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16 pages, 2122 KiB  
Article
Assessing a “Least-Concern” Red List Tree Species from Madagascar Used in Traditional Medicine: Morella spathulata (Myricaceae) Phyto-Compounds and Anti-Inflammatory Properties
by Annachiara Fioccardi, Dario Donno, Zoarilala Rinah Razafindrakoto, Nantenaina Tombozara, Sylvia Henintsoa, Elyna Mahitasoa, Valeria Torti, Marcellin Solofoniaina, Lorenzo Rosso, Giovanni Gamba, Charles Andrianjara, David Ramanitrahasimbola and Gabriele Loris Beccaro
Plants 2024, 13(20), 2899; https://doi.org/10.3390/plants13202899 (registering DOI) - 17 Oct 2024
Abstract
Morella spathulata (Myricaceae family) is a common plant from Madagascar and is present on the IUCN Red List of threatened species classified at the ’least concern’ level, used by the local population to treat numerous illnesses and pain. Despite its frequent use, comprehensive [...] Read more.
Morella spathulata (Myricaceae family) is a common plant from Madagascar and is present on the IUCN Red List of threatened species classified at the ’least concern’ level, used by the local population to treat numerous illnesses and pain. Despite its frequent use, comprehensive phytochemical and pharmacological research on the species is limited. This study evaluated the antioxidant, analgesic, and anti-inflammatory properties, as well as the toxicity of methanol extracts from the leaves (MS_L) and bark (MS_B) of M. spathulata. The research involved the analysis of nutritional traits such as sugars, organic acids, vitamin C, polyphenolic content (TPC) and the main phytochemicals by HPLC analysis. Antioxidant capacity was assessed through DPPH and FRAP assays. Analgesic and anti-inflammatory activities were evaluated using acetic acid-induced writhing and carrageenan-induced paw oedema tests in mice. The results showed a high content of phenolic and bioactive components in the leaf and bark extracts, associated with antioxidant, analgesic and anti-inflammatory properties. The interaction of key compounds such as ferulic acid and ellagic acid with proteins involved in pH regulation and immune modulation provides clues to the mechanisms underlying the therapeutic effects. However, conservation efforts are crucial due to habitat loss and illegal logging, and further studies are needed to fully explore the plant’s therapeutic potential. Full article
(This article belongs to the Special Issue Phytochemistry and Pharmacological Properties of Medicinal Plants)
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<p>Percentage contribution of phenolic compounds and vitamins in the analyzed samples. MS_L: <span class="html-italic">M. spathulata</span> leaf extract; MS_B: <span class="html-italic">M. spathulata</span> bark extract. Mean values are shown (N = 3).</p>
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21 pages, 868 KiB  
Review
Citrus Seed Waste and Circular Bioeconomy: Insights on Nutritional Profile, Health Benefits, and Application as Food Ingredient
by S. Seyyedi-Mansour, M. Carpena, P. Donn, P. Barciela, A. Perez-Vazquez, J. Echave, A. G. Pereira and M. A. Prieto
Appl. Sci. 2024, 14(20), 9463; https://doi.org/10.3390/app14209463 (registering DOI) - 16 Oct 2024
Abstract
Citrus fruits are widely grown, processed, and distributed in more than 140 countries, with annual global production exceeding 124.3 million metric tons. This substantial consumption generates significant organic waste, accounting for approximately 50–60% of the total fruit mass, primarily in the form of [...] Read more.
Citrus fruits are widely grown, processed, and distributed in more than 140 countries, with annual global production exceeding 124.3 million metric tons. This substantial consumption generates significant organic waste, accounting for approximately 50–60% of the total fruit mass, primarily in the form of peel, pulp, and seeds. Often discarded or reused as animal feed, these wastes contribute to significant environmental pollution and economic losses. Therefore, the valorization of these by-products represents an important opportunity to mitigate these challenges and improve the sustainability of the Citrus-related industry. This review highlights Citrus seed waste concerning its invaluable bioactive compounds, including fatty acids, phenolic compounds, limonoids, dietary fibers, vitamins, and carotenoids. Chemical compositions of Citrus seed biowaste differ depending on a variety of factors, such as Citrus variety, fruit maturity, environmental conditions, waste storage conditions, and extraction methods. The extraction and purification of phytochemicals from Citrus seed biowaste are one of the major procedures for valorizing waste. The two types of effective extraction methods are traditional (conventional extraction) and innovative (green extraction). Furthermore, Citrus seeds have been demonstrated to exhibit several biological activities and health-promoting properties including antioxidative, anti-inflammatory, and anti-cancer activities. Therefore, these wastes are safe and beneficial compounds used in the production of functional foods, nutraceuticals, pharmaceuticals, and cosmetics. A conclusion can be reached by emphasizing the abundance of bioactive compounds in Citrus seed wastes, which makes them an excellent opportunity for increased environmental and economic utilization. Full article
(This article belongs to the Special Issue Novel Food Technologies and Applications)
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<p>Examples of <span class="html-italic">Citrus</span> seeds waste applications in food and non-food industry. Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p>
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32 pages, 5551 KiB  
Review
Unveiling the Interplay—Vitamin D and ACE-2 Molecular Interactions in Mitigating Complications and Deaths from SARS-CoV-2
by Sunil J. Wimalawansa
Biology 2024, 13(10), 831; https://doi.org/10.3390/biology13100831 - 16 Oct 2024
Abstract
The interaction of the SARS-CoV-2 spike protein with membrane-bound angiotensin-converting enzyme-2 (ACE-2) receptors in epithelial cells facilitates viral entry into human cells. Despite this, ACE-2 exerts significant protective effects against coronaviruses by neutralizing viruses in circulation and mitigating inflammation. While SARS-CoV-2 reduces ACE-2 [...] Read more.
The interaction of the SARS-CoV-2 spike protein with membrane-bound angiotensin-converting enzyme-2 (ACE-2) receptors in epithelial cells facilitates viral entry into human cells. Despite this, ACE-2 exerts significant protective effects against coronaviruses by neutralizing viruses in circulation and mitigating inflammation. While SARS-CoV-2 reduces ACE-2 expression, vitamin D increases it, counteracting the virus’s harmful effects. Vitamin D’s beneficial actions are mediated through complex molecular mechanisms involving innate and adaptive immune systems. Meanwhile, vitamin D status [25(OH)D concentration] is inversely correlated with severity, complications, and mortality rates from COVID-19. This study explores mechanisms through which vitamin D inhibits SARS-CoV-2 replication, including the suppression of transcription enzymes, reduced inflammation and oxidative stress, and increased expression of neutralizing antibodies and antimicrobial peptides. Both hypovitaminosis D and SARS-CoV-2 elevate renin levels, the rate-limiting step in the renin-angiotensin-aldosterone system (RAS); it increases ACE-1 but reduces ACE-2 expression. This imbalance leads to elevated levels of the pro-inflammatory, pro-coagulatory, and vasoconstricting peptide angiotensin-II (Ang-II), leading to widespread inflammation. It also causes increased membrane permeability, allowing fluid and viruses to infiltrate soft tissues, lungs, and the vascular system. In contrast, sufficient vitamin D levels suppress renin expression, reducing RAS activity, lowering ACE-1, and increasing ACE-2 levels. ACE-2 cleaves Ang-II to generate Ang(1–7), a vasodilatory, anti-inflammatory, and anti-thrombotic peptide that mitigates oxidative stress and counteracts the harmful effects of SARS-CoV-2. Excess ACE-2 molecules spill into the bloodstream as soluble receptors, neutralizing and facilitating the destruction of the virus. These combined mechanisms reduce viral replication, load, and spread. Hence, vitamin D facilitates rapid recovery and minimizes transmission to others. Overall, vitamin D enhances the immune response and counteracts the pathological effects of SARS-CoV-2. Additionally, data suggests that widely used anti-hypertensive agents—angiotensin receptor blockers and ACE inhibitors—may lessen the adverse impacts of SARS-CoV-2, although they are less potent than vitamin D. Full article
(This article belongs to the Special Issue SARS-CoV-2 and Immunology)
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Graphical abstract

Graphical abstract
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<p>Infections and immune-related broader functions of vitamin D (calcitriol, 1,25(OH)<sub>2</sub>D). The figure illustrates muti-system-wide functions of vitamin D related through the modulation of innate and adaptive immune systems, resulting in lowering complications from infections and chronic disease burdens [⇧ = increased; ⇩ = reduced; RAS: renin-angiotensin-system; CVS: cardiovascular system] (after Wimalawansa, Nutrients, 2022) [<a href="#B51-biology-13-00831" class="html-bibr">51</a>].</p>
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<p>Pathological and physiological responses of the renin-angiotensin system. Peach and green boxes illustrate the renin-angiotensin system’s regulatory and counter-regulatory physiologic pathways. When excess angiotensin-II (Ang-II) is synthesized, as in the case of hypovitaminosis D and SARS-CoV-2 infection, this leads to the over-activation of the AT1 receptors (AT1-R) with pathological manifestations, as indicated in the peach colored boxes [⇧ = increased; ⇩ = reduced; ARDS = acute respiratory distress syndrome; RAS, renin-angiotensin system; ACE, angiotensin-converting enzyme; ACE-2, angiotensin-converting enzyme 2; Ang 1–7, angiotensin 1–7; Ang-I, angiotensin-I; Ang-II, angiotensin-II; AT1R, type 1 angiotensin-II receptor; MasR, MAS proto-oncogene receptor. PHT, pulmonary hypertension].</p>
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<p>This diagram outlines the status of the renin-angiotensin axis (RAS) axis: (<b>A</b>) physiological status, (<b>B</b>) pathological/activated status in the presence of vitamin D deficiency, and (<b>C</b>) following SARS-CoV-2 infection. RAS axis homeostasis is disrupted by hypovitaminosis D. SARS-CoV-2 or other coronal viral infections markedly activate the RAS, leading to pathologically elevated levels of angiotensin -II and the suppression of ACE-2. This hyperactivation of the RAS leads to increased complications and mortality (⇧ = increased; ⇩ = reduced; ACE: angiotensin-converting enzyme; ARB: angiotensin receptor blockers; AT1R: type 1 angiotensin-II receptor; ARDS: acute respiratory distress syndrome).</p>
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<p>Vit D strengthens innate and adaptive immune systems. This summary outlines the correlation between vitamin D, angiotensin-converting enzyme-2 (ACE-2), angiotensin-converting enzyme inhibitors (ACEi), and angiotensin II receptor blockers (ARBs) concerning severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and their impact on COVID-19 morbidity and mortality ([↑ = increased; ↓ = reduced; RAS: renin-angiotensin-system; CVS: cardiovascular system; ACE: angiotensin-converting enzyme; ARB: angiotensin receptor blockers; AT1R: type 1 angiotensin-II receptor; ARDS: acute respiratory distress syndrome; HTN: hypertension).</p>
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14 pages, 775 KiB  
Article
Nutritional Status, Diet, and Intestinal Permeability of Mexican Children with Autism Spectrum Disorders
by Karina Alejandra Pedroza-García, Miriam Aracely Anaya-Loyola, Dolores Ronquillo, María del Carmen Caamaño, David Masuoka, Jorge Palacios-Delgado and Jorge L. Rosado
Gastroenterol. Insights 2024, 15(4), 912-925; https://doi.org/10.3390/gastroent15040064 (registering DOI) - 16 Oct 2024
Abstract
Introduction: Autism spectrum disorder (ASD) comprises a group of developmental disorders characterized by deficits in social interaction and behavioral patterns. Children with ASD may face nutritional challenges, primarily due to their restrictive behaviors and frequent gastrointestinal issues. Objective: The objective of the present [...] Read more.
Introduction: Autism spectrum disorder (ASD) comprises a group of developmental disorders characterized by deficits in social interaction and behavioral patterns. Children with ASD may face nutritional challenges, primarily due to their restrictive behaviors and frequent gastrointestinal issues. Objective: The objective of the present study was to assess nutritional status, dietary habits, and intestinal permeability in a sample of individuals with ASD. Methods: A cross-sectional study was conducted with 24 children and adolescents (both sexes), aged 4 to 18 years, living in two cities of Mexico (Aguascalientes and Querétaro). Weight and height were measured, and body mass index for age was calculated and compared using WHO Z-scores. Diet was assessed through three 24 h dietary recalls and a food frequency questionnaire. Intestinal permeability was evaluated using a lactulose/mannitol test by HPLC. Results: A high prevalence of malnutrition was observed; 12.5% of the participants were underweight, and 45.8% were overweight or obese. Children had a low intake of fiber, vitamin E, folate, potassium, zinc, and phosphorus and a high intake of sodium. On average, the intestinal permeability ratio was 0.09 ± 0.05, with 54.2% of the children exhibiting high intestinal permeability. Conclusions: It is advisable to develop food counseling strategies for children with ASD to prevent micronutrient deficiencies, promote healthy weight, and improve gastrointestinal integrity. Full article
(This article belongs to the Section Gastrointestinal Disease)
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<p>Evaluation of body mass index-for-age (BMI/A) indicator in children and adolescents with ASD (Z-scores interpretation). (<b>A</b>) BMI/A in 4-to-8-year-old children (n = 9); (<b>B</b>) BMI/A in 9-to-13-year-old children (n = 9); (<b>C</b>) BMI/A in 14-to-18-year-old children (n = 6).</p>
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<p>Comparison of energy and macronutrient intake stratified by age group in children and adolescents with ASD. (<b>A</b>) Comparison of total energy intake (TEI) by age group. (<b>B</b>) Comparison of carbohydrate intake by age groups. (<b>C</b>) Comparison of protein intake by age groups. (<b>D</b>) Comparison of lipid intake by age groups. Data are presented as mean and SEM. Statistical test used: ANOVA, significance at <span class="html-italic">p</span> &lt; 0.05. ns: not significant.</p>
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15 pages, 275 KiB  
Article
A Qualitative Study of Rural Plant-Based Eaters’ Knowledge and Practices for Nutritional Adequacy
by Michelle Leonetti, Jane Kolodinsky, Amy Trubek and Emily H. Belarmino
Nutrients 2024, 16(20), 3504; https://doi.org/10.3390/nu16203504 - 16 Oct 2024
Abstract
(1) Background: Healthful plant-based diets, especially those rich in minimally processed plant-based foods such as fruits, vegetables, and whole grains, have been associated with a lower risk of diet-related chronic disease. However, individuals who limit or avoid animal products may be at risk [...] Read more.
(1) Background: Healthful plant-based diets, especially those rich in minimally processed plant-based foods such as fruits, vegetables, and whole grains, have been associated with a lower risk of diet-related chronic disease. However, individuals who limit or avoid animal products may be at risk of nutrient deficiencies, especially related to Vitamin B12, Vitamin D, omega-3 fatty acids, calcium, iron, iodine, zinc, and protein. Such deficiencies can result in both short- and long-term health challenges. We used qualitative methods to explore plant-based eaters’ knowledge and awareness of these eight nutrients of concern in diets that limit or exclude animal-source foods. (2) Methods: We conducted interviews with 28 rural flexitarian, pescatarian, vegan, or vegetarian adults in Vermont, USA. (3) Results: The participants positively viewed the healthfulness of plant-based diets, but many recognized limitations to accessing Vitamin B12, Vitamin D, and omega-3 fatty acids. They shared the strategies used to meet their needs including eating a varied diet, seeking out specific foods, and taking dietary supplements. Analyses identified gaps in the participants’ knowledge related to nutrient bioavailability, food sources of specific nutrients, and the importance of zinc and iodine. Vegans—the highest-risk group—generally presented as the most knowledgeable. The participants noted a lack of local plant-based nutrition expertise. (4) Conclusions: Addressing the identified knowledge gaps and challenges to dietary adequacy, especially among those who limit, but do not fully omit, animal-source foods, may support plant-based nutrition. Full article
(This article belongs to the Section Nutrition and Public Health)
42 pages, 2171 KiB  
Review
Vitamin C in the Management of Thyroid Cancer: A Highway to New Treatment?
by Francesca Gorini and Alessandro Tonacci
Antioxidants 2024, 13(10), 1242; https://doi.org/10.3390/antiox13101242 (registering DOI) - 15 Oct 2024
Viewed by 335
Abstract
Thyroid cancer (TC) is the most common endocrine malignancy, with an increased global incidence in recent decades, despite a substantially unchanged survival. While TC has an excellent overall prognosis, some types of TC are associated with worse patient outcomes, depending on the genetic [...] Read more.
Thyroid cancer (TC) is the most common endocrine malignancy, with an increased global incidence in recent decades, despite a substantially unchanged survival. While TC has an excellent overall prognosis, some types of TC are associated with worse patient outcomes, depending on the genetic setting. Furthermore, oxidative stress is related to more aggressive features of TC. Vitamin C, an essential nutrient provided with food or as a dietary supplement, is a well-known antioxidant and a scavenger of reactive oxygen species; however, at high doses, it can induce pro-oxidant effects, acting through multiple biological mechanisms that play a crucial role in killing cancer cells. Although experimental data and, less consistently, clinical studies, suggest the possibility of antineoplastic effects of vitamin C at pharmacological doses, the antitumor efficacy of this nutrient in TC remains at least partly unexplored. Therefore, this review discusses the current state of knowledge on the role of vitamin C, alone or in combination with other conventional therapies, in the management of TC, the mechanisms underlying this association, and the perspectives that may emerge in TC treatment strategies, and, also, in light of the development of novel functional foods useful to this extent, by implementing novel sensory analysis strategies. Full article
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<p>Schematic representation of the mutual relationships and risk factors of the components involved in the generation of oxidative stress and those belonging to the antioxidant defense systems and overall related to the development of thyroid cancer (see text for details). The direction of arrows indicates the increase or decrease in the depicted markers. Abbreviations: AMPK: AMP activated protein kinase; CAT: catalase; DUOX1: isoform belonging to NOX family; GPX: glutathione peroxidase; HIF-1α: hypoxia-inducible transcription factor 1 alpha; MDA: malondialdehyde; NIS: sodium/iodide symporter; NOX: nicotinamide adenine dinucleotide phosphate oxidase; OGG1: 8-oxoguanine DNA glycosylase; oxoG: 8-oxoguanine; PRDX1: peroxiredoxins 1; ROS: reactive oxygen species; Se: selenium; SOD: superoxide dismutase; TGF-β: transforming growth factor-beta.</p>
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<p>Recommended treatment for differentiated thyroid cancer following thyroidectomy. Risk stratification groups predictive for disease recurrence are based on 2015 American Thyroid Association recommendations [<a href="#B30-antioxidants-13-01242" class="html-bibr">30</a>]. The estimated risk of recurrence has been classified as high (&gt;20%), intermediate (6–20%), and low (≤5%). For the high- and intermediate-risk categories, at least one of the listed characteristics must be present. For the low-risk category, all the listed characteristics must be present. Modified from Filetti et al. [<a href="#B140-antioxidants-13-01242" class="html-bibr">140</a>]. Abbreviations: FTC: follicular thyroid cancer; mCi: millicurie; MEK: mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitors; N0: no evidence of locoregional lymph node metastasis according to the 8th edition of tumor-node-metastasis classification elaborated by the American Joint Committee on Cancer [<a href="#B146-antioxidants-13-01242" class="html-bibr">146</a>]; N1: regional lymph node metastasis according to the 8th edition of tumor-node-metastasis classification elaborated by the American Joint Committee on Cancer [<a href="#B146-antioxidants-13-01242" class="html-bibr">146</a>]; PTC: papillary thyroid cancer; RAI: radioactive iodine; Tg: thyroglobulin.</p>
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<p>Relationships between dietary intake and supplementation, plasma concentration, and effects of ascorbate in humans.</p>
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<p>The proposed mechanisms for anticancer effects of vitamin C (see text for more details). Abbreviations: GADPH: glyceraldehyde 3-phosphate dehydrogenase; GPX4: glutathione peroxidase 4; HIF-1α: hypoxia-inducible transcription factor 1 alpha; the MAPK/ERK: mitogen-activated protein kinase/extracellular signal-regulated kinase; NAD<sup>+</sup>: oxidized nicotinamide adenine dinucleotide; TCA: tricarboxylic acid; PI3K/AKT: phosphatidylinositol-3 kinase/protein kinase B.</p>
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<p>Risks related to food production in the age of circular economy.</p>
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21 pages, 3449 KiB  
Article
Effects of Different Additives on the Chemical Composition, Fermentation Quality, Bacterial Community and Gene Function Prediction of Caragana korshinskii Kom. Silage
by Yuxiang Wang, Manlin Wei, Fuyu Yang, Haiying Zheng, Junjie Gao, Wen Peng, Ming Xiao, Runze Zhang and Yongjie Zheng
Agronomy 2024, 14(10), 2386; https://doi.org/10.3390/agronomy14102386 - 15 Oct 2024
Viewed by 234
Abstract
The aim of this study was to investigate the effects of Lentilactobacillus plantarum (LP), cellulase (CE), and xylanase (XE) supplementation on the fermentation quality, chemical composition, and bacterial community of Caragana korshinskii Kom. silage. Four groups were designed for the study. No additives [...] Read more.
The aim of this study was to investigate the effects of Lentilactobacillus plantarum (LP), cellulase (CE), and xylanase (XE) supplementation on the fermentation quality, chemical composition, and bacterial community of Caragana korshinskii Kom. silage. Four groups were designed for the study. No additives were used in the control group (CK), and LP (1 × 106 cfu/g), CE (1 × 104 IU/g) and XE (2 × 105 IU/g) were added to the experimental groups on a fresh matter basis, with three replicates per group. To promote fermentation, 5% molasses was added to all of the groups. On days 15 and 60, fermentation quality, chemical composition and the bacterial community were analysed. The pH of groups CE and XE was lower than that of the CK group at 60 days. During ensiling, the lactic acid (LA) content in the experimental groups and the acetic acid (AA) content in the CK and LP groups increased. At 60 days, the dominant genera in the CK and LP groups was Weissella and the dominant genera in the CE and XE groups was Lentilactobacillus. At different times during silage, nucleotide metabolism was enhanced, whereas the metabolism of carbohydrate, amino acids, energy, cofactors and vitamins was inhibited in the LP group. However, the metabolism of amino acids, energy, cofactors and vitamins in the CE and XE groups was increased, whereas the metabolism of nucleotides was inhibited. In conclusion, LP, CE and XE could exert a positive effect on the fermentation quality of C. korshinskii Kom. silage by shifting the bacterial community composition. Full article
(This article belongs to the Section Agricultural Biosystem and Biological Engineering)
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<p>Venn diagram of the bacterial species. CK, control; LP, <span class="html-italic">Lentilactobacillus plantarum</span>; CE, cellulase; XE, xylanase. The numbers behind CK, LP, CE, and XE represent the days of ensiling.</p>
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<p>PCoA of the bacterial species diversity in <span class="html-italic">C. korshinskii</span> Kom. silage at 15 days (<b>A</b>) and 60 days (<b>B</b>). CK, control; LP, <span class="html-italic">Lentilactobacillus plantarum</span>; CE, cellulase; XE, xylanase. The numbers behind CK, LP, CE, and XE represent the days of ensiling.</p>
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<p>Distribution of bacterial communities at the phylum (<b>A</b>) and genus (<b>B</b>) levels at days 15 and 60 in <span class="html-italic">C. korshinskii</span> Kom. silage. Small populations with abundances less than 0.01 were combined as others. CK, control; LP, <span class="html-italic">Lentilactobacillus plantarum</span>; CE, cellulase; XE, xylanase. The numbers behind CK, LP, CE, and XE represent the days of ensiling.</p>
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<p>Species differences in bacterial genera (LDA = 3) between 15 days (<b>A</b>) and 60 days (<b>B</b>) of ensiling. CK, control; LP, <span class="html-italic">Lentilactobacillus plantarum</span>; CE, cellulase; XE, xylanase. The numbers behind CK, LP, CE, and XE represent the days of ensiling.</p>
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<p>Species differences in bacterial genera (LDA = 3) between 15 days (<b>A</b>) and 60 days (<b>B</b>) of ensiling. CK, control; LP, <span class="html-italic">Lentilactobacillus plantarum</span>; CE, cellulase; XE, xylanase. The numbers behind CK, LP, CE, and XE represent the days of ensiling.</p>
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<p>Heatmap of the Spearman correlation coefficients of chemical composition, fermentation quality and bacterial genera of <span class="html-italic">C. korshinskii</span> Kom. silage at 15 (<b>A</b>) and 60 (<b>B</b>) days. The colour of the heatmap indicates the Spearman correlation coefficient “R” (−1 to 1). R &gt; 0 indicates a positive correlation, and R &lt; 0 indicates a negative correlation. *, 0.01 &lt; <span class="html-italic">p</span> &lt; 0.05; **, 0.001 &lt; <span class="html-italic">p</span> &lt; 0.01; ***, <span class="html-italic">p</span> &lt; 0.001. CK, control; LP, <span class="html-italic">Lentilactobacillus plantarum</span>; CE, cellulase; XE, xylanase. The numbers behind CK, LP, CE, and XE represent the days of ensiling.</p>
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<p>Predicted pathways of the bacterial community in <span class="html-italic">C. korshinskii</span> Kom. at 15 days and 60 days of ensiling. (<b>A</b>) the first metabolic pathway at 15 days of <span class="html-italic">C. korshinskii</span> Kom. Silage. (<b>B</b>) the first metabolic pathway at 60 days of <span class="html-italic">C. korshinskii</span> Kom. Silage. (<b>C</b>) the second metabolic pathway at 15 days of <span class="html-italic">C. korshinskii</span> Kom. Silage. (<b>D</b>) the second metabolic pathway at 60 days of <span class="html-italic">C. korshinskii</span> Kom. Silage. (<b>E</b>) carbohydrate metabolism of the third pathway level at 15 days of <span class="html-italic">C. korshinskii</span> Kom. Silage. (<b>F</b>) carbohydrate metabolism of the third pathway level at 60 days of <span class="html-italic">C. korshinskii</span> Kom. Silage. CK, control; LP, <span class="html-italic">Lentilactobacillus plantarum</span>; CE, cellulase; XE, xylanase. The numbers behind CK, LP, CE, and XE represent the days of ensiling.</p>
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15 pages, 2531 KiB  
Article
In Vitro Functional Properties of Rosehips from ‘Aurora’ Edible Garden Rose’s Collection
by Nemanja Živanović, Biljana Božanić Tanjga, Nataša Simin, Marija Lesjak, Bojana Blagojević, Magdalena Pušić Devai, Mirjana Ljubojević and Tijana Narandžić
Foods 2024, 13(20), 3272; https://doi.org/10.3390/foods13203272 - 15 Oct 2024
Viewed by 292
Abstract
Although they have been extensively studied in many species of the genus Rosa L., garden roses’ hips have largely been overlooked. To investigate their potential use in the food industry, this study evaluated five cultivars from ‘Aurora’ collection: ‘Purple Aurora’, ‘Berry Bush Aurora’, [...] Read more.
Although they have been extensively studied in many species of the genus Rosa L., garden roses’ hips have largely been overlooked. To investigate their potential use in the food industry, this study evaluated five cultivars from ‘Aurora’ collection: ‘Purple Aurora’, ‘Berry Bush Aurora’, ‘Aromatic Aurora’, ‘Butterfly Aurora’, and ‘Rugose White Aurora’. Morphological characterization, along with the assessment of the phenolic profile, vitamin C levels, and biological activities—including antioxidant and neuroprotective effects—was conducted. The fruit mass reached 5.15 g, while the mesocarp mass ranged from 3 to 4 g, resulting in a mesocarp-to-fruit ratio of over 75%. The total phenolic content ranged from 37.1 to 63.9 mg GAE/g de, while total flavonoids were present in amounts from 0.85 to 2.14 mg QE/g de. Rosehip extracts from four out of five cultivars exhibited a very high vitamin C content, reaching 2384 µg/g fw. Quinic acid and 31 phenolic compounds were found in the rosehip extract of at least one cultivar. Results indicated ‘Aurora’ rosehips have potent antioxidant properties and a moderate inhibitory effect on acetylcholinesterase, highlighting their potential as a source of functional food. Additional research is needed to fully leverage these benefits and establish garden rosehips as a viable alternative to synthetic antioxidants. Full article
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Figure 1
<p>Fruits of the cultivar ‘Berry Bush Aurora’ (BBA) were evaluated for quantitative and qualitative features: (<b>a</b>) rosehips in the field; (<b>b</b>) the assessment of fruit, mesocarp, and seed traits in the laboratory.</p>
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<p>Two cultivars with contrasting fruit mass, dimensions, and flatness level: (<b>a</b>,<b>b</b>) ‘Purple Aurora’ (PAU) plant in the field and harvested rosehips; (<b>c</b>,<b>d</b>) ‘Butterfly Aurora’ (BA) plant in the field and harvested rosehips.</p>
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18 pages, 914 KiB  
Review
Exploring the Therapeutic Potential of Jujube (Ziziphus jujuba Mill.) Extracts in Cosmetics: A Review of Bioactive Properties for Skin and Hair Wellness
by Daniela Batovska, Anelia Gerasimova and Krastena Nikolova
Cosmetics 2024, 11(5), 181; https://doi.org/10.3390/cosmetics11050181 (registering DOI) - 15 Oct 2024
Viewed by 411
Abstract
Jujube (Ziziphus jujuba Mill.), native to Southern Asia, stands out for its significant nutritional and therapeutic properties. Its adaptability and resilience have enabled its global cultivation, highlighting the necessity for comprehensive scientific research to fully harness its potential. Rich in bioactive compounds [...] Read more.
Jujube (Ziziphus jujuba Mill.), native to Southern Asia, stands out for its significant nutritional and therapeutic properties. Its adaptability and resilience have enabled its global cultivation, highlighting the necessity for comprehensive scientific research to fully harness its potential. Rich in bioactive compounds like flavonoids, polyphenols, vitamin C, polysaccharides, tannins, and saponins, jujube extracts exhibit notable antioxidant, anti-inflammatory, antimicrobial, and wound healing properties. These qualities have made jujube a popular ingredient in various skin and hair care formulations. The versatility of jujube extracts, along with their synergy with other herbal active ingredients, enables the development of targeted personal care solutions. These solutions address a range of concerns, including anti-aging, UV protection, brightening, moisturizing, and calming effects, as well as promoting hair health. Despite its potential, research on the cosmetic applications of Z. jujuba is still in its early stages, with only one clinical trial to date focusing on its skin-brightening effects. This review aims to consolidate the current and emerging research on the applications of jujube in conventional and medical cosmetics, highlighting its potential in enhancing skin and hair wellness. By providing a comprehensive overview, it seeks to pave the way for further studies and innovations in utilizing jujube for personal care. Full article
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<p>Future directions in the utilization of the therapeutic potential of jujube in cosmetics.</p>
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29 pages, 1434 KiB  
Review
Intestinal Barrier Impairment, Preservation, and Repair: An Update
by Ayah Matar, John A. Damianos, Kara J. Jencks and Michael Camilleri
Nutrients 2024, 16(20), 3494; https://doi.org/10.3390/nu16203494 (registering DOI) - 15 Oct 2024
Viewed by 833
Abstract
Background/Objectives: Our objective was to review published studies of the intestinal barrier and permeability, the deleterious effects of dietary components (particularly fat), the impact of altered intestinal permeability in disease models and human diseases, the role of the microbiome and epigenomics in control [...] Read more.
Background/Objectives: Our objective was to review published studies of the intestinal barrier and permeability, the deleterious effects of dietary components (particularly fat), the impact of altered intestinal permeability in disease models and human diseases, the role of the microbiome and epigenomics in control of barrier function, and the opportunities to restore normal barrier function with dietary interventions and products of the microbiota. Methods: We conducted a literature review including the following keywords alone or in combination: intestinal barrier, permeability, microbiome, epigenomics, diet, irritable bowel syndrome, inflammatory bowel disease, probiotics. Results: Intestinal permeability is modified by a diet including fat, which increases permeability, and nutrients such as fiber, glutamine, zinc, vitamin D, polyphenols, emulsifiers, and anthocyanins, which decrease permeability. There is significant interaction of the microbiome and barrier function, including the inflammatory of luminal/bacterial antigens, and anti-inflammatory effects of commensals or probiotics and their products, including short-chain fatty acids. Epigenomic modification of barrier functions are best illustrated by effects on junction proteins or inflammation. Detailed documentation of the protective effects of diet, probiotics, prebiotics, and microbiota is provided. Conclusion: intestinal permeability is a critical factor in protection against gastrointestinal diseases and is impacted by nutrients that preserve or heal and repair the barrier and nurture anti-inflammatory effects. Full article
(This article belongs to the Special Issue Effects of Probiotics, Prebiotics, and Postbiotics on Human Health)
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<p>Composition of barrier, physiology of permeability, and factors which help or harm permeability (created in BioRender. matar, a. (2024) <a href="http://BioRender.com/m56y070" target="_blank">BioRender.com/m56y070</a> (accessed on 10 October 2024)). The left side of the figure summarizes the factors that damage the intestinal barrier resulting in increased permeability; the right side summarizes factors that enhance the intestinal barrier resulting in reduced intestinal permeability. Several amino acids, exemplified by glutamine in the figure, are associated with fortification of the intestinal barrier (as detailed in the text).</p>
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12 pages, 2354 KiB  
Article
Vitamin D Receptor—Interplay in COVID-19-Negative, -Infected, and -Vaccinated Women during Pregnancy
by Constantin Condac, Ludmila Lozneanu, Daniela Roxana Matasariu, Alexandra Ursache, Iuliana Elena Bujor, Maria Elena Niță, Vasile Lucian Boiculese, Mihai Sava, Paula Țăroi and Victoria Bîrluțiu
J. Clin. Med. 2024, 13(20), 6140; https://doi.org/10.3390/jcm13206140 (registering DOI) - 15 Oct 2024
Viewed by 294
Abstract
Background: The trophoblast is a significant source of vitamin D synthesis during pregnancy, with the literature suggesting its role in fetal growth. We aim to underline a possible mechanism that would explain negative fetal outcomes in COVID-19-positive mothers by examining the relationship between [...] Read more.
Background: The trophoblast is a significant source of vitamin D synthesis during pregnancy, with the literature suggesting its role in fetal growth. We aim to underline a possible mechanism that would explain negative fetal outcomes in COVID-19-positive mothers by examining the relationship between altered placental structure and function and throphoblast cells‘ vitamin D receptor levels. Methods: The study included 170 placental samples collected from women who gave birth at term without complications, divided into three groups: COVID-19-positive and unvaccinated, COVID-19-negative and vaccinated, and COVID-19-negative and unvaccinated, with exclusion criteria for any other medical complications. Immunohistochemistry (IHC) was performed to detect vitamin D receptor (VDR) expression, and immediate fetal outcomes (weight and Apgar score) were assessed. Results: We found lower gestational age at birth, lower birth weight, and reduced placental VDR (vitamin D receptor) levels in COVID-19-positive women compared to COVID-19-vaccinated and COVID-19-negative women. Conclusions: The presence of the vitamin D receptor in the placenta is related to fetal and placental growth. Its deficiency may contribute to negative fetal outcomes in COVID-19-positive cases. Full article
(This article belongs to the Special Issue New Advances in COVID-19 and Pregnancy)
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<p>Representative histopathological changes in placenta (H&amp;E). (<b>A</b>) COVID-19-positive pregnant women: small, well-vascularized chorionic villi. Syncytial knots and intervillous fibrin (HE × 10). (<b>B</b>) COVID-19-vaccinated pregnant women: chorionic villi, congestion, and fibrosis (HE × 20). (<b>C</b>) COVID-19-negative and unvaccinated pregnant women: different sizes of chorionic villi, congestion, and area of fibrosis (HE × 10).</p>
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<p>Representative images—immunohistochemical visualization of VDR in mononuclear cells of trophoblasts. (<b>A</b>) COVID-19-positive pregnant women (×20). (<b>B</b>) COVID-19-vaccinated pregnant women (×20). (<b>C</b>) COVID-19-negative and unvaccinated pregnant women (×10).</p>
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17 pages, 2874 KiB  
Article
Study on the Effect of Emulsifiers on the Properties of Oleogels Based on Olive Oil Containing Lidocaine
by Sonia Kudłacik-Kramarczyk, Alicja Przybyłowicz, Anna Drabczyk, Weronika Kieres, Robert P. Socha and Marcel Krzan
Int. J. Mol. Sci. 2024, 25(20), 11067; https://doi.org/10.3390/ijms252011067 (registering DOI) - 15 Oct 2024
Viewed by 255
Abstract
Oleogels are semi-solid materials that consist primarily of liquid oil immobilized in a network of organized structural molecules, which provide stability and maintain the oil in the desired shape. Due to their structure, oleogels can stabilize large amounts of liquid, making them excellent [...] Read more.
Oleogels are semi-solid materials that consist primarily of liquid oil immobilized in a network of organized structural molecules, which provide stability and maintain the oil in the desired shape. Due to their structure, oleogels can stabilize large amounts of liquid, making them excellent carriers for active substances, both lipophilic and hydrophilic. This study presents the synthesis methodology and investigations of olive oil-based oleogels, which are among the healthiest and most valuable vegetable fats, rich in unsaturated fatty acids and antioxidants such as vitamin E. Two types of surfactants were used: TWEEN 80, which lowers surface tension and stabilizes emulsions, and SPAN 80, which acts in oil-dominated phases. The oleogels were enriched with lidocaine, an active substance commonly used as a pain reliever and local anesthetic. This research characterized the obtained oleogels regarding their medical applications, paying particular attention to the influence of surfactant type and amount as well as the active substance on their physicochemical properties. Structural analyses were also conducted using Fourier transform infrared (FTIR) spectroscopy, alongside rheological and sorption studies, and the wettability of the materials was evaluated. The stability of the obtained oleogels was verified using the MultiScan MS20 system, allowing for an assessment of their potential suitability for long-term pharmaceutical applications. The results indicated that SPAN-stabilized oleogels exhibited better stability and favorable mechanical properties, making them promising candidates for medical applications, particularly in pain relief formulations. Full article
(This article belongs to the Special Issue New Perspectives of Colloids for Biological Applications)
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<p>Images presenting the appearance of oleogel samples directly after synthesis (<b>left</b>) and after two months (<b>right</b>) (blue arrows demonstrate the level of oleogel in the test tubes after the synthesis; pink arrows demonstrate the level of oleogel in the test tubes after 2 months storage; pink circle shows samples in the case of which any difference has been observed).</p>
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<p>Results of the stability analysis via the MultiScan system for the oleogel samples; analysis after synthesis and after two months (old).</p>
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<p>Schematic of the transmission measurement process using the MultiScan MS 20 device (The DataPhysics Instruments GmbH, Filderstadt, Germany) for the tested materials.</p>
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<p>FT-IR spectra of oleogel samples (<b>a</b>) and lidocaine (<b>b</b>).</p>
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<p>Approximation of the FT-IR spectrum from <a href="#ijms-25-11067-f004" class="html-fig">Figure 4</a>a after overlaying all spectra, revealing the precise depth of absorption bands originating from the surfactants TWEEN 80 and SPAN 80.</p>
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<p>Changes in the absolute (<b>AH</b>) and relative (<b>RH</b>) humidity of oleogels over time.</p>
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<p>Contact angles for the obtained oleogel materials with standard deviations calculated from five repetitions.</p>
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<p>Images of the oleogel drop behavior during the initial contact with the test material.</p>
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<p>Summary of G′ and G″ for materials tested immediately after synthesis (<b>a</b>,<b>c</b>,<b>e</b>,<b>g</b>,<b>i</b>,<b>k</b>) and 2 months after synthesis (<b>b</b>,<b>d</b>,<b>f</b>,<b>h</b>,<b>j</b>,<b>l</b>).</p>
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<p>Summary of G′ and G″ for materials tested immediately after synthesis (<b>a</b>,<b>c</b>,<b>e</b>,<b>g</b>,<b>i</b>,<b>k</b>) and 2 months after synthesis (<b>b</b>,<b>d</b>,<b>f</b>,<b>h</b>,<b>j</b>,<b>l</b>).</p>
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19 pages, 2597 KiB  
Article
Contrast Relative Humidity Response of Diverse Cowpea (Vigna unguiculata (L.) Walp.) Genotypes: Deep Study Using RNAseq Approach
by Ekaterina A. Krylova, Marina O. Burlyaeva, Varvara E. Tvorogova and Elena K. Khlestkina
Int. J. Mol. Sci. 2024, 25(20), 11056; https://doi.org/10.3390/ijms252011056 (registering DOI) - 15 Oct 2024
Viewed by 198
Abstract
Cowpea (Vigna unguiculata (L.) Walp.) is appreciated for its suitability for cultivation and obtaining good yields in relatively extreme farming conditions. It is resistant to high temperatures and drought. Moreover, food products prepared from Vigna are rich in many nutrients such as [...] Read more.
Cowpea (Vigna unguiculata (L.) Walp.) is appreciated for its suitability for cultivation and obtaining good yields in relatively extreme farming conditions. It is resistant to high temperatures and drought. Moreover, food products prepared from Vigna are rich in many nutrients such as proteins, amino acids, carbohydrates, minerals, fiber, vitamins, and other bioactive compounds. However, in East and Southeast Asia, where the products of this crop are in demand, the climate is characterized by excessive humidity. Under these conditions, the vast majority of cowpea varieties tend to have indeterminate growth (elongated shoot length) and are unsuitable for mechanized harvesting. The molecular mechanisms for tolerance to high relative humidity remain the least studied in comparison with those for other abiotic stress factors (drought, heat, cold, flooding, etc.). The purpose of the work was to reveal and investigate differentially expressed genes in cowpea accessions having contrasting growth habits (determinate and indeterminate) under humid and drought conditions. We performed RNA-seq analysis using selected cowpea accessions from the VIR collection. Among the genotypes used, some have significant changes in their plant architecture in response to high relative humidity, while others were tolerant to these conditions. In total, we detected 1697 upregulated and 1933 downregulated genes. The results showed that phytohormone-related genes are involved in cowpea response to high relative humidity. DEGs associated with jasmonic acid signaling are proposed to be key contributors in the maintenance of compact architecture under humid conditions. Full article
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<p>Principal component analysis (PCA) plot of all expressed genes in the RNA–seq data. The <span class="html-italic">X</span>-axis indicates the first principal component; the <span class="html-italic">Y</span>-axis indicates the second principal component. The percentage of variance explained by each PC is shown in each case. Rose color—control group (the relative humidity was equal to 60%), blue color—experimental group (the relative humidity—90%). Analysis was performed with the DESeq2 package version 1.38.3.</p>
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<p>Volcano plot representing 24,350 differentially expressed genes. The <span class="html-italic">X</span>-axis indicates the log2-transformed gene expression fold changes between control group and experimental group of cowpea accessions. The <span class="html-italic">Y</span>-axis indicates the log10-transformed <span class="html-italic">p</span>-value. Dashed lines indicate log<sub>2</sub>FC and <span class="html-italic">p</span>-value thresholds. The scattered points represent each gene. Significant differentially upregulated genes are highlighted in red, significant differentially downregulated genes are highlighted in blue. Genes with a nonsignificant log<sub>2</sub>FC value and nonsignificant <span class="html-italic">p</span>-value are highlighted in black.</p>
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<p>Number of DEGs identified in a comparison between the control and experimental groups for each cowpea accession.</p>
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<p>Principal component analysis (PCA) plots and volcano plots of expressed genes in the RNA-seq data for four comparisons. (<b>1a</b>,<b>1b</b>) PCA plot and volcano plot for k6; (<b>2a</b>,<b>2b</b>) PCA plot and volcano plot for k642; (<b>3a</b>,<b>3b</b>) PCA plot and volcano plot for k1783; (<b>4a</b>,<b>4b</b>) PCA plot and volcano plot for k2056. The <span class="html-italic">X</span>-axis on the PCA plots indicates the first principal component; the <span class="html-italic">Y</span>-axis indicates the second principal component. The percentage of variance explained by each PC is shown in each case. Rose color—control group (the relative humidity was equal to 60%), blue color—experimental group (the relative humidity—90%). Analysis was performed with the DESeq2 package version 1.38.3. The <span class="html-italic">X</span>-axis on the volcano plots indicates the log2-transformed gene expression fold changes between the control group and experimental group of cowpea accession. The <span class="html-italic">Y</span>-axis indicates the log10-transformed <span class="html-italic">p</span>-value. Dashed lines indicate log<sub>2</sub>FC and <span class="html-italic">p</span>-value thresholds. The scattered points represent each gene. Significantly differentially upregulated genes are highlighted in red, and significantly differentially downregulated genes are high-lighted in blue. Genes with a nonsignificant log<sub>2</sub>FC value and nonsignificant <span class="html-italic">p</span>-value are highlighted in black.</p>
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<p>Venn diagrams representing the overlap between DEGs identified in four cowpea accessions in the control and experimental groups (two relative humidity conditions): (<b>a</b>) upregulated genes and (<b>b</b>) downregulated genes. Accessions are marked by different colors in letters.</p>
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<p>GO enrichment analysis of the (<b>a</b>) upregulated genes and (<b>b</b>) downregulated genes identified in four cowpea accessions in the control and experimental groups (two relative humidity conditions). For the BP categories, the top 50 GO terms are presented.</p>
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<p>Number of DEGs associated with plant hormone biosynthesis, metabolism, and signal transduction pathways. Genes identified in four cowpea accessions in the control and experimental groups (two relative humidity conditions): (<b>a</b>) upregulated genes and (<b>b</b>) downregulated genes.</p>
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<p>qRT-PCR validation of nine DEGs for k-2056 in high RH (experimental) versus low RH (control). Data were normalized to the expression of <span class="html-italic">VuUBQ10</span> (<span class="html-italic">Vigun07g244400</span>) encoding ubiquitin. Each sample was amplified in three technical replicates. Significant differences between the mean values are indicated (* <span class="html-italic">p</span> ≤ 0.001, ** <span class="html-italic">p</span> ≤ 0.05) (<span class="html-italic">t</span>-test).</p>
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<p>Cowpea accessions k-2056 (<b>a</b>,<b>c</b>) and k-642 (<b>b</b>,<b>d</b>) in two climatic chambers: (<b>a</b>,<b>b</b>) 60% RH (control group), (<b>c</b>,<b>d</b>) 90% RH (experimental group). The formation of climbing shoot for k-642 in high RH was observed (<b>d</b>), and for k-2056, there was no formation of such shoots (<b>c</b>).</p>
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22 pages, 1049 KiB  
Review
Thalassemia: Pathophysiology, Diagnosis, and Advances in Treatment
by Idris Zubairu Sadiq, Fatima Sadiq Abubakar, Hauwa Salisu Usman, Aliyu Dantani Abdullahi, Bashiru Ibrahim, Babangida Sanusi Kastayal, Maryam Ibrahim and Hassan Aliyu Hassan
Thalass. Rep. 2024, 14(4), 81-102; https://doi.org/10.3390/thalassrep14040010 (registering DOI) - 15 Oct 2024
Viewed by 153
Abstract
Thalassemia represents a diverse group of inherited hematological disorders characterized by defective globin chain synthesis, leading to chronic anemia and associated complications. The complicated pathophysiology of beta-thalassemia involves genetic mutations or rarely deletions of the beta-globin gene on chromosome 11 whereas alpha-thalassemia involves [...] Read more.
Thalassemia represents a diverse group of inherited hematological disorders characterized by defective globin chain synthesis, leading to chronic anemia and associated complications. The complicated pathophysiology of beta-thalassemia involves genetic mutations or rarely deletions of the beta-globin gene on chromosome 11 whereas alpha-thalassemia involves deletions in the HBA1 and HBA2 genes or occasionally alterations to the DNA sequence in or around these genes. These mutation and deletion effects disrupt the balance of α/β-globin chain production, resulting in ineffective erythropoiesis, hemolysis, and a cascade of clinical manifestations including anemia, bone deformities, and iron overload. Advances in diagnostic techniques have enhanced our ability to detect and characterize these mutations, facilitating early and accurate diagnoses. Current management strategies encompass regular blood transfusions, the use of hydroxyurea to improve hemoglobin levels, and iron chelation therapy to prevent iron-related organ damage. Moreover, other therapeutics such as thalidomide for those not responding to hydroxyurea, Sirolimus for patients with immunodeficiencies, and use of vitamin E as an antioxidant have proven to be effective. Innovative therapies such as gene therapy and bone marrow transplantation offer promising curative potential, opening a new era in the treatment of thalassemia. This review focuses on pathophysiological mechanisms underlying thalassemia, explores the diagnostic methodologies, and highlights recent advancements in therapeutic approaches. Full article
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<p>Structure of hemoglobin: (<b>a</b>) 3D structure of hemoglobin, (<b>b</b>) 2D structure of hemoglobin showing α2β2 subunits of hemoglobin, (<b>c</b>) structure of hemoglobin showing binding of Fe<sup>2+</sup>, (<b>d</b>) Alpha Subunit showing number of amino acids, (<b>e</b>) Beta Subunit showing number of amino acids.</p>
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<p>Inherited pattern of thalassemia.</p>
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10 pages, 214 KiB  
Article
Validating Disease Associations of Drug-Metabolizing Enzymes through Genome-Wide Association Study Data Analysis
by Evan Leskiw, Adeline Whaley, Peter Hopwood, Tailyn Houston, Nehal Murib, Donna Al-Falih and Ryoichi Fujiwara
Genes 2024, 15(10), 1326; https://doi.org/10.3390/genes15101326 (registering DOI) - 15 Oct 2024
Viewed by 303
Abstract
Background and Objectives: Phase I and phase II drug-metabolizing enzymes are crucial for the metabolism and elimination of various endogenous and exogenous compounds, such as small-molecule hormones, drugs, and xenobiotic carcinogens. While in vitro and animal studies have suggested a link between genetic [...] Read more.
Background and Objectives: Phase I and phase II drug-metabolizing enzymes are crucial for the metabolism and elimination of various endogenous and exogenous compounds, such as small-molecule hormones, drugs, and xenobiotic carcinogens. While in vitro and animal studies have suggested a link between genetic mutations in these enzymes and an increased risk of cancer, human in vivo studies have provided limited supportive evidence. Methods: Genome-wide association studies (GWASs) are a powerful tool for identifying genes associated with specific diseases by comparing two large groups of individuals. In the present study, we analyzed a GWAS database to identify key diseases genetically associated with drug-metabolizing enzymes, focusing on UDP-glucuronosyltransferases (UGTs). Results: Our analysis confirmed a strong association between the UGT1 gene and hyperbilirubinemia. Additionally, over ten studies reported a link between the UGT1 gene and increased low-density lipoprotein (LDL) cholesterol levels. UGT2B7 was found to be associated with testosterone levels, total cholesterol levels, and vitamin D levels. Conclusions: Despite the in vitro capability of UGT1 and UGT2 family enzymes to metabolize small-molecule carcinogens, the GWAS data did not indicate their genetic association with cancer, except for one study that linked UGT2B4 to ovarian cancer. Further investigations are necessary to fill the gap between in vitro, animal, and human in vivo data. Full article
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