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22 pages, 4821 KiB  
Article
Robot Task-Constrained Optimization and Adaptation with Probabilistic Movement Primitives
by Guanwen Ding, Xizhe Zang, Xuehe Zhang, Changle Li, Yanhe Zhu and Jie Zhao
Biomimetics 2024, 9(12), 738; https://doi.org/10.3390/biomimetics9120738 (registering DOI) - 3 Dec 2024
Abstract
Enabling a robot to learn skills from a human and adapt to different task scenarios will enable the use of robots in manufacturing to improve efficiency. Movement Primitives (MPs) are prominent tools for encoding skills. This paper investigates how to learn MPs from [...] Read more.
Enabling a robot to learn skills from a human and adapt to different task scenarios will enable the use of robots in manufacturing to improve efficiency. Movement Primitives (MPs) are prominent tools for encoding skills. This paper investigates how to learn MPs from a small number of human demonstrations and adapt to different task constraints, including waypoints, joint limits, virtual walls, and obstacles. Probabilistic Movement Primitives (ProMPs) model movements with distributions, thus providing the robot with additional freedom for task execution. We provide the robot with three modes to move, with only one human demonstration required for each mode. We propose an improved via-point generalization method to generalize smooth trajectories with encoded ProMPs. In addition, we present an effective task-constrained optimization method that incorporates all task constraints analytically into a probabilistic framework. We separate ProMPs as Gaussians at each timestep and minimize Kullback–Leibler (KL) divergence, with a gradient ascent–descent algorithm performed to obtain optimized ProMPs. Given optimized ProMPs, we outline a unified robot movement adaptation method for extending from a single obstacle to multiple obstacles. We validated our approach with a 7-DOF Xarm robot using a series of movement adaptation experiments. Full article
12 pages, 607 KiB  
Review
Fibroblast Heterogeneity in Inflammatory Bowel Disease
by Bo-Jun Ke, Gabriele Dragoni and Gianluca Matteoli
Int. J. Mol. Sci. 2024, 25(23), 13008; https://doi.org/10.3390/ijms252313008 - 3 Dec 2024
Abstract
Intestinal fibroblasts are pivotal players in maintaining tissue homeostasis and orchestrating responses to injury and inflammation within the gastrointestinal (GI) tract. Fibroblasts contribute significantly to the pathogenesis of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis (UC), by secreting pro-inflammatory cytokines, [...] Read more.
Intestinal fibroblasts are pivotal players in maintaining tissue homeostasis and orchestrating responses to injury and inflammation within the gastrointestinal (GI) tract. Fibroblasts contribute significantly to the pathogenesis of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis (UC), by secreting pro-inflammatory cytokines, modulating immune cell activity, and promoting fibrosis. In addition, fibroblasts play crucial roles in tissue repair and regeneration following acute injury or chronic inflammation. The dysregulation of fibroblast functions can lead to fibrotic complications, such as intestinal strictures and obstruction, which are common in advanced stages of IBD. Understanding the complex interplay between fibroblasts and other cell types in the intestine is essential to elucidate the underlying mechanisms of intestinal diseases and identify novel therapeutic targets. Future research aimed at deciphering the heterogeneity of intestinal fibroblasts and their dynamic roles in disease progression holds promise for the development of precision therapies to mitigate fibrosis and inflammation in intestinal disorders. Full article
(This article belongs to the Section Molecular Immunology)
18 pages, 1217 KiB  
Systematic Review
Leadership and Climate Change Mitigation: A Systematic Literature Review
by Corey McPherson and Amelia Clarke
Climate 2024, 12(12), 207; https://doi.org/10.3390/cli12120207 (registering DOI) - 3 Dec 2024
Viewed by 76
Abstract
This systematic literature review (SLR) explores leadership and climate change mitigation in cities. In doing so, it investigates explicit meanings of leadership, enablers of leadership, and leadership similarities and differences across regions. The review utilized three databases on 8 March 2024—Scopus, ProQuest, and [...] Read more.
This systematic literature review (SLR) explores leadership and climate change mitigation in cities. In doing so, it investigates explicit meanings of leadership, enablers of leadership, and leadership similarities and differences across regions. The review utilized three databases on 8 March 2024—Scopus, ProQuest, and Web of Science—curating an initial 496 results, resulting in 30 studies in the final analysis, using a two-reviewer screening process to limit bias and ensure consistency of approach. Inclusion criteria included English-language peer-reviewed articles over a ten-year period. The timeframe used was limited to January 2014 to December 2023 (10 years) to focus on the lead up to and post-implementation of the Paris Agreement. Further, empirical and conceptual studies were included to provide readers of this review with a thorough understanding of leadership work completed since 2014. Exclusion criteria included any studies that focus on adaptation measures and forms of leadership where the focus is on the private business, state, or national level, including leadership and climate change mitigation outside the influence of the local government. The study highlights five distinct meanings of leadership using the Braun and Clarke method of thematic analysis. It found leadership themes related to people (e.g., mayors), policy (e.g., ambitious climate plans), ideas (e.g., new concepts), collective action (e.g., motivating others), and mobilizing power (e.g., through regulations). The enablers of leadership included polycentricity, social capital influences, co-creational and mayor leadership, climate governance, and multi-actor coordination. This review segments the studies based on the findings from the literature, which focus on three continents (North America, Europe, and Asia) with a distinct difference in the meaning and enablers of leadership based on region. The 30 articles shared similarities in content, such as strong mayoral influence, but also had some distinct differences, such as how leadership is enacted based on leveraging market mechanisms, policy, and horizontal and vertical coordination. Finally, research gaps were identified, such as the scant focus on leadership and climate change mitigation in the Global South, to enable future research. Limitations of this study include the utilization of three databases, a focus on only English-language peer-reviewed articles, and a strong climate change mitigation focus. Full article
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<p>Flow chart of the systematic literature review process [<a href="#B21-climate-12-00207" class="html-bibr">21</a>,<a href="#B26-climate-12-00207" class="html-bibr">26</a>].</p>
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<p>Number of publications published per year (January 2014 to December 2023).</p>
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<p>Explicit meanings of leadership theme distillation process.</p>
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<p>Enablers of leadership for climate mitigation across theme categories.</p>
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15 pages, 2235 KiB  
Article
Maternal Supplementation with Lacticaseibacillus rhamnosus GG Improves Glucose Tolerance and Modulates the Intestinal Microbiota of Offspring
by Dayane Correia Gomes, José Enrique Meza Alvarado, Jesus Alejandro Zamora Briseño, Cynthia Cano Sarmiento, Alberto Camacho Morales and Rubi Viveros Contreras
Diseases 2024, 12(12), 312; https://doi.org/10.3390/diseases12120312 (registering DOI) - 3 Dec 2024
Viewed by 92
Abstract
Introduction: Consuming hypercaloric diets during pregnancy induces metabolic, immune, and maternal intestinal dysbiosis disorders. These conditions are transferred to the offspring through the placenta and breastfeeding, increasing susceptibility to metabolic diseases. We investigated the effect of L. rhamnosus GG supplementation on offspring maternally [...] Read more.
Introduction: Consuming hypercaloric diets during pregnancy induces metabolic, immune, and maternal intestinal dysbiosis disorders. These conditions are transferred to the offspring through the placenta and breastfeeding, increasing susceptibility to metabolic diseases. We investigated the effect of L. rhamnosus GG supplementation on offspring maternally programmed with a hypercaloric diet. Methods: Our study involved sixteen female Wistar rats aged ten weeks, which were divided into four groups based on their diets: control (Ctrl), cafeteria (CAF), control + probiotic (PRO), and cafeteria + probiotic (CPRO). The control + probiotic and cafeteria + probiotic groups received a daily oral administration of 250 μL of L. rhamnosus GG cell suspension (equivalent to 109 UFC) for nine weeks. The body weight of the animals was recorded weekly, and their food intake was monitored every 24 h. An oral glucose tolerance test was conducted on the offspring at seven weeks of age. At the ninth week of age, animals were euthanized, and blood, tissues, and organs were collected. Results: Maternal supplementation with L. rhamnosus GG decreased food intake and the average birth weight, improved glucose sensitivity, and lowered the levels of LDL, cholesterol, triglycerides, and mesenteric adipose tissue in offspring compared with the control and cafeteria groups. Conclusions: Our findings indicate that supplementing with LGG during maternal programming could protect offspring from metabolic disruptions caused by a hypercaloric maternal diet. Full article
(This article belongs to the Special Issue Recent Advances in Gastroenterology and Nutrition)
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Figure 1
<p>Comparison of the results obtained from the evolution of the maternal body weight and the offspring. (<b>A</b>) Body weights of mothers (g) during the nine weeks of maternal programming (<span class="html-italic">n</span> = 4/group), (<b>B</b>) weights of offspring up to the eighth week of age (<span class="html-italic">n</span> = 8/group), (<b>C</b>) PCA of mother’s weight (<span class="html-italic">n</span> = 4/group), and (<b>D</b>) PCA of offspring’s weight (<span class="html-italic">n</span> = 8/group). Values in the superscript with different letters are statistically significant (<span class="html-italic">p</span> &lt; 0.05). CAF = cafeteria group, PRO = probiotic group and standard diet, and CPRO = cafeteria diet and probiotic group.</p>
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<p>Comparison of the glucose tolerance test results among the descendants of each analyzed group. *, ***, Values are statistically significant (<span class="html-italic">p</span> &lt; 0.05), (<b>A</b>) Basal glucose levels (mg/dL). (<b>B</b>) Oral glucose tolerance curve (mmol/L). (<b>C</b>) The area below the AUC curve. CAF = cafeteria group, PRO = probiotic group and standard diet, and CPRO = cafeteria diet and probiotic group. (<span class="html-italic">n</span> = 8/group).</p>
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<p>Effect of LGG supplementation on the intestinal microbiota profile of the study offspring. (<b>A</b>) Relative abundance at class level. (<b>B</b>) Gender-related abundance. Ctrl = control group, CAF = cafeteria group, PRO = probiotic group and standard diet, and CPRO = cafeteria diet and probiotic group.</p>
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<p>Effect of LGG supplementation on the diversity of the intestinal microbiota profile of male offspring. *, **, Values are statistically significant (<span class="html-italic">p</span> &lt; 0.05), (<b>A</b>) Simpson index. (<b>B</b>) Shannon index. Ctrl = control group, CAF = cafeteria group, PRO = probiotic group and standard diet, and CPRO = cafeteria diet and probiotic group.</p>
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<p>Analysis of the intestinal microbiota based on the average decrease in the Gini index using the Random Forest algorithm and relative abundance. Ctrl = control group, CAF = cafeteria group, PRO = probiotic group and standard diet, and CPRO = cafeteria diet and probiotic group.</p>
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15 pages, 680 KiB  
Review
Fusion Genes in Myeloid Malignancies
by Chieh Hwee Ang, Hein Than, Tertius T. Tuy and Yeow Tee Goh
Cancers 2024, 16(23), 4055; https://doi.org/10.3390/cancers16234055 - 3 Dec 2024
Viewed by 107
Abstract
Fusion genes arise from gross chromosomal rearrangements and have been closely linked to oncogenesis. In myeloid malignancies, fusion genes play an integral role in the establishment of diagnosis and prognostication. In the clinical management of patients with acute myeloid leukemia, fusion genes are [...] Read more.
Fusion genes arise from gross chromosomal rearrangements and have been closely linked to oncogenesis. In myeloid malignancies, fusion genes play an integral role in the establishment of diagnosis and prognostication. In the clinical management of patients with acute myeloid leukemia, fusion genes are deeply incorporated in risk stratification criteria to guide the choice of therapy. As a result of their intrinsic ability to define specific disease entities, oncogenic fusion genes also have immense potential to be developed as therapeutic targets and disease biomarkers. In the current era of genomic medicine, breakthroughs in innovation of sequencing techniques have led to a rise in the detection of novel fusion genes, and the concept of standard-of-care diagnostics continues to evolve in this field. In this review, we outline the molecular basis, mechanisms of action and clinical impact of fusion genes. We also discuss the pros and cons of available methodologies that can be used to detect fusion genes. To contextualize the challenges encountered in clinical practice pertaining to the diagnostic workup and management of myeloid malignancies with fusion genes, we share our experience and insights in the form of three clinical case studies. Full article
(This article belongs to the Special Issue Updates on the Genetics of Myeloid Malignancies)
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<p>Structural chromosome rearrangements that can lead to the formation of fusion genes [<a href="#B11-cancers-16-04055" class="html-bibr">11</a>,<a href="#B12-cancers-16-04055" class="html-bibr">12</a>]. Examples of chromosomal aberrations with respective fusion gene products and clinical associations are listed in the panel on the right. Abbreviations: APML; acute promyelocytic leukemia, AML-MRC; acute myeloid leukemia with myelodysplasia-related changes, Ph+ ALL; Philadelphia-positive acute lymphoblastic leukemia.</p>
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30 pages, 3254 KiB  
Article
Evaluation of In Vitro Biological Activity of Flavanone/Chromanone Derivatives: Molecular Analysis of Anticancer Mechanisms in Colorectal Cancer
by Pawel Hikisz, Piotr Wawrzyniak, Angelika A. Adamus-Grabicka, Damian Jacenik and Elzbieta Budzisz
Int. J. Mol. Sci. 2024, 25(23), 12985; https://doi.org/10.3390/ijms252312985 - 3 Dec 2024
Viewed by 148
Abstract
The primary objective of this study was to evaluate the anticancer activity of six flavanone/chromanone derivatives: 3-benzylideneflavanones/3-benzylidenechroman-4-ones and their 3-spiro-1-pirazolines analogs. We employed five colon cancer cell lines with varying degrees of metastasis and genetic profiles as [...] Read more.
The primary objective of this study was to evaluate the anticancer activity of six flavanone/chromanone derivatives: 3-benzylideneflavanones/3-benzylidenechroman-4-ones and their 3-spiro-1-pirazolines analogs. We employed five colon cancer cell lines with varying degrees of metastasis and genetic profiles as our research model. Our investigation focused primarily on assessing the pro-oxidant properties of the tested derivatives and their impact on overall antiproliferative activity. To comprehensively evaluate the cytotoxic properties of these compounds, we analyzed their genotoxic, pro-apoptotic, and autophagy-inducing effects. Our findings indicate that three of the six analyzed derivatives exhibited promising antiproliferative activity against cancer cells, with IC50 values ranging from 10 to 30 μM. Strong pro-oxidant properties were identified as a key mechanism underlying their cytotoxic activity. The generation of oxidative stress, which varied depending on the specific flavanone/chromanone derivative, resulted from increased intracellular reactive oxygen species (ROS) levels and decreased glutathione (GSH) concentrations. Furthermore, oxidative stress likely contributed to the induction of apoptosis/autophagy in cancer cells and the emergence of significant DNA damage. Full article
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Figure 1

Figure 1
<p>(<b>a</b>). Analysis of changes in the mitochondrial membrane potential (MMP) of HCT 116, SW620, LoVo, Caco-2, and HT-29 colon cancer cells treated with the investigated flavanone/chromanone derivatives (IC<sub>50</sub> concentrations) using the fluorescent probe JC-1. The results are expressed as a percentage of the control, calculated by comparing the fluorescence intensity ratio of the test sample to the control (100%). Data represent the mean ± SD of three independent experiments, with * <span class="html-italic">p</span> &lt; 0.05 indicating statistical significance compared to the control (untreated cells). Compounds are designated as <b>1</b>, <b>3</b>, and <b>5</b> on the chart. The dashed line on the Y axis indicates 100% as control cells. (<b>b</b>). Analysis of changes in the mitochondrial membrane potential (MMP) of HCT 116, LoVo colon cancer cells treated with the investigated flavanone/chromanone derivatives (IC<sub>50</sub> concentrations) using the fluorescent probe JC-1. The orange-red fluorescence of JC-1 aggregates is characteristic of non-apoptotic cells, whereas the green fluorescence of JC-1 monomers occurs in cells affected by PCD. The microscopic images were captured at a magnification of 20× with a Nikon Eclipse Te200 microscope with a ZEISS Axiocam 208 color microscope camera using a Nikon LWD Ph1 DL 20 × 0.40 lens.</p>
Full article ">Figure 1 Cont.
<p>(<b>a</b>). Analysis of changes in the mitochondrial membrane potential (MMP) of HCT 116, SW620, LoVo, Caco-2, and HT-29 colon cancer cells treated with the investigated flavanone/chromanone derivatives (IC<sub>50</sub> concentrations) using the fluorescent probe JC-1. The results are expressed as a percentage of the control, calculated by comparing the fluorescence intensity ratio of the test sample to the control (100%). Data represent the mean ± SD of three independent experiments, with * <span class="html-italic">p</span> &lt; 0.05 indicating statistical significance compared to the control (untreated cells). Compounds are designated as <b>1</b>, <b>3</b>, and <b>5</b> on the chart. The dashed line on the Y axis indicates 100% as control cells. (<b>b</b>). Analysis of changes in the mitochondrial membrane potential (MMP) of HCT 116, LoVo colon cancer cells treated with the investigated flavanone/chromanone derivatives (IC<sub>50</sub> concentrations) using the fluorescent probe JC-1. The orange-red fluorescence of JC-1 aggregates is characteristic of non-apoptotic cells, whereas the green fluorescence of JC-1 monomers occurs in cells affected by PCD. The microscopic images were captured at a magnification of 20× with a Nikon Eclipse Te200 microscope with a ZEISS Axiocam 208 color microscope camera using a Nikon LWD Ph1 DL 20 × 0.40 lens.</p>
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<p>Analysis of changes in the levels of ROS (superoxide anion O<sub>2</sub><sup>•−</sup>) of HCT 116, SW620, LoVo, Caco-2, and HT-29 colon cancer cells treated with the investigated flavanone/chromanone derivatives (IC<sub>50</sub> concentrations) using the fluorescent probe dihydroethidium (DHE). The results are expressed as a percentage of the control, calculated by comparing the fluorescence intensity ratio of the test sample to the control (100%). Data represent the mean ± SD of three independent experiments, with * <span class="html-italic">p</span> &lt; 0.05 indicating statistical significance compared to the control (untreated cells). Compounds are designated as <b>1</b>, <b>3</b>, and <b>5</b> on the chart. The dashed line on the Y axis indicates 100% as control cells.</p>
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<p>Analysis of changes in the levels of ROS (hydrogen peroxide H<sub>2</sub>O<sub>2</sub>) of HCT 116, SW620, LoVo, Caco-2, and HT-29 colon cancer cells treated with the investigated flavanone/chromanone derivatives (IC<sub>50</sub> concentrations) using the fluorescent probe dihydroethidium (H<sub>2</sub>DCFDA). The results are expressed as a percentage of the control, calculated by comparing the fluorescence intensity ratio of the test sample to the control (100%). Data represent the mean ± SD of three independent experiments, with * <span class="html-italic">p</span> &lt; 0.05 indicating statistical significance compared to the control (untreated cells). Compounds are designated as <b>1</b>, <b>3</b>, and <b>5</b> on the chart. The dashed line on the Y axis indicates 100% as control cells.</p>
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<p>Analysis of changes in the levels of RNS of HCT 116, SW620, LoVo, Caco-2, and HT-29 colon cancer cells treated with the investigated flavanone/chromanone derivatives (IC<sub>50</sub> concentrations) using the fluorescent probe 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate (DAF-FM). The results are expressed as a percentage of the control, calculated by comparing the fluorescence intensity ratio of the test sample to the control (100%). Data represent the mean ± SD of three independent experiments, with * <span class="html-italic">p</span> &lt; 0.05 indicating statistical significance compared to the control (untreated cells). Compounds are designated as <b>1</b>, <b>3</b>, and <b>5</b> on the chart. The dashed line on the Y axis indicates 100% as control cells.</p>
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<p>Changes in cytotoxic activity of the flavanone/chromanone derivatives <b>1</b>, <b>3,</b> and <b>5</b> toward cancer cells after 1 h of pre-incubation with NAC or Trolox or without antioxidants. The cells were incubated with the investigated compounds for 24 h. Results are expressed as the mean ± SD of three repeated experiments. IC<sub>50</sub> values (µM) indicate the concentration of a compound required to reduce the fraction of surviving cells to 50% compared to the control probe (i.e., an untreated cell) with * <span class="html-italic">p</span> &lt; 0.05 indicating statistical significance compared to cells without cells without pre-incubation with antioxidants. Compounds are designated as <b>1</b>, <b>3</b>, and <b>5</b> on the chart.</p>
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<p>Analysis of changes in the levels of GSH of HCT 116, SW620, LoVo, Caco-2, and HT-29 colon cancer cells treated with the investigated flavanone/chromanone derivatives (IC<sub>50</sub> concentrations) using the fluorescent Monochlorobimane (MCB) probe. The results are expressed as a percentage of the control, calculated by comparing the fluorescence intensity ratio of the test sample to the control (100%). Data represent the mean ± SD of three independent experiments, with * <span class="html-italic">p</span> &lt; 0.05 indicating statistical significance compared to the control (untreated cells). Compounds are designated as <b>1</b>, <b>3</b>, and <b>5</b> on the chart.</p>
Full article ">Figure 7
<p>Analysis of induction of autophagy in HCT 116, SW620, LoVo, Caco-2, and HT-29 colon cancer cells treated with the investigated flavanone/chromanone derivatives (IC<sub>50</sub> concentrations) using the fluorescent probe Monodansylcadaverine (MDC). The analysis was performed based on the level of MDC accumulation in autophagolysosomes. The results are expressed as a percentage of the control, calculated by comparing the fluorescence intensity ratio of the test sample to the control (100%). Data represent the mean ± SD of three independent experiments, with * <span class="html-italic">p</span> &lt; 0.05 indicating statistical significance compared to the control (untreated cells). Compounds are designated as <b>1</b>, <b>3</b>, and <b>5</b> on the chart. The dashed line on the Y axis indicates 100% as control cells.</p>
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<p>(<b>a</b>). Analysis of DNA damage levels in HCT 116, SW620, LoVo, Caco-2, and HT-29 colon cancer cells treated with the investigated flavanone/chromanone derivatives (IC<sub>50</sub> concentrations) using alkaline comet method (single-cell electrophoresis). Data represent the mean ± SD of three independent experiments, with * <span class="html-italic">p</span> &lt; 0.05 indicating statistical significance compared to the control (untreated cells). Each time, 100 cells were analyzed from a slide. Compounds are designated as <b>1</b>, <b>3</b>, and <b>5</b> on the chart. (<b>b</b>). Analysis of DNA damage levels of SW620 colon cancer cells treated with the investigated flavanone/chromanone derivatives (IC<sub>50</sub> concentrations) using alkaline comet method (single-cell electrophoresis). The microscopic images were captured at a magnification of 20× with a Nikon Eclipse fluorescence microscope equipped with a 4910 COHU video camera.</p>
Full article ">Figure 8 Cont.
<p>(<b>a</b>). Analysis of DNA damage levels in HCT 116, SW620, LoVo, Caco-2, and HT-29 colon cancer cells treated with the investigated flavanone/chromanone derivatives (IC<sub>50</sub> concentrations) using alkaline comet method (single-cell electrophoresis). Data represent the mean ± SD of three independent experiments, with * <span class="html-italic">p</span> &lt; 0.05 indicating statistical significance compared to the control (untreated cells). Each time, 100 cells were analyzed from a slide. Compounds are designated as <b>1</b>, <b>3</b>, and <b>5</b> on the chart. (<b>b</b>). Analysis of DNA damage levels of SW620 colon cancer cells treated with the investigated flavanone/chromanone derivatives (IC<sub>50</sub> concentrations) using alkaline comet method (single-cell electrophoresis). The microscopic images were captured at a magnification of 20× with a Nikon Eclipse fluorescence microscope equipped with a 4910 COHU video camera.</p>
Full article ">Figure 9
<p>Cell cycle distribution of HCT 116, SW620, LoVo, Caco-2, and HT-29 colon cancer cells treated for 24 h with the investigated flavanone/chromanone derivatives (<b>1</b>, <b>3</b>, <b>5</b>; IC<sub>50</sub> concentrations) and control (C) untreated cells. The percentage of DNA in a particular phase/point of the cell cycle was calculated from the DNA histograms using available software (FlowJo 10.10). DNA was stained using propidium iodide/RNAseA solution. Representative plot from each time point is shown (n = 3). Data represent the mean ± SD of three independent experiments, with * <span class="html-italic">p</span> &lt; 0.05 indicating statistical significance compared to the control (untreated cells).</p>
Full article ">Figure 10
<p>Flow cytometry plots from HCT 116, SW620, LoVo, Caco-2, and HT-29 colon cancer cells treated for 24 h with the investigated flavanone/chromanone derivatives (IC<sub>50</sub> concentrations). DNA was stained using propidium iodide/RNAse solution. Representative plot from each time point is shown (n = 3).</p>
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<p>The structures of tested compounds.</p>
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15 pages, 6268 KiB  
Review
A Review of the Consequences of Gut Microbiota in Neurodegenerative Disorders and Aging
by Amanda A. Menezes and Zahoor A. Shah
Brain Sci. 2024, 14(12), 1224; https://doi.org/10.3390/brainsci14121224 - 3 Dec 2024
Viewed by 140
Abstract
Age-associated alterations in the brain lead to cognitive deterioration and neurodegenerative disorders (NDDs). This review with a particular focus on Alzheimer’s disease (AD), emphasizes the burgeoning significance of the gut microbiota (GMB) in neuroinflammation and its impact on the gut–brain axis (GBA), a [...] Read more.
Age-associated alterations in the brain lead to cognitive deterioration and neurodegenerative disorders (NDDs). This review with a particular focus on Alzheimer’s disease (AD), emphasizes the burgeoning significance of the gut microbiota (GMB) in neuroinflammation and its impact on the gut–brain axis (GBA), a communication conduit between the gut and the central nervous system (CNS). Changes in the gut microbiome, including diminished microbial diversity and the prevalence of pro-inflammatory bacteria, are associated with AD pathogenesis. Promising therapies, such as fecal microbiota transplantation (FMT), probiotics, and prebiotics, may restore gut health and enhance cognitive performance. Clinical data remain insufficient, necessitating further research to elucidate causes, enhance therapy, and consider individual variances. This integrative approach may yield innovative therapies aimed at the GMB to improve cognitive function and brain health in older people. Full article
(This article belongs to the Special Issue Advances in Neuroinflammation)
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<p>Relationship between gut microbiome and central nervous system functioning in neurological disorders. Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p>
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<p>The hypothesis posits that environmental factors such as nutrition, sleep, and exercise, along with genetic predispositions, contribute to an inflammatory milieu inside the gut microbiota (GBM), resulting in alterations in composition and diversity over time. These alterations affect metabolites originating from the GMB and peripheral immunity, modifying the blood-brain barrier (BBB) and central nervous system (CNS) cell types, potentially influencing AD. Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p>
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<p>Mechanisms for bidirectional communication in the gut–brain axis (GBA). Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p>
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<p>Strategies to alter the GMB for treating neurodegenerative illnesses encompass dietary modifications, prebiotics, probiotics, synbiotics, and fecal microbiota transplantation (FMT). These approaches alter microbial populations and generate compounds such as neurotransmitters and short-chain fatty acids, facilitating neuroprotective effects. Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p>
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15 pages, 1362 KiB  
Article
MiRNA-34a, miRNA-145, and miRNA-222 Expression, Matrix Metalloproteinases, TNF-α and VEGF in Patients with Different Phenotypes of Coronary Artery Disease
by Alfiya Oskarovna Iusupova, Nikolay Nikolaevich Pakhtusov, Olga Alexandrovna Slepova, Natalia Vladimirovna Khabarova, Elena Vitalievna Privalova, Irina Vladimirovna Bure, Marina Vyacheslavovna Nemtsova and Yuri Nikitich Belenkov
Int. J. Mol. Sci. 2024, 25(23), 12978; https://doi.org/10.3390/ijms252312978 - 3 Dec 2024
Viewed by 140
Abstract
The development of different phenotypes of coronary artery (CA) lesions is regulated via many various factors, such as pro-inflammatory agents, zinc-dependent endopeptidases, growth factors and circulating microRNAs (miRs). To evaluate the expression levels of miR-34a, miR-145 and miR-222, tumor necrosis factor α (TNF-α), [...] Read more.
The development of different phenotypes of coronary artery (CA) lesions is regulated via many various factors, such as pro-inflammatory agents, zinc-dependent endopeptidases, growth factors and circulating microRNAs (miRs). To evaluate the expression levels of miR-34a, miR-145 and miR-222, tumor necrosis factor α (TNF-α), matrix metalloproteinases (MMP-1, -9, -13 and -14) and vascular endothelial growth factor (VEGF) in patients with different phenotypes of coronary artery disease (CAD): ischemia/angina with non-obstructive coronary arteries (INOCA/ANOCA) and obstructive CAD (oCAD) compared with a control group. This cross-sectional observational study included 157 subjects with a verified CAD diagnosis (51 patients with INOCA, 76 patients with oCAD and 30 healthy volunteers). The expression of miR-34a, miR-145 and miR-222 (RT-PCR) and the levels of VEGF, TNF-α, MMP-1, MMP-9, MMP-13 and MMP-14 (ELISA) were estimated in plasma samples. A higher concentration of MMP-9 was found in oCAD-group samples compared to the INOCA/ANOCA group. The INOCA/ANOCA group was characterized by higher levels of TNF-α. Based on multivariate regression analysis, a mathematical model predicting the type of CA lesion was constructed. MiR-145 was the independent predictor of INOCA/ANOCA (p = 0.006). Changes in concentrations of MMP-9 and MMP-14 were found in both investigated CAD groups, with MMP-9 levels being significantly higher in obstructive CAD samples than in INOCA/ANOCA, which confirms the role of inflammation in the development of atherosclerosis. A multivariate regression analysis allowed us to achieve a model that can predict the phenotype of stable CAD, and MiR-145 can be assumed as an independent predictor of INOCA/ANOCA. Full article
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<p>The design of the study. CAD—coronary artery disease; INOCA/ANOCA—ischemia/angina with non-obstructive coronary arteries; qPCR—quantitative polymerase chain reaction; MRI—magnetic resonance imaging; MSCT—multi-detector computed tomography.</p>
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<p>MiRNAs expression in plasma of CAD patients and healthy volunteers (control). All values are presented as the median and CI. Statistically significant—<span class="html-italic">p</span> &lt; 0.05; CAD—coronary artery disease, INOCA/ANOCA—ischemia/angina with non-obstructive coronary arteries.</p>
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<p>Diagnostic value analysis of the model by ROC curve.</p>
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19 pages, 2115 KiB  
Article
Class B Scavenger Receptor CD36 as a Potential Therapeutic Target in Inflammation Induced by Danger-Associated Molecular Patterns
by Irina N. Baranova, Alexander V. Bocharov, Tatyana G. Vishnyakova, Zhigang Chen, Yunbo Ke, Anna A. Birukova, Peter S. T. Yuen, Takayuki Tsuji, Robert A. Star, Konstantin G. Birukov, Amy P. Patterson and Thomas L. Eggerman
Cells 2024, 13(23), 1992; https://doi.org/10.3390/cells13231992 - 3 Dec 2024
Viewed by 120
Abstract
The class B scavenger receptor CD36 is known to bind and mediate the transport of lipid-related ligands and it functions as a pattern recognition receptor (PRR) for a variety of pathogens, including bacteria and viruses. In this study, we assessed CD36’s role as [...] Read more.
The class B scavenger receptor CD36 is known to bind and mediate the transport of lipid-related ligands and it functions as a pattern recognition receptor (PRR) for a variety of pathogens, including bacteria and viruses. In this study, we assessed CD36’s role as a PRR mediating pro-inflammatory effects of several known Danger-Associated Molecular Patterns (DAMPs) used either as a single preparation or as a combination of DAMPs in the form of total cell/skeletal muscle tissue lysates. Our data demonstrated that multiple DAMPs, including HMGB1, HSPs, histone H3, SAA, and oxPAPC, as well as cell/tissue lysate preparations, induced substantially higher (~7–10-fold) IL-8 cytokine responses in HEK293 cells overexpressing CD36 compared to control WT cells. At the same time, DAMP-induced secretion of IL-6 in bone marrow-derived macrophages (BMDM) from CD36−/− mice was markedly (~2–3 times) reduced, as compared to macrophages from normal mice. Synthetic amphipathic helical peptides (SAHPs), known CD36 ligands, efficiently blocked CD36-dependent inflammatory responses induced by both cell and tissue lysates, HMGB1 and histone H3 in CD36+ cells. IP injection of total cellular lysate preparation induced inflammatory responses that were assessed by the expression of liver and lung pro-inflammatory markers, including IL-6, TNF-α, CD68, and CXCL1, and was reduced by ~50% in CD36-deficient mice compared to normal mice. Our findings demonstrate that CD36 is a PRR contributing to the innate immune response via mediating DAMP-induced inflammatory signaling and highlight the importance of this receptor as a potential therapeutic target in DAMP-associated inflammatory conditions. Full article
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<p>Dose-dependent IL-8 secretion induced by HeLa cell and skeletal muscle CF in WT and CD36-overexpressing HEK293 cells. WT and CD36-overexpressing HEK293 cells were incubated with increasing concentrations of the CF preparations (see <a href="#sec2-cells-13-01992" class="html-sec">Section 2</a>) from HeLa cells, c-CF (<b>A</b>) or murine skeletal muscle, SM-CF (<b>B</b>) for 20 h. IL-8 levels were quantified in duplicate samples of cell culture supernatants by ELISA. Data represent one of three separate experiments that yielded similar results.</p>
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<p>Dose-dependent IL-8 secretion induced by the HMGB1 and LPS in WT and CD36-overexpressing HEK293 cells. Effect of heat treatment on the cytokine-inducing activity of HMGB1 and LPS. WT and CD36-overexpressing HEK293 cells were incubated with increasing concentrations of recombinant HMGB1 (<b>A</b>) or LPS (<b>B</b>) for 20 h. IL-8 levels were quantified in duplicate samples of cell culture supernatants by ELISA. Data represent one of three separate experiments that yielded similar results. The IL-8 levels were determined using duplicate samples of cell culture supernatants collected after a 20 h incubation of cells with either intact or heat-treated (100 °C for 45 min) HMGB1 (<b>C</b>) and LPS (<b>D</b>). The data presented are from one of two separate representative experiments.</p>
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<p>Effects of SAHPs on IL-8 secretion induced by the CF preparations and HMGB1 in CD36-overexpressing HEK293 cells. Cells were preincubated with or without increasing doses of L-37pA, ELK-B, or L3D-37pA for 1 h before a 20 h treatment with 1% c-CF (<b>A</b>) or 0.3% SM-CF (<b>B</b>). Cells were preincubated for 1 h with or without 10 µg/mL of L-37pA, ELK-B, or L3D-37pA before a 20 h treatment with increasing doses of HMGB1 (0.25, 1, and 5 µg/mL). IL-8 levels were determined in cell culture supernatants in duplicate (<b>C</b>). Data are from one of at least two representative experiments. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, and ns—nonsignificant, versus no peptide.</p>
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<p>Dose-dependent IL-8 secretion induced by the histone H3 in WT and CD36-overexpressing HEK293 cells. Effect of L-37pA on hH3-induced IL-8 secretion in CD36-HEK293 cells. WT and CD36-overexpressing HEK293 cells were incubated with increasing concentrations of histone H3 for 20 h. IL-8 levels were quantified in duplicate samples of cell culture supernatants by ELISA (<b>A</b>). Data represent one of three separate experiments that yielded similar results. CD36-HEK293 cells were preincubated for 1 h with 0, 10 µg/mL, and 25 µg/mL of L-37pA or L3D peptides before a 20 h treatment with 25 µg/mL of histone H3. IL-8 levels were determined in cell culture supernatants in duplicate (<b>B</b>). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and ns—nonsignificant, versus histone H3 alone. Data are from one of at least two representative experiments.</p>
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<p>DAMPs-induced dose-dependent pro-inflammatory responses in WT and CD36-overexpressing HEK293 cells. WT and CD36-overexpressing HEK293 cells were incubated with increasing concentrations of HSP60 (<b>A</b>), HSP70 (<b>B</b>), oxPAPC (<b>C</b>), and SAA (<b>D</b>) for 20 h. IL-8 levels were quantified in duplicate samples of cell culture supernatants by ELISA. Data represent one of two separate experiments that yielded similar results.</p>
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<p>Pro-inflammatory responses induced by the various DAMPs in BMDM from WT and CD36-knockout mice. BMDM isolated from WT and CD36−/− mice were incubated with increasing doses of cCF (<b>A</b>), HMGB1 (<b>B</b>), histone H3 (<b>C</b>), and LPS (<b>D</b>) for 20 h. IL-6 levels were quantified in duplicate samples of cell culture supernatants by ELISA. Data represent one of two separate experiments that yielded similar results.</p>
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<p>Effects of signaling pathways Inhibitors on CF-induced IL-6 secretion in BMDM from WT and CD36-knockout mice. BMDM isolated from WT and CD36−/− were pre-incubated for 1 h with increasing doses of PD98059 (<b>A</b>), SP600125 (<b>B</b>), SB202190 (<b>C</b>), or PP2 (<b>D</b>). Following pre-incubation, cells were incubated with CF preparation for the next 20 h. IL-6 levels were quantified in duplicate samples of cell culture supernatants by ELISA. Data represent one of two separate experiments that yielded similar results.</p>
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<p>Hepatic gene expression of inflammatory markers in WT and CD36-knockout mice IP injected with a TCL preparation. Livers were collected for mRNA extraction and qRT-PCR assay as described in Materials and Methods. Expression levels of IL-6 (<b>A</b>), TNF-α (<b>B</b>), CD68 (<b>C</b>), and CCL2 (<b>D</b>) were normalized by GAPDH expression and are presented as the fold change relative to the PBS-treated WT control mice. Values shown are the means ± STD (n = 12–15 for the WT group, n = 20 for the CD36-KO group). * <span class="html-italic">p</span> &lt; 0.05, versus WT TCL-treated mice.</p>
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<p>Pulmonary gene expression of inflammatory markers in WT and CD36-knockout mice IP injected with a TCL preparation. Lungs were collected for mRNA extraction and qRT-PCR assay as described in Materials and Methods. Expression levels of IL-6 (<b>A</b>), TNF-α (<b>B</b>), and CXCL1 (<b>C</b>) were normalized by GAPDH expression and are presented as the fold change relative to PBS-treated WT control mice. Values shown are the means ± STD (n = 10 for the WT group, n = 14 for the CD36-KO group). * <span class="html-italic">p</span> &lt; 0.05, versus WT TCL-treated mice.</p>
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17 pages, 4860 KiB  
Article
Comparative Analysis of the Carbon Footprint Value Resulting from the Selected Mode of Transport, Based on the Example of Transporting Neodymium Magnets
by Rafał Baron, Daniel Kowol, Piotr Matusiak, Paweł Friebe and Marcin Lutyński
Energies 2024, 17(23), 6078; https://doi.org/10.3390/en17236078 (registering DOI) - 3 Dec 2024
Viewed by 164
Abstract
The article presents a sensitivity analysis of the carbon footprint for different modes of transporting neodymium magnets over a selected route, in the context of their environmental impact and sustainable development. Neodymium magnets, widely used in modern technologies such as wind turbines, are [...] Read more.
The article presents a sensitivity analysis of the carbon footprint for different modes of transporting neodymium magnets over a selected route, in the context of their environmental impact and sustainable development. Neodymium magnets, widely used in modern technologies such as wind turbines, are essential for renewable energy sources, making the selection of environmentally optimal transportation crucial. The calculations included road, rail, inland waterway, and air transport, using available emission calculators, which allowed for an analysis using averaged emission indicators for each mode of transport. Additionally, a comparative analysis was conducted with the SimaPro program to verify the consistency and accuracy of the results. The findings indicated that rail transport, with access to low-emission infrastructure and a reduced carbon footprint per unit of mass, is the most efficient option for CO2 emissions reduction, whereas air transport, despite its speed, generates the highest emissions per ton of cargo, making it the least environmentally friendly alternative. A t-test analysis was also conducted to statistically validate the results for each transportation option. Full article
(This article belongs to the Special Issue Green, Low-Carbon and Sustainable Development)
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<p>The carbon footprint value in the comparative analysis for a delivery van transporting only neodymium magnets [<a href="#B21-energies-17-06078" class="html-bibr">21</a>].</p>
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<p>The carbon footprint value in the comparative analysis for a truck [<a href="#B20-energies-17-06078" class="html-bibr">20</a>].</p>
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<p>The route needed to transport neodymium magnets by rail [<a href="#B20-energies-17-06078" class="html-bibr">20</a>].</p>
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<p>The carbon footprint value in the comparative analysis for rail transport [<a href="#B20-energies-17-06078" class="html-bibr">20</a>].</p>
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<p>The route needed to transport neodymium magnets by inland navigation [<a href="#B20-energies-17-06078" class="html-bibr">20</a>]. In blue—transport using barge, grey—transport using road transport.</p>
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<p>The carbon footprint value in the comparative analysis for transport using inland navigation [<a href="#B20-energies-17-06078" class="html-bibr">20</a>].</p>
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<p>The route that needs to be covered by neodymium magnets using a short-haul aircraft [<a href="#B20-energies-17-06078" class="html-bibr">20</a>]. In orange—transport using aircraft, grey—transport using road transport.</p>
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<p>The carbon footprint value in the comparative analysis for transport using a short-haul aircraft [<a href="#B20-energies-17-06078" class="html-bibr">20</a>].</p>
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<p>Data for carbon footprint calculations in SimaPro software [own elaboration].</p>
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<p>Results of carbon footprint calculations in SimaPro software [own elaboration].</p>
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<p>Carbon Footprint Contribution for Each Transport Mode Scenario [own elaboration].</p>
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25 pages, 10169 KiB  
Article
Exploring Bioinformatics Tools to Analyze the Role of CDC6 in the Progression of Polycystic Ovary Syndrome to Endometrial Cancer by Promoting Immune Infiltration
by Yuhang Song, Jing Zhang, Yao Li, Lufeng Cheng, Hua Song, Yuhang Zhang, Guoqing Du, Sunyue Yu, Yizhou Zou and Qi Xu
Int. J. Mol. Sci. 2024, 25(23), 12974; https://doi.org/10.3390/ijms252312974 - 3 Dec 2024
Viewed by 200
Abstract
Cell division cycle 6 (CDC6) is essential for the initiation of DNA replication in eukaryotic cells and contributes to the development of various human tumors. Polycystic ovarian syndrome (PCOS) is a reproductive endocrine disease in women of childbearing age, with a significant risk [...] Read more.
Cell division cycle 6 (CDC6) is essential for the initiation of DNA replication in eukaryotic cells and contributes to the development of various human tumors. Polycystic ovarian syndrome (PCOS) is a reproductive endocrine disease in women of childbearing age, with a significant risk of endometrial cancer (EC). However, the role of CDC6 in the progression of PCOS to EC is unclear. Therefore, we examined CDC6 expression in patients with PCOS and EC. We evaluated the relationship between CDC6 expression and its prognostic value, potential biological functions, and immune infiltrates in patients with EC. In vitro analyses were performed to investigate the effects of CDC6 knockdown on EC proliferation, migration, invasion, and apoptosis. CDC6 expression was significantly upregulated in patients with PCOS and EC. Moreover, this protein caused EC by promoting the aberrant infiltration of macrophages into the immune microenvironment in patients with PCOS. A functional enrichment analysis revealed that CDC6 exerted its pro-cancer and pro-immune cell infiltration functions via the PI3K-AKT pathway. Moreover, it promoted EC proliferation, migration, and invasion but inhibited apoptosis. This protein significantly reduced EC survival when mutated. These findings demonstrate that CDC6 regulates the progression of PCOS to EC and promotes immune infiltration. Full article
(This article belongs to the Special Issue Molecular Research of Multi-omics in Cancer)
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<p>Illustration of the research flow chart.</p>
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<p>Abnormal invasion of immune cells promotes the occurrence of PCOS carcinogenesis. (<b>A</b>) Heatmap of immune cell subsets in PCOS samples with a tendency to become cancerous. (<b>B</b>) Heatmap of immune cell subsets in an endometrial cancer sample. The expression (<b>C</b>) and expression ratio (<b>D</b>) of each immune cell subset in the GSE139555 dataset, as analyzed based on the TISCH database. The expression (<b>E</b>) and expression ratio (<b>F</b>) of each immune cell in the GSE154763 dataset, as analyzed based on the TISCH database.</p>
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<p>CDC6 promotes the formation of an immune tumor microenvironment. (<b>A</b>) Volcanogram of DEGs between normal and PCOS endometrial tissues. (<b>B</b>) Volcanogram of DEGs between EC breast and non-breast metastases. (<b>C</b>) Heatmap of the top 50 upregulated DEGs between normal and PCOS endometrial tissue. (<b>D</b>) Heat map of the top 50 upregulated DEGs between EC breast and non-breast metastases. (<b>E</b>) Heatmap of the correlation between module-characteristic genes and immune cells in a PCOS sample. The black, green, pink, sky blue, and yellow modules indicate high association with innate immunity and T cells. The rows represent module-characteristic genes (MEs) and their colors, whereas the columns represent immune cells. Red indicates a positive correlation between the module gene and immune cell. Blue indicates a negative correlation. The darker the color, the greater the relevance. The correlation coefficient and <span class="html-italic">p</span>-value are displayed in each cell. (<b>F</b>) Heatmap of the correlation between module-characteristic genes and immune cells in EC samples. The green, brown, and blue modules indicate high correlation with the innate immune system. (<b>G</b>) The top 20 genes with the degree value of the central module in the PCOS sample. (<b>H</b>) The top 20 genes in the degree value of the central module in the EC sample.</p>
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<p>CDC6 is abnormally overexpressed in PCOS carcinogenesis and EC and exerts oncogenic effects through the PI3K-AKT pathway. (<b>A</b>) GO enrichment analysis of CDC6-related DEGs in PCOS samples with a tendency to be carcinogenic. (<b>B</b>) Correlation network diagram of CDC6-related DEGs with GO enrichment functional pathways in PCOS samples with carcinogenic potential. (<b>C</b>) Significant enrichment bubble map of the KEGG pathway of CDC6-related DEGs in PCOS samples with a tendency to be carcinogenic. (<b>D</b>) Correlation network diagram of CDC6-related DEGs with KEGG enrichment functional pathway in PCOS samples with carcinogenic potential. (<b>E</b>) GO pathway enrichment bar graph of CDC6-related DEGs in EC samples. (<b>F</b>) Diagram of the association network between CDC6-related DEGs and GO-enriched functional pathways in EC samples. (<b>G</b>) Significant enrichment bubble map of the KEGG pathway for CDC6-related DEGs in EC samples. (<b>H</b>) Correlation network diagram of CDC6-related DEGs with KEGG-enriched functional pathways in EC samples. (<b>I</b>) Downregulated DEG pathway enrichment bubble map in PCOS samples with carcinogenesis potential. Of these, the PI3K-AKT pathway was significantly enriched. (<b>J</b>) Downregulated DEG pathway enrichment bubble map in EC samples; the PI3K-AKT pathway was significantly enriched. (<b>K</b>) Gene set enrichment analysis of DEGs upregulated in PCOS samples with a tendency to be carcinogenic. (<b>L</b>) Gene set enrichment analysis of DEGs in PCOS samples with carcinogenic potential.</p>
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<p>CDC6 causes the progression of PCOS to EC through abnormal macrophage invasion. (<b>A</b>) Venn diagram of the intersection of DEGs between normal and PCOS endometrial tissue, DEGs between EC breast and non-breast metastasis samples, central module genes in PCOS samples, and central module genes in EC samples. PPI network diagram of seven candidate genes, with <span class="html-italic">CDC6</span>/<span class="html-italic">EGFR</span> at the core. (<b>B</b>) GO and KEGG enrichment analyses of the seven genes. (<b>C</b>) Variable coefficient change characteristic plot of the PCOS sample with a carcinogenic tendency, minimum absolute contraction = 0. The value of the dataset as a biomarker was analyzed. (<b>D</b>) Variation characteristics of the variable coefficient of the EC samples, with minimum absolute contraction. (<b>E</b>) The genes in the PCOS sample dataset with a carcinogenic tendency after LASSO analysis, the Venn diagram of the genes after LASSO analysis, and the seven candidate genes in the EC sample dataset. The identification genes <span class="html-italic">CDC6</span> and <span class="html-italic">HAUS6</span> were obtained. (<b>F</b>) Expression and diagnostic values of <span class="html-italic">CDC6</span>, <span class="html-italic">EGFR</span>, and <span class="html-italic">HAUS6</span> in PCOS samples with a tendency to become cancerous. (<b>G</b>) Heatmap of the correlation between innate immune subset module genes and immune cell invasion in the EC sample dataset. WGCNA of module–feature relationships between innate immune subsets and immune cell infiltration. The red and pink modules associated with the innate immune subset have the highest correlation coefficients and were identified as the core modules in the EC sample dataset. (<b>H</b>) Heatmap of the correlation between T cell subset module genes and immune cell infiltration in PCOS samples with a tendency to become cancerous. (<b>I</b>) Heatmap of the correlation between innate immune subset module genes and immune cell infiltration in PCOS samples with a carcinogenic tendency.</p>
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<p>The infiltration of endometrial immune cells, as analyzed through single-cell sequencing in the HPA database. (<b>A</b>) Types and distribution of immune cells in the endometrium. (<b>B</b>) Heatmap of the correlation between CDC6 and immune cell marker genes in the endometrium.</p>
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<p>CDC6 is significantly expressed in macrophages of EC. (<b>A</b>) and (<b>B</b>) show CDC6 expression profiles in the single-cell GSE139555 and GSE154763 datasets; (<b>C</b>) CDC6 expression in patients with EC in the TIMER data was significantly correlated with macrophage immune infiltration.</p>
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<p>(<b>A</b>) mRNA expression levels of CDC6 in EC and normal tissues, as determined based on TCGA database. (<b>B</b>) mRNA expression levels of CDC6 in EC and paired adjacent tissues, as determined using TCGA database. The correlation between CDC6 expression and the pathological stages of UCEC (<b>C</b>), the histologic G grades in UCEC (<b>D</b>), and tumor invasion in UCEC (<b>E</b>). (<b>F</b>) The protein levels of CDC6 in normal and UCEC tissues, as determined based on the GEPIA database. (<b>G</b>) Receiver operating characteristic (ROC) curve for CDC6 expression in UCEC. (<b>H</b>,<b>I</b>) Kaplan–Meier survival curves showing that elevated CDC6 expression is associated with a worse survival (6 and 24 months) in UCEC. (<b>J</b>) The overall survival time related to CDC6 mutation was statistically poorer.(* <span class="html-italic">p</span> &lt; 0.05, *** <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>(<b>A</b>) Variation types and frequency of CDC6 in UCEC, as determined based on the cBioPortal database. (<b>B</b>) and (<b>C</b>) show the mutation types of CDC6 in UCEC, as determined based on the COSMIC database. (<b>D</b>) Mutation sites are shown. (<b>E</b>) The Oncoplot of the somatic mutant landscape in high- and low-CDC6 expression groups in UCEC (* <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01).</p>
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<p>(<b>A</b>) Relative protein expression of CDC6 in EC cells determined the efficiency of siRNA, as evaluated using Western blotting. (<b>B</b>) CCK8 analysis of the promotion of EC cell proliferation by CDC6. (<b>C</b>) Flow cytometric analysis of the silencing of CDC6 to inhibit apoptosis. (<b>D</b>) The silencing of CDC6 inhibited the migratory ability of EC cells in the wound healing assay. (<b>E</b>,<b>F</b>) CDC6 knockdown in EC cells reduced their invasion ability in the Transwell assay (* <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, **** <span class="html-italic">p</span> &lt; 0.0001).</p>
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17 pages, 739 KiB  
Article
Hepatic Gene Expression Changes of Zebrafish Fed Yeast Prebiotic, Yeast Probiotic, Black Soldier Fly Meal, and Butyrate
by Nancy Gao, Junyu Zhang, Umesh K. Shandilya, John S. Lumsden, Amir Behzad Barzrgar, David Huyben and Niel A. Karrow
Fishes 2024, 9(12), 495; https://doi.org/10.3390/fishes9120495 - 2 Dec 2024
Viewed by 236
Abstract
As global fish consumption rises, improving fish health through immunomodulatory feed ingredients shows promise while also supporting growth performance. This study investigated the effects of yeast prebiotics, probiotics, a postbiotic (butyrate), and black soldier fly larvae (BSFL) meal on fish immune responses. Zebrafish [...] Read more.
As global fish consumption rises, improving fish health through immunomodulatory feed ingredients shows promise while also supporting growth performance. This study investigated the effects of yeast prebiotics, probiotics, a postbiotic (butyrate), and black soldier fly larvae (BSFL) meal on fish immune responses. Zebrafish were fed diets containing these ingredients for 63 days and then exposed to either Pseudomonas aeruginosa lipopolysaccharide (LPS) or live Flavobacterium psychrophilum to assess hepatic candidate gene expression and weight gain. No mortalities were observed post-immune challenges, and weight gains were not significantly different across treatments. Liver samples were collected for mRNA analysis, and real-time qPCR was used to evaluate the expression of immune-related genes such as TNF-ɑ, IL-1β, hepcidin, and NF-κB/p65. NF-κB/p65 was upregulated in response to immune challenges, indicating a reaction to both LPS and pathogen exposure. Fish on the BSFL diet showed decreased NF-κB/p65 expression after the pathogen challenge, while probiotic-fed fish had reduced angiopoietin-like 4 (angptl4) levels following LPS exposure. Butyrate supplementation had the most significant impact, downregulating pro-inflammatory cytokines and other immune-related genes, suggesting a protective effect. These findings support the health benefits of BSFL and sodium butyrate during an immune challenge. Full article
16 pages, 1461 KiB  
Review
Macrophages in Calcific Aortic Valve Disease: Paracrine and Juxtacrine Disease Drivers
by Polina Klauzen, Liubov Basovich, Daria Shishkova, Victoria Markova and Anna Malashicheva
Biomolecules 2024, 14(12), 1547; https://doi.org/10.3390/biom14121547 - 2 Dec 2024
Viewed by 251
Abstract
A significant role in the pathogenesis of CAVD is played by innate immunity cells, such as macrophages. In stenotic valves, macrophages have enhanced inflammatory activity, and the population’s balance is shifted toward pro-inflammatory ones. Pro-inflammatory macrophages release cytokines, chemokines, and microRNA, which can [...] Read more.
A significant role in the pathogenesis of CAVD is played by innate immunity cells, such as macrophages. In stenotic valves, macrophages have enhanced inflammatory activity, and the population’s balance is shifted toward pro-inflammatory ones. Pro-inflammatory macrophages release cytokines, chemokines, and microRNA, which can directly affect the resident valvular cells and cause valve calcification. In CAVD patients, macrophages may have more pronounced pro-inflammatory properties, enhanced not only by paracrine signals but also by juxtacrine Notch signaling and epigenetic factors, which influence the maturation of macrophages’ progenitors. In this review, we observe the accumulated data on the involvement of macrophages in CAVD development via paracrine and juxtacrine interactions. Full article
(This article belongs to the Special Issue Tissue Calcification in Normal and Pathological Environments)
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<p>Schematic representation of the pathogenesis of aortic valve calcification in cases where osteoblastic differentiation is involved. (<b>A</b>) Simplified structure of a healthy valve. The aortic valve leaflets contain valvular endothelial cells (VECs), valvular interstitial cells (VICs), and the valvular extracellular matrix, where (i) collagen fibrils/fibers (represented by three collagen triple helices in purple) are prominent in the lamina fibrosa, (ii) proteoglycans (in blue) are abundant in the lamina spongiosa, and (iii) elastin fibers (yellow network) are present in the lamina ventricularis. VECs cover the leaflets and regulate valve permeability and homeostasis. VICs are distributed throughout the entire interstitium regulating valve remodeling via synthesis and degradation of valvular extracellular matrix components. Few resident macrophages and dendritic cells as well as a small number of myofibroblast-like VICs, although also present [<a href="#B13-biomolecules-14-01547" class="html-bibr">13</a>] are not depicted here. (<b>B</b>) Further simplified representation of cellular events leading to calcific aortic valve disease (CAVD), where the three-valve laminae are not displayed. Notch signaling is essential for maintaining endothelial barrier integrity and proper function (upper figure). Mechanical stress compromises the integrity of the endothelial layer contributing to CAVD development (lower figure): disruption of the barrier function leads to lipoproteins entering the interstitium of the valve leaflets and their oxidation by reactive oxygen species. This process is associated with (i) fibrogenic and/or osteogenic response of VICs, (ii) abnormal differentiation of VECs, and (iii) immune cell infiltration into the leaflet, triggering inflammation and further enhancing the alteration of extracellular matrix composition, ultimately leading to valve dysfunction.</p>
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<p>Juxtacrine Notch signaling may play a role at different stages of macrophage involvement in CAVD development. In CAVD, monocytes infiltrate valve tissues due to reduced integrity of VECs and then turn into naive macrophages M0. The reduction in VECs integrity occurs due to mechanical stress and loss of cell–cell Notch contacts after Notch receptor glycosylation observed in inflammatory conditions. In addition to monocytes and other immune cells, low-density lipoproteins (LDLs) also infiltrate the valve and act as osteogenic provocateurs in various ways. LDLs can activate TLRs in macrophages, which in turn induce the expression of Notch receptors and ligands, including Jagged1, Dll1, and Dll4. Activation of the Notch pathway in macrophages can lead to their differentiation into pro-inflammatory M1 phenotype and impact CAVD progression. Furthermore, VECs can induce macrophage M1 transition by losing the Notch4 receptor (while Notch1-3 remain expressed) and increasing the production of Dll4 by both VECs and immune cells. M1 macrophages express cytokines that promote inflammation and influence the osteogenic differentiation of resident valve cells. These cytokines can regulate the Notch signaling pathway by increasing the expression of <span class="html-italic">NOTCH1</span>, potentially in VICs as well. Dysregulation of Notch signaling, in turn, stimulates VICs to differentiate into myofibroblast-like cells or osteoblast-like cells. However, it is still unclear whether direct contact between macrophages and VICs via Notch receptors and ligands occurs in CAVD.</p>
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19 pages, 3099 KiB  
Article
An Improved Generative Adversarial Network-Based and U-Shaped Transformer Method for Glass Curtain Crack Deblurring Using UAVs
by Jiaxi Huang and Guixiong Liu
Sensors 2024, 24(23), 7713; https://doi.org/10.3390/s24237713 (registering DOI) - 2 Dec 2024
Viewed by 195
Abstract
Drones have emerged as a critical tool for the detection of high-altitude glass curtain cracks. However, their utility is often compromised by vibrations and other environmental factors that can induce motion blur, compromising image quality and the accuracy of crack detection. This paper [...] Read more.
Drones have emerged as a critical tool for the detection of high-altitude glass curtain cracks. However, their utility is often compromised by vibrations and other environmental factors that can induce motion blur, compromising image quality and the accuracy of crack detection. This paper presents a novel GAN-based and enhanced U-shaped Transformer network, named GlassCurtainCrackDeblurNet, designed specifically for the deblurring of drone-captured images of glass curtain cracks. To optimize the performance of our proposed method for this application, we have meticulously created the GlassCurtainCrackDeblur Dataset. Our method demonstrates superior qualitative and quantitative outcomes when compared to other established deblurring techniques on both the GoPro Dataset and the GlassCurtainCrackDeblur Dataset. Full article
(This article belongs to the Section Remote Sensors)
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<p>Schematic architecture of GlassCurtainCrackDeblurNet.</p>
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<p>Flow scheme of the GlassCurtainCrackDeblurImage generator G.</p>
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<p>Flow scheme of the GlassCurtainCrackDeblurImage generator G.</p>
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<p>Sample images of GlassCurtainCrackDeblur Dataset: (<b>a</b>) one of the sharp images in the dataset; (<b>b</b>) one of the sharp images in the dataset; (<b>c</b>) one of the sharp images in the dataset; (<b>d</b>) one of the blur images in the dataset; (<b>e</b>) one of the blur images in the dataset; (<b>f</b>) one of the blur images in the dataset.</p>
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<p>Deblurring results on the GoPro Dataset. The first column (<b>a<sub>1</sub></b>–<b>a<sub>3</sub></b>) shows the input blurred images; the second column (<b>b<sub>1</sub></b>–<b>b<sub>3</sub></b>) shows the output images from DeblurGANv2 [<a href="#B19-sensors-24-07713" class="html-bibr">19</a>]; the third column (<b>c<sub>1</sub></b>–<b>c<sub>3</sub></b>) shows the output images from Method [<a href="#B35-sensors-24-07713" class="html-bibr">35</a>]; the fourth column (<b>d<sub>1</sub></b>–<b>d<sub>3</sub></b>) shows the output images from Restormer [<a href="#B43-sensors-24-07713" class="html-bibr">43</a>]; the fifth column (<b>e<sub>1</sub></b>–<b>e<sub>3</sub></b>) shows the output images from GlassCurtainCrackDeblurNet; the sixth column(<b>f<sub>1</sub></b>–<b>f<sub>3</sub></b>) shows the real sharp images.</p>
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<p>Deblurring results on the GlassCurtainCrackDeblur Dataset. The first column (<b>a<sub>1</sub></b>–<b>a<sub>3</sub></b>) shows the input blurred images; the second column (<b>b<sub>1</sub></b>–<b>b<sub>3</sub></b>) shows the output images from DeblurGANv2 [<a href="#B19-sensors-24-07713" class="html-bibr">19</a>]; the third column (<b>c<sub>1</sub></b>–<b>c<sub>3</sub></b>) shows the output images from Method [<a href="#B35-sensors-24-07713" class="html-bibr">35</a>]; the fourth column (<b>d<sub>1</sub></b>–<b>d<sub>3</sub></b>) shows the output images from Restormer [<a href="#B43-sensors-24-07713" class="html-bibr">43</a>]; the fifth column (<b>e<sub>1</sub></b>–<b>e<sub>3</sub></b>) shows the output images from GlassCurtainCrackDeblurNet; the sixth column (<b>f<sub>1</sub></b>–<b>f<sub>3</sub></b>) shows the real sharp images.</p>
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<p>Failure deblurring results for the GoPro Dataset and the GlassCurtainCrackDeblur Dataset from GlassCurtainCrackDeblurNet. The first column (<b>a<sub>1</sub></b>,<b>a<sub>2</sub></b>) shows the real sharp images; the second column (<b>b<sub>1</sub></b>,<b>b<sub>2</sub></b>) shows the input blurred images; the third column (<b>c<sub>1</sub></b>,<b>c<sub>2</sub></b>) shows the failure output images from GlassCurtainCrackDeblurNet.</p>
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20 pages, 2554 KiB  
Article
In Vitro Biological Activities of Paederia grandidieri Leaf Extracts
by Faratiana Jenny Rasoariseheno, Nicoletta Fidanza, Elena Coccia, Dyana Jackson Ratovomanarivo, Daniela Sateriale, Lucia Abbatiello, Caterina Pagliarulo, Rosanna Filosa, Jeanne Angelphine Rasoamananjara and Marina Paolucci
Int. J. Mol. Sci. 2024, 25(23), 12960; https://doi.org/10.3390/ijms252312960 - 2 Dec 2024
Viewed by 241
Abstract
In many developing countries, human health problems are solved using local plants. Knowledge of their chemical composition and biological activities can contribute to the creation of natural-based products usefully employed in human health. In this work, we analysed Paederia grandidieri leaves extracted with [...] Read more.
In many developing countries, human health problems are solved using local plants. Knowledge of their chemical composition and biological activities can contribute to the creation of natural-based products usefully employed in human health. In this work, we analysed Paederia grandidieri leaves extracted with diverse eco-compatible procedures and subjected to chemical, microbiological, and cellular compatibility assays. Fresh leaves of P. grandidieri were harvested in southern Madagascar, where most of the population relies on P. grandidieri for daily dental care. Leaves were dried and powdered. Distilled water and ethanol at 25 °C and 60 °C from 6 to 24 h were used for extraction. Polyphenol composition, antioxidant activity, and antibacterial, prebiotic, and cytotoxic properties of the extracts were analysed. The aqueous extracts contained higher levels of flavan-3-ols and flavanones, while the hydro-alcoholic extracts were richer in flavonols and flavones. The aqueous extracts showed the highest total phenolic and total flavonoid contents, and antioxidant activity. The hydro-alcoholic extracts showed antibacterial effects against Listeria monocytogenes and Pseudomonas aeruginosa, two key foodborne and environmental pathogens, while the aqueous extracts showed prebiotic effects against Streptococcus salivarius. The cytotoxic effects of P. grandidieri leaf extracts were evaluated using the MTT assay on mouse fibroblasts (L929 cell line). The most cytotoxic extract was the aqueous extract at 25 °C. Given that P. grandidieri is routinely employed by the southern Madagascar population with healthy and strong teeth with fewer cases of tooth decay with respect to other regions, and in light of the significant chemical and microbiological properties, we maintain that P. grandidieri can be a suitable candidate for the production of pro-health products for the oral cavity. More in-depth studies will ensure a broader picture of the impact of extracts, especially for possible oral use. Full article
(This article belongs to the Special Issue Bioactive Phenolics and Polyphenols 2024)
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<p>Representative chromatograms of <span class="html-italic">Paederia grandidieri</span> leaf extracts recorded by (<b>A</b>) UV-Vis 280 nm, (<b>B</b>) UV-Vis 360 nm, and (<b>C</b>) FDL/FP conditions. PG1: aqueous extract at 25 °C for 24 h; PG3: aqueous extract at 60 °C for 24 h; and PG5: hydro-alcoholic extract at 25 °C for 24 h. The chromatogram profiles of PG2 and PG4 are similar to those of PG3 and PG5, respectively.</p>
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<p>UV spectra of representative peaks at a wavelength of 280 nm. (<b>A</b>,<b>B</b>) UV spectra of compounds such as rutin analogues and rutin, respectively. Rutin was assigned based on a comparison with retention time and UV spectra of a standard reference; the rutin analogue was assigned based on UV spectra. (<b>C</b>,<b>D</b>) UV spectra of compounds such as caffeic acid and caffeic acid analogues, respectively. Caffeic acid was assigned based on a comparison with retention time and UV spectra of a standard reference; the caffeic acid analogue was assigned based on UV spectra.</p>
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<p>Effect of PG1 aqueous extract (25 °C for 24 h) on the survival of <span class="html-italic">Streptococcus salivarius</span> K12 (<b>a</b>) and <span class="html-italic">S. mutans</span> ATCC 25175 (<b>b</b>) in pure culture in the absence and in the presence of 100 µg µL<sup>−1</sup>, 150 µg µL<sup>−1</sup>, and 200 µg µL<sup>−1</sup> of PG1. The experiments were performed in triplicate with independent cultures, and data were analysed with GraphPad Prism version 8.0.2 software. Statistical significance was examined by the two-way ANOVA test with Dunnett’s correction. Results are indicated as means ± SDs. Asterisks indicate statistical significance (**** <span class="html-italic">p</span> &lt; 0.0001; *** <span class="html-italic">p</span> &lt; 0.001; ** <span class="html-italic">p</span> &lt; 0.01; * <span class="html-italic">p</span> &lt; 0.05). ns: not significant.</p>
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<p>Viability of L929 cells against different concentrations of <span class="html-italic">Paederia grandidieri</span> extracts at 24 h (<b>A</b>) and 48 h (<b>B</b>). PG1: aqueous extract at 25 °C for 24 h; PG2: aqueous extract at 60 °C for 6 h; PG3: aqueous extract at 60 °C for 24 h; PG4: hydro-alcoholic extract at 25 °C for 4 h; and PG5: hydro-alcoholic extract at 25 °C for 24 h. Data represent mean ± SD. Significant differences from the control are defined as * <span class="html-italic">p</span> &lt; 0.01, ** <span class="html-italic">p</span> &lt; 0.001, and *** <span class="html-italic">p</span> &lt; 0.0001. The dashed line represents the 80% cell survival threshold, corresponding to the inhibitory concentration 20 (IC20) values.</p>
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<p><span class="html-italic">Paederia grandidieri</span>.</p>
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