  
Sang-Joon Ahn ◽  
Zezhang T. Wen ◽  
Robert A. Burne
Keyword(s):  
Streptococcus Mutans ◽  
Regulatory Networks ◽  
Nadh Oxidase ◽  
Tricarboxylic Acid Cycle ◽  
Virulence Gene ◽  
Virulence Gene Expression ◽  
Virulence Traits ◽  
Oral Biofilms ◽  
Underlying Mechanisms ◽  
Upregulated Genes

ABSTRACT Oxygen profoundly affects the composition of oral biofilms. Recently, we showed that exposure of Streptococcus mutans to oxygen strongly inhibits biofilm formation and alters cell surface biogenesis. To begin to dissect the underlying mechanisms by which oxygen affects known virulence traits of S. mutans, transcription profiling was used to show that roughly 5% of the genes of this organism are differentially expressed in response to aeration. Among the most profoundly upregulated genes were autolysis-related genes and those that encode bacteriocins, the ClpB protease chaperone subunit, pyruvate dehydrogenase, the tricarboxylic acid cycle enzymes, NADH oxidase enzymes, and certain carbohydrate transporters and catabolic pathways. Consistent with our observation that the ability of S. mutans to form biofilms was severely impaired by oxygen exposure, transcription of the gtfB gene, which encodes one of the primary enzymes involved in the production of water-insoluble, adhesive glucan exopolysaccharides, was down-regulated in cells growing aerobically. Further investigation revealed that transcription of gtfB, but not gtfC, was responsive to oxygen and that aeration causes major changes in the amount and degree of cell association of the Gtf enzymes. Moreover, inactivation of the VicK sensor kinase affected the expression and localization the GtfB and GtfC enzymes. This study provides novel insights into the complex transcriptional and posttranscriptional regulatory networks used by S. mutans to modulate virulence gene expression and exopolysaccharide production in response to changes in oxygen availability.

scholarly journals The Relationship of Psychiatric Symptoms with Performance-Based and Self-Reported Cognitive Function After Ischemic Stroke

2021 ◽  
pp. 1-13
Author(s):  
Elisabeth Kliem ◽  
Elise Gjestad ◽  
Truls Ryum ◽  
Alexander Olsen ◽  
Bente Thommessen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Executive Function ◽  
Depressive Symptoms ◽  
Cognitive Function ◽  
Psychiatric Symptoms ◽  
Post Stroke ◽  
Cognitive Difficulties ◽  
Memory And Attention ◽  
Relationship Of ◽  
The Relationship

Abstract Objective: Findings on the relationship of psychiatric symptoms with performance-based and self-reported cognitive function post-stroke are inconclusive. We aimed to (1) study the relation of depression and anxiety to performance-based cognitive function and (2) explore a broader spectrum of psychiatric symptoms and their association with performance-based versus self-reported cognitive function. Method: Individuals with supratentorial ischemic stroke performed neuropsychological examination 3 months after stroke. For primary analyses, composite scores for memory and attention/executive function were calculated based on selected neuropsychological tests, and the Hospital Anxiety and Depression Scale (HADS) was used. Psychiatric symptoms and self-reported cognitive function for secondary aims were assessed using the Symptom-Checklist-90 – Revised (SCL-90-R). Results: In a sample of 86 patients [mean (M) age: 64.6 ± 9.2; Mini-Mental State Examination (MMSE), 3–7 days post-stroke: M = 28.4 ± 1.7; National Institutes of Health Stroke Scale (NIHSS) after 3 months: M = 0.7 ± 1.6] depressive symptoms (HADS) were associated with poorer memory performance after controlling for age, sex, and education (p ≤ .01). In a subsample (n = 41; Age: M = 65.7 ± 8.1; MMSE: M = 28.4 ± 1.8; NIHSS: M = 1.0 ± 1.9), symptoms of phobic anxiety (SCL-90-R) were associated with poorer performance-based memory and attention/executive function, and symptoms of anxiety (SCL-90-R) with lower attention/executive function. Higher levels of self-reported cognitive difficulties were associated with higher scores in all psychiatric domains (p ≤ .05). Conclusion: Even in relatively well-functioning stroke patients, depressive symptoms are associated with poorer memory. The results also suggest that various psychiatric symptoms are more related to self-reported rather than to performance-based cognitive function. Screening for self-reported cognitive difficulties may not only help to identify patients with cognitive impairment, but also those who need psychological treatment.

scholarly journals Metabolism of Epithelial Cells in Health and Allergic Disease: Collegium Internationale Allergologicum Update 2021

2021 ◽  
pp. 1-16
Author(s):  
Ashley M. Queener ◽  
Sergio E. Chiarella ◽  
Lyda Cuervo-Pardo ◽  
Mackenzie E. Coden ◽  
Hiam Abdala-Valencia ◽  
...  
Keyword(s):  
Allergic Disease ◽  
Clinical Evidence ◽  
Metabolic Diseases ◽  
Tricarboxylic Acid Cycle ◽  
Allergic Diseases ◽  
Atopic Disease ◽  
Airway Disease ◽  
Epithelial Barrier ◽  
Metabolic Dysfunction ◽  
New Research

Concomitant dramatic increase in prevalence of allergic and metabolic diseases is part of a modern epidemic afflicting technologically advanced societies. While clinical evidence points to clear associations between various metabolic factors and atopic disease, there is still a very limited understanding of the mechanisms that link the two. Dysregulation of central metabolism in metabolic syndrome, obesity, diabetes, and dyslipidemia has a systemic impact on multiple tissues and organs, including cells of the epithelial barrier. While much of epithelial research in allergy has focused on the immune-driven processes, a growing number of recent studies have begun to elucidate the role of metabolic components of disease. This review will revisit clinical evidence for the relationship between metabolic and allergic diseases, as well as discuss potential mechanisms driving metabolic dysfunction of the epithelial barrier. Among them, novel studies highlight links between dysregulation of the insulin pathway, glucose metabolism, and loss of epithelial differentiation in asthma. Studies of mitochondrial structure and bioenergetics in lean and obese asthmatic phenotypes recently came to light to provide a novel framework linking changes in tricarboxylic acid cycle and oxidative phosphorylation with arginine metabolism and nitric oxide bioavailability. New research established connections between arachidonate metabolism, autophagy, and airway disease, as well as systemic dyslipidemia in atopic dermatitis and ceramide changes in the epidermis. Taken together, studies of metabolism have a great potential to open doors to a new class of therapeutic strategies, better characterization of disease endotypes, as well as enable a systems biology approach to mechanisms of allergic disease.

Experience sampling research in psychopathology: opening the black box of daily life

2009 ◽  
Vol 39 (9) ◽  
pp. 1533-1547 ◽  
Author(s):  
I. Myin-Germeys ◽  
M. Oorschot ◽  
D. Collip ◽  
J. Lataster ◽  
P. Delespaul ◽  
...  
Keyword(s):  
Daily Life ◽  
Experience Sampling ◽  
Added Value ◽  
Cross Sectional ◽  
Gene Environment ◽  
Psychological Models ◽  
Research Findings ◽  
Underlying Mechanisms ◽  
New Research ◽  
Momentary Assessment

A growing body of research suggests that momentary assessment technologies that sample experiences in the context of daily life constitute a useful and productive approach in the study of behavioural phenotypes and a powerful addition to mainstream cross-sectional research paradigms. Momentary assessment strategies for psychopathology are described, together with a comprehensive review of research findings illustrating the added value of daily life research for the study of (1) phenomenology, (2) aetiology, (3) psychological models, (4) biological mechanisms, (5) treatment and (6) gene–environment interactions in psychopathology. Overall, this review shows that variability over time and dynamic patterns of reactivity to the environment are essential features of psychopathological experiences that need to be captured for a better understanding of their phenomenology and underlying mechanisms. The Experience Sampling Method (ESM) allows us to capture the film rather than a snapshot of daily life reality of patients, fuelling new research into the gene–environment–experience interplay underlying psychopathology and its treatment.

The potential synergism by combining external counterpulsation with intermittent theta burst stimulation in post-stroke motor function recovery

2016 ◽  
Vol 93 ◽  
pp. 140-142
Author(s):  
Weijia He ◽  
Suk-yin Stephanie Au-Yeung ◽  
Margaret Mak ◽  
Thomas Wai Hong Leung ◽  
Howan Leung ◽  
...  
Keyword(s):  
Motor Function ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
External Counterpulsation ◽  
Post Stroke ◽  
Function Recovery ◽  
Theta Burst

scholarly journals Integrin αvβ3 Engagement Regulates Glucose Metabolism and Migration through Focal Adhesion Kinase (FAK) and Protein Arginine Methyltransferase 5 (PRMT5) in Glioblastoma Cells

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1111
Author(s):  
Pulin Che ◽  
Lei Yu ◽  
Gregory K. Friedman ◽  
Meimei Wang ◽  
Xiaoxue Ke ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Focal Adhesion ◽  
Aerobic Glycolysis ◽  
Integrin Αvβ3 ◽  
Metabolic Reprogramming ◽  
Migration And Invasion ◽  
Metabolic Shift ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Glioblastoma Cells ◽  
Arginine Methyltransferase

Metabolic reprogramming promotes glioblastoma cell migration and invasion. Integrin αvβ3 is one of the major integrin family members in glioblastoma multiforme cell surface mediating interactions with extracellular matrix proteins that are important for glioblastoma progression. The role of αvβ3 integrin in regulating metabolic reprogramming and its mechanism of action have not been determined in glioblastoma cells. Integrin αvβ3 engagement with osteopontin promotes glucose uptake and aerobic glycolysis, while inhibiting mitochondrial oxidative phosphorylation. Blocking or downregulation of integrin αvβ3 inhibits glucose uptake and aerobic glycolysis and promotes mitochondrial oxidative phosphorylation, resulting in decreased migration and growth in glioblastoma cells. Pharmacological inhibition of focal adhesion kinase (FAK) or downregulation of protein arginine methyltransferase 5 (PRMT5) blocks metabolic shift toward glycolysis and inhibits glioblastoma cell migration and invasion. These results support that integrin αvβ3 and osteopontin engagement plays an important role in promoting the metabolic shift toward glycolysis and inhibiting mitochondria oxidative phosphorylation in glioblastoma cells. The metabolic shift in cell energy metabolism is coupled to changes in migration, invasion, and growth, which are mediated by downstream FAK and PRMT5 in glioblastoma cells.

scholarly journals SAT-666 Possible Amelioration of Diabetic State After Intravesical BCG Instillations for Bladder Cancer

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jana Havranova ◽  
Thomas Gallagher ◽  
Mohammad Ishaq Arastu
Keyword(s):  
Bladder Cancer ◽  
Oxidative Phosphorylation ◽  
Aerobic Glycolysis ◽  
White Blood Cells ◽  
Diabetic Patients ◽  
Insulin Regimen ◽  
Intravesical Administration ◽  
Bcg Vaccination ◽  
Intravesical Bcg

Abstract Introduction - Current research provides strong evidence that intradermal Bacillus Calmette-Guerin (BCG) vaccination improves glucose metabolism by a mechanism of switching oxidative phosphorylation to aerobic glycolysis inducing a state of high glucose utilization. We present a case that demonstrates improvement in blood sugar levels upon administration of a series of intravesical BCG instillations. There is no research, in current literature, correlating blood sugars lowering after intravesical administration of BCG vaccines. Case Description - An 81 years old male with a medical history of type 2 diabetes mellitus, coronary artery disease, and bladder cancer underwent a series of BCG instillations, as therapy for his bladder cancer. He underwent BCG treatments according the Southwest oncology protocol for bladder cancer. During his BCG treatments, the patient was on Humalog 75/25, 30 units twice a day. Upon completion of his treatments, the patient experienced an episode of hypoglycemia that required hospitalization. His insulin regimen was decreased from 30 to 25 units BID. His A1C at the time of diagnosis was 8.7% and after insulin adjustments declined to 8.1%. We are reviewing a list of type II diabetic patients with bladder cancer who were treated with BCG and analyzing blood sugars before and after BCG exposure. We hypothesize that BCG vaccination precipitated the improvement in his blood sugars. Conclusion - Additional studies on BCG vaccinated, diabetic, bladder cancer patients are needed for confirmation of this effect. Our case illustrates a probable reduction in blood sugars attributable to his BCG vaccinations. Research suggests that intradermal BCG switches cellular metabolism from oxidative phosphorylation to early aerobic glycolysis. Another effect of BCG is the increasing levels of tumor necrosis factor (TNF) that leads to elimination of self-reactive white blood cells and inducing regulatory T cells. More research is needed to confirm whether intravesical administration of BCG has the same effect as intradermal BCG vaccination, which would have a potential impact on the clinical management of both type 1 and type 2 diabetic patients.

scholarly journals Non-canonical regulation of glycogenolysis and the Warburg phenotype by soluble adenylyl cyclase

2020 ◽  
Author(s):  
Jung-Chin Chang ◽  
Simei Go ◽  
Eduardo H. Gilglioni ◽  
Hang Lam Li ◽  
Hsu-Li Huang ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Adenylyl Cyclase ◽  
Energy Homeostasis ◽  
Aerobic Glycolysis ◽  
Glycogen Metabolism ◽  
Adenylyl Cyclases ◽  
Soluble Adenylyl Cyclase ◽  
Atp Level ◽  
Downstream Effectors ◽  
Different Types

AbstractCyclic AMP is produced in cells by two very different types of adenylyl cyclases: the canonical transmembrane adenylyl cyclases (tmACs, ADCY1∼9) and the evolutionarily more conserved soluble adenylyl cyclase (sAC, ADCY10). While the role and regulation of tmACs is well documented, much less is known of sAC in cellular metabolism. We demonstrate here that sAC is an acute regulator of glycolysis, oxidative phosphorylation and glycogen metabolism, tuning their relative bioenergetic contributions. Suppression of sAC activity leads to aerobic glycolysis, enhanced glycogenolysis, decreased oxidative phosphorylation, and an elevated cytosolic NADH/NAD+ ratio, resembling the Warburg phenotype. Importantly, we found that glycogen metabolism is regulated in opposite directions by cAMP depending on its location of synthesis and downstream effectors. While the canonical tmAC-cAMP-PKA axis promotes glycogenolysis, we identify a novel sAC-cAMP-Epac1 axis that suppresses glycogenolysis. These data suggest that sAC is an autonomous bioenergetic sensor that suppresses aerobic glycolysis and glycogenolysis when ATP levels suffice. When the ATP level falls, diminished sAC activity induces glycogenolysis and aerobic glycolysis to maintain energy homeostasis.

scholarly journals Severe Pantothenic Acid Deficiency Induces Alterations in the Intestinal Mucosal Proteome of Starter Pekin Ducks

2020 ◽  
Author(s):  
Jing Tang ◽  
Yulong Feng ◽  
Bo Zhang ◽  
Yongbao Wu ◽  
Zhanbao Guo ◽  
...  
Keyword(s):  
Intestinal Absorption ◽  
Tricarboxylic Acid Cycle ◽  
Pantothenic Acid ◽  
Energy Generation ◽  
Growth Depression ◽  
Pekin Ducks ◽  
Acid Deficiency ◽  
Underlying Mechanisms ◽  
Fasting Hypoglycemia ◽  
Pantothenic Acid Deficiency

Abstract Background: Pantothenic acid deficiency (PAD) results in growth depression and intestinal hypofunction of animals. The underlying mechanisms, however, remain to be established and an overview of molecular alterationsis still lacking.We investigated intestinal mucosalproteome changes induced by PADin ducks to explain its effects on growth and intestine.Methods:A total of128 one-day-oldPekinducks were divided into two groups,with 8 replicates and 8 birds per replicate. All the ducks were fed either a PAD or a pantothenic acid adequate (control, CON) dietfor 16 days.Results:High mortality, growthretardation,fasting hypoglycemia,reduced plasma insulin, and oxidative stresswere observed in the PAD group compared to the CON group. Furthermore, PAD induced morphological alterationsof the small intestine indicated by reduced villus height and villus surface area of duodenum, jejunum, and ileum.The duodenum mucosal proteome of ducks showed that 198 proteins were upregulated and 223 proteins were downregulated (> 1.5-fold change) in the PAD group compared to those in the CON group. Pathway analysis of these proteins exhibited the suppression of glycolysis and gluconeogenesis, fatty acid beta oxidation, tricarboxylic acid cycle, oxidative phosphorylation, oxidative stress, and intestinal absorption in the PAD group, indicating impaired energy generation and abnormal intestinal absorption.Wealso show that nine out of eleven proteins involved in regulation of actin cytoskeleton were upregulated by PAD, probably indicates reduced intestinal integrity.Conclusion:PAD leads to growth depression and intestinal hypofunctionof ducks, which are associated with impaired in energy generation, abnormal intestinal absorption, and regulation of actin cytoskeletonprocesses. These findings contribute to our understanding of the mechanisms of intestinal mucosa metabolic disorders due to PAD.

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