scholarly journals An endothelial link between the benefits of physical exercise in dementia

2017 ◽  
Vol 37 (8) ◽  
pp. 2649-2664 ◽  
Author(s):  
Lianne J Trigiani ◽  
Edith Hamel
Keyword(s):  
Physical Exercise ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Inflammatory Responses ◽  
Vascular Cognitive Impairment ◽  
Endothelial Cell Function ◽  
Positive Effects ◽  
Disease Modifying ◽  
Disease Modifying Treatment

The current absence of a disease-modifying treatment for Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID) highlights the necessity for investigating the benefits of non-pharmacological approaches such as physical exercise (PE). Although evidence exists to support an association between regular PE and higher scores on cognitive function tests, and a slower rate of cognitive decline, there is no clear consensus on the underlying molecular mechanisms of the advantages of PE. This review seeks to summarize the positive effects of PE in human and animal studies while highlighting the vascular link between these benefits. Lifestyle factors such as cardiovascular diseases, metabolic syndrome, and sleep apnea will be addressed in relation to the risk they pose in developing AD and VCID, as will molecular factors known to have an impact on either the initiation or the progression of AD and/or VCID. This will include amyloid-beta clearance, oxidative stress, inflammatory responses, neurogenesis, angiogenesis, glucose metabolism, and white matter integrity. Particularly, this review will address how engaging in PE can counter factors that contribute to disease pathogenesis, and how these alterations are linked to endothelial cell function.

scholarly journals CD40/CD40L contributes to hypercholesterolemia-induced microvascular inflammation

2009 ◽  
Vol 296 (3) ◽  
pp. H689-H697 ◽  
Author(s):  
Karen Y. Stokes ◽  
LeShanna Calahan ◽  
Candiss M. Hamric ◽  
Janice M. Russell ◽  
D. Neil Granger
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
T Cell ◽  
Blood Cell ◽  
Cell Function ◽  
Inflammatory Responses ◽  
Microvascular Dysfunction ◽  
Cd40 Ligand ◽  
Scid Mice ◽  
Endothelial Cell Function

Hypercholesterolemia is associated with phenotypic changes in endothelial cell function that lead to a proinflammatory and prothrombogenic state in different segments of the microvasculature. CD40 ligand (CD40L) and its receptor CD40 are ubiquitously expressed and mediate inflammatory responses and platelet activation. The objective of this study was to determine whether CD40/CD40L, in particular T-cell CD40L, contributes to microvascular dysfunction induced by hypercholesterolemia. Intravital microscopy was used to quantify blood cell adhesion in cremasteric postcapillary venules, endothelium-dependent vasodilation responses in arterioles, and microvascular oxidative stress in wild-type (WT) C57BL/6, CD40-deficient (−/−), CD40L−/−, or severe combined immune deficient (SCID) mice placed on a normal (ND) or high-cholesterol (HC) diet for 2 wk. WT-HC mice exhibited an exaggerated leukocyte and platelet recruitment in venules and impaired vasodilation responses in arterioles compared with ND counterparts. A deficiency of CD40, CD40L, or lymphocytes attenuated these responses to HC. The HC phenotype was rescued in CD40L−/− and SCID mice by a transfer of WT T cells. Bone marrow chimeras revealed roles for both vascular- and blood cell-derived CD40 and CD40L in the HC-induced vascular responses. Hypercholesterolemia induced an oxidative stress in both arterioles and venules of WT mice, which was abrogated by either CD40 or CD40L deficiency. The transfer of WT T cells into CD40L−/− mice restored the oxidative stress. These results implicate CD40/CD40L interactions between circulating cells and the vascular wall in both the arteriolar and venular dysfunction elicited by hypercholesterolemia and identify T-cell-associated CD40L as a key mediator of these responses.

scholarly journals Physical Exercise as a Preventive or Disease-Modifying Treatment of Dementia and Brain Aging

2011 ◽  
Vol 86 (9) ◽  
pp. 876-884 ◽  
Author(s):  
J. Eric Ahlskog ◽  
Yonas E. Geda ◽  
Neill R. Graff-Radford ◽  
Ronald C. Petersen
Keyword(s):  
Physical Exercise ◽  
Brain Aging ◽  
Disease Modifying ◽  
Disease Modifying Treatment

scholarly journals Effects of sevoflurane and propofol anesthesia on intraoperative endothelial cell function in patients undergoing laparoscopic cholecystectomy

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052091840
Author(s):  
Yu Fan ◽  
Hao Wang ◽  
Qi Ma
Keyword(s):  
Laparoscopic Cholecystectomy ◽  
Cell Function ◽  
Inflammatory Responses ◽  
Vascular Endothelial Cells ◽  
Structure Stability ◽  
Vascular Endothelial ◽  
Endothelial Cell Function ◽  
Inflammatory Reactions ◽  
And Function ◽  
Cell Adhesion Molecule 1

Objectives To investigate the effects of sevoflurane and propofol anesthesia on inflammatory or anti-inflammatory responses in patients undergoing laparoscopic cholecystectomy (LC). Methods Patients undergoing LC (n = 23) were divided into sevoflurane (S) (n = 11) and propofol (P) (n = 12) anesthesia groups. A blood sample was taken before induction (T0), after induction but before pneumoperitoneum (T1), 15 minutes after pneumoperitoneum (T2), immediately after extubation (T3), and 30 minutes after extubation (T4). P-selectin-positive platelets and intercellular cell adhesion molecule-1 (ICAM-1)-positive lymphocytes, and plasma P-selectin, ICAM-1 and thrombomodulin (TM) levels were analyzed. Results Sevoflurane significantly increased P-selectin expression in platelets at T2, T3, and T4 and in plasma at T1, T2, T3, and T4, but it did not affect ICAM-1 and TM. Propofol had no significant effects on P-selectin, ICAM-1, and TM expression during anesthesia and surgery. P-selectin, ICAM-1, and TM expression was higher in the S compared with P group at T1, T2, and T3 for platelet P-selectin; T2 and T4 for plasma P-selectin; T1 and T2 for lymphocyte ICAM-1; and T1, T2, and T3 for plasma TM. Conclusions Propofol anesthesia can delay the inflammatory reactions during laparoscopic surgery and better maintain the structure stability and function in vascular endothelial cells.

Mechanisms for Radioprotection by Melatonin; Can it be Used as a Radiation Countermeasure?

2019 ◽  
Vol 12 (1) ◽  
pp. 2-11 ◽  
Author(s):  
Peyman Amini ◽  
Hanifeh Mirtavoos-Mahyari ◽  
Elahe Motevaseli ◽  
Dheyauldeen Shabeeb ◽  
Ahmed Eleojo Musa ◽  
...  
Keyword(s):  
Animal Studies ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Experimental Studies ◽  
Antioxidant Property ◽  
Interesting Property ◽  
Ir Studies ◽  
Radiation Induced ◽  
Radiosensitive Organs ◽  
Clinical Radiotherapy

Background:Melatonin is a natural body product that has shown potent antioxidant property against various toxic agents. For more than two decades, the abilities of melatonin as a potent radioprotector against toxic effects of ionizing radiation (IR) have been proved. However, in the recent years, several studies have been conducted to illustrate how melatonin protects normal cells against IR. Studies proposed that melatonin is able to directly neutralize free radicals produced by IR, leading to the production of some low toxic products.Discussion:Moreover, melatonin affects several signaling pathways, such as inflammatory responses, antioxidant defense, DNA repair response enzymes, pro-oxidant enzymes etc. Animal studies have confirmed that melatonin is able to alleviate radiation-induced cell death via inhibiting pro-apoptosis and upregulation of anti-apoptosis genes. These properties are very interesting for clinical radiotherapy applications, as well as mitigation of radiation injury in a possible radiation disaster. An interesting property of melatonin is mitochondrial ROS targeting that has been proposed as a strategy for mitigating effects in radiosensitive organs, such as bone marrow, gastrointestinal system and lungs. However, there is a need to prove the mitigatory effects of melatonin in experimental studies.Conclusion:In this review, we aim to clarify the molecular mechanisms of radioprotective effects of melatonin, as well as possible applications as a radiation countermeasure in accidental exposure or nuclear/radiological disasters.

Inhibition of pro-inflammatory cytokine receptor signalling by cAMP in vascular endothelial cells

2005 ◽  
Vol 33 (5) ◽  
pp. 1126-1128 ◽  
Author(s):  
W.A. Sands ◽  
T.M. Palmer
Keyword(s):  
Molecular Mechanisms ◽  
Cell Function ◽  
Vascular Endothelial Cell ◽  
Janus Kinase ◽  
Cytokine Receptor ◽  
Intracellular Camp ◽  
Vascular Endothelial ◽  
Endothelial Cell Function ◽  
Inhibitory Processes ◽  
Inflammatory Signalling

The anti-inflammatory effects of the prototypical second messenger cAMP have been extensively documented in multiple cell types. However, in many instances, the molecular mechanisms by which cAMP elevation disrupts specific pro-inflammatory signalling cascades are unknown. In this review, we will describe the importance of the JAK–STAT (where JAK stands for Janus kinase and STAT for signal transducer and activator of transcription) signalling pathway in vascular endothelial cell function, outline key inhibitory processes that serve to reduce cytokine-stimulated tyrosine phosphorylation and activation of STAT proteins, and discuss possible mechanisms by which intracellular cAMP sensors could interact with these inhibitory processes to diminish cytokine receptor-mediated pro-inflammatory signalling.

scholarly journals Muscle stem cell and physical activity: what point is the debate at?

Open Medicine ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 144-156 ◽  
Author(s):  
Gabriele Ceccarelli ◽  
Laura Benedetti ◽  
Maria Luisa Arcari ◽  
Cecilia Carubbi ◽  
Daniela Galli
Keyword(s):  
Physical Activity ◽  
Stem Cells ◽  
Physical Exercise ◽  
Cardiac Muscle ◽  
Weight Control ◽  
Molecular Mechanisms ◽  
Post Injury ◽  
Muscle Stem Cells ◽  
Positive Effects ◽  
Differentiated Cells

AbstractIn the last 15 years, it emerged that the practice of regular physical activity reduces the risks of many diseases (cardiovascular diseases, diabetes, etc.) and it is fundamental in weight control and energy consuming to contrast obesity. Different groups proposed many molecular mechanisms as responsible for the positive effects of physical activity in healthy life. However, many points remain to be clarified. In this mini-review we reported the latest observations on the effects of physical exercise on healthy skeletal and cardiac muscle focusing on muscle stem cells. The last ones represent the fundamental elements for muscle regeneration post injury, but also for healthy muscle homeostasis.Interestingly, in both muscle tissues the morphological consequence of physical activity is a physiological hypertrophy that depends on different phenomena both in differentiated cells and stem cells. The signaling pathways for physical exercise effects present common elements in skeletal and cardiac muscle, like activation of specific transcription factors, proliferative pathways, and cytokines. More recently, post translational (miRNAs) or epigenetic (DNA methylation) modifications have been demonstrated. However, several points remain unresolved thus requiring new research on the effect of exercise on muscle stem cells.

scholarly journals The Interaction between microRNAs and the Wnt/β-catenin Signaling Pathway in Osteoarthritis

2021 ◽  
Vol 22 (18) ◽  
pp. 9887
Author(s):  
Xiaobin Shang ◽  
Kai Oliver Böker ◽  
Shahed Taheri ◽  
Thelonius Hawellek ◽  
Wolfgang Lehmann ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Signaling Pathway ◽  
Metabolic Activity ◽  
Molecular Mechanisms ◽  
Microrna Regulation ◽  
Cellular Processes ◽  
Disease Modifying ◽  
Disease Modifying Treatment ◽  
And Cartilage

Osteoarthritis (OA) is a chronic disease affecting the whole joint, which still lacks a disease-modifying treatment. This suggests an incomplete understanding of underlying molecular mechanisms. The Wnt/β-catenin pathway is involved in different pathophysiological processes of OA. Interestingly, both excessive stimulation and suppression of this pathway can contribute to the pathogenesis of OA. microRNAs have been shown to regulate different cellular processes in different diseases, including the metabolic activity of chondrocytes and osteocytes. To bridge these findings, here we attempt to give a conclusive overview of microRNA regulation of the Wnt/β-catenin pathway in bone and cartilage, which may provide insights to advance the development of miRNA-based therapeutics for OA treatment.

scholarly journals Diverse Mechanisms of Allergen Specific Immunotherapy

2019 ◽  
Vol 23 (3) ◽  
pp. 233-249 ◽  
Author(s):  
Lacin Cevhertas ◽  
Mübeccel Akdis
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Allergen Immunotherapy ◽  
Specific Immunotherapy ◽  
Prognostic Markers ◽  
Recent Literature ◽  
Administration Route ◽  
Allergen Specific Immunotherapy ◽  
Disease Modifying ◽  
Disease Modifying Treatment

Allergen immunotherapy (AIT) is widely used to establish a tolerant immune response and it is currently the only disease modifying treatment. There are different routes to administer the allergen, including subcutaneous, sublingual, intralymphatic, epicutaneous, intradermal, and oral and local nasal allergen immunotherapy. Although the optimal administration route depends on the type of allergen, some patients remain unresponsive and so it is important to predict the outcome before and during treatment. Therefore, there is a need to identify candidate prognostic markers for allergen immunotherapy. Herein, we discuss the recent literature on the molecular mechanisms of AIT.

Diabetes-associated Erectile Dysfunction

2009 ◽  
Vol 05 (0) ◽  
pp. 75 ◽  
Author(s):  
Pedro Vendeira ◽  
Carla Costa ◽  
Ronald Virag ◽  
◽  
◽  
...  
Keyword(s):  
Risk Factor ◽  
Erectile Dysfunction ◽  
Endothelial Dysfunction ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Experimental Models ◽  
Vascular Pathology ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Endothelial Cell Function ◽  
The Metabolic Syndrome

Erectile dysfunction (ED) is a common complication of diabetes, with a prevalence ranging from 15 to 55%. The basis underlying diabetesassociated ED is multifactorial, involving changes in peripheral nerve activity and alterations in endothelial cell function. Due to the complexity of this pathology, the development of experimental models has been crucial in evaluating and translating fundamental results into clinical diabetes-associated ED. The concept of hard-to-treat patients, such as men with diabetes, is now fully accepted due to the complex mechanisms involved. In these men, the response to common oral treatments with phosphodiesterase type 5 inhibitors (PDE5Is) is far from desired, and maximal doses of the drugs are often needed. In addition, diabetes is commonly associated with other co-morbidities, such as hypertension, hypercholesterolaemia and obesity, clusters of the metabolic syndrome (MetS). ED is considered an early warning sentinel for coronary artery disease, just as endothelial dysfunction is seen as a major risk factor for ED. Testosterone deficiency syndrome, a very common syndrome in diabetes and MetS, has been shown to be an independent determinant of endothelial dysfunction, thus contributing to vascular pathology, including ED. This syndrome should be identified among patients, and therapeutic intervention may be required. PDE5Is may improve erectile function with or without the help of other second- or third-line treatments. Other strategies to maximise the response to PDE5Is include risk factor modification and daily dosing of the drugs, instead of on-demand treatment. However, better understanding of the fundamental molecular mechanisms underlying diabetes-associated ED is essential to improving and developing more effective therapies.

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