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Search Results (22,166)

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24 pages, 663 KiB  
Article
Investigating the Effects of Dietary Supplementation and High-Intensity Motor Learning on Nutritional Status, Body Composition, and Muscle Strength in Children with Moderate Thinness in Southwest Ethiopia: A Cluster-Randomized Controlled Trial
by Melese Sinaga Teshome, Evi Verbecque, Sarah Mingels, Marita Granitzer, Teklu Gemechu Abessa, Liesbeth Bruckers, Tefera Belachew and Eugene Rameckers
Nutrients 2024, 16(18), 3118; https://doi.org/10.3390/nu16183118 (registering DOI) - 15 Sep 2024
Abstract
Abstract: Background: In Ethiopia, moderate thinness (MT) is a persistent issue among children. Yet, evidence on the effects of dietary supplementation and motor skills training in these children is limited. Objective: This study aimed to assess the effect of Ready-to-Use Supplementary Food (RUSF), [...] Read more.
Abstract: Background: In Ethiopia, moderate thinness (MT) is a persistent issue among children. Yet, evidence on the effects of dietary supplementation and motor skills training in these children is limited. Objective: This study aimed to assess the effect of Ready-to-Use Supplementary Food (RUSF), whether or not combined with high-intensity motor learning (HiML), on weight, height, body composition, and muscle strength in children 5–7 years old with MT living in Jimma Town, Ethiopia. Methods: A cluster-randomized controlled trial was carried out among 69 children (aged 5–7) with MT assigned to receive RUSF (n = 23), RUSF + HiML (n = 25), or no intervention (control group, n = 21). A multivariable Generalized Estimating Equations model was used and the level of significance was set at alpha < 0.05. Results:At baseline, there were no significant differences in the outcome measurements between the RUSF, RUSF + HiML, and control groups. However, after 12 weeks of intervention, there were significant mean differences in differences (DIDs) between the RUSF group and the control arm, with DIDs of 1.50 kg for weight (p < 0.001), 20.63 newton (N) for elbow flexor (p < 0.001), 11.00 N for quadriceps (p = 0.023), 18.95 N for gastrocnemius sup flexor of the leg (p < 0.001), and 1.03 kg for fat-free mass (p = 0.022). Similarly, the mean difference in differences was higher in the RUSF + HiML group by 1.62 kg for weight (p < 0.001), 2.80 kg for grip strength (p < 0.001), 15.93 for elbow flexor (p < 0.001), 16.73 for quadriceps (p < 0.001), 9.75 for gastrocnemius sup flexor of the leg (p = 0.005), and 2.20 kg for fat-free mass (p < 0.001) compared the control arm. Conclusion: RUSF alone was effective, but combining it with HiML had a synergistic effect. Compared to the control group, the RUSF and RUSF + HiML interventions improved the body composition, height, weight, and muscle strength of the studied moderately thin children. The findings of this study suggest the potential that treating moderately thin children with RUSF and combining it with HiML has for reducing the negative effects of malnutrition in Ethiopia. Future research should explore these interventions in a larger community-based study. This trial has been registered at the Pan African Clinical Trials Registry (PACTR) under trial number PACTR202305718679999. Full article
(This article belongs to the Section Pediatric Nutrition)
12 pages, 881 KiB  
Review
From a Cup of Tea to Cardiovascular Care: Vascular Mechanisms of Action
by Marios Sagris, Panayotis K. Vlachakis, Spyridon Simantiris, Panagiotis Theofilis, Maria Gerogianni, Paschalis Karakasis, Konstantinos Tsioufis and Dimitris Tousoulis
Life 2024, 14(9), 1168; https://doi.org/10.3390/life14091168 (registering DOI) - 15 Sep 2024
Viewed by 87
Abstract
Tea consumption is increasingly recognized for its potential benefits to cardiovascular health. This study reviews the available research, concentrating on the major components of tea and their mechanisms of action in the cardiovascular system. Tea is abundant in bioactive compounds, such as flavonoids [...] Read more.
Tea consumption is increasingly recognized for its potential benefits to cardiovascular health. This study reviews the available research, concentrating on the major components of tea and their mechanisms of action in the cardiovascular system. Tea is abundant in bioactive compounds, such as flavonoids and polysaccharides, which possess significant antioxidant and anti-inflammatory properties. These compounds play a crucial role in mitigating oxidative stress and inflammation, thereby supporting cardiovascular health. They enhance endothelial function, leading to improved vascular relaxation and reduced arterial stiffness, and exhibit antithrombotic effects. Additionally, regular tea consumption is potentially associated with better regulation of blood pressure, improved cholesterol profiles, and effective blood sugar control. It has been suggested that incorporating tea into daily dietary habits could be a practical strategy for cardiovascular disease prevention and management. Despite the promising evidence, more rigorous clinical trials are needed to establish standardized consumption recommendations and fully understand long-term effects. This review offers a more comprehensive analysis of the current evidence based on endothelium function and identifies the gaps that future research should address. Full article
(This article belongs to the Special Issue Diet and Vascular Disease)
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<p>Chemical components of tea and their influence on the endothelium.</p>
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<p>Tea targets in cardiovascular health. Created with <a href="https://www.biorender.com/" target="_blank">https://www.biorender.com/</a>.</p>
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24 pages, 2304 KiB  
Systematic Review
Targeting NETosis in Acute Brain Injury: A Systematic Review of Preclinical and Clinical Evidence
by Marzia Savi, Fuhong Su, Elda Diletta Sterchele, Elisa Gouvêa Bogossian, Zoé Demailly, Marta Baggiani, Giuseppe Stefano Casu and Fabio Silvio Taccone
Cells 2024, 13(18), 1553; https://doi.org/10.3390/cells13181553 (registering DOI) - 14 Sep 2024
Viewed by 360
Abstract
Acute brain injury (ABI) remains one of the leading causes of death and disability world-wide. Its treatment is challenging due to the heterogeneity of the mechanisms involved and the variability among individuals. This systematic review aims at evaluating the impact of anti-histone treatments [...] Read more.
Acute brain injury (ABI) remains one of the leading causes of death and disability world-wide. Its treatment is challenging due to the heterogeneity of the mechanisms involved and the variability among individuals. This systematic review aims at evaluating the impact of anti-histone treatments on outcomes in ABI patients and experimental animals and defining the trend of nucleosome levels in biological samples post injury. We performed a search in Pubmed/Medline and Embase databases for randomized controlled trials and cohort studies involving humans or experimental settings with various causes of ABI. We formulated the search using the PICO method, considering ABI patients or animal models as population (P), comparing pharmacological and non-pharmacological therapy targeting the nucleosome as Intervention (I) to standard of care or no treatment as Control (C). The outcome (O) was mortality or functional outcome in experimental animals and patients affected by ABI undergoing anti-NET treatments. We identified 28 studies from 1246 articles, of which 7 were experimental studies and 21 were human clinical studies. Among these studies, only four assessed the effect of anti-NET therapy on circulating markers. Three of them were preclinical and reported better outcome in the interventional arm compared to the control arm. All the studies observed a significant reduction in circulating NET-derived products. NETosis could be a target for new treatments. Monitoring NET markers in blood and cerebrospinal fluid might predict mortality and long-term outcomes. However, longitudinal studies and randomized controlled trials are warranted to fully evaluate their potential, as current evidence is limited. Full article
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<p>PRISMA flowchart of the review.</p>
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<p>Summary of preclinical and clinical findings and future directions for the clinical application of research on NETosis (illustration created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>). Acronyms: NET: neutrophil extracellular trap; ABI: acute brain injury; TBI: traumatic brain injury; SAH: subarachnoid aneurysmal haemorrhage; MPO-DNA: myeloperoxidase-deoxy-ribonuclease acid; CSF: cerebral spinal fluid.</p>
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<p>The main pathways of NET formation involved in neuroinflammation (illustration created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>).</p>
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15 pages, 2673 KiB  
Systematic Review
Timing of Tracheostomy in ICU Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
by Raffaele Merola, Carmine Iacovazzo, Stefania Troise, Annachiara Marra, Antonella Formichella, Giuseppe Servillo and Maria Vargas
Life 2024, 14(9), 1165; https://doi.org/10.3390/life14091165 (registering DOI) - 14 Sep 2024
Viewed by 237
Abstract
Background: The ideal timing for tracheostomy in critically ill patients is still debated. This systematic review and meta-analysis examined whether early tracheostomy improves clinical outcomes compared to late tracheostomy or prolonged intubation in critically ill patients on mechanical ventilation. Methods: We conducted a [...] Read more.
Background: The ideal timing for tracheostomy in critically ill patients is still debated. This systematic review and meta-analysis examined whether early tracheostomy improves clinical outcomes compared to late tracheostomy or prolonged intubation in critically ill patients on mechanical ventilation. Methods: We conducted a comprehensive search of randomized controlled trials (RCTs) assessing the risk of clinical outcomes in intensive care unit (ICU) patients who underwent early (within 7–10 days of intubation) versus late tracheostomy or prolonged intubation. Databases searched included PubMed, Embase, and the Cochrane Library up to June 2023. The primary outcome evaluated was mortality, while secondary outcomes included the incidence of ventilator-associated pneumonia (VAP), ICU length of stay, and duration of mechanical ventilation. No language restriction was applied. Eligible studies were RCTs comparing early to late tracheostomy or prolonged intubation in critically ill patients that reported on mortality. The risk of bias was evaluated using the Cochrane Risk of Bias Tool for RCTs, and evidence certainty was assessed via the GRADE approach. Results: This systematic review and meta-analysis included 19 RCTs, covering 3586 critically ill patients. Early tracheostomy modestly decreased mortality compared to the control (RR −0.1511 [95% CI: −0.2951 to −0.0070], p = 0.0398). It also reduced ICU length of stay (SMD −0.6237 [95% CI: −0.9526 to −0.2948], p = 0.0002) and the duration of mechanical ventilation compared to late tracheostomy (SMD −0.3887 [95% CI: −0.7726 to −0.0048], p = 0.0472). However, early tracheostomy did not significantly reduce the duration of mechanical ventilation compared to prolonged intubation (SMD −0.1192 [95% CI: −0.2986 to 0.0601], p = 0.1927) or affect VAP incidence (RR −0.0986 [95% CI: −0.2272 to 0.0299], p = 0.1327). Trial sequential analysis (TSA) for each outcome indicated that additional trials are needed for conclusive evidence. Conclusions: Early tracheostomy appears to offer some benefits across all considered clinical outcomes when compared to late tracheostomy and prolonged intubation. Full article
(This article belongs to the Special Issue New Trends in Otorhinolaryngology)
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<p>PRISMA 2020 flow diagram for new systematic reviews.</p>
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<p>Forest plot of estimated risk ratio comparing risk of mortality in the early tracheostomy vs. control group [<a href="#B10-life-14-01165" class="html-bibr">10</a>,<a href="#B12-life-14-01165" class="html-bibr">12</a>,<a href="#B13-life-14-01165" class="html-bibr">13</a>,<a href="#B20-life-14-01165" class="html-bibr">20</a>,<a href="#B21-life-14-01165" class="html-bibr">21</a>,<a href="#B22-life-14-01165" class="html-bibr">22</a>,<a href="#B23-life-14-01165" class="html-bibr">23</a>,<a href="#B24-life-14-01165" class="html-bibr">24</a>,<a href="#B25-life-14-01165" class="html-bibr">25</a>,<a href="#B26-life-14-01165" class="html-bibr">26</a>,<a href="#B27-life-14-01165" class="html-bibr">27</a>,<a href="#B28-life-14-01165" class="html-bibr">28</a>,<a href="#B29-life-14-01165" class="html-bibr">29</a>,<a href="#B30-life-14-01165" class="html-bibr">30</a>,<a href="#B32-life-14-01165" class="html-bibr">32</a>,<a href="#B33-life-14-01165" class="html-bibr">33</a>].</p>
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<p>Forest plot of estimated risk ratio comparing risk of VAP in the early tracheostomy vs. control group [<a href="#B10-life-14-01165" class="html-bibr">10</a>,<a href="#B12-life-14-01165" class="html-bibr">12</a>,<a href="#B13-life-14-01165" class="html-bibr">13</a>,<a href="#B20-life-14-01165" class="html-bibr">20</a>,<a href="#B21-life-14-01165" class="html-bibr">21</a>,<a href="#B22-life-14-01165" class="html-bibr">22</a>,<a href="#B23-life-14-01165" class="html-bibr">23</a>,<a href="#B24-life-14-01165" class="html-bibr">24</a>,<a href="#B25-life-14-01165" class="html-bibr">25</a>,<a href="#B26-life-14-01165" class="html-bibr">26</a>,<a href="#B27-life-14-01165" class="html-bibr">27</a>,<a href="#B28-life-14-01165" class="html-bibr">28</a>,<a href="#B29-life-14-01165" class="html-bibr">29</a>,<a href="#B30-life-14-01165" class="html-bibr">30</a>,<a href="#B32-life-14-01165" class="html-bibr">32</a>,<a href="#B33-life-14-01165" class="html-bibr">33</a>].</p>
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<p>Forest plot of estimated standardized mean difference comparing ICU length of stay in the early tracheostomy vs. control group [<a href="#B10-life-14-01165" class="html-bibr">10</a>,<a href="#B12-life-14-01165" class="html-bibr">12</a>,<a href="#B20-life-14-01165" class="html-bibr">20</a>,<a href="#B24-life-14-01165" class="html-bibr">24</a>,<a href="#B25-life-14-01165" class="html-bibr">25</a>,<a href="#B26-life-14-01165" class="html-bibr">26</a>,<a href="#B27-life-14-01165" class="html-bibr">27</a>,<a href="#B28-life-14-01165" class="html-bibr">28</a>,<a href="#B29-life-14-01165" class="html-bibr">29</a>,<a href="#B30-life-14-01165" class="html-bibr">30</a>,<a href="#B31-life-14-01165" class="html-bibr">31</a>,<a href="#B32-life-14-01165" class="html-bibr">32</a>,<a href="#B33-life-14-01165" class="html-bibr">33</a>].</p>
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<p>Forest plot of estimated standardized mean difference comparing duration of mechanical ventilation in the early tracheostomy vs. control group [<a href="#B10-life-14-01165" class="html-bibr">10</a>,<a href="#B12-life-14-01165" class="html-bibr">12</a>,<a href="#B20-life-14-01165" class="html-bibr">20</a>,<a href="#B24-life-14-01165" class="html-bibr">24</a>,<a href="#B25-life-14-01165" class="html-bibr">25</a>,<a href="#B26-life-14-01165" class="html-bibr">26</a>,<a href="#B27-life-14-01165" class="html-bibr">27</a>,<a href="#B28-life-14-01165" class="html-bibr">28</a>,<a href="#B29-life-14-01165" class="html-bibr">29</a>,<a href="#B30-life-14-01165" class="html-bibr">30</a>,<a href="#B31-life-14-01165" class="html-bibr">31</a>,<a href="#B32-life-14-01165" class="html-bibr">32</a>,<a href="#B33-life-14-01165" class="html-bibr">33</a>].</p>
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<p>GRADE evidence profile for the considered outcomes.</p>
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<p>Trial sequential analysis performed for each considered outcome.</p>
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15 pages, 851 KiB  
Article
Effects of Cashew Nuts (Anacardium occidentale L.) and Cashew Nut Oil on Intestinal Permeability and Inflammatory Markers during an Energy-Restricted 8-Week Intervention: A Randomized Controlled Trial (Brazilian Nuts Study)
by Talitha Silva Meneguelli, Aline Lage Wendling, Ana Claudia Pelissari Kravchychyn, Daniela Mayumi Usuda Prado Rocha, Ana Paula Dionísio, Josefina Bressan, Hércia Stampini Duarte Martino, Elad Tako and Helen Hermana Miranda Hermsdorff
Foods 2024, 13(18), 2917; https://doi.org/10.3390/foods13182917 (registering DOI) - 14 Sep 2024
Viewed by 224
Abstract
Cashew nuts can contribute to improving intestinal permeability and inflammation as they contain essential nutrients and bioactive compounds, but no clinical trials have evaluated these potential effects. This randomized trial aimed to assess the effects of cashew nuts and their oil on intestinal [...] Read more.
Cashew nuts can contribute to improving intestinal permeability and inflammation as they contain essential nutrients and bioactive compounds, but no clinical trials have evaluated these potential effects. This randomized trial aimed to assess the effects of cashew nuts and their oil on intestinal permeability and inflammatory markers. Sixty-four adults with overweight or obesity were allocated into three groups receiving energy restriction (−500 kcal/day): control (CT, free nuts), cashew nuts (CN, 30 g/day), or cashew nut oil (OL, 30 mL/day). Urine lactulose and mannitol, plasma zonulin and the lipopolysaccharide-binding protein (LBP), plasma interleukins (IL-6, TNF-α, IL-10, IL-1β, IL-8, and IL-12p70), and C-reactive proteins were analyzed. Energy restriction reduced body fat and other indicators of adiposity without differences between the groups. Only the control group increased LBPs after an 8-week intervention. There were no statistically significant differences found between the groups in terms of intestinal permeability and inflammatory markers. In conclusion, incorporating cashew nuts or cashew nut oil into an energy-restricted 8-week dietary intervention did not change intestinal permeability and inflammatory markers. As studies evaluating cashew nuts on these markers remain scarce, further research is needed, perhaps with a longer study period and a higher concentration of cashew nuts and oil. Full article
(This article belongs to the Section Food Nutrition)
21 pages, 1365 KiB  
Review
Recent Advances and Mechanisms of Phage-Based Therapies in Cancer Treatment
by Vivian Y. Ooi and Ting-Yu Yeh
Int. J. Mol. Sci. 2024, 25(18), 9938; https://doi.org/10.3390/ijms25189938 (registering DOI) - 14 Sep 2024
Viewed by 373
Abstract
The increasing interest in bacteriophage technology has prompted its novel applications to treat different medical conditions, most interestingly cancer. Due to their high specificity, manipulability, nontoxicity, and nanosize nature, phages are promising carriers in targeted therapy and cancer immunotherapy. This approach is particularly [...] Read more.
The increasing interest in bacteriophage technology has prompted its novel applications to treat different medical conditions, most interestingly cancer. Due to their high specificity, manipulability, nontoxicity, and nanosize nature, phages are promising carriers in targeted therapy and cancer immunotherapy. This approach is particularly timely, as current challenges in cancer research include damage to healthy cells, inefficiency in targeting, obstruction by biological barriers, and drug resistance. Some cancers are being kept at the forefront of phage research, such as colorectal cancer and HCC, while others like lymphoma, cervical cancer, and myeloma have not been retouched in a decade. Common mechanisms are immunogenic antigen display on phage coats and the use of phage as transporters to carry drugs, genes, and other molecules. To date, popular phage treatments being tested are gene therapy and phage-based vaccines using M13 and λ phage, with some vaccines having advanced to human clinical trials. The results from most of these studies have been promising, but limitations in phage-based therapies such as reticuloendothelial system clearance or diffusion inefficiency must be addressed. Before phage-based therapies for cancer can be successfully used in oncology practice, more in-depth research and support from local governments are required. Full article
(This article belongs to the Special Issue Bacteriophages Biology and Bacteriophage-Derived Technologies)
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Graphical abstract
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<p>Mechanisms of phage-based cancer therapies (using filamentous phage as an example). (<b>A</b>) Cancer cell antigens can be displayed on phage surface using peptide display technique. These antigens can trigger an immune response, encourage production of anti-cancer antibodies, or activate cytotoxic T cells against cancer cells. (<b>B</b>) Phages can be used as transporters to deliver photosensitizers, cytokines, or transgenes to cancer cells. APC, antigen presenting cell; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; pIII, M13 pIII coat protein; pVIII, M13 pVIII coat protein.</p>
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18 pages, 308 KiB  
Review
Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer Under-Represented by Clinical Trials
by Daniel E. Meyers, Rebekah Rittberg, David E. Dawe and Shantanu Banerji
Curr. Oncol. 2024, 31(9), 5498-5515; https://doi.org/10.3390/curroncol31090407 (registering DOI) - 14 Sep 2024
Viewed by 266
Abstract
Since the initial US FDA approval of an immune checkpoint inhibitor (ICI) for the treatment of non-oncogene-driven non-small-cell lung cancer (NSCLC) nine years ago, this therapeutic strategy has been cemented as a crucial component of treatment for most of these patients. However, there [...] Read more.
Since the initial US FDA approval of an immune checkpoint inhibitor (ICI) for the treatment of non-oncogene-driven non-small-cell lung cancer (NSCLC) nine years ago, this therapeutic strategy has been cemented as a crucial component of treatment for most of these patients. However, there is a clear efficacy–effectiveness gap whereby patients in the ‘real world’ seem to have more modest clinical outcomes compared to those enrolled in landmark clinical trials. This gap may be driven by the under-representation of important patient populations, including populations defined by clinical or molecular characteristics. In this review, we summarize the data outlining the evidence of ICIs in patients with poor Eastern Cooperative Oncology Group performance status (ECOG PS), underlying autoimmune disease (AID), older age, active brain metastases (BMs), and molecular aberrations such as EGFR mutations, ALK fusions, BRAF mutations and ROS1 fusions. Full article
(This article belongs to the Special Issue Immunotherapy in Thoracic Malignancies)
12 pages, 1292 KiB  
Article
Clinical Investigation of Bioelectric Toothbrush for Dentin Hypersensitivity Management: A Randomized Double-Blind Study
by Hyun-Kyung Kang, Yu-Rin Kim, Ji-Young Lee, Da-Jeong Kim and Young-Wook Kim
Bioengineering 2024, 11(9), 923; https://doi.org/10.3390/bioengineering11090923 (registering DOI) - 14 Sep 2024
Viewed by 186
Abstract
Background: The objective of this study was to evaluate how effectively the bioelectric toothbrush can alleviate dentin hypersensitivity (DHS) by using electrostatic forces to remove biofilm from the tooth surface. Methods: This study divided inpatients of a preventative dental clinic between March and [...] Read more.
Background: The objective of this study was to evaluate how effectively the bioelectric toothbrush can alleviate dentin hypersensitivity (DHS) by using electrostatic forces to remove biofilm from the tooth surface. Methods: This study divided inpatients of a preventative dental clinic between March and October 2023 into the following two groups: a bioelectric toothbrush group (BET, n = 25) and a non-bioelectric toothbrush group (NBET, n = 18) as a control group. This was a randomized double-blind, placebo-controlled trial study. A survey, the number of hypersensitive teeth, the O’Leary index, the visual analogue scale (VAS), and the Schiff Cold Air Sensitivity Scale (SCASS) were also investigated. Results: When fluoride toothpaste was applied with a bioelectric toothbrush, the subjects’ VAS and SCASS scores reflecting symptoms of hyperesthesia significantly decreased over time, as did the number of hypersensitive teeth and the O’Leary index. Moreover, the bioelectric toothbrush was confirmed to be effective in removing dental plaque. Conclusions: Dental clinics must actively promote bioelectric toothbrushes and fluoride toothpaste for patients suffering from hyperesthesia and pain. Furthermore, these items can be suggested as preventative oral care products to patients with potential hyperesthesia. Full article
(This article belongs to the Section Biomedical Engineering and Biomaterials)
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<p>Schematics of the BE and non-BE toothbrush (ProxiHealthcare, Seoul, Republic of Korea).</p>
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<p>Flowchart of participants.</p>
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<p>Flowchart of study method.</p>
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16 pages, 1920 KiB  
Article
Nutraceutical Supplementation as a Potential Non-Drug Treatment for Fibromyalgia: Effects on Lipid Profile, Oxidative Status, and Quality of Life
by Salvador de la Cruz Cazorla, Santos Blanco, Alma Rus, Francisco Javier Molina-Ortega, Esther Ocaña, Raquel Hernández, Francesco Visioli and María Luisa del Moral
Int. J. Mol. Sci. 2024, 25(18), 9935; https://doi.org/10.3390/ijms25189935 (registering DOI) - 14 Sep 2024
Viewed by 203
Abstract
Fibromyalgia (FM) is a chronic syndrome of unknown etiology, although many studies point to inflammation, oxidative stress, and altered mitochondrial metabolism as some of the cornerstones of this disease. Despite its socioeconomic importance and due to the difficulties in diagnosis, there are no [...] Read more.
Fibromyalgia (FM) is a chronic syndrome of unknown etiology, although many studies point to inflammation, oxidative stress, and altered mitochondrial metabolism as some of the cornerstones of this disease. Despite its socioeconomic importance and due to the difficulties in diagnosis, there are no effective treatments. However, the use of non-drug treatments is increasingly becoming a recommended strategy. In this context, the effects of supplementation of FM patients with an olive (poly)phenol, vitamin C, and vitamin B preparation were investigated in this work, analyzing complete blood count, biochemical, lipid, and coagulation profiles, and inflammation and oxidation status in blood samples. To gain a better understanding of the molecular mechanisms and pathways involved in the etiology of FM, a proteomic study was also performed to investigate the mechanisms of action of the supplement. Our results show that the nutraceutical lowers the lipid profile, namely cholesterol, and improves the oxidative status of patients as well as their quality of life, suggesting that this product could be beneficial in the co-treatment of FM. ClinicalTrials.gov (ID: NCT06348537). Full article
(This article belongs to the Collection Feature Papers in Bioactives and Nutraceuticals)
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<p>A significant decrease in aldolase concentration was observed in both groups, being greater in the patients treated with Mygrium<sup>®</sup>. * <span class="html-italic">p</span> ≤ 0.05; ** <span class="html-italic">p</span> ≤ 0.01.</p>
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<p>Total cholesterol, LDL cholesterol, and cholesterol ratio data showed a decrease after 60 days of treatment in both groups. * <span class="html-italic">p</span> ≤ 0.05; ** <span class="html-italic">p</span> ≤ 0.01.</p>
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<p>Cortisol values increased significantly only in patients treated with Mygrium<sup>®</sup>. * <span class="html-italic">p</span> ≤ 0.05.</p>
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<p>Thiobarbituric acid reactive substances (TBARS) levels decreased significantly in patients administered Mygrium<sup>®</sup>. ** <span class="html-italic">p</span> ≤ 0.01.</p>
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<p>The physical dimension outcomes showed better performance in the group of individuals treated with Mygrium<sup>®</sup>. ** <span class="html-italic">p</span> ≤ 0.01.</p>
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<p>Volcanoes of the comparisons of proteins detected between the different groups of patients and between different times (<span class="html-italic">p</span>-value ≤ 0.05; fold change ≥ 1). The points in the center of these volcanoes correspond to those proteins that do not vary in the two situations foreseen in our experimental design. The proteins with statistically significant differences are presented at the right (overexpressed or upregulated) and left (less expressed or downregulated) of the graph.</p>
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17 pages, 657 KiB  
Article
Intravenous Levosimendan versus Inhalational Milrinone in the Management of Pulmonary Hypertension during Adult Cardiac Surgery: A Randomized Clinical Trial
by Panagiotis Ftikos, Georgios Gkantinas, Vlasios Karageorgos, Anna Smirli, Nektarios Kogerakis, Evangelos Leontiadis, Konstantinos Petsios, Theofani Antoniou and Kassiani Theodoraki
Life 2024, 14(9), 1164; https://doi.org/10.3390/life14091164 (registering DOI) - 14 Sep 2024
Viewed by 168
Abstract
Introduction: The perioperative management of patients with pulmonary hypertension (PH) undergoing cardiac surgery is challenging, mainly due to the potential risk of right ventricular failure (RVF). Levosimendan is a calcium-sensitizing agent that has primarily been used in the treatment of decompensated heart failure. [...] Read more.
Introduction: The perioperative management of patients with pulmonary hypertension (PH) undergoing cardiac surgery is challenging, mainly due to the potential risk of right ventricular failure (RVF). Levosimendan is a calcium-sensitizing agent that has primarily been used in the treatment of decompensated heart failure. However, recently levosimendan has been shown to be an effective and safe therapeutic strategy for patients with pulmonary arterial hypertension and PH associated with left heart disease. The aim of this study was to investigate the potential utility of the preemptive administration of levosimendan in cardiac surgical patients with preexisting PH and to compare its effectiveness with milrinone, which represents an already established therapeutic option in the management of PH during cardiac surgery. Materials and Methods: In this study, 40 adult cardiac surgical patients with PH were randomly assigned to receive either levosimendan intravenously or milrinone via inhalation in a double-blind fashion prior to a cardiopulmonary bypass (CPB). Hemodynamic and echocardiographic parameters were recorded and evaluated before and after the administration of the drugs. Results and Conclusions: The results of this study demonstrated that both levosimendan and milrinone administered before CPB in cardiac surgical patients with PH may offer protective benefits, reducing pulmonary artery pressure and preventing the exacerbation of PH and RVF. Pulmonary vasodilation attributed to levosimendan is of longer duration and greater magnitude compared to pulmonary vasodilation afforded by milrinone. Full article
(This article belongs to the Special Issue Pulmonary Hypertension: From Bench to Bedside: 2nd Edition)
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<p>SPAP changes across the follow-up period.</p>
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<p>MPAP/MAP changes across the follow-up period.</p>
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13 pages, 946 KiB  
Article
A Mediterranean Diet-Oriented Intervention Rescues Impaired Blood Cell Bioenergetics in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease
by Agnese Segala, Marika Vezzoli, Alice Vetturi, Emirena Garrafa, Barbara Zanini, Emanuela Bottani, Monica Marullo, Silvia Marconi, Chiara Ricci and Alessandra Valerio
Diagnostics 2024, 14(18), 2041; https://doi.org/10.3390/diagnostics14182041 (registering DOI) - 14 Sep 2024
Viewed by 146
Abstract
Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), a novel term for Non-Alcoholic Fatty Liver Disease (NAFLD), is associated with liver mitochondrial dysfunction. We previously demonstrated that mitochondrial respiratory capacity in peripheral blood mononuclear cells (PBMCs) was significantly reduced in patients with MASLD [...] Read more.
Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), a novel term for Non-Alcoholic Fatty Liver Disease (NAFLD), is associated with liver mitochondrial dysfunction. We previously demonstrated that mitochondrial respiratory capacity in peripheral blood mononuclear cells (PBMCs) was significantly reduced in patients with MASLD compared to non-MASLD controls. For MASLD treatment, guidelines recommend behavioral and dietary changes to reduce body weight. A recent 12-month clinical trial demonstrated that ameliorating patients’ lifestyles through improved adherence to the Mediterranean diet and encouraged physical activity results in MASLD remission or regression. Methods: As a sub-study of the 12-month clinical trial, we evaluated the effects of the Mediterranean diet-oriented intervention on PBMC mitochondrial DNA content and respiratory parameters and on various biomarkers associated with MASLD. Results: Contrary to what was found at the baseline, after twelve months of intervention, systemic inflammatory and bioenergetics parameters did not differ between MASLD patients (N = 15) and control subjects (N = 17). PBMCs from MASLD subjects showed rescued basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity. The observed recovery coincided with a significant increase in the patients’ adherence to the Mediterranean diet (Medscore). Conclusions: Our findings indicate that a Mediterranean diet-oriented intervention, without calorie reduction, preserves blood cell mitochondrial function in MASLD subjects. Thus, PBMC bioenergetics-based assays might be taken into account not only for diagnosing but also for monitoring therapeutic responses in MASLD. Full article
(This article belongs to the Special Issue Advances in the Diagnosis of Steatotic Liver Disease)
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<p>Mediterranean diet adherence score (Medscore) from patients with MASLD and non-MASLD controls at the baseline T0 (<b>a</b>) and at T12 (<b>b</b>). Data represent median ± interquartile range. Statistical analysis has been performed with Wilcoxon Rank Sum test. ** corresponds to <span class="html-italic">p</span>-value &lt; 0.01. Graphs were performed using Prism 9.0.0 (GraphPad).</p>
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<p>Mitochondrial DNA content and respiratory function in PBMCs from MASLD patients and non-MASLD controls at T12. (<b>a</b>) Quantification of mitochondrial DNA copy number (mtDNAcn) with values log-transformed. (<b>b</b>) Time-course representation of oxygen consumption rate (OCR) measured in live PBMCs during the Mito Stress Test. Three measurements for each condition were performed at different times by the Seahorse XFe24 analyzer. OCR values were normalized to DNA content. (<b>c</b>–<b>h</b>) Scatter dot plots of OCR values from individual subjects, normalized to DNA content, for each respiratory parameter. Data represent median ± interquartile range (<b>a</b>,<b>c</b>–<b>h</b>) or mean ± SEM (<b>b</b>). The Wilcoxon Rank Sum test was applied to compare the non-MASLD and MASLD subpopulations. Graphs were performed using Prism 9.0.0 (GraphPad).</p>
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14 pages, 665 KiB  
Review
Therapeutic Opportunities for Biomarkers in Metastatic Spine Tumors
by Christian Schroeder, Beatrice Campilan, Owen P. Leary, Jonathan Arditi, Madison J. Michles, Rafael De La Garza Ramos, Oluwaseun O. Akinduro, Ziya L. Gokaslan, Margot Martinez Moreno and Patricia L. Zadnik Sullivan
Cancers 2024, 16(18), 3152; https://doi.org/10.3390/cancers16183152 (registering DOI) - 14 Sep 2024
Viewed by 159
Abstract
For many spine surgeons, patients with metastatic cancer are often present in an emergent situation with rapidly progressive neurological dysfunction. Since the Patchell trial, scoring systems such as NOMS and SINS have emerged to guide the extent of surgical excision and fusion in [...] Read more.
For many spine surgeons, patients with metastatic cancer are often present in an emergent situation with rapidly progressive neurological dysfunction. Since the Patchell trial, scoring systems such as NOMS and SINS have emerged to guide the extent of surgical excision and fusion in the context of chemotherapy and radiation therapy. Yet, while multidisciplinary decision-making is the gold standard of cancer care, in the middle of the night, when a patient needs spinal surgery, the wealth of chemotherapy data, clinical trials, and other medical advances can feel overwhelming. The goal of this review is to provide an overview of the relevant molecular biomarkers and therapies driving patient survival in lung, breast, prostate, and renal cell cancer. We highlight the molecular differences between primary tumors (i.e., the patient’s original lung cancer) and the subsequent spinal metastasis. This distinction is crucial, as there are limited data investigating how metastases respond to their primary tumor’s targeted molecular therapies. Integrating information from primary and metastatic markers allows for a more comprehensive and personalized approach to cancer treatment. Full article
(This article belongs to the Special Issue Surgical Treatment of Spinal Tumors)
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<p>Genetic mutations in primary lung, breast, prostate, and renal cancers and their subsequent mutations upon metastasis to the spine. Mutations in italics represent known therapeutic targets discussed in this study.</p>
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15 pages, 773 KiB  
Review
Therapeutic Advances in Psoriasis: From Biologics to Emerging Oral Small Molecules
by Francesco Ferrara, Chiara Verduci, Emanuela Laconi, Andrea Mangione, Chiara Dondi, Marta Del Vecchio, Veronica Carlevatti, Andrea Zovi, Maurizio Capuozzo and Roberto Langella
Antibodies 2024, 13(3), 76; https://doi.org/10.3390/antib13030076 (registering DOI) - 14 Sep 2024
Viewed by 186
Abstract
Psoriasis is a persistent, inflammatory condition affecting millions globally, marked by excessive keratinocyte proliferation, immune cell infiltration, and widespread inflammation. Over the years, therapeutic approaches have developed significantly, shifting from conventional topical treatments and phototherapy to more sophisticated systemic interventions such as biologics [...] Read more.
Psoriasis is a persistent, inflammatory condition affecting millions globally, marked by excessive keratinocyte proliferation, immune cell infiltration, and widespread inflammation. Over the years, therapeutic approaches have developed significantly, shifting from conventional topical treatments and phototherapy to more sophisticated systemic interventions such as biologics and, recently, oral small-molecule drugs. This review seeks to present a comprehensive investigation of the existing psoriasis treatment options, focusing on biologic agents, oral small molecules, and emerging treatments. Several categories of biologic treatments have received regulatory approval for psoriasis, including TNF-α, IL-17, IL-12/23, and IL-23 inhibitors. Biologics have revolutionized the treatment of psoriasis. These targeted therapies offer significant improvement in disease control and quality of life, with acceptable safety profiles. However, limitations such as cost, potential immunogenicity, and administration challenges have driven the exploration of alternative treatment modalities. Oral small molecules, particularly inhibitors of Janus kinase (JAK), have emerged as options due to their convenience and efficacy. These agents represent a paradigm shift in the management of the condition, offering oral administration and targeted action on specific signaling pathways. In addition to existing therapies, the review explores emerging treatments that hold promise for the future of psoriasis care. These include innovative small-molecule inhibitors. Early-stage clinical trials suggest these agents may enhance outcomes for psoriasis patients. In conclusion, the therapeutic landscape of psoriasis is rapidly evolving, emphasizing targeted, patient-centered treatments. Ongoing research and development are expected to lead to more personalized and effective management strategies for this complex condition. Full article
(This article belongs to the Section Antibody-Based Therapeutics)
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<p>The interplay of cytokine pathways in psoriasis. A sophisticated web connects the fundamental molecules involved in the development of psoriasis. This interconnection is regarded as pivotal for advancement. On one front, the reciprocal enhancement of the adaptive and innate immune systems generates multiple cytokines and sustains characteristic psoriatic traits in both the dermis and epidermis. Conversely, keratinocytes foster the mediators and bolster the proliferation of activation.</p>
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<p>A schematic figure of the JAK/STAT pathway illustrating the mechanism of action of JAK inhibitors. P is the chemical symbol for phosphorus.</p>
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16 pages, 2820 KiB  
Article
Olea europaea L. Leaves as a Source of Anti-Glycation Compounds
by Marzia Vasarri, Maria Camilla Bergonzi, Emilija Ivanova Stojcheva, Anna Rita Bilia and Donatella Degl’Innocenti
Molecules 2024, 29(18), 4368; https://doi.org/10.3390/molecules29184368 (registering DOI) - 14 Sep 2024
Viewed by 138
Abstract
High concentrations of advanced glycation end products (AGEs) have been linked to diseases, including diabetic complications. The pathophysiological effects of AGEs are mainly due to oxidative stress and inflammatory processes. Among the proteins most affected by glycation are albumin, the most abundant circulating [...] Read more.
High concentrations of advanced glycation end products (AGEs) have been linked to diseases, including diabetic complications. The pathophysiological effects of AGEs are mainly due to oxidative stress and inflammatory processes. Among the proteins most affected by glycation are albumin, the most abundant circulating protein, and collagen, which has a long biological half-life and is abundant in the extracellular matrix. The potential cellular damage caused by AGEs underscores the importance of identifying and developing natural AGE inhibitors. Indeed, despite initial promise, many synthetic inhibitors have been withdrawn from clinical trials due to issues such as cytotoxicity and poor pharmacokinetics. In contrast, natural products have shown significant potential in inhibiting AGE formation. Olea europaea L. leaves, rich in bioactive compounds like oleuropein and triterpenoids, have attracted scientific interest, emphasizing the potential of olive leaf extracts in health applications. This study investigates the anti-glycation properties of two polyphenol-rich extracts (OPA40 and OPA70) and a triterpene-enriched extract (TTP70) from olive leaves. Using in vitro protein glycation methods with bovine serum albumin (BSA)–glucose and gelatin–glucose systems, this study assesses AGE formation inhibition by these extracts through native polyacrylamide gel electrophoresis (N-PAGE) and autofluorescence detection. OPA40 and OPA70 exhibited strong, dose-dependent anti-glycation effects. These effects were corroborated by electrophoresis and further supported by similar results in a gelatin–glucose system. Additionally, TTP70 showed moderate anti-glycation activity, with a synergistic effect of its components. The results support the real possibility of using olive leaf bioproducts in ameliorating diabetic complications, contributing to sustainable bio-economy practices. Full article
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<p>In vitro glycation of albumin and the inhibitory effect of OPA40 and OPA70 on A-AGE formation. Relative fluorescence intensity (λex/λem 335/385 nm) of unglycated albumin (BSA), A-AGE, and A-AGE with OPA40 (0.5–2.5 mg/mL), OPA70 (0.5–2.5 mg/mL), or AG (10 mM) obtained at 60 °C for 72 h. All values are reported as percentage ratio with respect to unglycated BSA. Data are the mean of three independent experiments. Error bars represent standard deviation. Tukey’s test: *** <span class="html-italic">p</span> &lt; 0.001 vs. unglycated BSA; °°° <span class="html-italic">p</span> &lt; 0.001 vs. A-AGE formed in the absence of the extracts.</p>
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<p>Representative N-PAGE image of unglycated albumin (BSA) and A-AGE obtained at 60 °C for 72 h in the absence or presence of OPA40 and OPA70 extracts. A-AGE obtained in the presence of AG was used as a protein glycation inhibition control. The symbols (+) and (−) represent the anode and cathode in the N-PAGE gel, respectively.</p>
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<p>Time-dependent formation of G-AGE. The relative fluorescence intensity of G-AGE was measured from time 0 to 96 h at 335 and 385 nm excitation and emission wavelength. Values are reported as percentages compared to the fluorescence intensity of gelatin at time 0. Values are the mean ± standard deviation of three experiments.</p>
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<p>In vitro glycation of gelatin and the inhibitory effect of the OPA40 and OPA70 on G-AGE formation. Relative fluorescence intensity (λ<sub>ex</sub>/λ<sub>em</sub> 335/385 nm) of unglycated gelatin, G-AGE, and G-AGE with OPA40 (0.5–2.5 mg/mL), OPA70 (0.5–2.5 mg/mL), or AG (10 mM) obtained at 45 °C for 72 h. All values are reported as percentage ratio with respect to unglycated gelatin. Data are the mean of three independent experiments. Error bars represent standard deviation. Tukey’s test: *** <span class="html-italic">p</span> &lt; 0.001 vs. unglycated gelatin; °°° <span class="html-italic">p</span> &lt; 0.001 vs. G-AGE formed in the absence of the extracts.</p>
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<p>In vitro glycation of albumin and the inhibitory effect of TTP70 and OA on A-AGE formation. (<b>A</b>) Relative fluorescence intensity (λ<sub>ex</sub>/λ<sub>em</sub> 335/385 nm) of unglycated albumin (BSA), A-AGE, and A-AGE obtained in the presence of OA (0.15 and 0.2 mg/mL), TTP70 (0.3 and 0.4 mg/mL), or AG (10 mM) at 60 °C for 72 h. All values are reported as percentage ratio to unglycated albumin (BSA). Data are the mean of three independent experiments. Error bars represent standard deviation. Tukey’s test: *** <span class="html-italic">p</span> &lt; 0.001 vs. unglycated BSA; °° <span class="html-italic">p</span> &lt; 0.01, °°° <span class="html-italic">p</span> &lt; 0.001 vs. A-AGE formed in the absence of OA or TTP70. (<b>B</b>) Representative N-PAGE image of unglycated BSA and A-AGE obtained at 60 °C for 72 h in the presence or absence of OA and TTP70 extracts. A-AGE obtained in the presence of AG was used as a control for protein glycation inhibition. The symbols (+) and (−) represent the anode and cathode in the N-PAGE gel, respectively.</p>
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<p>In vitro glycation of gelatin and the inhibitory effect of the TTP70 and OA on G-AGE formation. Relative fluorescence intensity (λ<sub>ex</sub>/λ<sub>em</sub> 335/385 nm) of unglycated gelatin, G-AGE, and G-AGE with OA (0.15–0.2 mg/mL), TTP70 (0.3–0.4 mg/mL), or AG (10 mM) obtained at 45 °C for 72 h. All values are reported as percentage ratio with respect to unglycated gelatin. Data are the mean of three independent experiments. Error bars represent standard deviation. Tukey’s test: *** <span class="html-italic">p</span> &lt; 0.001 vs. unglycated gelatin; °°° <span class="html-italic">p</span> &lt; 0.001 vs. G-AGE formed in the absence of the extracts.</p>
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<p>(<b>a</b>) In vitro AGE formation by albumin–glucose system (A-AGE), in the presence of (<b>b</b>) <span class="html-italic">Olea europea</span> L. leaf extracts or (<b>c</b>) aminoguanidine (AG). The image of the BSA was taken from the following website: <a href="https://www.chemicalbook.com/Article/Classification-of-bovine-serum-albumin.htm" target="_blank">https://www.chemicalbook.com/Article/Classification-of-bovine-serum-albumin.htm</a>, accessed on 17 July 2024.</p>
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<p>(<b>a</b>) In vitro AGE formation by gelatin–glucose system (G-AGE), in the presence of (<b>b</b>) <span class="html-italic">Olea europea</span> L. leaf extracts or (<b>c</b>) aminoguanidine (AG).</p>
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22 pages, 2436 KiB  
Review
The Role of Programmed Types of Cell Death in Pathogenesis of Heart Failure with Preserved Ejection Fraction
by Jan Jankowski, Kamil Oskar Kozub, Marcin Kleibert, Katarzyna Camlet, Klaudia Kleibert and Agnieszka Cudnoch-Jędrzejewska
Int. J. Mol. Sci. 2024, 25(18), 9921; https://doi.org/10.3390/ijms25189921 (registering DOI) - 14 Sep 2024
Viewed by 301
Abstract
Heart failure with preserved ejection fraction (HFpEF) is a condition that develops in the course of many diseases and conditions, and its pathophysiology is still not well understood, but the involvement of programmed types of cell death in the development of this type [...] Read more.
Heart failure with preserved ejection fraction (HFpEF) is a condition that develops in the course of many diseases and conditions, and its pathophysiology is still not well understood, but the involvement of programmed types of cell death in the development of this type of heart failure is becoming increasingly certain. In addition, drugs already widely used in clinical practice, with a good safety profile and efficacy demonstrated in large-group clinical trials, seem to be exerting their beneficial effects on cardiovascular health. Perhaps new drugs that reduce the susceptibility of cells to programmed types of cell death are under investigation and may improve the prognosis of patients with HFpEF. In this article, we summarize the current knowledge about the pathogenesis of HFpEF and the role of programmed types of cell death in its development. Additionally, we have described the future directions of research that may lead to the improvement of a patient’s prognosis and potential treatment. Full article
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<p>The classification of heart failure based on ejection fraction. LVEF—left ventricle ejection fraction, HFrEF—heart failure with reduced ejection fraction, HFmrEF—heart failure with mildly reduced ejection fraction, HFpEF—heart failure with preserved ejection fraction. Created with <a href="http://Biorender.com" target="_blank">Biorender.com</a>.</p>
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<p>The division of cell death types. Red color—that type of cell death is not described in this article due to the lack of data in HFpEF; green color—that type of cell death is described. Created with <a href="http://Biorender.com" target="_blank">Biorender.com</a>.</p>
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<p>The mechanism of the extrinsic and intrinsic apoptotic pathways. TRAIL—tumor necrosis factor-related apoptosis-inducing ligand, Fas receptor—Fas cell surface death receptor, FADD—Fas-associated death domain, BID—BH3 interacting-domain death agonist, tBID—truncated BID, Bcl-2—B cell lymphoma 2, Bcl-xL—B-cell lymphoma-extra-large, MCL1—myeloid leukemia 1 protein, BH3—Bcl-2 homology domain 3, Bax—Bcl-2-associated X protein, BAK—Bcl-2 antagonist/killer, APAF1—apoptotic protease activating factor 1, Created with <a href="http://Biorender.com" target="_blank">Biorender.com</a>.</p>
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<p>The factors that activate (green arrows) or inhibit (red arrows) apoptosis of cardiomyocytes among patients with HFpEF. FOXO3a—Forkhead box O3a, L-NAME—Nω-nitrol-arginine methyl ester, NaCl—sodium chloride, AngII—angiotensin II, FNDC5—Fibronectin type III domain-containing protein 5, microRNA—micro ribonucleic acid, IgG—immunoglobulin G. Created with <a href="http://Biorender.com" target="_blank">Biorender.com</a>.</p>
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<p>Molecular mechanism of pyroptosis. Ca<sup>2+</sup>—calcium ions, DAMPs—Danger/Damage Associated Molecular Patterns, TLR—toll-like receptor, GSDMD—gasdermin D, N-GSDMD—N-terminal domain of gasdermin D, IL—interleukin, pro-IL—pro-interleukin, NLRP3—NLR family pyrin domain containing 3, NLRC4—NLR family CARD domain-containing 4, Pycard—PYD and CARD domain containing, Il1b—interleukin 1b gene, NF-κB—nuclear factor kappa-light-chain-enhancer of activated B cells. Created with <a href="http://Biorender.com" target="_blank">Biorender.com</a>.</p>
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