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19 pages, 6169 KiB  
Article
The Antioxidant and Anti-Inflammatory Properties of Bee Pollen from Acorn (Quercus acutissima Carr.) and Darae (Actinidia arguta)
by Jeong-Eun Kwak, Joo-Yeon Lee, Ji-Yoon Baek, Sun Wook Kim and Mok-Ryeon Ahn
Antioxidants 2024, 13(8), 981; https://doi.org/10.3390/antiox13080981 (registering DOI) - 13 Aug 2024
Abstract
Aging is a complex biological process characterized by a progressive decline in physical function and an increased risk of age-related chronic diseases. Additionally, oxidative stress is known to cause severe tissue damage and inflammation. Pollens from acorn and darae are extensively produced in [...] Read more.
Aging is a complex biological process characterized by a progressive decline in physical function and an increased risk of age-related chronic diseases. Additionally, oxidative stress is known to cause severe tissue damage and inflammation. Pollens from acorn and darae are extensively produced in Korea. However, the underlying molecular mechanisms of these components under the conditions of inflammation and oxidative stress remain largely unknown. This study aimed to investigate the effect of bee pollen components on lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophages. This study demonstrates that acorn and darae significantly inhibit the LPS-induced production of inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), in RAW 264.7 cells. Specifically, bee pollen from acorn reduces NO production by 69.23 ± 0.04% and PGE2 production by 44.16 ± 0.08%, while bee pollen from darae decreases NO production by 78.21 ± 0.06% and PGE2 production by 66.23 ± 0.1%. Furthermore, bee pollen from acorn and darae reduced active oxygen species (ROS) production by 47.01 ± 0.5% and 60 ± 0.9%, respectively. It increased the nuclear potential of nuclear factor erythroid 2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 cells. Moreover, treatment with acorn and darae abolished the nuclear potential of nuclear factor κB (NF-κB) and reduced the expression of extracellular signal-associated kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation in LPS-stimulated RAW 264.7 cells. Specifically, acorn decreased NF-κB nuclear potential by 90.01 ± 0.3%, ERK phosphorylation by 76.19 ± 1.1%, and JNK phosphorylation by 57.14 ± 1.2%. Similarly, darae reduced NF-κB nuclear potential by 92.21 ± 0.5%, ERK phosphorylation by 61.11 ± 0.8%, and JNK phosphorylation by 59.72 ± 1.12%. These results suggest that acorn and darae could be potential antioxidants and anti-inflammatory agents. Full article
(This article belongs to the Special Issue Bee Products as a Source of Natural Antioxidants: Second Edition)
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Figure 1
<p>EEBP from acorn and darae does not affect the cell viability and growth of RAW 264.7 cells. (<b>A</b>,<b>B</b>) The MTT test was used to assess the viability of the cells after they were exposed to different doses of EEBP from acorn and darae for 24 h. The data were obtained from three separate experiments and are shown as the mean ± SD. (<b>C</b>) Raw 264.7 cell morphological alterations were observed under treatment of EEBP from acorn and darae.</p>
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<p>EEBP of acorn and darae inhibits LPS-induced ROS generation in RAW 264.7 cells. LPS (1 µg/mL)-stimulated RAW 264.7 cells were treated with various concentrations of EEBP from acorn and darae and incubated for 24 h. DCFH-DA was then applied for 30 min. The white arrow points to representative examples of the co-localization of the nucleus and DCFH-DA. (<b>A</b>,<b>B</b>) Confocal microscopy was used to visualize the effects of EEBP from acorn and darae on LPS-induced ROS generation by DCFH-DA staining. (<b>C</b>) The amount of ROS production is expressed as mean fluorescence intensity (DCFH-DA). Data for <span class="html-italic">n</span> = 3 are shown as mean ± SD. ### <span class="html-italic">p</span> &lt; 0.001, compared with the control group.*** <span class="html-italic">p</span> &lt; 0.001, compared with the LPS group.</p>
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<p>EEBP from acorn and darae induces nuclear translocation of Nrf2 in RAW 264.7 macrophages. Various amounts of bee pollens from acorn and darae were applied to the LPS-stimulated RAW264.7 cells (1 µg/mL). Cells were incubated for 24 h prior to the analysis. Using an immunofluorescence assay, the nuclear translocation of Nrf2 was investigated in cells treated with bee pollens from (<b>A</b>) acorn and (<b>B</b>) darae.</p>
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<p>EEBP from acorn and darae inhibits pro-inflammatory mediators in LPS-stimulated RAW 264.7 macrophages. (<b>A</b>) The Griess reaction was used to quantify the nitrite content. (<b>B</b>) A commercial ELISA kit was used to assess the PGE2 levels in the culture medium. (<b>C</b>) Representative Western blot analysis was performed to measure iNOS and COX-2 expression. (<b>D</b>,<b>E</b>) The quantification of Western blot analysis by pollens from acorn and darae in LPS-stimulated RAW 264.7 macrophages. Every value represents the mean ± standard deviation and reflects the findings from three different experiments. ### <span class="html-italic">p</span> &lt; 0.001, compared with the control group. ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001, compared with the LPS group.</p>
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<p>EEBP from acorn and darae reduces LPS-stimulated pro-inflammatory cytokines in RAW 264.7 macrophages. After the 24-h incubation period, (<b>A</b>) TNF-α, (<b>B</b>) IL-1β, and (<b>C</b>) IL-6 concentrations in cell-free supernatants were determined by ELISA. Every value represents the mean ± standard deviation and reflects the findings from three separate studies. ### <span class="html-italic">p</span> &lt; 0.001, compared with the control group. *** <span class="html-italic">p</span> &lt; 0.001, compared with the LPS group.</p>
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<p>LPS-induced NF-κB p65 nuclear translocation is induced by EEBP from acorn and darae. Western blot analyses were used to examine the levels of p65 and IkB (<b>A</b>–<b>C</b>). Cells were treated with and without EEBP from acorn and darae, fixed, and subjected to total p65 antibody immunostaining (green) counterstained with DAPI for nuclei (blue). Confocal microscopy was used to obtain fluorescence images of EEBP treatment group from (<b>D</b>) acorn and (<b>E</b>) darae. Scale bar: 400 μm. The three experiments’ mean ± SD data are displayed. ### <span class="html-italic">p</span> &lt; 0.001, compared with the control group. * <span class="html-italic">p</span> &lt; 0.05 and *** <span class="html-italic">p</span> &lt; 0.001, compared with the LPS group.</p>
Full article ">Figure 6 Cont.
<p>LPS-induced NF-κB p65 nuclear translocation is induced by EEBP from acorn and darae. Western blot analyses were used to examine the levels of p65 and IkB (<b>A</b>–<b>C</b>). Cells were treated with and without EEBP from acorn and darae, fixed, and subjected to total p65 antibody immunostaining (green) counterstained with DAPI for nuclei (blue). Confocal microscopy was used to obtain fluorescence images of EEBP treatment group from (<b>D</b>) acorn and (<b>E</b>) darae. Scale bar: 400 μm. The three experiments’ mean ± SD data are displayed. ### <span class="html-italic">p</span> &lt; 0.001, compared with the control group. * <span class="html-italic">p</span> &lt; 0.05 and *** <span class="html-italic">p</span> &lt; 0.001, compared with the LPS group.</p>
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<p>EEBP from acorn and darae diminishes LPS-stimulated activation of MAPKs in RAW 264.7 macrophages. RAW 264.7 macrophages were pretreated with EEBP from acorn and darae for 24 h, followed by the LPS treatment. The protein levels of ERK, JNK, and p38 were measured using Western blot experiments. Representative results are displayed in (<b>A</b>). Quantification of Western blot analysis of phosphorylation of (<b>B</b>) ERK, (<b>C</b>) JNK, and (<b>D</b>) p38 in cytoplasmic proteins is shown. The data are the densitometric value mean ± SD (<span class="html-italic">n</span> = 3) adjusted using β-actin. ### <span class="html-italic">p</span> &lt; 0.001, compared with the control group. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001, compared with the LPS group.</p>
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<p>EEBP from acorn and darae induces cell cycle arrest in LPS-stimulated RAW 264.7 macrophages. (<b>A</b>) The cell cycle of LPS-stimulated RAW 264.7 cells with or without EEBP from acorn and darae was assessed using flow cytometry. (<b>B</b>) The percentage of apoptotic cells relative to the total cell population is quantified. Data for <span class="html-italic">n</span> = 3 are shown as mean ± SD.</p>
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7 pages, 1864 KiB  
Brief Report
Unbiased Proteomic Exploration Suggests Overexpression of Complement Cascade Proteins in Plasma from Patients with Psoriasis Compared with Healthy Individuals
by Bjørn Kromann, Lili Niu, Line B. P. Møller, Julie Sølberg, Karolina Sulek, Mette Gyldenløve, Beatrice Dyring-Andersen, Lone Skov and Marianne B. Løvendorf
Int. J. Mol. Sci. 2024, 25(16), 8791; https://doi.org/10.3390/ijms25168791 (registering DOI) - 13 Aug 2024
Viewed by 92
Abstract
Knowledge about the molecular mechanisms underlying the systemic inflammation observed in psoriasis remains incomplete. In this study, we applied mass spectrometry-based proteomics to compare the plasma protein levels between patients with psoriasis and healthy individuals, aiming to unveil potential systemically dysregulated proteins and [...] Read more.
Knowledge about the molecular mechanisms underlying the systemic inflammation observed in psoriasis remains incomplete. In this study, we applied mass spectrometry-based proteomics to compare the plasma protein levels between patients with psoriasis and healthy individuals, aiming to unveil potential systemically dysregulated proteins and pathways associated with the disease. Plasma samples from adult patients with moderate-to-severe psoriasis vulgaris (N = 59) and healthy age- and sex-matched individuals (N = 21) were analyzed using liquid chromatography–tandem mass spectrometry. Patients did not receive systemic anti-psoriatic treatment for four weeks before inclusion. A total of 776 protein groups were quantified. Of these, 691 were present in at least 60% of the samples, providing the basis for the downstream analysis. We identified 20 upregulated and 22 downregulated proteins in patients with psoriasis compared to controls (p < 0.05). Multiple proteins from the complement system were upregulated, including C2, C4b, C5, and C9, and pathway analysis revealed enrichment of proteins involved in complement activation and formation of the terminal complement complex. On the other end of the spectrum, periostin was the most downregulated protein in sera from patients with psoriasis. This comprehensive proteomic investigation revealed significantly elevated levels of complement cascade proteins in psoriatic plasma, which might contribute to increased systemic inflammation in patients with psoriasis. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Skin Diseases)
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<p>Plasma-derived proteins from patients with psoriasis reveal enrichment of the complement cascade. (<b>A</b>) In this study, we analyzed the proteomic differences between plasma from 59 patients with psoriasis and 21 healthy individuals by DIA LC-MS/MS. (<b>B</b>) Rank plot showing the overall mean label-free quantification (LFQ) intensities of the quantified proteins. As expected, albumin was the most abundant protein in this study of non-depleted plasma. (<b>C</b>) String network analysis of the 20 upregulated proteins (<span class="html-italic">p</span> &lt; 0.05). The red nodes are proteins present in the ‘immune system’. Reactome pathway and blue nodes represent proteins from the ‘Complement activation, classical pathway’ in the Gene Ontology knowledgebase. The string interaction score cut-off was set to 0.4. (<b>D</b>) Enrichment analysis based on the 20 upregulated proteins. The bar chart shows the top five enriched terms from the Reactome database, along with their corresponding <span class="html-italic">p</span>-values. All <span class="html-italic">p</span>-values remained significant after correction for multiple testing (FDR &lt; 0.05). (<b>E</b>) Boxplots of protein intensities of selected proteins in plasma from patients with psoriasis compared with healthy controls (* = <span class="html-italic">p</span> &lt; 0.05; ** = <span class="html-italic">p</span> &lt; 0.01). Abbreviations: DIA = data-independent acquisition; LC-MS/MS = liquid chromatography–tandem mass spectrometry; LFQ = label-free quantification.</p>
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15 pages, 1034 KiB  
Article
Frequency of Topical Immunomodulatory and Immunosuppressive Therapies for Ocular Chronic Graft-versus-Host Disease
by David Sinan Koca and Tina Dietrich-Ntoukas
J. Clin. Med. 2024, 13(16), 4728; https://doi.org/10.3390/jcm13164728 - 12 Aug 2024
Viewed by 246
Abstract
Introduction: The purpose of the study was to evaluate the frequency of topical immunomodulatory and immunosuppressive therapies in patients with ocular chronic graft-versus-host disease (cGVHD) in consideration of inflammatory activity and systemic immunosuppressive therapies in a tertiary care university hospital setting. Methods: We [...] Read more.
Introduction: The purpose of the study was to evaluate the frequency of topical immunomodulatory and immunosuppressive therapies in patients with ocular chronic graft-versus-host disease (cGVHD) in consideration of inflammatory activity and systemic immunosuppressive therapies in a tertiary care university hospital setting. Methods: We included 95 adult patients (48 male, 47 female) with ocular chronic graft-versus-host disease (cGVHD) after alloHSCT (median age 49.5 years). Clinical ophthalmological findings and the grade of ocular cGVHD according to the NIH eye score and the German–Austrian–Swiss Consensus (GAS) Grading were analyzed. Systemic GVHD manifestations as well as the prevalence of topical and systemic (immunomodulatory) therapies were assessed. Results: A total of 74 of 95 patients (77.8%) had manifestations of systemic chronic graft-versus-host disease other than ocular GVHD. 68.42% (65/95) of patients were under systemic immunosuppressive therapy with at least one immunosuppressive medication. All patients (95/95) received lid-margin hygiene and phosphate- and preservative-free lubricating eye drops. Twenty-five percent of the cohort (24/95) were treated with autologous serum eye drops (ASEDs). In total, 80% (76/95) of patients required topical steroid therapy to treat acute exacerbation of inflammation at least once; continuous topical steroid therapy was only necessary for a minor part (12%) with refractory chronic inflammation. A total of 92.63% (88/95) were primarily treated with ciclosporin A 0.1% as Ikervis®, of whom at least one third did not continue the therapy because of intolerable side effects during follow-up and received alternative topical formulations. Conclusions: Our data show that patients with ocular cGVHD mostly need topical therapy including anti-inflammatory agents despite systemic immunosuppressive therapy. In our cohort, 80% of patients received topical steroids, and more than 90% received topical ciclosporin A eye drops, which were tolerated by only two thirds of patients due to side effects. Full article
(This article belongs to the Section Ophthalmology)
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<p>Slit lamp images of an 81-year-old female patient with ocular chronic GVHD with involvement of lids, conjunctiva (including symblephara), and cornea (punctate keratitis) and ongoing inflammatory activity despite systemic and topical immunomodulatory treatments. Because of the side effects of commercially available CSA eye drops, alternative cyclosporine A formulations in different concentrations and tacrolimus eye drops were prescribed, but showed no effect on the inflammatory activity; the patient received prolonged topical steroid therapy.</p>
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<p>Slit lamp images of a 59-year-old female patient with ocular chronic GVHD with good response to Ikervis<sup>®</sup>. After 6 months of therapy, the inflammatory surface disease decreased with a reduction in conjunctival hyperemia and punctate keratopathy. In March 2019, the patient stopped Ikervis<sup>®</sup> by herself and continued only systemic immunosuppression with ibrutinib according to the treating hemato-oncologists.</p>
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19 pages, 2289 KiB  
Article
Anti-Aging Effects of Low-Molecular-Weight Collagen Peptide Supplementation on Facial Wrinkles and Skin Hydration: Outcomes from a Six-Week Randomized, Double-Blind, Placebo-Controlled Trial
by Juan Antonio Carrillo-Norte, Baldomero García-Mir, Lluis Quintana, Bruno Buracchio and Rafael Guerrero-Bonmatty
Cosmetics 2024, 11(4), 137; https://doi.org/10.3390/cosmetics11040137 - 12 Aug 2024
Viewed by 276
Abstract
In recent decades, there has been a rising demand for anti-aging interventions aimed at postponing or potentially reversing indicators of skin aging. The use of collagen-based nutraceutical supplements has gained popularity as they have shown promise in enhancing skin health and reducing signs [...] Read more.
In recent decades, there has been a rising demand for anti-aging interventions aimed at postponing or potentially reversing indicators of skin aging. The use of collagen-based nutraceutical supplements has gained popularity as they have shown promise in enhancing skin health and reducing signs of aging. The aim of this randomized, placebo-controlled, blinded study was to investigate the effects of 2.5 g COLLinstant® LMW, a novel cosmeceutical containing low-molecular-weight (≤1000 Da) collagen peptides, on skin aging and health. The trial was conducted with 80 healthy women aged 30 years and older. They received a daily oral dose of either the food supplement (n = 40) or placebo (n = 40) for six weeks. Skin assessment was performed based on validated objective methods, such as Visioface 1000D (skin wrinkling), cutometry (elasticity and fatigue), and corneometry (skin hydration) at baseline (T0) and at week 6 (T6). After 6 weeks, participants that received collagen had significant improvements in biometric skin wrinkle parameters from baseline, with a reduction in volume by 46%, in area by 44%, and in depth by 9%, along with a greater increase in skin moisturization (by 34%) than those in the placebo group (p < 0.001). The food supplement did not significantly modify skin firmness or fatigue and had only slight beneficial effects on skin elasticity. The investigational product was well tolerated. The observed effects aligned closely with the subjective assessments reported by study participants. The study provides substantiated evidence supporting the efficacy of low-molecular-weight collagen peptides in restoring altered skin biometric parameters, as objectively assessed. Thus, regular supplementation with this nutraceutical may contribute to achieving smoother and more radiant skin. Full article
(This article belongs to the Special Issue Skin Anti-Aging Strategies)
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<p>Flow chart of subjects’ recruitment, randomization, and follow-up.</p>
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<p>Box plot representing skin wrinkle volume at crow’s feet region before (T0) and after intake of the product for 6 weeks (T6) in the group of women receiving a low-molecular-weight (LMW) collagen preparation or placebo (<span class="html-italic">n</span> = 40/group). The mean value (x) is also represented. The asterisks indicate statistically significant differences in the intergroup comparison (* <span class="html-italic">p</span> &lt; 0.01; ** <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Box plot representing skin wrinkle area at crow’s feet region before (T0) and after intake of the product for 6 weeks (T6) in the group of women receiving a low-molecular-weight (LMW) collagen preparation or placebo (<span class="html-italic">n</span> = 40/group). The mean value (x) is also represented. The asterisk (*) indicates statistically significant differences in the intergroup comparison (* <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Box plot representing skin wrinkle depth at crow’s feet region before (T0) and after intake of the product for a 6-week period (T6) in the group of women receiving a low-molecular-weight (LMW) collagen preparation or placebo (<span class="html-italic">n</span> = 40/group). The mean value (x) is also represented. The asterisk (*) indicates statistically significant differences in the intergroup comparison (<span class="html-italic">p</span> &lt; 0.001). ° represent outliers.</p>
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<p>Appearance of wrinkles at the crow’s feet region during the treatment period with the investigational product. Photographs of the frown lines in three volunteers, no. 13 (top), no. 60 (middle), and no. 70 (bottom), at baseline (images (<b>a</b>,<b>c</b>,<b>e</b>) and at T6 after 6 weeks of oral supplementation with the test product (images (<b>b</b>,<b>d</b>,<b>f</b>). The green lines provide a visual guide to researchers to precisely observe and analyze skin features. Data obtained from Visioface<sup>®</sup> 1000D.</p>
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<p>Boxplot representing skin hydration before (T0) and after intake of the product for a 6-week period (T6) in the group of women receiving a low-molecular-weight (LMW) collagen preparation or placebo (<span class="html-italic">n</span> = 40/group). The mean value (x) is also represented. The asterisk (*) indicates statistically significant differences in the intergroup comparison (<span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Percentage change in biometric skin parameters between the baseline visit and the end of the 6 weeks of the interventional period (T0–T6) in the placebo group (red bars) and in the group taking the investigational product (green bars). Error bars indicate the standard error of the mean. The asterisk (*) indicates <span class="html-italic">p</span> &lt; 0.001 for intergroup comparison (placebo group vs. collagen group).</p>
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12 pages, 1217 KiB  
Article
Plasma Somatostatin Levels Are Lower in Patients with Coronary Stenosis and Significantly Increase after Stent Implantation
by Balázs Sütő, József Kun, Teréz Bagoly, Timea Németh, Erika Pintér, Dorottya Kardos and Zsuzsanna Helyes
J. Clin. Med. 2024, 13(16), 4727; https://doi.org/10.3390/jcm13164727 - 12 Aug 2024
Viewed by 253
Abstract
Background/Objectives: Stimulated capsaicin-sensitive peptidergic sensory nerves release somatostatin (SST), which has systemic anti-inflammatory and analgesic effects, correlating with the severity of tissue injury. Previous studies suggest that SST release into the systemic circulation is likely to serve as a protective mechanism during [...] Read more.
Background/Objectives: Stimulated capsaicin-sensitive peptidergic sensory nerves release somatostatin (SST), which has systemic anti-inflammatory and analgesic effects, correlating with the severity of tissue injury. Previous studies suggest that SST release into the systemic circulation is likely to serve as a protective mechanism during thoracic and orthopedic surgeries, scoliosis operations, and septic conditions, all involving significant tissue damage, pain, and inflammation. In a severe systemic inflammation rat model, SST released from sensory nerves into the bloodstream enhanced innate defense, reducing mortality. Inflammation is the key pathophysiological process responsible for the formation, progression, instability, and healing of atherosclerotic plaques. Methods: We measured SST-like immunoreactivity (SST-LI) in the plasma of healthy volunteers in different age groups and also that of stable angina patients with coronary heart disease (CHD) using ELISA and tracked changes during invasive coronary interventions (coronarography) with and without stent implantation. Samples were collected at (1) pre-intervention, (2) after coronarography, (3) 2 h after coronarography initiation and coronary stent placement, and (4) the next morning. Results: There was a strong negative correlation between SST-LI concentrations and age; the plasma SST-LI of older healthy volunteers (47–73 years) was significantly lower than in young ones (24–27 years). Baseline SST-LI in CHD patients who needed stents was significantly reduced compared to those not requiring stents. Plasma SST-LI significantly increased two hours post stent insertion and the next morning compared to pre-intervention levels. Conclusions: Age-related SST decrease might be a consequence of lower gene expression within specific hypo-thalamic nuclei as has been previously demonstrated in rodent animals. Reperfusion of ischemic myocardium post-stent implantation may trigger SST release, potentially offering protective benefits in coronary heart disease. Investigating this SST-mediated mechanism could offer valuable insights for future therapies. Full article
(This article belongs to the Section Vascular Medicine)
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<p>Plasma SST-LI in healthy volunteers in two age groups. In the boxplots, summary statistics are visualized for the two groups, 24–27 years (n = 10) and 47–73 years (n = 21): the median, two hinges (lower: first quartile or 25th percentile; upper: third quartile or 75th percentile), and two whiskers. The upper whisker extends from the hinge to the largest value no further than 1.5×. Inter-quartile range (IQR: the distance between the first and third quartiles). The lower whisker extends from the hinge to the smallest value at most 1.5 × IQR of the hinge. ### represents a large effect size, * <span class="html-italic">p</span> &lt; 0.05 (Welch’s <span class="html-italic">t</span>-test for unpaired comparison). The results of the statistical evaluation are provided in <a href="#app1-jcm-13-04727" class="html-app">Table S1</a>.</p>
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<p>Plasma SST-LI levels (pg/mL) in age-matched controls and in coronarography patients without stents and with stents before intervention. Age-matched healthy controls (47–73 years, n = 21), no-stent patient group (n = 16), and stent patient group (n = 8). Effect size: ### large; <span class="html-italic">p</span>-value: ** <span class="html-italic">p</span> &lt; 0.01, * <span class="html-italic">p</span> &lt; 0.05. In the boxplots, five summary statistics are visualized: the median, two hinges (lower: first quartile or 25th percentile; upper: third quartile or 75th percentile), and two whiskers. The upper whisker extends from the hinge to the largest value no further than 1.5 * IQR from the hinge (where the IQR is the inter-quartile range or the distance between the first and third quartiles). The lower whisker extends from the hinge to the smallest value, at most 1.5 * IQR of the hinge.</p>
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<p>Plasma SST-LI in patients having coronarography with and without stent implantation before, right after, 2 h, and 24 h following the intervention compared to the age-matched healthy controls. Boxplots demonstrate the medians, two hinges (lower: first quartile or 25th percentile; upper: third quartile or 75th percentile), and two whiskers with the greatest value no further than 1.5 * inter-quartile range (IQR) from the hinge (where the IQR is the distance between the first and third quartiles and the lower whisker extends from the hinge to the smallest value at most 1.5 * IQR of the hinge. Effect size: ### large; ## moderate. Dunnett’s <span class="html-italic">p</span>-value: * <span class="html-italic">p</span> &lt; 0.05. Pairwise <span class="html-italic">t</span>-test for stent patients <span class="html-italic">p</span>-value: ∧ <span class="html-italic">p</span> &lt; 0.05.</p>
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60 pages, 1805 KiB  
Systematic Review
Mechanistic Insights into the Biological Effects and Antioxidant Activity of Walnut (Juglans regia L.) Ellagitannins: A Systematic Review
by Letiția Mateș, Roxana Banc, Flaviu Andrei Zaharie, Marius Emil Rusu and Daniela-Saveta Popa
Antioxidants 2024, 13(8), 974; https://doi.org/10.3390/antiox13080974 (registering DOI) - 10 Aug 2024
Viewed by 476
Abstract
Walnuts (Juglans regia L.) are an important source of ellagitannins. They have been linked to positive effects on many pathologies, including cardiovascular disorders, neurodegenerative syndromes, and cancer. The limited bioavailability of ellagitannins prevents them from reaching significant circulatory levels, despite their antioxidant, [...] Read more.
Walnuts (Juglans regia L.) are an important source of ellagitannins. They have been linked to positive effects on many pathologies, including cardiovascular disorders, neurodegenerative syndromes, and cancer. The limited bioavailability of ellagitannins prevents them from reaching significant circulatory levels, despite their antioxidant, anti-inflammatory, and chemopreventive properties. Urolithins are ellagitannin gut microbiota-derived metabolites. They have better intestinal absorption and may be responsible for the biological activities of ellagitannins. Recent evidence showed that walnut ellagitannins and their metabolites, urolithins, could have positive outcomes for human health. This study aims to synthesize the current literature on the antioxidant activity and mechanistic pathways involved in the therapeutic potential of walnut ellagitannins and their metabolites. In the eligible selected studies (n = 31), glansreginin A, pedunculagin, and casuarictin were the most prevalent ellagitannins in walnuts. A total of 15 urolithins, their glucuronides, and sulfate metabolites have been identified in urine, blood, feces, breast milk, and prostate tissue in analyzed samples. Urolithins A and B were associated with antioxidant, anti-inflammatory, cardioprotective, neuroprotective, anticarcinogenic, and anti-aging activities, both in preclinical and clinical studies. Despite the promising results, further well-designed studies are necessary to fully elucidate the mechanisms and confirm the therapeutic potential of these compounds in human health. Full article
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<p>PRISMA flow diagram of study selection.</p>
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<p>The main metabolites of ETs and EA formed after walnut <span class="html-italic">(J. regia</span> L.) intake by intestinal microbiota (created with BioRender.com).</p>
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<p>The mechanisms of ellagitannins, ellagic acid, and urolithins and their multiple beneficial health effects after walnut consumption (AGEs—advanced glycation end products; BDNF—brain-derived neurotrophic factor; CA2—carbonic anhydrase 2; CAT—catalase; CRC—colorectal cancer; CPS1—carbamoylphosphate synthetase; CREB—cAMP-response element binding protein; CSCs—cancer stem cells; EA—ellagic acid; ETs—ellagitannins; HOC—hippocampal occupancy score; HOMA-IR—Homeostatic Model Assessment for Insulin Resistance; ICAM-1—intracellular adhesion molecule 1; IL—interleukin; INF-γ—interferon gamma; LDL-c—low-density lipoprotein cholesterol; MDA—malondialdehyde; NAFLD—non-alcoholic fatty liver disease; NF-κB—nuclear factor kappa-light-chain-enhancer of activated B cells; NASH—non-alcoholic steatohepatitis; ORAC—oxygen radical absorbance capacity; PCa—prostate cancer; PKA—protein kinase A; ROS—reactive oxygen species; SCFA—short-chain fatty acids; SOD—superoxide dismutase; TG—triglycerides; TNFα—tumor necrosis factor-α; T-AOC—total antioxidant capacity; UM—urolithin metabotypes; Uros—urolithins; VCAM-1—vascular cell adhesion molecule 1; WAT—white adipose tissue; ↑—increases; ↓—decreases).</p>
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16 pages, 2682 KiB  
Article
Bacillus coagulans LMG S-24828 Impairs Candida Virulence and Protects Vaginal Epithelial Cells against Candida Infection In Vitro
by Luca Spaggiari, Andrea Ardizzoni, Natalia Pedretti, Ramona Iseppi, Carla Sabia, Rosario Russo, Samyr Kenno, Francesco De Seta and Eva Pericolini
Microorganisms 2024, 12(8), 1634; https://doi.org/10.3390/microorganisms12081634 - 10 Aug 2024
Viewed by 289
Abstract
Probiotics are living microbes that provide benefits to the host. The growing data on health promotion, following probiotics administration, increased interest among researchers and pharmaceutical companies. Infections of the lower genital tract in females, caused by a wide range of pathogens, represent one [...] Read more.
Probiotics are living microbes that provide benefits to the host. The growing data on health promotion, following probiotics administration, increased interest among researchers and pharmaceutical companies. Infections of the lower genital tract in females, caused by a wide range of pathogens, represent one of the main areas for the use of probiotics and postbiotics. Vulvovaginal candidiasis (VVC) affects 75% of women of reproductive age at least once during their lifetime, with 5–8% developing the recurrent form (RVVC). The disease is triggered by the overgrowth of Candida on the vaginal mucosa. Here, in order to establish its probiotic potential in the context of VVC, we evaluated the anti-fungal effects of the spore-producing Bacillus coagulans LMG S-24828 against C. albicans and C. parapsilosis as well as its beneficial effects in counteracting Candida vaginal infection in vitro. Our results show that both live B. coagulans and its Cell-Free Supernatant (CFS) exerted antifungal activity against both fungi. Moreover, live B. coagulans reduced hyphal formation, inhibited C. albicans adhesion to vaginal epithelial cells, showed co-aggregation capacity, and exerted a protective effect on vaginal epithelial cells infected with C. albicans. These data suggest that B. coagulans LMG S-24828 may provide benefits in the context of Candida vaginal infections. Full article
(This article belongs to the Special Issue Microbe–Host Interactions in Human Infections)
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<p>Anti-<span class="html-italic">Candida</span> effect exerted by <span class="html-italic">B. coagulans</span>. (<b>A</b>) Mono-cultures and co-cultures of <span class="html-italic">C. albicans</span> (Ca), <span class="html-italic">C. parapsilosis</span> (Cp), and <span class="html-italic">B. coagulans</span> (Bc) pH values after 24 h of incubation at 37 °C. The chart reports the mean values of pH ± SEM from three different experiments. The range highlighted in light green represents the mean pH levels of the healthy vaginal environment. Statistical analysis was performed by the one-way ANOVA test followed by the uncorrected Fisher’s LSD test. Ca vs. Bc + Ca **** <span class="html-italic">p</span> &lt; 0.0001. Cp vs. Bc + Cp **** <span class="html-italic">p</span> &lt; 0.0001. Effect of <span class="html-italic">B. coagulans</span> (Bc) on <span class="html-italic">C. albicans</span> (Ca) (<b>B</b>) and <span class="html-italic">C. parapsilosis</span> (Cp) (<b>C</b>) growth capacity and acidification contribution upon 24 h of incubation at 37 °C. The graph shows the mean <span class="html-italic">C. albicans</span> (CFU × 10<sup>5</sup>/mL) ± SEM from three different experiments. Statistical analysis was performed by the one-way ANOVA test followed by the uncorrected Fisher’s LSD test. Ca vs. Bc + Ca **** <span class="html-italic">p</span> &lt; 0.0001. Cp vs. Bc + Cp *** <span class="html-italic">p</span> &lt; 0.001. ns = not significant.</p>
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<p>Kinetic measurement of <span class="html-italic">C. albicans</span> (Ca) (<b>A</b>) or <span class="html-italic">C. parapsilosis</span> (<b>B</b>) growth when cultivated with <span class="html-italic">B. coagulans</span> CFS (Bc CFS) or a sterile medium at 37 °C. Culture OD at 570 nm wavelength was automatically detected every 120 min for a total of 18 h. The graphs report the mean OD values ± SEM from triplicate samples of three different experiments. The Area Under the Curve (AUC) analysis was performed on kinetic data from <span class="html-italic">C. albicans</span> (<b>C</b>) and <span class="html-italic">C. parapsilosis</span> (<b>D</b>) samples. Each line represents one single experiment. Statistical analysis was performed on AUC values through the unpaired two-tailed Student’s <span class="html-italic">t</span>-test. Ca vs. Bc CFS + Ca and Cp vs. Bc CFS + Cp * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Evaluation of <span class="html-italic">C. albicans</span> (Ca) adhesion capacity to a vaginal epithelial cell monolayer in the presence of <span class="html-italic">B. coagulans</span> (Bc) (<b>A</b>). The histogram graph shows the average % ± SEM of fungal adhesion inhibition exerted by <span class="html-italic">B. coagulans</span> (Bc). Data are from three independent experiments. (<b>B</b>) Assessment of <span class="html-italic">B. coagulans</span> (Bc) capacity to co-aggregate with <span class="html-italic">C. albicans</span> (Ca) after 1 h of co-incubation. Boxes in the heatmap represent the score assigned to each sample in three independent experiments—0: no aggregation; 1: aggregates with small clusters; 2: aggregates with larger numbers of yeasts; 3: clumps visible with the naked eye containing large numbers of yeast cells; 4: maximum score for large clumps visible with the naked eye in the well center. (<b>C</b>–<b>E</b>) Effect of <span class="html-italic">B. coagulans</span> (Bc) on <span class="html-italic">C. albicans</span> (Ca) hyphal formation upon 4 h of co-incubation. Hyphal fragments were optically counted by fluorescent microscopy imaging. The fungal cell wall was stained with Uvitex 2B fluorescent dye. (<b>C</b>) The bars chart reports the mean percentage ± SEM of hyphal fragments counted in three different fields from three independent experiments. Statistical analysis was performed by the unpaired, two-tailed Student <span class="html-italic">t</span>-test. Ca vs. Bc + Ca * <span class="html-italic">p</span> &lt; 0.05. (<b>D</b>) The heatmap shows the % of hyphal fragments counted in each field; the squares’ color indicates the abundance of hyphae in the field (red: high % hyphal fragments; green: low % hyphal fragments). (<b>E</b>) Representative images from fluorescence microscopy analysis are shown from <span class="html-italic">C. albicans</span> (Ca) or <span class="html-italic">C. albicans</span> plus <span class="html-italic">B. coagulans</span> (Bc + Ca) taken at 40× magnification.</p>
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<p>(<b>A</b>) Percentage of vaginal cell damage pre-colonized or not by <span class="html-italic">B. coagulans</span> (Bc) for 6 h and infected for further 18 h with <span class="html-italic">C. albicans</span> (Ca). The chart reports the average percentage of cell damage ± SEM of triplicate samples from three different experiments. Statistical analysis was performed by the unpaired, two-tailed Student <span class="html-italic">t</span>-test. Ca vs. Bc + Ca * <span class="html-italic">p</span> &lt; 0.05. (<b>B</b>) Production of β-defensin-2 by vaginal epithelial cells pre-colonized or not by <span class="html-italic">B. coagulans</span> (Bc) for 6 h and infected for further 18 h with <span class="html-italic">C. albicans</span> (Ca). Uninfected cells (Ctrl) and cells colonized by the bacterium without <span class="html-italic">C. albicans</span> were also included in the experiments. The graph reports the mean ± SEM from three independent experiments. Statistical analysis was performed by the one-way ANOVA test followed by the uncorrected Fisher’s LSD test. Untreated cells vs. Bc pre-colonized cells * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Evaluation of antifungal effect permanency upon <span class="html-italic">B. coagulans</span> removal. <span class="html-italic">C. albicans</span> (Ca) (<b>A</b>) and <span class="html-italic">C. parapsilosis</span> (Cp) (<b>B</b>) metabolic activity quantification after being incubated with <span class="html-italic">B. coagulans</span> or sterile medium for 24 h and subsequent fungal isolation and cultivation for 24 h in the lack of bacteria. The graphs show the mean OD at 492 nm wavelength ± SEM from triplicate sample of three different experiments. Statistical analysis was performed by the one-way ANOVA test followed by the uncorrected Fisher’s LSD test. ns = not significant. (<b>C</b>) Capacity of <span class="html-italic">B. coagulans</span> spores to germinate on intestinal epithelial cells CaCo-2. Bacterial spores were seeded on an intestinal epithelial cell monolayer of CaCo-2 and incubated at 37 °C + 5% CO<sub>2</sub> for 24 h. After incubation, monolayers were photographed (upper images) and subsequently lysed. A Gram staining was then performed to visualize the presence of germinated <span class="html-italic">B. coagulans</span> (Bc) (lower images).</p>
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<p>Evaluation of antifungal effect permanency upon <span class="html-italic">B. coagulans</span> removal. <span class="html-italic">C. albicans</span> (Ca) (<b>A</b>) and <span class="html-italic">C. parapsilosis</span> (Cp) (<b>B</b>) metabolic activity quantification after being incubated with <span class="html-italic">B. coagulans</span> or sterile medium for 24 h and subsequent fungal isolation and cultivation for 24 h in the lack of bacteria. The graphs show the mean OD at 492 nm wavelength ± SEM from triplicate sample of three different experiments. Statistical analysis was performed by the one-way ANOVA test followed by the uncorrected Fisher’s LSD test. ns = not significant. (<b>C</b>) Capacity of <span class="html-italic">B. coagulans</span> spores to germinate on intestinal epithelial cells CaCo-2. Bacterial spores were seeded on an intestinal epithelial cell monolayer of CaCo-2 and incubated at 37 °C + 5% CO<sub>2</sub> for 24 h. After incubation, monolayers were photographed (upper images) and subsequently lysed. A Gram staining was then performed to visualize the presence of germinated <span class="html-italic">B. coagulans</span> (Bc) (lower images).</p>
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<p>Schematic representation of biological activities of <span class="html-italic">B. coagulans</span> LMG S-24828 against <span class="html-italic">Candida</span>. Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p>
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15 pages, 1055 KiB  
Article
The Immunological and Epidemiological Effectiveness of Pediatric Single-Dose Vaccination against Hepatitis A 9 to 11 Years after Its Implementation in the Tyva Republic, the Russian Federation
by Maria A. Lopatukhina, Karen K. Kyuregyan, Anastasia A. Karlsen, Fedor A. Asadi Mobarkhan, Ilya A. Potemkin, Vera S. Kichatova, Olga V. Isaeva, Lyudmila Yu. Ilchenko, Anna A. Saryglar and Mikhail I. Mikhailov
Vaccines 2024, 12(8), 907; https://doi.org/10.3390/vaccines12080907 (registering DOI) - 10 Aug 2024
Viewed by 376
Abstract
Since 2012, universal single-dose HAV vaccination in children aged 3 years and older has been implemented in the Tyva Republic, a region of the Russian Federation. The aim of this prospective non-interventional observational single-center study was to determine the immunological and epidemiological effectiveness [...] Read more.
Since 2012, universal single-dose HAV vaccination in children aged 3 years and older has been implemented in the Tyva Republic, a region of the Russian Federation. The aim of this prospective non-interventional observational single-center study was to determine the immunological and epidemiological effectiveness of single-dose vaccination against hepatitis A 9 to 11 years after its implementation. The anti-HAV IgG antibodies were determined in two independent cohorts of children who were vaccinated with a single dose of monovalent pediatric inactivated vaccine (HAVRIX® 720 EU) in Tyva in 2012 and recruited 9 years (Year 9 Cohort) and 11 years (Year 11 Cohort) after immunization. The seroprotection rates defined as anti-HAV antibody concentrations ≥10 mIU/mL reached 99.4% (95% CI: 98.2–99.9% [501/504]) in the Year 9 Cohort, but decreased significantly to 75.4% (95% CI: 73.0–77.6% [1006/1335]) in the Year 11 Cohort (p < 0.0001). The anti-HAV geometric mean concentrations decreased from 1446.3 mIU/mL (95% CI: 1347.1–1545.4 mIU/mL) in the Year 9 Cohort to 282.6 mIU/mL (95% CI: 203.8–360.8, p < 0.0001) in the Year 11 Cohort. The HAV vaccination program resulted in zero rates of hepatitis A incidence in the Tyva Republic since 2016. However, the limited monitoring of HAV RNA in sewage and environmental samples demonstrated the ongoing circulation of both the regional epidemic strain of HAV genotype IA and another genotype IA strain imported recently from other parts of the Russian Federation, probably due to subclinical infections in non-vaccinated children under 3 years of age. Taken together, these data indicate the effectiveness of the single-dose HAV vaccination strategy but suggest the need to expand the vaccination program to include children aged 12 months and older to achieve maximum effectiveness. Full article
(This article belongs to the Special Issue Immunology and Epidemiology of Infectious Diseases and Infection)
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<p>Study design and timeline. N indicates the number of samples.</p>
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<p>Hepatitis A annual incidence rates from 2001 to 2023 in Tyva and in the Russian Federation on average among the total population (<b>A</b>), children aged 0–14 years (<b>B</b>), and children aged 0–17 years (<b>C</b>).</p>
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<p>Maximum likelihood phylogenetic tree for the HAV VP1/2A sequences. For each sequence, the number in the GenBank database, the country, the city (in the case of Russian sequences), and the year of isolation are indicated. Sequences from the environmental samples collected in the Tyva Republic are shown in blue with the indicated year of isolation. The tree branches shown in red have a posterior probability of &gt;90%.</p>
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13 pages, 1884 KiB  
Article
Anti-Skin Aging and Cytotoxic Effects of Methanol-Extracted Solanum betaceum Red Fruit Seed Extract on Ca9-22 Gingival Carcinoma Cells
by Yen-Hua Huang and Cheng-Yang Huang
Plants 2024, 13(16), 2215; https://doi.org/10.3390/plants13162215 - 9 Aug 2024
Viewed by 273
Abstract
The tamarillo, or Solanum betaceum, recognized for its comprehensive nutritional profile, has long been valued for its diverse ethnobotanical uses. This study delves into the potential therapeutic applications of S. betaceum by analyzing its polyphenolic content (TPC), total flavonoid content (TFC), anti-skin [...] Read more.
The tamarillo, or Solanum betaceum, recognized for its comprehensive nutritional profile, has long been valued for its diverse ethnobotanical uses. This study delves into the potential therapeutic applications of S. betaceum by analyzing its polyphenolic content (TPC), total flavonoid content (TFC), anti-skin aging activities against key enzymes like elastase, tyrosinase, and hyaluronidase, and its cytotoxic effects on oral carcinoma cells. Extracts from the seeds, pulp, and peel of red and yellow fruits were prepared using methanol, ethanol, and acetone. The highest TPC was found in the methanol extract from red fruit seeds (9.89 mg GAE/g), and the highest TFC was found in the methanol extract of yellow fruit peel (3.02 mg QUE/g). Some of these extracts significantly inhibited skin aging-associated enzymes with the red fruit seed extract (100 μg/mL) showing up to 50.4% inhibition of tyrosinase. Additionally, the red fruit seed extract obtained using methanol demonstrated potential anticancer effects against Ca9-22 oral carcinoma cells by inhibiting cell survival, migration, and proliferation as well as inducing apoptosis. These results underscore the potential of S. betaceum fruit extracts, especially from red fruit seeds, as promising agents for anti-skin aging and anticancer applications, meriting further exploration for therapeutic uses. Full article
(This article belongs to the Special Issue Biological Activities of Plant Extracts 2023)
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<p>Anticancer potential of methanol-extracted red fruit seeds on Ca9-22 gingival carcinoma cells. (<b>A</b>) The impact of the seed extract on cell survival, migration, proliferation, and nuclear condensation in Ca9-22 cells. The black and white dashed lines indicate the positions of cell migration before and after treatment with the extract. (<b>B</b>) Trypan blue exclusion assay results demonstrating cell viability after exposure to various concentrations of the seed extract. (<b>C</b>) Wound-healing assay depicting Ca9-22 cell migration before and 24 h after treatment at different concentrations of the extract. (<b>D</b>) Clonogenic assay assessing the ability of individual cells to form colonies, indicating the survival and proliferative potential of Ca9-22 cells treated with the seed extract. (<b>E</b>) Hoechst staining results showing levels of apoptosis and DNA fragmentation at various seed extract concentrations. Statistical significance is denoted by * (<span class="html-italic">p</span> &lt; 0.05), ** (<span class="html-italic">p</span> &lt; 0.01), and *** (<span class="html-italic">p</span> &lt; 0.001) compared to control. ns, not significant.</p>
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11 pages, 1334 KiB  
Article
Rhegmatogenous Retinal Detachment with Giant Retinal Tear: Case Series and Literature Review
by Siyun Lee and Joonhyung Kim
J. Clin. Med. 2024, 13(16), 4690; https://doi.org/10.3390/jcm13164690 - 9 Aug 2024
Viewed by 282
Abstract
Background/Objectives: This paper reviews three cases of rhegmatogenous retinal detachment (RRD) with giant retinal tear (GRT), focusing on surgical management and outcomes, and synthesizes the current literature on the subject. Methods: We retrospectively analyzed three cases of male patients diagnosed with [...] Read more.
Background/Objectives: This paper reviews three cases of rhegmatogenous retinal detachment (RRD) with giant retinal tear (GRT), focusing on surgical management and outcomes, and synthesizes the current literature on the subject. Methods: We retrospectively analyzed three cases of male patients diagnosed with RRD with GRT at our hospital from April 2022 to November 2023. The patients, aged 57, 66, and 60, underwent surgical interventions, with postoperative follow-up extending up to six months. All patients underwent pars plana vitrectomy (PPV), endolaser photocoagulation, fluid–air exchange, and intravitreal gas injection (perfluoropropane (C3F8) 14%) in each case. Surgeries were performed within four days of the patients’ initial visits. Outcome measures included visual acuity improvement, intraocular pressure stabilization, and retinal reattachment rates. Complications in the patients were also evaluated. Results: The patient who had not previously undergone cataract surgery (Case 1) had it concurrently with the retinal surgery. Four months after the initial surgery, Case 3 developed a secondary epiretinal membrane (ERM) and subsequently underwent ERM removal surgery. Postoperative care involved the tailored use of anti-inflammatory medications and frequent monitoring to mitigate complications such as proliferative vitreoretinopathy, epiretinal membrane formation, and redetachment. Conclusions: While limited by the small sample size, this report underscores the potential benefits of prompt surgical intervention, meticulous postoperative care, and proactive management of complications in RRD with GRT. Insights from these cases, supported by multiple literature reviews, may inform treatment strategies and highlight areas for further research in larger, more diverse patient populations. Full article
(This article belongs to the Section Ophthalmology)
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<p>Case 1 patient’s left eye images. (<b>A</b>–<b>C</b>) On the day of presentation. (<b>A</b>) Color fundus photography (FP) showed rhegmatogenous retinal detachment (RRD) with giant retinal tear (GRT) at a 9–12 o’clock direction. (<b>B</b>) Optical coherence tomography (OCT) showed vitreous hemorrhage. (<b>C</b>) B-scan ultrasound (B-scan) showed vitreous hemorrhage and retinal detachment. (<b>D</b>,<b>E</b>) Six months after surgery. (<b>D</b>) FP showed a flat, well-attached retina. (<b>E</b>) OCT showed a flat, well-attached retina.</p>
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<p>Case 2 patient’s left eye images (<b>A</b>,<b>B</b>). On the day of presentation. (<b>A</b>) FP showed RRD with GRT at the temporal area. (<b>B</b>) OCT showed macula-off retinal detachment (RD). (<b>C</b>,<b>D</b>) Six months after surgery. (<b>C</b>) FP showed a flat, well-attached retina. (<b>D</b>) OCT showed a flat, well-attached retina.</p>
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<p>Case 3 patient’s left eye images. (<b>A</b>–<b>C</b>) On the day of presentation. (<b>A</b>) FP showed RRD with GRT in the superotemporal direction. (<b>B</b>) OCT showed macula-off RD. (<b>C</b>) B-scan showed RD. (<b>D</b>,<b>E</b>) Four months after the initial surgery. (<b>D</b>) FP showed a secondary epiretinal membrane (ERM). (<b>E</b>) OCT showed a secondary ERM. (<b>F</b>,<b>G</b>) Six months after the initial surgery. (<b>F</b>) FP showed a flat, well-attached retina. (<b>G</b>) OCT showed a flat, well-attached retina.</p>
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12 pages, 918 KiB  
Article
Underreporting of Cases in the COVID-19 Outbreak of Borriana (Spain) during Mass Gathering Events in March 2020: A Cross-Sectional Study
by Salvador Domènech-Montoliu, Maria Rosario Pac-Sa, Diego Sala-Trull, Alba Del Rio-González, Manuel Sanchéz-Urbano, Paloma Satorres-Martinez, Roser Blasco-Gari, Juan Casanova-Suarez, Maria Gil-Fortuño, Laura López-Diago, Cristina Notari-Rodríguez, Óscar Pérez-Olaso, Maria Angeles Romeu-Garcia, Raquel Ruiz-Puig, Isabel Aleixandre-Gorriz, Carmen Domènech-León and Alberto Arnedo-Pena
Epidemiologia 2024, 5(3), 499-510; https://doi.org/10.3390/epidemiologia5030034 - 9 Aug 2024
Viewed by 393
Abstract
Determining the number of cases of an epidemic is the first function of epidemiological surveillance. An important underreporting of cases was observed in many locations during the first wave of the COVID-19 pandemic. To estimate this underreporting in the COVID-19 outbreak of Borriana [...] Read more.
Determining the number of cases of an epidemic is the first function of epidemiological surveillance. An important underreporting of cases was observed in many locations during the first wave of the COVID-19 pandemic. To estimate this underreporting in the COVID-19 outbreak of Borriana (Valencia Community, Spain) in March 2020, a cross-sectional study was performed in June 2020 querying the public health register. Logistic regression models were used. Of a total of 468 symptomatic COVID-19 cases diagnosed in the outbreak through anti-SARS-CoV-2 serology, 36 cases were reported (7.7%), resulting in an underreporting proportion of 92.3% (95% confidence interval [CI], 89.5–94.6%), with 13 unreported cases for every reported case. Only positive SARS-CoV-2 polymerase chain reaction cases were predominantly reported due to a limited testing capacity and following a national protocol. Significant factors associated with underreporting included no medical assistance for COVID-19 disease, with an adjusted odds ratio [aOR] of 10.83 (95% CI 2.49–47.11); no chronic illness, aOR = 2.81 (95% CI 1.28–6.17); middle and lower social classes, aOR = 3.12 (95% CI 1.42–6.85); younger age, aOR = 0.97 (95% CI 0.94–0.99); and a shorter duration of illness, aOR = 0.98 (95% CI 0.97–0.99). To improve the surveillance of future epidemics, new approaches are recommended. Full article
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<p>Adjusted for potential confounding factors using directed acyclic graphs (DAGs) of the COVID-19 medical assistance (exposure) effect on COVID-19 case reporting (outcome). Ancestors of exposure: age, sex, social class, lifestyles, chronic illness, duration of illness (in red) and outcome (in blue). Based on DAGitty version 3.1.</p>
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<p>Flow diagram showing the population under study in the underreporting of COVID-19 cases in Borriana during the period January–June 2020.</p>
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25 pages, 2826 KiB  
Review
Phytotherapy in Alzheimer’s Disease—A Narrative Review
by Julia Piekarz, Natalia Picheta, Oliwia Burdan, Marcelina Kurek and Magdalena Chrościńska-Krawczyk
Biomedicines 2024, 12(8), 1812; https://doi.org/10.3390/biomedicines12081812 - 9 Aug 2024
Viewed by 418
Abstract
Alzheimer’s disease (AD) affects 50–70% of patients with dementia, making it the leading cause of dementia. The condition is classified as a neurodegenerative, progressive and incurable disease. The disease is affecting more and more people around the world. AD has a multifactorial nature, [...] Read more.
Alzheimer’s disease (AD) affects 50–70% of patients with dementia, making it the leading cause of dementia. The condition is classified as a neurodegenerative, progressive and incurable disease. The disease is affecting more and more people around the world. AD has a multifactorial nature, spreading from beta-amyloid deposition to inflammation in patients’ brains. Patients experience cognitive impairment and functional decline. Although it is a disease that occurs mainly in the elderly, it is increasingly being diagnosed in young people between the ages of 30 and 40. It not only affects the patient themself but also reduces the quality of life of their closest caregivers. According to the WHO, the treatment of AD consumes USD 1.3 trillion globally, but it is only symptomatic, as there are no drugs to prevent the onset of AD or treat the cause of its onset. Due to the numerous side effects of therapy and the lack of proactive drugs that act on the pathomechanism of AD, alternative therapies are being sought. One possible option that has many studies confirming its effect is phytotherapy. Many herbs have pharmacological properties, such as antioxidant, anti-inflammatory, or neuroprotective effects, making them the future of cognitive disorders and AD treatment. This review focuses on some of the most promising herbs that have potentially potent properties and effects in AD therapy. These include Curcuma longa, Panax ginseng, Berberis and Crocus sativus. These herbs may perhaps be key in the future to make functioning and life easier for patients struggling with AD. Full article
(This article belongs to the Special Issue Phytochemicals: Current Status and Future Prospects)
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<p>Summary of AD pathomechanism.</p>
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<p>Summary of the pharmacological properties of the herbs included in the article.</p>
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<p>Potential therapeutic targets for AD alternative therapy (MAO-B monoamine oxidase B).</p>
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<p>Pharmacological properties showing potential use of curcumin in AD therapy.</p>
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<p>Pharmacological properties of ginsenosides affecting the inhibition of AD progression and symptoms.</p>
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<p>Summary of berberine handle points in AD therapy.</p>
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<p>Presentation of the properties of substances contained in <span class="html-italic">Crocus sativus</span> in alternative therapy of AD.</p>
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13 pages, 1274 KiB  
Article
The Humoral Immune Response against Human Endogenous Retroviruses in Celiac Disease: A Case–Control Study
by Marco Bo, Roberto Manetti, Marilù Biggio and Leonardo A. Sechi
Biomedicines 2024, 12(8), 1811; https://doi.org/10.3390/biomedicines12081811 - 9 Aug 2024
Viewed by 349
Abstract
Background: Celiac disease (CD) is an immune-mediated disease characterized by disruptions of the small intestine. Factors such as viral and bacterial infections can trigger CD. Recently, the reactivation of Human Endogenous Retroviruses (HERVs) has also been implicated, but little is known about their [...] Read more.
Background: Celiac disease (CD) is an immune-mediated disease characterized by disruptions of the small intestine. Factors such as viral and bacterial infections can trigger CD. Recently, the reactivation of Human Endogenous Retroviruses (HERVs) has also been implicated, but little is known about their specific role in patients with celiac disease. Methods: The purpose of this study is to explore the humoral immune response mounted against epitopes derived from the envelope portion of three families of HERVs (HERV-K, HERV-H, and HERV-W) in CD patients. Reactivity against the HERV-K, HERV-H, and HERV-W env-su peptides was tested by indirect ELISAs in plasma of 40 patients with celiac disease and 41 age-matched healthy subjects (HCs). Results: HERV-K, HERV-H, and HERV-W env-su peptides triggered different antibody responses in CD patients compared to HCs, with a stronger reactivity (p = 0.0001). Conclusions: Present results show, for the first time, that epitopes of HERV-K, HERV-H, and HERV-W are more recognized in patients with CD. Taking into consideration their proinflammatory and autoimmune features, this might suggest that HERVs may contribute to the development of CD or its exacerbation in genetically predisposed subjects. Finally, to elucidate the interplay between gut inflammation and HERVs during the inflammatory process, further studies are required. Those investigations should focus on the expression levels of HERVs and their relationship with the immune response, specifically examining anti-transglutaminase 2 (TG2) antibody levels under both gluten-free and gluten-containing dietary conditions. Full article
(This article belongs to the Special Issue Epigenetic Regulation and Its Impact for Medicine)
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<p>An ELISA-based analysis of Ab reactivity against viral derived peptides in the patients with celiac disease (CD) and in the healthy controls (HCs). (<b>A</b>) The sera were tested against the plate-coated HERV-K env-su<sub>19-37</sub>, (<b>B</b>) the HERV-H env-su<sub>229-241</sub>, (<b>C</b>) the HERV-W env-su<sub>129-14</sub>, and (<b>D</b>) INF-α peptides. The bars represent the median ± interquartile range. (<b>A</b>–<b>D</b>) The thresholds for Abs are indicated with dashed lines. The <span class="html-italic">p</span>-values and the AUC are indicated above the distributions. (<b>E</b>) The prevalence of the Abs tested against the HERV epitopes and INF-α in the patients with CD and in the HCs. Total percentage of Abs positivity to at least one peptide is represented by the first bar in each group. The other bars correspond to a single-peptide positivity relative to each epitope. (<b>F</b>) The prevalence of multiple Abs in patients with CD and in HCs. Seroreactivity against the INF-α antigen is compared to the humoral responses to the HERV-K, HERV-H, and HERV-W peptides. The horizontal bars indicate Abs against at least two antigens identified in the samples.</p>
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<p>A scatter plot showing the correlations between Ab titers identifying (<b>A</b>) HERV-H env-su<sub>229-241</sub> and HERV-K env-su<sub>19-37</sub>, (<b>B</b>) HERV-W env-su<sub>129-143</sub> and HERV-K env-su<sub>19-37</sub>, (<b>C</b>) HERV-W env-su<sub>129-143</sub> and HERV-H env-su<sub>229-241</sub>, (<b>D</b>) HERV-K env-su<sub>19-37</sub> and α-transglutaminase, (<b>E</b>) HERV-H env-su<sub>229-241</sub> and α-transglutaminase, and (<b>F</b>) HERV-W env-su<sub>129-143</sub> and α-transglutaminase in 40 patients with CD. Person’s correlation was calculated through GraphPad Prism version. 8.0 software.</p>
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<p>Scatter plot showing correlations between Abs titers recognizing: (<b>A</b>) HERV-K env-su19-37 and INF-α, (<b>B</b>) HERV-H env-su229-241 and INF-α, (<b>C</b>) HERV-W env-su129-143 and INF-α, (<b>D</b>) anti-transglutaminase 2 Abs and INF-α in CD patients. Scatter plot showing correlations between Abs titers recognizing: (<b>E</b>) HERV-K env-su19-37 and INF-α, (<b>F</b>) HERV-H env-su229-241 and INF-α, (<b>G</b>) HERV-W env-su129-143 and INF-α in 41 HCs. Person’s correlation was calculated through GraphPad Prism v. 8.0 software.</p>
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17 pages, 8251 KiB  
Article
Dynamic Changes in Endogenous Substances in Flowering Organs of Camellia drupifera during the Flowering Stage
by Zhen Liu, Jialu Tao, Chunhua Ma, Mengling Wen, Ruchun Xi and Xiaomei Deng
Forests 2024, 15(8), 1391; https://doi.org/10.3390/f15081391 - 9 Aug 2024
Viewed by 247
Abstract
Camellia drupifera is an important woody oil plant in South China, renowned for its seed oil that is rich in unsaturated fatty acids and possesses significant antioxidant, anti-cancer, and immune-enhancing properties. The low fruit-setting rate of C. drupifera is influenced by multiple factors, [...] Read more.
Camellia drupifera is an important woody oil plant in South China, renowned for its seed oil that is rich in unsaturated fatty acids and possesses significant antioxidant, anti-cancer, and immune-enhancing properties. The low fruit-setting rate of C. drupifera is influenced by multiple factors, including flowering stage climate, flowering habits, pollination biology, soil conditions, and self-incompatibility. Among these, large-scale pure forest plantations are the primary cause of the low fruit-setting rate. Although previous studies have explored the impact of self-incompatibility on fruit-setting in C. drupifera, research on the dynamic changes of endogenous substances during the flowering stage in pure forest environments remains limited. Research findings indicate that tannase activity is relatively high in the pistils of C. drupifera, creating a favorable environment for pollen tube growth. Plant hormones such as indole-3-acetic acid (IAA), cytokinin (CTK), gibberellin (GA), and ethylene (ETH) regulate the development and aging of floral organs through complex interactions. Specifically, high levels of IAA in the pistil promote pollen tube growth, while changes in ETH and ABA are closely related to the aging of floral organs. Under oxidative stress conditions, high levels of H2O2 in the pistil may contribute to self-incompatibility. The activity of superoxide dismutase (SOD) in the floral organs during the flowering stage is significantly higher compared to peroxidase (POD) and catalase (CAT), highlighting the critical role of SOD in regulating oxidative stress during this stage. This study provides new insights into the changes in endogenous substances in the floral organs of C. drupifera during the flowering stage. It offers theoretical references for understanding its sexual reproduction process and for the application of plant growth regulators to improve fruit setting. Full article
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<p>Morphological Changes in Floral Organs of <span class="html-italic">C. drupifera</span> during the Flowering Stage. Note: Panels (<b>A</b>–<b>F</b>) illustrate the morphological changes at different stages: two days before flowering (K(−2)), on the day of flowering (K(0)), one day after flowering (K(1)), two days after flowering (K(2)), four days after flowering (K(4)), and six days after flowering (K(6)). (a) Petals (P); (b) Stamens (S); (c) Pistils (P); (d) Sepals (S); (e) Buds (B). The grid size varies among the images: the minimum square length is 1 cm, and this measurement remains consistent across all images.</p>
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<p>Heatmap of Endogenous Substance Abundance during Flowering Stage of <span class="html-italic">C. drupifera.</span> Note: (<b>A</b>); Pistils; (<b>B</b>): Stamens. The heatmap color gradient from red to blue represents the relative changes in endogenous substance content in floral organs during the flowering stage, with red indicating above-average levels and blue indicating below-average levels. The dendrogram on the left side of the heatmap shows the similarity in substance content changes, with closer branches representing more similar trends. The raw data were standardized using Z-score normalization. TNS: tannase, H<sub>2</sub>O<sub>2:</sub> Hydrogen peroxide, ROS: Reactive oxygen species, SP: Soluble proteins, SS: Soluble sugars, ABA: Abscisic acid, IAA: Indole-3-acetic acid, GA: Gibberellins, CTK: Cytokinin, ETH: Ethylene, BR: Brassinosteroids, POD: Peroxidase, SOD: Superoxide dismutase, CAT: Catalase.</p>
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<p>Dynamic Changes in Tannin Synthase Activity of Floral Organs during the Flowering Stage of <span class="html-italic">C. drupifera.</span> Note: different capital letters following data in the same row indicate significant differences (<span class="html-italic">p</span> &lt; 0.05) between different floral organs at the same sampling stage; different lowercase letters following data in the same column indicate significant differences (<span class="html-italic">p</span> &lt; 0.05) between different sampling stages of the same floral organ. Error bars represent the standard deviation (SD) of the mean. The red fill represents pistils, and the green dashed line represents stamens. The same notation and color coding apply to all relevant figures and tables in the text.</p>
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<p>Dynamic Changes in Hormone Content of Floral Organs during Flowering Stage of <span class="html-italic">C. drupifera.</span> Note: Panels (<b>A</b>–<b>F</b>) represent the content of IAA, CTK, GA, ETH, ABA, and BR, respectively.</p>
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<p>Dynamic Changes in Hormone Ratios of Floral Organs during Flowering Stage of <span class="html-italic">C. drupifera.</span> Note: Panels (<b>A</b>–<b>D</b>) represent the ratios of IAA/ABA, CTK/ABA, BR/ABA, and GA/ABA, respectively.</p>
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<p>Dynamic Changes in ROS, H<sub>2</sub>O<sub>2</sub> Content, and Antioxidant Enzyme Activity of Floral Organs during Flowering Stage of <span class="html-italic">C. drupifera.</span> Note: Panels (<b>A</b>–<b>E</b>) represent the ROS content, H<sub>2</sub>O<sub>2</sub> content, POD, SOD, and CAT activity, respectively.</p>
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<p>Dynamic Changes in Soluble Protein (SP) and Soluble Sugar (SS) Contents of Floral Organs during Flowering Stage of <span class="html-italic">C. drupifera.</span> Note: Panels (<b>A</b>,<b>B</b>) represent the Soluble Protein content and Soluble Sugar content, respectively.</p>
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<p>Correlation of Endogenous Substances in Floral Organs during Flowering Stage of <span class="html-italic">C. drupifera.</span> Note: (<b>A</b>): Correlation in pistils; (<b>B</b>): Correlation in stamens. Colors in the correlation analysis represent positive (red) and negative (blue) correlations, with darker colors indicating stronger correlations. “*” indicates significant correlation at the 0.05 level (<span class="html-italic">p</span> &lt; 0.05); “**” indicates highly significant correlation at the 0.01 level (<span class="html-italic">p</span> &lt; 0.01).</p>
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9 pages, 230 KiB  
Article
Nonadherence to Cardiovascular Drugs Predicts Risk for Non-Arthritic Anterior Ischemic Optic Neuropathy: A Large-Scale National Study
by Anan Hammud, Yosef. S. Haviv, Eyal Walter, Nir Amitai, Tomer Kerman, Samuel Leeman and Erez Tsumi
J. Clin. Med. 2024, 13(16), 4670; https://doi.org/10.3390/jcm13164670 - 9 Aug 2024
Viewed by 318
Abstract
Purpose: While patients with cardiovascular comorbidities are at a higher risk for the occurrence of non-arteritic anterior ischemic optic neuropathy (NAION), it is unclear whether adherence to medication results in risk reduction. The purpose of this study was to investigate whether nonadherence [...] Read more.
Purpose: While patients with cardiovascular comorbidities are at a higher risk for the occurrence of non-arteritic anterior ischemic optic neuropathy (NAION), it is unclear whether adherence to medication results in risk reduction. The purpose of this study was to investigate whether nonadherence to medical therapy for cardiovascular morbidity correlates with a higher risk for NAION when compared to patients with strict adherence. Methods: A retrospective case-control study was conducted among members of Clalit Health Services in Israel from 2001 to 2022. For each of the 757 NAION cases, three controls (totaling 2271 patients) were matched based on birth year and sex, with a propensity score analysis employed to adjust for a range of comorbidities. A patient was deemed nonadherent with medical treatment if their purchased quantity of medication was less than 60% of the prescribed annual dosage. Mixed models were used to evaluate exposure differences, and conditional logistic regression was applied, incorporating adjustments for socioeconomic status and ethnicity, to examine the impact of medication nonadherence on NAION risk. Results: A total of 3028 patients were included in the study; 757 patients with the diagnosis of NAION and 2271 in the matched control group. The average age of NAION patients was 69 ± 9 years and 55% were male. After adjustments for socioeconomic status and ethnicity, nonadherence to calcium channel blockers (CCBs) (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.03–1.71) and anti-arrhythmic (OR: 5.67, 95% CI: 1.89–21.2) medications emerged as significant risk factors. Similarly, nonadherence to cardioprotective medications (OR: 1.46, 95% CI: 1.23–1.74) was also identified as a significant risk factor. Conclusions: Nonadherence to treatments for cardiovascular disease, specifically to medications known to improve prognosis, is associated with a higher risk for NAION. Full article
(This article belongs to the Special Issue Clinical Treatment and Management of Neuro-Ophthalmic Disease)
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