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15 pages, 4917 KiB  
Article
Optimization of Ultraviolet-B Treatment for Enrichment of Total Flavonoids in Buckwheat Sprouts Using Response Surface Methodology and Study on Its Metabolic Mechanism
by Jiyuan Xue, Meixia Hu, Jia Yang, Weiming Fang and Yongqi Yin
Foods 2024, 13(23), 3928; https://doi.org/10.3390/foods13233928 (registering DOI) - 5 Dec 2024
Abstract
Buckwheat possesses significant nutritional content and contains different bioactive compounds, such as total flavonoids, which enhance its appeal to consumers. This study employed single-factor experiments and the response surface methodology to identify the optimal germination conditions for enhancing the total flavonoid content in [...] Read more.
Buckwheat possesses significant nutritional content and contains different bioactive compounds, such as total flavonoids, which enhance its appeal to consumers. This study employed single-factor experiments and the response surface methodology to identify the optimal germination conditions for enhancing the total flavonoid content in buckwheat sprouts through ultraviolet-B treatment. The research showed that buckwheat sprouts germinated for 3 days at a temperature of 28.7 °C while being exposed to ultraviolet-B radiation at an intensity of 30.0 μmol·m−2·s−1 for 7.6 h per day during the germination period resulted in the highest total flavonoid content of 1872.84 μg/g fresh weight. Under these specified conditions, ultraviolet-B treatment significantly elevated the activity and gene expression levels of enzymes related to the phenylpropanoid metabolic pathway, including phenylalanine ammonia-lyase, cinnamic acid 4-hydroxylase, 4-coumarate coenzyme A ligase, and chalcone isomerase. Ultraviolet-B treatment caused oxidative damage to buckwheat sprouts and inhibited their growth, but ultraviolet-B treatment also enhanced the activity of key enzymes in the antioxidant system, such as catalase, peroxidase, superoxide dismutase, and ascorbate peroxidase. This research provided a technical reference and theoretical support for enhancing the isoflavone content in buckwheat sprouts through ultraviolet-B treatment. Full article
(This article belongs to the Section Food Engineering and Technology)
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<p>Effects of germination time (<b>a</b>), UV-B treatment time (<b>b</b>), germination temperature (<b>c</b>), and UV-B intensity (<b>d</b>) on total flavonoid content. Different lowercase letters represent significant differences between treatment groups.</p>
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<p>Plots of the interaction of variables on total flavonoid enrichment. Response surface plot of UV−B treatment time and Germination time (<b>a</b>), contour map of UV−B treatment time and Germination time (<b>b</b>), response surface plot of Germination temperature and Germination time (<b>c</b>), contour map of Germination temperature and Germination time (<b>d</b>), response surface plot of UV−B intensity and Germination time (<b>e</b>), contour map of UV−B intensity and Germination time (<b>f</b>), response surface plot of Germination temperature and UV−B treatment time (<b>g</b>), contour map of Germination temperature and UV−B treatment time (<b>h</b>), response surface plot of UV−B intensity and UV−B treatment time (<b>i</b>), contour map of UV−B intensity and UV−B treatment time (<b>j</b>), response surface plot of UV−B intensity and Germination temperature (<b>k</b>) and contour map of UV−B intensity and Germination temperature (<b>l</b>).</p>
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<p>Effects of UV-B treatment on the content of total flavonoid content (<b>a</b>), total phenolic (<b>b</b>), and growth performance (<b>c</b>) of buckwheat sprouts. * Indicates significant differences in indicators among treatments according to ANOVA and Tukey’s test (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Effect of UV-B treatment on the content of MDA (<b>a</b>), <math display="inline"><semantics> <mrow> <msubsup> <mrow> <mi>O</mi> </mrow> <mrow> <mn>2</mn> </mrow> <mrow> <mo>−</mo> </mrow> </msubsup> </mrow> </semantics></math>. (<b>b</b>), and H<sub>2</sub>O<sub>2</sub> (<b>c</b>), ABTS free-radical scavenging rate (<b>d</b>), DPPH scavenging capacity (<b>e</b>), and FRAP (<b>f</b>). * Indicates significant differences in indicators among treatments according to ANOVA and Tukey’s test (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Effects of UV-B treatment on the activity of APX (<b>a</b>), SOD (<b>b</b>), POD (<b>c</b>), and CAT (<b>d</b>), and the relative expression of <span class="html-italic">FtAPX</span> (<b>e</b>), <span class="html-italic">FtSOD</span> (<b>f</b>), <span class="html-italic">FtPOD</span> (<b>g</b>), and <span class="html-italic">FtCAT</span> (<b>h</b>). * Indicates significant differences in indicators among treatments according to ANOVA and Tukey’s test (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Effects of UV-B treatment on the activity of 4CL (<b>a</b>), PAL (<b>b</b>), C4H (<b>c</b>), and CHI (<b>d</b>), and the relative expression of <span class="html-italic">Ft4CL</span> (<b>e</b>), <span class="html-italic">FtPAL</span> (<b>f</b>), <span class="html-italic">FtC4H</span> (<b>g</b>), <span class="html-italic">FtCHI</span> (<b>h</b>), <span class="html-italic">FtCHS</span> (<b>i</b>) and <span class="html-italic">FtF3H</span> (<b>j</b>). * Indicates significant differences in indicators among treatments according to ANOVA and Tukey’s test (<span class="html-italic">p</span> &lt; 0.05).</p>
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16 pages, 3250 KiB  
Article
Enhancing Lettuce (Lactuca sativa) Productivity: Foliar Sprayed Fe-Alg-CaCO3 MPs as Fertilizers for Aquaponics Cultivation
by Davide Frassine, Roberto Braglia, Francesco Scuderi, Enrico Luigi Redi, Federica Valentini, Michela Relucenti, Irene Angela Colasanti, Andrea Macchia, Ivo Allegrini, Angelo Gismondi, Gabriele Di Marco and Antonella Canini
Plants 2024, 13(23), 3416; https://doi.org/10.3390/plants13233416 (registering DOI) - 5 Dec 2024
Abstract
Aquaponics is an innovative agricultural method combining aquaculture and hydroponics. However, this balance can lead to the gradual depletion of essential micronutrients, particularly iron. Over time, decreasing iron levels can negatively impact plant health and productivity, making the monitoring and management of iron [...] Read more.
Aquaponics is an innovative agricultural method combining aquaculture and hydroponics. However, this balance can lead to the gradual depletion of essential micronutrients, particularly iron. Over time, decreasing iron levels can negatively impact plant health and productivity, making the monitoring and management of iron in aquaponic systems vital. This study investigates the use of Fe-Alg-CaCO3 microparticles (MPs) as foliar fertilizer on lettuce plants in an aquaponic system. The research investigated Lactuca sativa L. cv. Foglia di Quercia Verde plants as the experimental cultivar. Three iron concentrations (10, 50, and 250 ppm) were tested, with 15 plants per treatment group, plus a control group receiving only sterile double-distilled water. The Fe-Alg-CaCO3 MPs and ultrapure water were applied directly to the leaves using a specialized nebulizer. Foliar nebulization was chosen for its precision and minimal resource use, aligning with the sustainability goals of aquaponic cultivation. The research evaluated rosette diameter, root length, fresh weight, soluble solids concentration, levels of photosynthetic pigments, and phenolic and flavonoid content. The 250 ppm treatment produced the most notable enhancements in both biomass yield and quality, highlighting the potential of precision fertilizers to boost sustainability and efficiency in aquaponic systems. In fact, the most significant increases involved biomass production, particularly in the edible portions, along with photosynthetic pigment levels. Additionally, the analysis of secondary metabolite content, such as phenols and flavonoids, revealed no reduction compared to the control group, meaning that the proposed fertilizer did not negatively impact the biosynthetic pathways of these bioactive compounds. This study opens new possibilities in aquaponics cultivation, highlighting the potential of precision fertilizers to enhance sustainability and productivity in soilless agriculture. Full article
(This article belongs to the Section Horticultural Science and Ornamental Plants)
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<p>(<b>A</b>) SEM magnification 10 K: a microsphere is illustrated, it has a rough surface, due to incomplete fusion of constituent subunits. (<b>B</b>) SEM magnification 10 K: this image shows the microsphere inner cavity; the surface is roughest than (<b>A</b>), and constituent subunits are well visible; they have a minimum diameter of 100 nm, inset. (<b>C</b>) Region of interest (ROI) for EDX analysis. (<b>D</b>) EDX analysis element graph shows the presence of calcium, oxygen, and a small amount of Fe. Platinum, copper, and silver peaks are due to the platinum coating, the copper grid where the sample is placed, and the aluminum supporting stub.</p>
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<p>Plant samples collected on the 55th day from sowing at the end of each Fe-Alg-CaCO<sub>3</sub> MPs treatment (CT, 10, 50, and 250 ppm).</p>
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<p>Morpho-biometrical parameters. In detail, (<b>A</b>) rosette diameter; (<b>B</b>) root length; (<b>C</b>) rosette fresh weight; (<b>D</b>) root fresh weight. The <span class="html-italic">x</span>-axis denotes the treatments, while the <span class="html-italic">y</span>-axis represents the units of measurement. The significance resulting from the comparisons between the various treatments is indicated by asterisks: * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.005.</p>
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<p>Qualitative and quantitative data from spectrophotometric assays. In detail, (<b>A</b>) chlorophyll <span class="html-italic">a</span>; (<b>B</b>) chlorophyll <span class="html-italic">b</span>; (<b>C</b>) total chlorophyll; (<b>D</b>) carotenoids; (<b>E</b>) total phenolic content; (<b>F</b>) total flavonoid content. The <span class="html-italic">x</span>-axis denotes the treatments, and the <span class="html-italic">y</span>-axis represents units of measurement. The significance resulting from the comparisons between the various treatments is indicated by asterisks: * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.005.</p>
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<p>Representative flow chart for the biomineralization synthetic approach able to produce CaCO<sub>3</sub> NPs (i.e., the chemical precursor) for the second step to obtain functionalized Fe-Alg-CaCO<sub>3</sub> MPs, which can be able to act as micro-carriers for plant nutrients. Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p>
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19 pages, 3649 KiB  
Review
Unlocking the Therapeutic Potential of Adipose-Derived Stem Cell Secretome in Oral and Maxillofacial Medicine: A Composition-Based Perspective
by Chiara Giannasi, Francesca Cadelano, Elena Della Morte, Camilla Baserga, Camilla Mazzucato, Stefania Niada and Alessandro Baj
Biology 2024, 13(12), 1016; https://doi.org/10.3390/biology13121016 (registering DOI) - 5 Dec 2024
Abstract
The adipose-derived stem cell (ADSC) secretome is widely studied for its immunomodulatory and regenerative properties, yet its potential in maxillofacial medicine remains largely underexplored. This review takes a composition-driven approach, beginning with a list of chemokines, cytokines, receptors, and inflammatory and growth factors [...] Read more.
The adipose-derived stem cell (ADSC) secretome is widely studied for its immunomodulatory and regenerative properties, yet its potential in maxillofacial medicine remains largely underexplored. This review takes a composition-driven approach, beginning with a list of chemokines, cytokines, receptors, and inflammatory and growth factors quantified in the ADSC secretome to infer its potential applications in this medical field. First, a review of the literature confirmed the presence of 107 bioactive factors in the secretome of ADSCs or other types of mesenchymal stem cells. This list was then analyzed using the Search Tool for Retrieval of Interacting Genes/Proteins (STRING) software, revealing 844 enriched biological processes. From these, key processes were categorized into three major clinical application areas: immunoregulation (73 factors), bone regeneration (13 factors), and wound healing and soft tissue regeneration (27 factors), with several factors relevant to more than one area. The most relevant molecules were discussed in the context of existing literature to explore their therapeutic potential based on available evidence. Among these, TGFB1, IL10, and CSF2 have been shown to modulate immune and inflammatory responses, while OPG, IL6, HGF, and TIMP1 contribute to bone regeneration and tissue repair. Although the ADSC secretome holds great promise in oral and maxillofacial medicine, further research is needed to optimize its application and validate its clinical efficacy. Full article
(This article belongs to the Special Issue Advances in Biological Research of Adipose-Derived Stem Cells)
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<p>(<b>a</b>) Overview of the protein−protein interaction network of the 107 factors quantified in the ADSC secretome, generated using STRING software (version 12.0) with the interaction score threshold set to 0.900 for the highest confidence level. (<b>b</b>) Histogram showing the fold enrichment and false discovery rate (FDR) for seven selected pathways within the enriched biological processes highlighted by STRING analysis (<a href="#app1-biology-13-01016" class="html-app">Supplementary S3</a>). Fold enrichment was calculated as follows: (number of observed proteins/number of proteins in the list)/(background gene count/number of protein-coding genes).</p>
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<p>(<b>a</b>) Overview of the protein−protein interaction network of the 107 factors quantified in the ADSC secretome, generated using STRING software (version 12.0) with the interaction score threshold set to 0.900 for the highest confidence level. (<b>b</b>) Histogram showing the fold enrichment and false discovery rate (FDR) for seven selected pathways within the enriched biological processes highlighted by STRING analysis (<a href="#app1-biology-13-01016" class="html-app">Supplementary S3</a>). Fold enrichment was calculated as follows: (number of observed proteins/number of proteins in the list)/(background gene count/number of protein-coding genes).</p>
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<p>Venn diagram showing the unique and shared factors across the three major fields of ADSC secretome application in oral and maxillofacial medicine: immunomodulation, bone regeneration, wound healing, and soft tissue regeneration.</p>
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<p>Protein–protein interaction network of the 73 factors associated with the pathways GO:0006955 (immune response) and GO:0006954 (inflammatory response). The network visualization was generated using STRING software (version 12.0, minimum required interaction score set to 0.900).</p>
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<p>Protein–protein interaction network of the 13 factors associated with the pathways GO:0045667 (regulation of osteoblast differentiation) and GO:0045670 (regulation of osteoclast differentiation). The network visualization was generated using STRING software (version 12.0, minimum required interaction score set to 0.900).</p>
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<p>Protein–protein interaction network of the 27 factors associated with the pathways GO:0042060 (wound healing), GO:0031099 (regeneration), and GO:0050678 (regulation of epithelial cell proliferation). The network visualization was generated using STRING software (version 12.0, minimum required interaction score set to 0.900).</p>
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19 pages, 1053 KiB  
Article
Effect of the Storage Conditions on the Microbiological Quality and Selected Bioactive Compound Content in Fruit Mousses for Infants and Young Children
by Aleksandra Purkiewicz, Patryk Wiśniewski, Małgorzata Tańska, Gulden Goksen and Renata Pietrzak-Fiećko
Appl. Sci. 2024, 14(23), 11347; https://doi.org/10.3390/app142311347 (registering DOI) - 5 Dec 2024
Abstract
Fruit mousses, as low-processed products, are highly susceptible to external conditions, and storage leads to the degradation of bioactive compounds, particularly phenolic compounds and vitamins, as well as promoting the growth of yeasts and molds. This study investigated the impact of storage conditions [...] Read more.
Fruit mousses, as low-processed products, are highly susceptible to external conditions, and storage leads to the degradation of bioactive compounds, particularly phenolic compounds and vitamins, as well as promoting the growth of yeasts and molds. This study investigated the impact of storage conditions on the microbiological quality and degradation of selected bioactive compounds in fruit mousses from various producers (from apples, pears, and multi-components). Total phenolic (TPC) and total flavonoid (TFC) contents, vitamin C level, antioxidant capacity (AC, measured by the DPPH assay), and concentrations of macro- and microminerals were evaluated in fresh mousses and those stored for 48 h at 23 °C and 4 °C. Changes in total aerobic mesophilic bacteria (TAMB), yeast and mold counts, and selected microbial groups were also checked. It was found that the analyzed compounds varied depending on the components of the mousses. Multi-component mousses contained the highest levels of TPC, TFC, and vitamin C, and had 2–5 times higher AC values compared to apple and pear mousses. Storage at room temperature resulted in TFC lowering of up to 25% in apple mousses and vitamin C reductions of up to 22% in multi-component mousses. During refrigerated storage, the highest losses were observed in pear mousses, with TPC decreasing by up to 13% and vitamin C by up to 11%. Among the minerals, magnesium and zinc levels decreased most significantly in apple mousses stored at 23 °C (up to 33% and up to 29%, respectively). Microbiological analysis revealed variability in TAMB, yeast, and mold counts, with refrigeration (4 °C) generally limiting microbial growth compared to room temperature (23 °C). Notably, no pathogenic bacteria were detected under any storage conditions, and the mousses retained a high microbiological quality even after room-temperature storage. Full article
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<p>Antioxidant capacity (DPPH assay values) of the studied fruit mousses (fresh and stored at room temperature and refrigerated temperature). Different lowercase letters (a,b,c,d) placed above the bars for mousses of the same type, separate for fresh, stored at 23 °C, and stored at 4 °C, indicate significant differences (<span class="html-italic">p</span> ≤ 0.05), whereas different uppercase letters (A,B,C) placed above the bars for various storage conditions, separate for each mousse sample, indicate significant differences (<span class="html-italic">p</span> ≤ 0.05).</p>
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<p>Principal component analysis (PCA) results presented as score plots of the analyzed fresh fruit mousses (<b>a</b>,<b>c</b>,<b>e</b>) and loading plots of the analyzed parameters (TPC, TFC, DPPH, sum of macrominerals, and sum of microminerals) in the analyzed fresh fruit mousses (<b>b</b>,<b>d</b>,<b>f</b>). Explanations: A1, A2, A3, A4—apple mousses; P1, P2, P3, P4—pear mousses; M1, M2, M3, M4—multi-component mousses; F—fresh mousses; CT—mousses stored at refrigerated temperature (48 h/4 °C); RT—mousses stored at room temperature (48 h/23 °C).</p>
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21 pages, 3538 KiB  
Article
Hemostatic Antimicrobial Hydrogels Based on Silicon, Iron, Zinc, and Boron Glycerolates for Wound Healing Applications
by Tat’yana Khonina, Semyon Alekseenko, Elena Shadrina, Il’ya Ganebnykh, Alexander Mekhaev, Leonid Larionov, Maria Dobrinskaya, Nadezhda Izmozherova, Irina Antropova, Maxim Karabanalov, Muza Kokhan, Natali’ya Evstigneeva and Oleg Chupakhin
Gels 2024, 10(12), 795; https://doi.org/10.3390/gels10120795 (registering DOI) - 5 Dec 2024
Abstract
The use of glycerolates of biogenic elements as biocompatible precursors in sol–gel synthesis is an innovative direction and opens up new scientific and practical prospects in chemistry and technology of producing practically important biomedical materials, including hemostatic, antimicrobial, and wound healing materials. Using [...] Read more.
The use of glycerolates of biogenic elements as biocompatible precursors in sol–gel synthesis is an innovative direction and opens up new scientific and practical prospects in chemistry and technology of producing practically important biomedical materials, including hemostatic, antimicrobial, and wound healing materials. Using biocompatible precursors, silicon, zinc, boron, and iron glycerolates, new bioactive nanocomposite hydrogels were obtained by the sol–gel method. The composition and structural features of the hydrogels were studied using a complex of modern analytical techniques, including TEM, XRD, AES, and ESI MS. Hemostatic activity of the hydrogels was studied in the in vivo experiments; using the example of silicon-iron-zinc-boron glycerolates hydrogel, primary toxicological studies were carried out. Antimicrobial properties of hydrogels were studied using the agar diffusion method. The structural features of hydrogels and their relationship to medical and biological properties were revealed. It was shown that glycerolates hydrogels are non-toxic, and exhibit pronounced hemostatic activity, generally comparable to the commercial hemostatic drug Capramine. Antimicrobial activity is more pronounced for silicon-iron-zinc-boron and silicon-iron-boron glycerolates gel. The results obtained indicate that these glycerolates hydrogels are potential hemostatic and antibiotic-independent antimicrobial agents for topical wound healing applications in medical and veterinary practice. Full article
(This article belongs to the Special Issue Designing Gels for Antibacterial and Antiviral Agents)
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Graphical abstract

Graphical abstract
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<p>The biocompatible precursors used in the sol–gel synthesis of the glycerolates hydrogels: (<b>a</b>) silicon tetraglycerolate, (<b>b</b>) boron bisglycerolates, (<b>c</b>) zinc monoglycerolate, and (<b>d</b>) iron(III) monoglycerolate.</p>
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<p>IR spectra of (<b>a</b>) Si-Fe– (for comparison), (<b>b</b>) Si-Fe-Zn–, (<b>c</b>) Si-Fe-B–, and (<b>d</b>) Si-Fe-Zn-B–gel.</p>
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<p>TEM micrographs of dried suspension: (<b>a</b>) Si-Fe–(for comparison), (<b>b</b>) Si-Fe-Zn–, (<b>c</b>) Si-Fe-B–, (<b>d</b>) Si-Fe-Zn-B–gel in ethanol. (<b>a</b>–<b>d</b>) High-resolution TEM image, inserts show electron diffraction area.</p>
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<p>Thermal analysis data for (<b>a</b>) Si-Fe–, (<b>b</b>) Si-Fe-Zn–, (<b>c</b>) Si-Fe-B–, (<b>d</b>) Si-Fe-Zn-B–gel.</p>
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<p>ESI mass spectrum in negative mode of Si-Fe-Zn-B–gel liquid medium (* averaged for scan number from 60 to 80).</p>
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<p>XRD patterns of extracted solid phase of (<b>a</b>) Si-Fe– (for comparison), (<b>b</b>) Si-Fe-Zn–gel, (<b>c</b>) Si-Fe-B–gel, and (<b>d</b>) Si-Fe-Zn-B–gel.</p>
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<p>Histological analysis of Si-Fe-Zn-B–gel treated group 14 days after administration, hematoxylin-eosin, magnification ×100.</p>
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<p>Comparative assessment of bleeding time in mice with incised liver wounds.</p>
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<p>Strain growth inhibition zones: (<b>1</b>) <span class="html-italic">E. coli</span> ATCC 8739; (<b>2</b>) <span class="html-italic">P. aeruginosa</span> ATCC 9027; (<b>3</b>) clinical strain <span class="html-italic">S. aureus</span> (MRSA); (<b>4</b>) <span class="html-italic">S. pyogenes</span> ATCC 19615. (<b>5</b>) <span class="html-italic">C. albicans</span> RCPF <sub>Y</sub>-401/NCTC-885-653: (<b>a</b>) Si-Fe-Zn-B-gel; (<b>b</b>) positive control; (<b>c</b>) silicon glycerolates gel (negative control).</p>
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18 pages, 3157 KiB  
Article
Bioactivated Glucoraphanin Improves Cell Survival, Upregulating Phospho-AKT, and Modulates Genes Involved in DNA Repair in an In Vitro Alzheimer’s Disease Model: A Network-Transcriptomic Analysis
by Aurelio Minuti, Emanuela Mazzon, Renato Iori, Luigi Chiricosta and Osvaldo Artimagnella
Nutrients 2024, 16(23), 4202; https://doi.org/10.3390/nu16234202 (registering DOI) - 5 Dec 2024
Abstract
Background/Objectives: Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases, for which a definitive cure is still missing. Recently, natural compounds have been investigated for their possible neuroprotective role, including the bioactivated product of glucoraphanin (GRA), the sulforaphane (SFN), which is [...] Read more.
Background/Objectives: Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases, for which a definitive cure is still missing. Recently, natural compounds have been investigated for their possible neuroprotective role, including the bioactivated product of glucoraphanin (GRA), the sulforaphane (SFN), which is highly rich in cruciferous vegetables. It is known that SFN alleviates neuronal dysfunction, apoptosis, and oxidative stress in the brain. In the light of this evidence, the aim of this study was to investigate the molecular effects of SFN pre-treatment in differentiated SH-SY5Y neurons exposed to β-amyloid (Aβ). Methods: To this end, we first evaluated first cell viability via the Thiazolyl Blue Tetrazolium Bromide (MTT) assay, and then we analyzed the transcriptomic profiles by next-generation sequencing (NGS). Finally, we used a network analysis in order to understand which biological processes are affected, validating them by Western blot assay. Results: SFN pre-treatment counteracted Aβ-induced loss of cell viability. The network-transcriptomic analysis revealed that SFN upregulates genes associated with DNA repair, such as ABRAXAS1, BRCA1, BRCA2, CDKN1A, FANCA, FANCD2, FANCE, NBN, and XPC. Finally, SFN also increased the phosphorylation of AKT, which is associated with DNA repair and cell survival. Conclusions: These data suggest that SFN is a natural compound that could be suitable in the prevention of AD, thanks to its neuroprotective role in increasing cell survival, potentially restoring DNA damage induced by Aβ exposure. Full article
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Figure 1
<p>Chemical structures of glucoraphanin (GRA) and sulforaphane (SFN), along with a graphical representation of SFN’s biochemistry. Glucoraphanin is converted into sulforaphane through the action of the enzyme myrosinase. The chemical structures of GRA and SFN were obtained using PubChem compound records (accessed on 28 November 2024). Information about the molecule’s properties is available at the following links: <a href="https://pubchem.ncbi.nlm.nih.gov/compound/9548634" target="_blank">https://pubchem.ncbi.nlm.nih.gov/compound/9548634</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Sulforaphane" target="_blank">https://pubchem.ncbi.nlm.nih.gov/compound/Sulforaphane</a> (both accessed on 28 November 2024).</p>
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<p>(<b>A</b>) Cell viability after SFN treatment. SFN at the concentrations tested did not affect cell viability. (<b>B</b>) Exposure with Aβ 10 µM decreased the cell viability of RA-SH-SY5Y-differentiated neurons. Interestingly, SFN at a concentration of 5 µM was able to increase cell viability. <span class="html-italic">N</span> = 6 independent biological replicates. Data are expressed as mean ± Standard Error of the Mean (SEM). ** <span class="html-italic">p</span> &lt; 0.01; **** <span class="html-italic">p</span> &lt; 0.0001. The complete primary data are reported in <a href="#app1-nutrients-16-04202" class="html-app">Table S1</a>.</p>
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<p>Cluster of over-represented biological terms obtained by ShinyGO. The terms are sorted by fold enrichment after FDR. The color palette shows the log FDR. The size of the bubble represents the number of DEGs in the cluster.</p>
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<p>Final subnetworks of DEGs included in the network with the highest diameter excluding ribosomal proteins. The color of the nodes represents the deregulation of DEGs; green nodes are downregulated DEGs while red nodes are upregulated.</p>
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<p>Degree and betweenness score values for DEGs included in the network with the highest diameter excluding ribosomal proteins. The color of the nodes represents the deregulation of DEGs so that green nodes are downregulated while red nodes are upregulated DEGs. Labels are shown only for nodes with betweenness higher than 0.5 and degree higher than 2 for higher readability.</p>
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<p>KEGG pathway terms obtained by ShinyGO. The terms are sorted by FDR. The color palette shows the fold enrichment. The size of the bubble represents the number of DEGs in the cluster.</p>
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<p>Western blot analysis for p-AKT and cleaved-CASP3. (<b>Left</b>) Aβ treatment induced a light decrease in p-AKT, while SFN increased p-AKT levels. (<b>Right</b>) In addition, SFN treatment reduced levels of cleaved-CASP3 compared to Aβ. <span class="html-italic">N</span> = 3 independent biological replicates. The results are indicated by mean ± Standard Error of the Mean (SEM). * <span class="html-italic">p</span> &lt; 0.05. The complete primary data are reported in <a href="#app1-nutrients-16-04202" class="html-app">Table S1</a>.</p>
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<p>Schematic representation of putative molecular mechanism of how SFN could be involved in DNA repair process and cell survival in AD model. In red we indicated all genes/proteins upregulated. The arrow in red indicates the upregulation of DNA repair and cell survival process. β-amyloid structure (9CZP) was retrieved by PDB. Figure was drawn using vector image bank of Servier Medical Art by Servier (<a href="http://smart.servier.com" target="_blank">smart.servier.com</a>) (accessed on 3 November 2024). Licensed under Creative Commons Attribution 3.0 Unported License (<a href="http://creativecommons.org/licenses/by/3.0/" target="_blank">creativecommons.org/licenses/by/3.0/</a>) (accessed on 3 November 2024).</p>
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7 pages, 495 KiB  
Article
A Preliminary Lexicon for Juçara (Euterpe edulis Martius) Pulp: Possible Applications for Industry and Clinical Practice
by Ana Paula Silva Siqueira, Jéssika Martins Siqueira, Mirella de Paiva Lopes, Bárbara Silva Carneiro and Gustavo Duarte Pimentel
Appl. Sci. 2024, 14(23), 11334; https://doi.org/10.3390/app142311334 (registering DOI) - 5 Dec 2024
Abstract
Juçara is an important element for biodiversity in the Atlantic Forest, not only providing a rich source of nutritional and bioactive compounds, but also holding promising potential for sustainability. However, despite its virtues, there remains a dearth of studies fully exploring its potential. [...] Read more.
Juçara is an important element for biodiversity in the Atlantic Forest, not only providing a rich source of nutritional and bioactive compounds, but also holding promising potential for sustainability. However, despite its virtues, there remains a dearth of studies fully exploring its potential. In our pioneering study, conducted using a panel of eight trained specialists, we delved into a sensory analysis of dehydrated juçara pulp, employing both descriptive analysis and the temporal dominance of sensations (TDS) technique. The findings revealed striking differences between juçara and açaí, not only in terms of flavor and aroma, but also in their potential to drive more mindful eating habits. By promoting the consumption of juçara, we are supporting the sustainability of the Atlantic Forest, where it is cultivated in an environmentally responsible manner. Thus, we are contributing to the preservation of this unique ecosystem and the well-being of local communities. Full article
(This article belongs to the Section Food Science and Technology)
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<p>Temporal dominance of juçara pulp sensations. The dotted line represents chance (the expected chance level) and the solid line represents the significance level.</p>
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16 pages, 1816 KiB  
Article
Antioxidant Peptides from Sacha Inchi Meal: An In Vitro, Ex Vivo, and In Silico Approach
by Erwin Torres-Sánchez, Iván Lorca-Alonso, Sandra González-de la Fuente, Blanca Hernández-Ledesma and Luis-Felipe Gutiérrez
Foods 2024, 13(23), 3924; https://doi.org/10.3390/foods13233924 (registering DOI) - 5 Dec 2024
Abstract
Plant-derived antioxidant peptides safeguard food against oxidation, helping to preserve its flavor and nutrients, and hold significant potential for use in functional food development. Sacha Inchi Oil Press-Cake (SIPC), a by-product of oil processing, was used to produce Sacha Inchi Protein Concentrate (SPC) [...] Read more.
Plant-derived antioxidant peptides safeguard food against oxidation, helping to preserve its flavor and nutrients, and hold significant potential for use in functional food development. Sacha Inchi Oil Press-Cake (SIPC), a by-product of oil processing, was used to produce Sacha Inchi Protein Concentrate (SPC) in vitro, hydrolyzed by a standardized static INFOGEST 2.0 protocol. This study aimed to integrate in vitro, ex vivo, and in silico methods to evaluate the release of antioxidant peptides from SPC during gastrointestinal digestion. In vitro and ex vivo methods were used to investigate the antioxidant potential of SPC digests. Bioinformatics tools (find-pep-seq, AnOxPP, AnOxPePred-1.0, PepCalc, MLCPP 2.0, Pasta 2.0, PlifePred, Rapid Peptide Generator, and SwissADME) were employed to characterize antioxidant peptides. The gastric and intestinal digests exhibited higher ABTS and ORAC values than those of SPC. Under basal conditions, gastric digest fractions GD1, GD2, and GD3 (<3, 3–10, and >10 kDa, respectively), separated by ultrafiltration, significantly reduced the ROS levels in the RAW264.7 macrophages while, under LPS stimulation, GD1 (16 µg/mL) and GD2 (500 and 1000 µg/mL) reversed the induced damage. From the de novo peptidome determined, 416 peptides were selected based on their resistance to digestion. Through in silico tools, 315 resistant peptides were identified as antioxidants. Despite low predicted bioavailability, the peptides SVMGPYYNSK, EWGGGGCGGGGGVSSLR, RHWLPR, LQDWYDK, and ALEETNYELEK showed potential for extracellular targets and drug delivery. In silico digestion yielded the sequences SVMGPY, EW, GGGGCGGGGGVSS, PQY, HGGGGGG, GGGG, HW, and SGGGY, which are promising free radical scavengers with increased bioavailability. However, these hypotheses require confirmation through chemical synthesis and further validation studies. Full article
(This article belongs to the Special Issue Research and Application of Bioactive Peptides in Food)
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Figure 1
<p>Electrophoretic (SDS-PAGE) analysis. (Std) Lines with Precision Plus Protein<sup>TM</sup> Dual Xtra Standard. (1) Sacha Inchi Protein Concentrate (SPC); (2) gastric (B-GD1) and (3) intestinal (B-ID1) (Blanks, &gt;10 kDa); (4) gastric (GD1) and (5) intestinal (ID1) (digests, &gt;10 kDa); (6) gastric (B-GD2) and (7) intestinal (B-ID2) (Blanks, 3–10 kDa); (8) gastric (GD2) and (9) intestinal (ID2) (digests, 3–10 kDa); (10) intestinal (B-ID3) (Blank, &lt;3 kDa); (11) gastric (GD3) and (12) intestinal (ID3) (digests, &lt;3 kDa). Note the different polypeptides in the lines classified in the albumins (◊), globulins (*), prolamins (▪), glutelins (+), and higher molecular weight polypeptides (¬), as well as the various peptides derived from the digestion assay (꙳).</p>
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<p>Viability of RAW 264.7 cells treated with Sacha Inchi Protein Concentrate and its fractioned digests. Control treatment represents 100.00 ± 3.83% cell viability. Doses below the dashed black line (75%) are toxic. SPC: Sacha Inchi Protein Concentrate; GD1 and ID1: gastric and intestinal digests fractions (&gt;10 kDa), respectively; GD2 and ID2: gastric and intestinal digests fractions (3–10 kDa), respectively; GD3 and ID3: gastric and intestinal digests fractions (&lt;3 kDa), respectively. Values are presented as mean ± SD, n = 8.</p>
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<p>Reactive oxygen species (ROS) production (expressed as %) in RAW264.7 macrophages under basal and stimulated conditions. (<b>a</b>) Gastric (GD1) and (<b>b</b>) intestinal (ID1) (digests, &gt;10 kDa); (<b>c</b>) gastric (GD2) and (<b>d</b>) intestinal (ID2) (digests, 3–10 kDa); (<b>e</b>) gastric (GD3) and (<b>f</b>) intestinal (ID3) (digests, &lt;3 kDa). Lipopolysaccharide (LPS) stimulus (10 μg/well). <sup>a–d</sup> Different letters indicate significant differences between samples (LSD Test, <span class="html-italic">p</span> &lt; 0.05).</p>
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22 pages, 374 KiB  
Article
Enzyme Inhibitory, Physicochemical, and Phytochemical Properties and Botanical Sources of Honey, Bee Pollen, Bee Bread, and Propolis Obtained from the Same Apiary
by Yusuf Can Gercek, Eda Dagsuyu, Fatma Nur Basturk, Seran Kırkıncı, Nazlıcan Yıldırım, Gamze Kıskanç, Bahar Özmener, Yigit Sabri Unlu, Seda Nur Kalkan, Kadir Boztaş, Gül Cevahir Oz, Refiye Yanardağ, Nesrin Ecem Bayram and Aleksandar Ž. Kostić
Antioxidants 2024, 13(12), 1483; https://doi.org/10.3390/antiox13121483 (registering DOI) - 5 Dec 2024
Abstract
Bee products are an important source of nutrients and bioactive phytochemicals. This study aimed to determine the chemical composition (proximate composition, general phytochemical composition, sugar, and phenolic profiles) of four different products (honey, bee pollen, bee bread, and propolis), obtained from the same [...] Read more.
Bee products are an important source of nutrients and bioactive phytochemicals. This study aimed to determine the chemical composition (proximate composition, general phytochemical composition, sugar, and phenolic profiles) of four different products (honey, bee pollen, bee bread, and propolis), obtained from the same apiary, as well as to assess their biological activity through antioxidant and enzyme inhibition assays (α-amylase, α-glucosidase, lipase, AchE, neuraminidase, angiotensin-converting enzyme, urease, trypsin, tyrosinase, carbonic anhydrase, thioredoxin reductase, adenosine deaminase). Clear differences were observed among the samples in terms of both chemical composition and biological activity. The analysis revealed that bee pollen exhibited the highest carbohydrate content (87.9%), while propolis was identified as the richest source of phenolic compounds (14,858.9 mg/kg) among the analyzed samples. Propolis exhibited the highest biological activity in all applied antioxidant assays (CUPRAC, DPPH, and ABTS•+) and in most enzyme inhibition assays. Notably, the α-glucosidase inhibition activity of propolis was comparable to that of the reference standard. In addition, honey exhibited remarkable trypsin inhibition, also comparable to the applied standard. These findings highlight the diverse bioactivities of hive products, which could play a key role in promoting health and preventing diseases. Full article
(This article belongs to the Special Issue Bee Products as a Source of Natural Antioxidants: Second Edition)
16 pages, 906 KiB  
Article
An In Vitro Evaluation of Robin’s Pincushion Extract as a Novel Bioactive-Based Antistaphylococcal Agent—Comparison to Rosehip and Black Rosehip
by Olja Šovljanski, Milica Aćimović, Teodora Cvanić, Vanja Travičić, Aleksandra Popović, Jelena Vulić, Gordana Ćetković, Aleksandra Ranitović and Ana Tomić
Antibiotics 2024, 13(12), 1178; https://doi.org/10.3390/antibiotics13121178 (registering DOI) - 4 Dec 2024
Abstract
Introduction: This study explores the bioactive properties of extracts obtained from Robin’s pincushion (Diplolepis rosae) collected in Sokobanja, Serbia. Results: Comprehensive in vitro assessments reveal high concentrations of total phenolics (186.37 mg GAE/g), along with significant levels of carotenoids (44.10 μg [...] Read more.
Introduction: This study explores the bioactive properties of extracts obtained from Robin’s pincushion (Diplolepis rosae) collected in Sokobanja, Serbia. Results: Comprehensive in vitro assessments reveal high concentrations of total phenolics (186.37 mg GAE/g), along with significant levels of carotenoids (44.10 μg β-car/g). Robin’s pincushion exhibited superior antioxidant capacities across DPPH, ABTS, and reducing power assays, significantly outperforming comparable extracts from rosehip (Rosa canina) and black rosehip (Rosa spinosissima) in these activities. Additionally, high inhibitory effects were observed in antimicrobial assays, with the extract demonstrating minimal inhibitory concentrations (MIC) as low as 1.56 mg/mL against the Staphylococcus species. Notably, the extract achieved full bactericidal effect within 24 h in time-kill kinetic studies which additionally highlight its potent antistaphylococcal potential. Materials and methods: Analyzing their phytochemical profiles and evaluating their potential as antioxidant, anti-inflammatory, antihyperglycemic, and antimicrobial agents, wide-ranging evaluation of bioactivity of Robin’s pincushion was conducted. Conclusions: These findings highlight Robin’s pincushion as a promising natural source of bioactive compounds with potential applications in traditional and modern medicine for managing oxidative stress, inflammation, hyperglycemia, and microbial infections. Full article
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<p>Time-kill kinetics study for (<b>a</b>) <span class="html-italic">S. aureus</span>; (<b>b</b>) <span class="html-italic">S. saprophyticus</span>; (<b>c</b>) <span class="html-italic">S. sciuri</span>; (<b>d</b>) <span class="html-italic">S. epidermidis</span>; and (<b>e</b>) <span class="html-italic">S. warneri</span> (dots indicate experimentally obtained data (see <a href="#antibiotics-13-01178-t006" class="html-table">Table 6</a>), while lines represent kinetic modeled values).</p>
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<p>Samples used in this study: (<b>a</b>) <span class="html-italic">Robin’s pincushion</span> in nature; (<b>b</b>) rosehip; and (<b>c</b>) black rosehip (photo by Milica Aćimović).</p>
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43 pages, 14604 KiB  
Review
Asymmetric Synthesis of 2-Arylethylamines: A Metal-Free Review of the New Millennium
by Alejandro Manchado, Ángel García-González, Carlos T. Nieto, David Díez and Narciso M. Garrido
Molecules 2024, 29(23), 5729; https://doi.org/10.3390/molecules29235729 - 4 Dec 2024
Abstract
2-Arylethylamines are presented in several natural bioactive compounds, as well as in nitrogen-containing drugs. Their ability to surpass the blood–brain barrier makes this family of compounds of especial interest in medicinal chemistry. Asymmetric methodologies towards the synthesis of 2-arylethylamine motives are of great [...] Read more.
2-Arylethylamines are presented in several natural bioactive compounds, as well as in nitrogen-containing drugs. Their ability to surpass the blood–brain barrier makes this family of compounds of especial interest in medicinal chemistry. Asymmetric methodologies towards the synthesis of 2-arylethylamine motives are of great interest due to the challenges they may present. Thus, a concise metal-free review presenting recent advances in the asymmetric synthesis of 2-arylethylamines is presented, covering last-millennium studies, considering different methodologies towards the aforementioned motif, including chiral induction, organocatalysis, organophotocatalysis and enzymatic catalysis. Full article
(This article belongs to the Section Organic Chemistry)
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Graphical abstract

Graphical abstract
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<p>2-Arylethylamine derivatives.</p>
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<p>(<b>A</b>)<b>:</b> 2-Arylethylamines covered in this review. (<b>B</b>): 2-Arylethylamines not covered in this review.</p>
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<p>Chiral α-amino acid containing AEA synthesized by Sharpless chiral induction and subsequent derivatization.</p>
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<p>Chiral AEA and derived dihydroindoles obtained by Dineen et al.’s methodology [<a href="#B19-molecules-29-05729" class="html-bibr">19</a>].</p>
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<p>Multikilogram-scale synthesis of etamicastat.</p>
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<p>Different chiral AEAs and plausible 1,4-phenyl radical rearrangement mechanism from Garrido et al. [<a href="#B21-molecules-29-05729" class="html-bibr">21</a>].</p>
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<p>Chiral AEA and paclobutrazol derivative accessible from Race et al.’s methodology [<a href="#B22-molecules-29-05729" class="html-bibr">22</a>].</p>
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<p>Different diastereoselective AEA syntheses from Bower et al. [<a href="#B23-molecules-29-05729" class="html-bibr">23</a>].</p>
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<p>(<b>A</b>) Use of bifunctional chiral urea organocatalysis for the synthesis of different nitro-compounds and their application towards the synthesis of chiral AEA (<span class="html-italic">R</span>)-(-)-Baclofen by Takemoto et al. in 2005 [<a href="#B30-molecules-29-05729" class="html-bibr">30</a>]. (<b>B</b>) Synthesis of chiral α-carboxyl AEA by Takemoto et al. in 2021 and its application towards the synthesis of (-)-Nakinadine B.</p>
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<p>DKR to obtain polysubstituted chiral AEA enabled by bifunctional urea organocatalysis by Alemán et al. [<a href="#B32-molecules-29-05729" class="html-bibr">32</a>].</p>
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<p>Chiral tetrahydroisoquinoline containing AEA synthesized by phosphorous organocatalysis by Hiemstra et al. [<a href="#B34-molecules-29-05729" class="html-bibr">34</a>].</p>
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<p>Chiral AEA synthesis, enabled by phosphorous organocatalyst, either with α-aryl substituents (<b>A</b>), α-F substituents (<b>B</b>), or α-Cl substituents (<b>C</b>) by Watson et al. in 2018, 2020, and 2022, [<a href="#B35-molecules-29-05729" class="html-bibr">35</a>,<a href="#B36-molecules-29-05729" class="html-bibr">36</a>,<a href="#B37-molecules-29-05729" class="html-bibr">37</a>] respectively.</p>
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<p>Li et al.’s methodology towards the synthesis of β,β-diaryl-α-amino acid esters [<a href="#B38-molecules-29-05729" class="html-bibr">38</a>].</p>
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<p>Chiral synthesis of pyridine containing AEA by Terada et al. [<a href="#B39-molecules-29-05729" class="html-bibr">39</a>].</p>
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<p>Chiral oxirane containing AEA enabled by phosphorous organocatalyst, from Mao et al. in 2024 [<a href="#B40-molecules-29-05729" class="html-bibr">40</a>].</p>
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<p>Total synthesis of BIRT-377 using L-proline-derived catalyst by Barbas et al. in 2005 [<a href="#B41-molecules-29-05729" class="html-bibr">41</a>].</p>
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<p>Asymmetric synthesis of L-phenylalanine derivative by Patterson et al. in 2007 [<a href="#B42-molecules-29-05729" class="html-bibr">42</a>].</p>
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<p>Synthesis of chiral AEA whose nitrogen is embedded into a CN group, from Izquierdo et al. in 2016 [<a href="#B43-molecules-29-05729" class="html-bibr">43</a>].</p>
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<p>Total synthesis of hemiasterlin by Lindal et al. in 2017 [<a href="#B44-molecules-29-05729" class="html-bibr">44</a>].</p>
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<p><span class="html-italic">N</span>-heterocyclic olefin bifunctional organocatalyst used by Dong et al. in 2022 [<a href="#B45-molecules-29-05729" class="html-bibr">45</a>] for the synthesis of chiral AEA.</p>
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<p>Asymmetric synthesis of AEA by Liu et al. in 2024 [<a href="#B46-molecules-29-05729" class="html-bibr">46</a>].</p>
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<p>Chiral aminophosphonate-based AEA by Deng et al. in 2024 [<a href="#B47-molecules-29-05729" class="html-bibr">47</a>].</p>
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<p>Magic-blue-enabled synthesis of chiral AEA by Ghorai et al. in 2024 [<a href="#B48-molecules-29-05729" class="html-bibr">48</a>].</p>
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<p>(<b>A</b>) Chiral aryl iodide organocatalyst used in the synthesis of 1,1-di-fluorinated AEA. (<b>B</b>) Synthesis of 1,3-di-fluorinated AEA.</p>
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<p>Chiral AEA obtained through Kürt et al.’s methodology in 2020 [<a href="#B51-molecules-29-05729" class="html-bibr">51</a>].</p>
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<p>Chiral pyrrolidinone-containing AEA synthesized by Wen et al. in 2022 [<a href="#B52-molecules-29-05729" class="html-bibr">52</a>].</p>
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<p><sup>13</sup>C labelling of chiral AEA by Lundgren et al. in 2024 [<a href="#B53-molecules-29-05729" class="html-bibr">53</a>].</p>
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<p>Piperidine-containing chiral AEA enabled by boron organocatalyst from Zhang et al. in 2024 [<a href="#B54-molecules-29-05729" class="html-bibr">54</a>].</p>
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<p>Selenium organocatalyst used by Denmark et al. [<a href="#B57-molecules-29-05729" class="html-bibr">57</a>] to produce chiral AEA. (<b>A</b>) <span class="html-italic">N</span>,<span class="html-italic">N</span>’-bistosyl urea are used, as the bifunctional nucleophile. (<b>B</b>) <span class="html-italic">N</span>-Boc amines are used.</p>
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<p>Different chiral AEA arrays synthesized by Nicewicz et al. [<a href="#B66-molecules-29-05729" class="html-bibr">66</a>] (<b>A</b>) Intramolecular anti-Markonikov hydroamination. (<b>B</b>) Radical cycloaddition to produce γ-lactams and (<b>C</b>) pyrrolidines. (<b>D</b>) Intermolecular anti-Markonikov hydroamination.</p>
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<p>Asymmetric synthesis of AEA through organophotocatalysis by Xia et al. [<a href="#B70-molecules-29-05729" class="html-bibr">70</a>] (<b>A</b>) Nitrone 1,3-dipolar addition. (<b>B</b>) Intermolecular amino(hetero)arylation.</p>
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<p>Chiral (TMS)<sub>3</sub>Si containing 2-arylethylacetamides by Jing et al. in 2023 [<a href="#B72-molecules-29-05729" class="html-bibr">72</a>].</p>
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<p>Hydroamination of olefins to produce asymmetric AEA by Zeng et al. in 2023 [<a href="#B73-molecules-29-05729" class="html-bibr">73</a>].</p>
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<p>Organophotocatalysis to produce chiral δ-lactam-containing AEA by Shu et al. in 2023 [<a href="#B74-molecules-29-05729" class="html-bibr">74</a>].</p>
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<p>Tetrahydroisoquinoline-containing chiral AEA by Li et al. in 2004 [<a href="#B75-molecules-29-05729" class="html-bibr">75</a>].</p>
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<p>DKR by Kroutil et al. to produce γ-lactam containing chiral AEA in 2009 (<b>A</b>) and 1-methyl AEA in 2014 (<b>B</b>) [<a href="#B79-molecules-29-05729" class="html-bibr">79</a>].</p>
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<p>Novel enzymatic process replacement towards the synthesis of sitagliptin phosphate by Savile et al. in 2010 [<a href="#B81-molecules-29-05729" class="html-bibr">81</a>].</p>
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<p>Convergent routes towards the synthesis of niraparib derivative enabled by transaminases by Chung et al. in 2014 [<a href="#B82-molecules-29-05729" class="html-bibr">82</a>].</p>
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<p>Turner et al.’s synthesis of chiral AEA enabled by transaminase, in 2014 [<a href="#B83-molecules-29-05729" class="html-bibr">83</a>].</p>
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<p>Chiral amino alcohol from styrenyl derivatives (<b>A</b>) and epoxide derivatization through chiral AEA (<b>B</b>) by Li et al. [<a href="#B84-molecules-29-05729" class="html-bibr">84</a>].</p>
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<p>α-Methyl AEA enabled by transaminase catalysis by Rebolledo et al. in 2017 [<a href="#B87-molecules-29-05729" class="html-bibr">87</a>].</p>
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<p>γ-Secretase inhibitor synthesis by Burns et al. in 2017 [<a href="#B88-molecules-29-05729" class="html-bibr">88</a>].</p>
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<p>One-pot enantioselective deracemization to produce chiral AEA by Yun et al. in 2019 [<a href="#B89-molecules-29-05729" class="html-bibr">89</a>].</p>
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<p>Methodology to produce four amino alcohol enantiomers enabled by carbolygase-transaminase catalysis (<b>A</b>) and tetrahydroisoquinoline-containing AEA (<b>B</b>) by Rother et al. in 2019 [<a href="#B90-molecules-29-05729" class="html-bibr">90</a>] and 2023 [<a href="#B91-molecules-29-05729" class="html-bibr">91</a>], respectively.</p>
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<p>Sitagliptin synthesis by transaminase catalysis by Yun et al. in 2021 [<a href="#B92-molecules-29-05729" class="html-bibr">92</a>].</p>
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<p>Transaminase catalyzed synthesis of rimegepant intermediate by Jiao et al. [<a href="#B93-molecules-29-05729" class="html-bibr">93</a>].</p>
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<p>D-amino acid-based AEA by Bezsudnova et al. in 2022 [<a href="#B94-molecules-29-05729" class="html-bibr">94</a>].</p>
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<p>Enzymatic methodology with both (<span class="html-italic">S</span>)- and (<span class="html-italic">R</span>)-selectivity to produce chiral AEA by Ferrandi et al. in 2024 [<a href="#B95-molecules-29-05729" class="html-bibr">95</a>].</p>
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<p>In situ product crystallization of chiral AEA salt by Langermann et al. 2024 [<a href="#B96-molecules-29-05729" class="html-bibr">96</a>].</p>
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<p>Chiral α-amino acid-containing AEA by Dunham et al. [<a href="#B97-molecules-29-05729" class="html-bibr">97</a>].</p>
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<p>One-pot cascade reaction to produce chiral AEA enabled by transaminase catalysis by Wang et al. in 2024 [<a href="#B98-molecules-29-05729" class="html-bibr">98</a>].</p>
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<p>Amine dehydrogenase-based synthesis of chiral AEA by Bommarius et al. [<a href="#B99-molecules-29-05729" class="html-bibr">99</a>].</p>
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<p>Chiral AEA synthesis by alcohol conversion into amine products by Turner et al. in 2015 [<a href="#B100-molecules-29-05729" class="html-bibr">100</a>].</p>
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<p>New amino dehydrogenase used by Li et al. in 2015 to produce chiral AEA [<a href="#B101-molecules-29-05729" class="html-bibr">101</a>].</p>
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<p>Amino dehydrogenase new scope to synthesize dilevalol and medroxalol by Chen et al. [<a href="#B102-molecules-29-05729" class="html-bibr">102</a>].</p>
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<p>Shield machine-like substrate used by Mu et al. to produce chiral AEA [<a href="#B103-molecules-29-05729" class="html-bibr">103</a>].</p>
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<p>Reductive amination of ketones enabled by amino dehydrogenase to produce chiral AEA by Zhy et al. [<a href="#B104-molecules-29-05729" class="html-bibr">104</a>].</p>
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<p>IRED used by Hörne et al. in 2017 [<a href="#B105-molecules-29-05729" class="html-bibr">105</a>] to produce chiral AEA from the corresponding ketone derivatives.</p>
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<p>Chiral synthesis by Roiban et al. [<a href="#B106-molecules-29-05729" class="html-bibr">106</a>] enabled by IRED catalysis in 2017 (<b>A</b>) and 2019 (<b>B</b>).</p>
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<p>Chiral synthesis of dextromethorphan intermediates (<b>A</b>) and chiral amino alcohol-containing AEA synthesis (<b>B)</b> enabled by IRED by Zhu et al. in 2019 and 2022, [<a href="#B108-molecules-29-05729" class="html-bibr">108</a>,<a href="#B109-molecules-29-05729" class="html-bibr">109</a>] respectively.</p>
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<p>IRED used for the synthesis of chiral AEA from α-ketoesters by Turner et al. in 2021 [<a href="#B110-molecules-29-05729" class="html-bibr">110</a>].</p>
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<p>Rotigotine and derivatives synthesized by Wang et al. in 2022, [<a href="#B111-molecules-29-05729" class="html-bibr">111</a>] enabled by IRED catalysis.</p>
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<p>Benzazepine-containing AEA by IRED catalysis synthesized in 2023 by Husain et al. [<a href="#B112-molecules-29-05729" class="html-bibr">112</a>].</p>
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<p>IRED-catalyzed synthesis of β-aryl propanamines by Yao et al. [<a href="#B113-molecules-29-05729" class="html-bibr">113</a>].</p>
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<p>Chiral amino alcohol-containing AEA by Zhu et al. in 2023 [<a href="#B114-molecules-29-05729" class="html-bibr">114</a>].</p>
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<p>Photobiocatalyzed synthesis of chiral AEA by Yang et al. in 2024 [<a href="#B115-molecules-29-05729" class="html-bibr">115</a>,<a href="#B116-molecules-29-05729" class="html-bibr">116</a>].</p>
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<p>Chiral AEA synthesis by Zhao et al. in 2024 [<a href="#B117-molecules-29-05729" class="html-bibr">117</a>] enabled by photobiocatalysis.</p>
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<p>Reductive aminase used for the synthesis of chiral AEA by Turner et al. in 2017 [<a href="#B118-molecules-29-05729" class="html-bibr">118</a>].</p>
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<p>Chiral synthesis of AEA enabled by ammonia lyase in 2015, by Turner et al. [<a href="#B119-molecules-29-05729" class="html-bibr">119</a>].</p>
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<p>Phenyl alanine lyase in combination with amino acid decarboxylase to produce chiral AEA by Flitch et al. in 2019 [<a href="#B120-molecules-29-05729" class="html-bibr">120</a>].</p>
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<p>Aminotransferase-catalysis used for the synthesis of chiral AEA by Servi et al. in 2012 [<a href="#B121-molecules-29-05729" class="html-bibr">121</a>].</p>
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<p>Aldoxime dehydratase-catalysis in order to produce a wide range of chiral AEAs by Groger et al. in 2017 [<a href="#B122-molecules-29-05729" class="html-bibr">122</a>].</p>
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<p>Methodology used to produce polysubstituted amino alcohol-containing chiral AEA enabled by cytochrome c by Arnold et al. in 2019 [<a href="#B123-molecules-29-05729" class="html-bibr">123</a>].</p>
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<p>One-pot D-amino acid synthesis by Shin et al. [<a href="#B124-molecules-29-05729" class="html-bibr">124</a>] using amino acid decarboxylase.</p>
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<p>Enzymatic DK reduction by ketoreductase to produce chiral AEA by Xu et al. [<a href="#B125-molecules-29-05729" class="html-bibr">125</a>].</p>
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<p>Styrosinase, tyrosine decarboxylase, transaminase, and norcoclaurine synthase to produce chiral AEA, by Hailes et al. [<a href="#B126-molecules-29-05729" class="html-bibr">126</a>].</p>
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18 pages, 6951 KiB  
Review
Glycine-Based [3+2] Cycloaddition for the Synthesis of Pyrrolidine-Containing Polycyclic Compounds
by Tieli Zhou, Xiaofeng Zhang, Desheng Zhan and Wei Zhang
Molecules 2024, 29(23), 5726; https://doi.org/10.3390/molecules29235726 - 4 Dec 2024
Abstract
The synthesis of pyrrolidine compounds with biological interest is an active research topic. Glycine could be a versatile starting material for making pyrrolidine derivatives. This review covers recent works on glycine-based [3+2] cycloaddition and combines other annulation reactions in the one-pot synthesis of [...] Read more.
The synthesis of pyrrolidine compounds with biological interest is an active research topic. Glycine could be a versatile starting material for making pyrrolidine derivatives. This review covers recent works on glycine-based [3+2] cycloaddition and combines other annulation reactions in the one-pot synthesis of pyrrolidine-containing heterocyclic compounds. Synthetic method development, substrate scope, and reaction mechanisms are discussed. Applications of the compounds in drug discovery are briefly mentioned. This paper is helpful for chemists in the development of efficient and sustainable methods for the preparation of bioactive pyrrolidine compounds. Full article
(This article belongs to the Special Issue Cyclization Reactions in the Synthesis of Heterocyclic Compounds)
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<p>Representative pyrrolidine-containing natural products.</p>
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<p>Representative FDA-approved pyrrolidine-containing drugs.</p>
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<p>Pyrrolizidine- and indolizidine-bearing natural products.</p>
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<p>Bioactive compounds containing pyrrolidine.</p>
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<p>Examples of HCV NS5B inhibitors.</p>
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<p>Pyrrolidine-containing fused and spiro natural products.</p>
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<p>Pyrrolidine-containing congregated polycyclic natural products.</p>
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<p>The formation of semi- and non-stabilized AMYs from glycines.</p>
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<p>Synthesis of pyrrolizidines <b>30</b>.</p>
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<p>Synthesis of indolizidines <b>31</b>.</p>
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<p>Preparation of aldehyde <b>35</b>.</p>
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<p>Intermolecular cycloaddition for indolizidine <b>36</b>.</p>
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<p>Preparation of intermediates <b>44</b>, <b>47</b>, and <b>49</b>.</p>
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<p>Synthesis of octahydro-1<span class="html-italic">H</span>-pyrrolo[3,2-<span class="html-italic">c</span>]pyridines and octahydropyrano[4,3-<span class="html-italic">b</span>]pyrroles.</p>
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<p>The synthesis of cis-pentacyclic compounds <b>41</b>.</p>
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<p>Synthesis of <span class="html-italic">trans</span>-pentacyclic compounds <b>42</b> and their bioactivities.</p>
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<p>Two enantiomers of compound <b>42j</b> and their bioactivities.</p>
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<p>Pseudo five-component synthesis of tetracyclic pyrrolizidines <b>73</b>.</p>
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<p>Synthesis of tetracyclic pyrrolizidines <b>74</b>.</p>
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<p>One-pot and two-step synthesis of tetracyclic pyrrolizidines <b>75</b>.</p>
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<p>Double cycloaddition involving glycine and olefinic oxindoles.</p>
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<p>Comparison of maleimides and olefinic oxindoles in double cycloadditions.</p>
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<p>Cyclization and cycloaddition cascade for constructing tricyclic amines.</p>
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<p>Preparation of multi-functional aldehydes <b>99</b>–<b>101</b>.</p>
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<p>The synthesis of tricyclic amines <b>102</b> and <b>103</b>.</p>
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<p>Synthesis of tricyclic amines <b>104</b> and <b>105</b>.</p>
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<p>Preparation of multi-functional compound <b>115</b>.</p>
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<p>Synthesis of aspidosperma alkaloids <b>82</b>, <b>83</b>, and <b>118</b>.</p>
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<p>Preparation of multi-functional aldehydes <b>122</b> (<b>A</b>) and <b>126</b> (<b>B</b>).</p>
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<p>The synthesis of tricyclic amine <b>129</b>.</p>
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<p>The synthesis of tricyclic amine <b>132</b>.</p>
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<p>Preparation of multi-functional aldehydes <b>133</b> and <b>135</b>.</p>
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<p>Synthesis of tricyclic amines <b>136</b>, <b>138</b>, and <b>139</b>.</p>
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<p>Synthesis of tricyclic amines <b>140</b> and <b>141</b>.</p>
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<p>Preparation of multi-functional aldehyde <b>147</b>.</p>
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<p>The synthesis of bridged tricyclic amines <b>148</b> and <b>149</b>.</p>
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<p>The synthesis of bridged tricyclic amines <b>152</b>.</p>
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15 pages, 2471 KiB  
Article
The Anti-Inflammatory Properties of Polysaccharides Extracted from Moringa oleifera Leaves on IEC6 Cells Stimulated with Lipopolysaccharide In Vitro
by Hosameldeen Mohamed Husien, Weilong Peng, Mohamed Osman Abdalrahem Essa, Saber Y. Adam, Shahab Ur Rehman, Rahmat Ali, Ahmed A. Saleh, Mengzhi Wang and Jingui Li
Animals 2024, 14(23), 3508; https://doi.org/10.3390/ani14233508 - 4 Dec 2024
Abstract
Moringa oleifera (M. oleifera) is a plant with significant medicinal and nutritional value and contains various bioactive compounds, particularly in its leaves (MOL). This study sought to explore the impact of M. oleifera leaf polysaccharides (MOLPs) on lipopolysaccharide (LPS)-activated intestinal epithelial [...] Read more.
Moringa oleifera (M. oleifera) is a plant with significant medicinal and nutritional value and contains various bioactive compounds, particularly in its leaves (MOL). This study sought to explore the impact of M. oleifera leaf polysaccharides (MOLPs) on lipopolysaccharide (LPS)-activated intestinal epithelial cells (IEC6) and to uncover the mechanisms involved. The cytotoxicity of MOLP on IEC6 cells was assessed using the Cell Counting Kit-8 (CCK-8) assay, which demonstrated a safe concentration range of 0–1280 µg/mL. The impact of MOLP on cell viability was further evaluated over 12 to 48 h. IEC6 cells were treated with three concentrations of MOLP low (25 µg/mL), medium (50 µg/mL), and high (100 µg/mL) alongside LPS (50 µg/mL) stimulation for one day. The findings revealed that treatment with MOLP significantly promoted cell migration and increased the production of interleukin-10 (IL-10), while it simultaneously decreased cell apoptosis and the levels of pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6). Additionally, MOLP treatments across all concentrations significantly reduced the expression of Toll-like receptor 4 (TLR-4), myeloid differentiation primary response 88 (MyD88), phosphorylated nuclear factor kappa B-alpha (pIκB-α), and phosphorylated NF-κB p65 signalling pathways. Moreover, MOLP restored the expression of tight junction proteins, such as zonula occludens-1 (ZO-1) and occludin, which had been disrupted by LPS. These results indicate that MOLP exhibits anti-inflammatory properties by inhibiting inflammatory signalling pathways and maintaining intestinal barrier integrity through the upregulation of tight junction proteins in IEC6 cells. This study enhances our understanding of the anti-inflammatory capabilities of MOLP. Full article
(This article belongs to the Section Animal Nutrition)
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Figure 1
<p>Impact of MOLP on IEC6 viability at (<b>A</b>) 12 h, (<b>B</b>) one day, and (<b>C</b>) two days. Results are shown as mean ± SEM (n = 3), with statistical significance denoted by * <span class="html-italic">p</span> &lt; 0.05 and *** <span class="html-italic">p</span> &lt; 0.001 compared to the Control group.</p>
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<p>The impact of MOLP on the migration of IEC6 cells (<b>A</b>) was analysed statistically as presented (<b>B</b>). The results are shown as mean ± SEM (n = 3), with * <span class="html-italic">p</span> &lt; 0.05 indicating significant differences between LPS and the Control, and # <span class="html-italic">p</span> &lt; 0.05 indicating significance between the highest concentration of MOLP (MOLP-H) and LPS.</p>
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<p>MOLP promotes apoptosis in LPS-stimulated IEC6 cells. The effect of MOLP on apoptosis induction in IEC6 cells following LPS stimulation was evaluated through flow cytometry (<b>A</b>) and statistically analysed (<b>B</b>). Cells were classified as viable apoptotic (Annexin: V<sup>+</sup>/PI<sup>−</sup>), non-viable apoptotic (Annexin: V<sup>+</sup>/PI<sup>+</sup>), and necrotic (Annexin V<sup>−</sup>/PI<sup>+</sup>). The results are displayed as mean ± SEM (n = 3). Significant differences are denoted as ** <span class="html-italic">p</span> &lt; 0.01 and *** <span class="html-italic">p</span> &lt; 0.001 between LPS and the Control; # <span class="html-italic">p</span> &lt; 0.05 and ### <span class="html-italic">p</span> &lt; 0.001 indicate significant differences between various MOLP concentrations (MOLP-L, MOLP-M, MOLP-H) and LPS.</p>
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<p>Impact of MOLP on mRNA expression levels of pro-inflammatory cytokines in LPS-activated IEC6 cells. The influence of MOLP on the mRNA expression of pro-inflammatory cytokines in IEC6 cells stimulated with LPS was examined. The cytokines analysed were (<b>A</b>) <span class="html-italic">TNF-α</span>, (<b>B</b>) <span class="html-italic">IL-1β</span>, (<b>C</b>) <span class="html-italic">IL-6,</span> and (<b>D</b>) <span class="html-italic">IL-10</span>. The data are presented as mean ± SEM (n = 3). Statistical significance is denoted as * <span class="html-italic">p</span> &lt; 0.05 and *** <span class="html-italic">p</span> &lt; 0.001 for comparisons between LPS and Control, and # <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 for comparisons between MOLP-L, -M, -H, and LPS.</p>
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<p>Impact of MOLP on inflammatory signalling pathways in IEC6 Cells. The influence of MOLP on inflammatory signalling pathways in IEC-6 cells was investigated. Key signalling proteins were evaluated utilising (<b>A</b>) Western blot analysis, with the relative protein levels quantified for (<b>B</b>) TLR4, (<b>C</b>) MyD88, NF-κB, (<b>D</b>) p65/p-P65, and (<b>E</b>) IκBα/p-IκBα; see Supplementary Files. The results are presented as mean ± SEM (n = 3). Statistical significance is denoted as *** <span class="html-italic">p</span> &lt; 0.001 for comparisons between LPS and Control, and # <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 for comparisons among MOLP-L, -M, and -H against LPS.</p>
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<p>Effect of MOLP on the immunolocalisation and relative fluorescence intensity of TJ proteins in LPS-stimulated IEC6 cells. Panels (<b>A</b>,<b>B</b>) show the immunolocalisation of ZO-1 and occludin, respectively, in LPS-stimulated IEC-6 cells. Panels (<b>C</b>,<b>D</b>) present the quantitative results derived from (<b>A</b>,<b>B</b>). The images were captured at 100× magnification, with a scale bar representing 50 μm. Results are shown as mean ± SEM (n = 3), with *** <span class="html-italic">p</span> &lt; 0.001 indicating significance between LPS and Control, and ## <span class="html-italic">p</span> &lt; 0.01 between MOLP-M, MOLP-H, and LPS.</p>
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43 pages, 762 KiB  
Review
Comprehensive Analysis of Bioactive Compounds, Functional Properties, and Applications of Broccoli By-Products
by Iris Gudiño, Rocío Casquete, Alberto Martín, Yuanfeng Wu and María José Benito
Foods 2024, 13(23), 3918; https://doi.org/10.3390/foods13233918 - 4 Dec 2024
Abstract
Broccoli by-products, traditionally considered inedible, possess a comprehensive nutritional and functional profile. These by-products are abundant in glucosinolates, particularly glucoraphanin, and sulforaphane, an isothiocyanate renowned for its potent antioxidant and anticarcinogenic properties. Broccoli leaves are a significant source of phenolic compounds, including kaempferol [...] Read more.
Broccoli by-products, traditionally considered inedible, possess a comprehensive nutritional and functional profile. These by-products are abundant in glucosinolates, particularly glucoraphanin, and sulforaphane, an isothiocyanate renowned for its potent antioxidant and anticarcinogenic properties. Broccoli leaves are a significant source of phenolic compounds, including kaempferol and quercetin, as well as pigments, vitamins, and essential minerals. Additionally, they contain proteins, essential amino acids, lipids, and carbohydrates, with the leaves exhibiting the highest protein content among the by-products. Processing techniques such as ultrasound-assisted extraction and freeze-drying are crucial for maximizing the concentration and efficacy of these bioactive compounds. Advanced analytical methods, such as high-performance liquid chromatography–mass spectrometry (HPLC-MS), have enabled precise characterization of these bioactives. Broccoli by-products have diverse applications in the food industry, enhancing the nutritional quality of food products and serving as natural substitutes for synthetic additives. Their antioxidant, antimicrobial, and anti-inflammatory properties not only contribute to health promotion but also support sustainability by reducing agricultural waste and promoting a circular economy, thereby underscoring the value of these often underutilized components. Full article
(This article belongs to the Section Nutraceuticals, Functional Foods, and Novel Foods)
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<p>Visual overview of future perspectives on use of broccoli and broccoli by-product extracts.</p>
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15 pages, 1819 KiB  
Article
Efficacy and Safety of Anthocyanin-Rich Extract in Patients with Ulcerative Colitis: A Randomized Controlled Trial
by Luc Biedermann, Michael Doulberis, Philipp Schreiner, Ole Haagen Nielsen, Frans Olivier The, Stephan Brand, Sabine Burk, Petr Hruz, Pascal Juillerat, Claudia Krieger-Grübel, Kristin Leu, Gabriel E. Leventhal, Benjamin Misselwitz, Sylvie Scharl, Alain Schoepfer, Frank Seibold, Hans Herfarth and Gerhard Rogler
Nutrients 2024, 16(23), 4197; https://doi.org/10.3390/nu16234197 - 4 Dec 2024
Abstract
Background: Bilberries are effective in inducing clinical, endoscopic, and biochemical improvement in ulcerative colitis (UC) patients. The aim of this study was to investigate the efficacy of anthocyanin-rich extract (ACRE), the bioactive ingredient of bilberries, in a controlled clinical trial in moderate-to-severe UC. [...] Read more.
Background: Bilberries are effective in inducing clinical, endoscopic, and biochemical improvement in ulcerative colitis (UC) patients. The aim of this study was to investigate the efficacy of anthocyanin-rich extract (ACRE), the bioactive ingredient of bilberries, in a controlled clinical trial in moderate-to-severe UC. Methods: A multi-center, randomized, placebo-controlled, double-blind study with a parallel group was conducted. Initially, the study was planned for 100 patients; nevertheless, it prematurely ended due to COVID-19. Patients had moderate-to-severe active UC at screening (a Mayo score of 6–12, an endoscopic sub-score ≥ 2) and were randomized at baseline. The primary endpoint was a clinical response (week 8, a total Mayo score reduction ≥ 3 points). Fecal calprotectin (FC) and a centrally read endoscopic response were among the secondary endpoints. Results: Out of 48 patients (6 Swiss centers), 34 were randomized. Eighteen ACRE and eight placebo patients could be analyzed (per protocol set). Half (9/18) of ACRE patients and 3/8 of placebo patients responded clinically (p = 0.278). An improvement in the Mayo score was observed in the ACRE arm (77.8% vs. 62.5% placebo). FC dropped from 1049 ± 1139 to 557 ± 756 μg/g for ACRE but not for the placebo group (947 ± 1039 to 1040 ± 1179; p = 0.035). Serious adverse events were rare. Conclusions: ACRE treatment did not yield significant superiority to the placebo. Furthermore, the placebo response was unusually high. Moreover, there was a significant calprotectin decrease at the end of treatment, indicative of ACRE efficacy in UC. Full article
(This article belongs to the Special Issue Anthocyanins and Human Health—2nd Edition)
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<p>CONSORT flow diagram with study design and participants progression. It details the number of patients screened, randomized, and allocated to treatment groups and those included in the final analysis.</p>
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<p>Illustration of the mean reduction in the partial Mayo score from baseline to week 8 for participants treated with ACRE (anthocyanin-rich extract) and placebo. Error bars represent the 90% confidence intervals for the mean reduction. Although the results indicate a trend toward amelioration in the ACRE group, the differences remain statistically non-significant.</p>
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<p>Illustration of fecal calprotectin levels (μg/g) across the observation period in patients treated with ACRE (anthocyanin-rich extract) and placebo. Measurements were taken at screening, baseline, week 4, and week 8. A statistically significant reduction in calprotectin levels was observed in the ACRE group compared to the placebo (<span class="html-italic">p</span> = 0.035), suggesting potential anti-inflammatory effects of ACRE.</p>
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