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56 pages, 3830 KiB  
Review
Marine Fungi Bioactives with Anti-Inflammatory, Antithrombotic and Antioxidant Health-Promoting Properties Against Inflammation-Related Chronic Diseases
by Maria-Aliki Papikinou, Konstantinos Pavlidis, Paschalis Cholidis, Dimitrios Kranas, Theodora Adamantidi, Chryssa Anastasiadou and Alexandros Tsoupras
Mar. Drugs 2024, 22(11), 520; https://doi.org/10.3390/md22110520 (registering DOI) - 18 Nov 2024
Abstract
Fungi play a fundamental role in the marine environment, being promising producers of bioactive molecules in the pharmacological and industrial fields, which have demonstrated potential health benefits against cardiovascular and other chronic diseases. This review pertains to the analysis of the lipid compositions [...] Read more.
Fungi play a fundamental role in the marine environment, being promising producers of bioactive molecules in the pharmacological and industrial fields, which have demonstrated potential health benefits against cardiovascular and other chronic diseases. This review pertains to the analysis of the lipid compositions across various species of marine fungi and their constantly discovered substances, as well as their anti-inflammatory, antioxidant, and antithrombotic effects. The health-promoting aspects of these microorganisms will be explored, through the investigation of several mechanisms of action and interference of their bioactives in biochemical pathways. Despite exceptional results in this field, the potential of marine microorganisms remains largely unexplored due to the limited number of specialists in marine microbiology and mycology, a relatively recent science with significant contributions and potential in biodiversity and biotechnology. Full article
37 pages, 2386 KiB  
Review
Cajaninstilbene Acid and Its Derivative as Multi-Therapeutic Agents: A Comprehensive Review
by Wen Hou, Lejun Huang, Jinyang Wang, Walter Luyten, Jia Lai, Zhinuo Zhou, Sishuang Kang, Ping Dai, Yanzhu Wang, Hao Huang and Jinxia Lan
Molecules 2024, 29(22), 5440; https://doi.org/10.3390/molecules29225440 (registering DOI) - 18 Nov 2024
Abstract
: Pigeon pea (Cajanus cajan (L.) Millsp.) is a traditional Chinese medicinal plant widely utilized in folk medicine due to its significant pharmacological and nutritional properties. Cajaninstilbene acid (CSA), a stilbene compound derived from pigeon pea leaves, has been extensively investigated [...] Read more.
: Pigeon pea (Cajanus cajan (L.) Millsp.) is a traditional Chinese medicinal plant widely utilized in folk medicine due to its significant pharmacological and nutritional properties. Cajaninstilbene acid (CSA), a stilbene compound derived from pigeon pea leaves, has been extensively investigated since the 1980s. A thorough understanding of CSA’s mechanisms of action and its therapeutic effects on various diseases is crucial for developing novel therapeutic approaches. This paper presents an overview of recent research advancements concerning the biological activities and mechanisms of CSA and its derivatives up to February 2024. The review encompasses discussions on the in vivo metabolism of CSA and its derivatives, including antipathogenic micro-organisms activity, anti-tumor activity, systematic and organ protection activity (such as bone protection, cardiovascular protection, neuroprotection), anti-inflammatory activity, antioxidant activity, immune regulation as well as action mechanism of CSA and its derivatives. The most studied activities are antipathogenic micro-organisms activities. Additionally, the structure–activity relationships of CSA and its derivatives as well as the total synthesis of CSA are explored, highlighting the potential for developing new pharmaceutical agents. This review aims to provide a foundation for future clinical applications of CSA and its derivatives. Full article
(This article belongs to the Special Issue Advances in Natural Products and Their Biological Activities)
14 pages, 717 KiB  
Review
The Effects of SGLT2 Inhibitors on Blood Pressure and Other Cardiometabolic Risk Factors
by Alexandra Katsimardou, Panagiotis Theofilis, Aikaterini Vordoni, Michael Doumas and Rigas G. Kalaitzidis
Int. J. Mol. Sci. 2024, 25(22), 12384; https://doi.org/10.3390/ijms252212384 - 18 Nov 2024
Abstract
Beyond their established hypoglycemic, cardioprotective, and nephroprotective properties, sodium–glucose cotransporters 2 (SGLT2) inhibitors exert other pleiotropic actions on blood pressure levels, body weight, and lipid metabolism. Blood pressure (BP) reduction varies based on the background history, including an effect on systolic, diastolic BP, [...] Read more.
Beyond their established hypoglycemic, cardioprotective, and nephroprotective properties, sodium–glucose cotransporters 2 (SGLT2) inhibitors exert other pleiotropic actions on blood pressure levels, body weight, and lipid metabolism. Blood pressure (BP) reduction varies based on the background history, including an effect on systolic, diastolic BP, and 24 h BP measurements. The reduction in body weight between 1 and 2 kg for the first months is caused by a reduction in visceral and subcutaneous fat due to glycosuria and loss of calories. Regarding lipid metabolism, a reduction in triglycerides and an increase in total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) have been reported, although these alterations are small and could provide additional cardiovascular protection. Various pathophysiologic mechanisms have been proposed to explain the above-mentioned pleiotropic actions of SGLT2 inhibitors. Natriuresis, osmotic diuresis, body weight reduction, amelioration of endothelial dysfunction and arterial stiffness, sympathetic tone decrease, and uric acid reduction are among those that have been suggested for BP reduction. Apart from glycosuria and calorie loss, other mechanisms seem to contribute to body weight reduction, such as the beiging of white adipose tissue, while the mechanisms involved in lipid metabolism alterations have not been clearly determined. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
28 pages, 1231 KiB  
Review
Managing Type 2 Diabetes Mellitus via the Regulation of Gut Microbiota: A Chinese Medicine Perspective
by Chester Yan Jie Ng, Linda Zhong, Han Seong Ng, Kia Seng Goh and Yan Zhao
Nutrients 2024, 16(22), 3935; https://doi.org/10.3390/nu16223935 (registering DOI) - 18 Nov 2024
Abstract
Background: Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by insulin resistance and inadequate insulin production. Given the increased frequency of T2DM and the health issues it can cause, there is an increasing need to develop alternative T2DM management strategies. One [...] Read more.
Background: Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by insulin resistance and inadequate insulin production. Given the increased frequency of T2DM and the health issues it can cause, there is an increasing need to develop alternative T2DM management strategies. One such approach is Chinese Medicine (CM), a complementary therapy widely used in T2DM treatment. Given the emphasis on gut microbiota in current research, studying CM in the treatment of T2DM via gut microbiota modulation could be beneficial. Scope and approach: The use of various CM methods for managing T2DM via gut microbiota modulation is highlighted in this review. Following an introduction of the gut microbiota and its role in T2DM pathogenesis, we will review the potential interactions between gut microbiota and T2DM. Thereafter, we will review various CM treatment modalities that modulate gut microbiota and provide perspectives for future research. Key findings and discussion: In T2DM, Akkermansia, Bifidobacterium, and Firmicutes are examples of gut microbiota commonly imbalanced. Studies have shown that CM therapies can modulate gut microbiota, leading to beneficial effects such as reduced inflammation, improved metabolism, and improved immunity. Among these treatment modalities, Chinese Herbal Medicine and acupuncture are the most well-studied, and several in vivo studies have demonstrated their potential in managing T2DM by modulating gut microbiota. However, the underlying biomolecular mechanisms of actions are not well elucidated, which is a key area for future research. Future studies could also investigate alternate CM therapies such as moxibustion and CM exercises and conduct large-scale clinical trials to validate their effectiveness in treatment. Full article
16 pages, 1157 KiB  
Article
Insight into the Mechanical Properties and Microstructure of Recycled Aggregate Concrete Containing Carbon Fibers and Nano-SiO2
by Tong Xing, Shaofeng Zhang and Lei Guan
Materials 2024, 17(22), 5633; https://doi.org/10.3390/ma17225633 (registering DOI) - 18 Nov 2024
Abstract
This study aimed to improve the mechanical properties and microstructure of recycled aggregate concrete (RAC) by incorporating carbon fibers (CFs) and nano-SiO2 (NS) to promote the optimal utilization of RAC. The mechanical properties of the RAC were enhanced by both single and [...] Read more.
This study aimed to improve the mechanical properties and microstructure of recycled aggregate concrete (RAC) by incorporating carbon fibers (CFs) and nano-SiO2 (NS) to promote the optimal utilization of RAC. The mechanical properties of the RAC were enhanced by both single and hybrid additions of CFs and NS, and the hybrid addition had a better strengthening effect. From the experimental results, it was found that the addition of CFs could increase the 28 d compressive strength and splitting strength of the RAC by 9.05% and 22.36%, respectively. The hybrid CFs and NS were more conducive to improving the mechanical properties of the RAC, and the enhancement effect increased first and then decreased with an increase in the NS content. The optimal content of NS was 0.8 wt%, which increased the 28 d compressive strength and splitting strength of the RAC by 20.51% and 14.53%, respectively. The microstructure results indicated that the addition of CFs had little effect on the optimized pore structure of the RAC, but the crack inhibition action of the CFs could improve the mechanical properties of the RAC. The addition of NS reduced the content of CH and facilitated the formation of more (C–S–H) gel. The hydrated calcium silicate (C–S–H) gel significantly decreased the porosity and transformed harmful capillary pores and harmful pores into harmless capillary pores and gel pores, thus improving the mechanical properties of the RAC. Therefore, the use of hybrid CFs and NS was more conducive to enhancing the performance of RAC for building materials. Full article
18 pages, 2514 KiB  
Article
Aloe Vera as a Printed Coating to Mitigate the Wear of Textiles
by Michail Karypidis, Amalia Stalika, Maria Zarkogianni, Apostolos Korlos and Eleftherios G. Andriotis
Coatings 2024, 14(11), 1467; https://doi.org/10.3390/coatings14111467 - 18 Nov 2024
Abstract
Aloe vera is well known for its biological properties as a bioflavonoid anti-inflammatory and antibacterial agent. It has been used frequently in the food sector as a food coating due to its hygroscopic properties and as an ingredient in the lucrative cosmetic industry. [...] Read more.
Aloe vera is well known for its biological properties as a bioflavonoid anti-inflammatory and antibacterial agent. It has been used frequently in the food sector as a food coating due to its hygroscopic properties and as an ingredient in the lucrative cosmetic industry. Studies have also included aloe vera as an eco-friendly green solution based on these properties. The current research focuses on the use of aloe vera gel in printing pastes as an alternative sustainable solution to synthetic thickeners, evaluating its wet performance and ease of fabric stitching, and has been inspired by studies that similarly used this substance and measured its effect on the fabric’s coefficient of friction and antimicrobial action. In the current study, printing pastes with natural colourants, such as saffron, curcumin, and annatto, and aloe vera gel thickener derived from natural leaves from Crete increased the fabric’s mechanical resistance to abrasion compared to the untreated pastes. The measured performance did not differ substantially from prints with traditional synthetic pastes, hence tolerating the substitution with the non-contaminant variant. The enhanced resistance to abrasion and wear extends the fabric’s serviceable life and resulting garments, decreasing the need for high industry processing volumes and, as a result, reducing pollution. The resistance to wear was evaluated using the dominant method in textile testing of the Martindale apparatus, which measured the cycles to failure, weight loss, and general appearance deterioration using the official photographic standards. Full article
(This article belongs to the Special Issue Coatings for Antimicrobial Textiles)
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<p>Experimental set up of (<b>a</b>) abrasion resistance on Martindale abrasion apparatus, (<b>b</b>) microscope, and (<b>c</b>) test specimen failing point.</p>
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<p>Abrasion resistance cycles to failure for knitted fabric.</p>
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<p>Abrasion resistance cycles to failure for woven fabric.</p>
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<p>Percentage mass loss due to abrasion for knitted fabric.</p>
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<p>Percentage mass loss due to abrasion for woven fabric.</p>
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<p>Surface fuzzing of fabric samples comes at a later stage in the coated samples. (<b>a</b>) Untreated knitted fabric; (<b>b</b>) printed knitted fabric; (<b>c</b>) untreated woven fabric; (<b>d</b>) printed woven fabric.</p>
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<p>Longer fibrils protruding from the surface of the knitted (<b>a</b>) untreated samples compared to (<b>b</b>) aloe-treated pastes coated samples, after 6000 rubbing cycles.</p>
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<p>Abrasion resistance cycles to failure plot of knitted fabric substrates for stepwise statistical analysis.</p>
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<p>Abrasion resistance cycles to failure plot of woven fabric substrates for stepwise statistical analysis.</p>
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<p>The abraded fabric under SEM analysis. (<b>a</b>) Low magnification (<b>b</b>) and high magnification at 5000 cycles.</p>
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20 pages, 9058 KiB  
Article
Response of Yields, Soil Physiochemical Characteristics, and the Rhizosphere Microbiome to the Occurrence of Root Rot Caused by Fusarium solani in Ligusticum chuanxiong Hort.
by Xiaofang Sun, Yong Liu, Lian He, Zaiyin Kuang, Shundong Dai, Lixia Hua, Qiuping Jiang, Taiyang Wei, Pengsheng Ye and Hualan Zeng
Microorganisms 2024, 12(11), 2350; https://doi.org/10.3390/microorganisms12112350 - 18 Nov 2024
Abstract
Ligusticum chuanxiong Hort. is considered an important medicinal herb with extremely high economic value and medicinal value due to its various effects, including anti-oxidation, sedative action, hepatoprotection, and invigorating blood circulation. However, L. chuanxiong cultivation is hampered by various plant diseases, especially the [...] Read more.
Ligusticum chuanxiong Hort. is considered an important medicinal herb with extremely high economic value and medicinal value due to its various effects, including anti-oxidation, sedative action, hepatoprotection, and invigorating blood circulation. However, L. chuanxiong cultivation is hampered by various plant diseases, especially the root rot caused by Fusarium solani, hindering the sustainable development of the L. chuanxiong industry. The occurrence of soil-borne diseases is closely linked to imbalances in the microbial community structure. Here, we studied the yields, rhizosphere microbiota, and soil physiochemical characteristics of healthy and diseased L. chuanxiong plants affected by root rot with high-throughput sequencing and microbial network analysis, aiming to explore the relationships between soil environmental factors, microbiomes, and plant health of L. chuanxiong. According to the results, L. chuanxiong root rot significantly decreased the yields, altered microbial community diversity and composition, enriched more pathogenic fungi, recruited some beneficial bacteria, and reduced microbial interaction network stability. The Mantel test showed that soil organic matter and pH were the major environmental factors modulating plant microbiome assembly. The root rot severity was significantly affected by soil physiochemical properties, including organic matter, cation exchange capacity, available nitrogen, phosphorus, potassium, and pH. Furthermore, two differential microbes that have great potential in the biocontrol of L. chuanxiong root rot were dug out in the obtained results, which were the genera Trichoderma and Bacillus. This study provided a theoretical basis for further studies revealing the microecological mechanism of L. chuanxiong root rot and the ecological prevention and control of L. chuanxiong root rot from a microbial ecology perspective. Full article
(This article belongs to the Section Plant Microbe Interactions)
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<p>Effects of root rot on the fresh weight (<b>A</b>) and dry weight (<b>B</b>) of both the shoot and rhizoma in <span class="html-italic">L. chuanxiong</span>. Different lowercase letters positioned above the error bars indicate statistically significant differences (<span class="html-italic">p</span> &lt; 0.05; Duncan’s test).</p>
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<p>Rarefaction curves for rhizosphere soil bacteria (<b>A</b>) and fungi (<b>B</b>). The letter H indicates healthy plants, while D denotes diseased plants.</p>
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<p>OTU Venn diagram analysis of rhizosphere soil bacteria (<b>A</b>) and fungi (<b>B</b>).</p>
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<p>Alpha diversity indexes between the healthy and diseased plants rhizosphere soil bacteria (<b>A</b>) and fungi (<b>B</b>). * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Principle coordinates analysis of dimension reduction analysis based on Bray−Curtis distances according to the abundance of rhizosphere bacteria (<b>A</b>) and fungi (<b>B</b>).</p>
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<p>Taxonomic summary of the relative abundance of the rhizosphere bacterial phyla (<b>A</b>) and fungal phyla (<b>B</b>) in healthy and diseased soil.</p>
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<p>Taxonomic summary of the relative abundance of the rhizosphere bacterial genera (<b>A</b>) and fungal genera (<b>B</b>) in healthy and diseased soil; Phylogenetic trees of the top 100 genera of bacteria (<b>C</b>) and fungi (<b>D</b>) based on their relative abundance.</p>
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<p>Connection between microbial communities and environmental factors. (<b>A</b>,<b>B</b>) Redundancy analysis triplots of bacterial (<b>A</b>) and fungal (<b>B</b>) communities; (<b>C</b>) The Mantel test, which indicates the correlation between microbial community and soil properties and their pairwise comparisons through pearson correlations; (<b>D</b>,<b>E</b>) Pearson correlation coefficient diagrams for the top 35 bacterial (<b>D</b>) and fungal (<b>E</b>) genera in relation to soil environmental factors. CEC: cation exchange capacity; OM: organic matter; TN: total nitrogen; TP: total phosphorus; TK: total potassium; AN: available nitrogen; AP: available phosphorus; AK: available potassium. * denotes significance <span class="html-italic">p</span> &lt; 0.05. ** represent significance <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>The interconnections among keystone microbiomes, soil pH levels, and the disease index associated with root rot. (<b>A</b>) Disease index of root rot in response to the concentration of <span class="html-italic">Bacillus</span>; (<b>B</b>) Disease index of root rot in response to the concentration of <span class="html-italic">Trichoderma</span>; (<b>C</b>) Disease index of root rot in response to soil pH. The shaded area represents the 95% confidence interval for the corresponding regression lines.</p>
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<p>Co-occurrence networks of bacterial and fungal amplicon sequence variants in both healthy and diseased soil. Edges colored in red indicate positive correlations; edges in green indicate negative correlations. (<b>A</b>) Bacteria in healthy; (<b>B</b>) bacteria in diseased; (<b>C</b>) fungi in healthy; and (<b>D</b>) fungi in diseased. The different sizes of circles represent the abundance of the taxa of microbes, the larger the circle, the higher the abundance.</p>
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17 pages, 5675 KiB  
Article
Antibacterial and Inhibitory Activity of Nora and Mepa Efflux Pumps of Estragole Complexed to β-Cyclodextrin (ES/β-CD) In Vitro Against Staphylococcus aureus Bacteria, Molecular Docking and MPO-Based Pharmacokinetics Prediction
by Roger Henrique Sousa da Costa, Renata Torres Pessoa, Eduardo dos Santos Silva, Isaac Moura Araujo, Sheila Alves Gonçalves, Janaína Esmeraldo Rocha, Francisco Nascimento Pereira Junior, Naiara Cipriano Oliveira, Victor Moreira de Oliveira, Matheus Nunes da Rocha, Emmanuel Silva Marinho, Natália Kelly Gomes de Carvalho, José Galberto Martins da Costa, Hélcio Silva dos Santos and Irwin Rose Alencar de Menezes
Pharmaceutics 2024, 16(11), 1469; https://doi.org/10.3390/pharmaceutics16111469 - 18 Nov 2024
Abstract
Background/Objectives: The work investigates the effect of the estragole complex encapsulated in beta-cyclodextrin (ES/β-CD) in modulating bacterial resistance, specifically in Staphylococcus aureus strains expressing NorA and MepA efflux pumps. Efflux pumps are mechanisms that bacteria use to resist antibiotics by expelling them from [...] Read more.
Background/Objectives: The work investigates the effect of the estragole complex encapsulated in beta-cyclodextrin (ES/β-CD) in modulating bacterial resistance, specifically in Staphylococcus aureus strains expressing NorA and MepA efflux pumps. Efflux pumps are mechanisms that bacteria use to resist antibiotics by expelling them from the cell. Methodology: Several compounds and antibiotics, such as ciprofloxacin and norfloxacin, were used to evaluate the antimicrobial activity and the ability of the ES/β-CD complex to reverse resistance. Methods: The study included scanning electron microscopy assays, minimum inhibitory concentration (MIC) determination, and efflux pump inhibition tests. Results: The ES/β-CD complex did not show significant direct antibacterial activity. However, it modulated the action of norfloxacin, decreasing the MIC when combined with this antibiotic in the 1199B (NorA) strain. These results suggest a potential for synergy but not a direct inhibition of efflux pumps. Conclusion: ES/β-CD can potentiate the efficacy of some antibiotics but does not directly act as an efflux pump inhibitor; it is more of an antibiotic potentiator than a direct solution to bacterial resistance. The molecular docking simulation data suggest its high affinity for forming the ES/β-CD complex. The pharmacokinetic predictions based on MPO suggest that the compound has moderate lipophilicity, highly effective cellular permeability, and low incidence of organic toxicity, pointing to a promising pharmacological principle with controlled daily oral dosing. Conclusions: These results indicate this complex’s possible and relevant association as an adjuvant in antibiotic therapy to reduce multidrug-resistant bacteria; however, new in vivo assays are necessary to confirm this effect. Full article
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Figure 1
<p>SEM images of pure β-cyclodextrin (β-CD) (<b>A</b>–<b>C</b>) and β-cyclodextrin associated with estragole (ES/β-CD) (<b>D</b>–<b>F</b>) are presented. To provide further details of the surface morphology before and after estragole association, higher-magnification images of the regions highlighted in red ((<b>A</b>,<b>B</b>) for β-CD, and (<b>C</b>,<b>D</b>) for ES/β-CD) are shown in (<b>C</b>,<b>F</b>), respectively.</p>
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<p>GC/FID profile of the estragole pattern (RT: 7.648 min).</p>
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<p>GC/FID profile of the β-cyclodextrin complex in estragole. Estragole (RT: 7.646 min).</p>
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<p>Evaluation of efflux pump inhibition of the products when associated with norfloxacin and ethidium bromide against <span class="html-italic">S. aureus</span> strain-overexpressing NorA efflux pumps. Each result is expressed as geometric mean ± geometric standard deviation (SD) of three simultaneous experiments. Statistical significance was determined by one-way ANOVA and Bonferroni’s post hoc test. The control contains only the vehicle solution of dimethyl sulfoxide (DMSO). (** <span class="html-italic">p</span> &lt; 0.01, **** <span class="html-italic">p</span> &lt; 0.0001 when compared to the negative control group).</p>
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<p>Evaluation of efflux pump inhibition of the products when associated with ciprofloxacin and ethidium bromide against <span class="html-italic">S. aureus</span> strain-overexpressing MepA efflux pumps. Each result is expressed as geometric mean ± geometric standard deviation (SD) of three simultaneous experiments. Statistical significance was determined by one-way ANOVA and Bonferroni’s post hoc test (ns—no significance; * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01, **** <span class="html-italic">p</span> &lt; 0.0001 when compared to the negative control group).</p>
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<p>(<b>A</b>) Frontal view of β-CD in two units and (<b>B</b>) β-CD presented in the lateral plane.</p>
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<p>(<b>A</b>) Complex formed between β-CD and ES. (<b>B</b>) Surface of the complex formed in the frontal plane. (<b>C</b>) Surface of the complex with lateral view.</p>
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<p>(<b>A</b>) Global view of interactions formed from the ES-β-CD complex. (<b>B</b>) Specific moieties that formed interactions.</p>
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<p>(<b>A</b>) Molecular lipophilicity potential (MLP) surface map, where the color spectrum ranges from blue (low MLP) to red (high MLP). (<b>B</b>) Alignment between lipophilicity (logP) and polarity (TPSA) for estimating the MPO drug candidate profile and CNS toxicity.</p>
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<p>Prediction of pharmacokinetic properties and toxicity expressed in (<b>A</b>) a similarity test involving compounds present in the DrugBank<sup>®</sup> database, (<b>B</b>) prediction of lethal dose (LD50) for different routes of administration (oral, IP—intraperitoneal, IV—intravenous and SC—subcutaneous), (<b>C</b>) statistical limit of the similarity test of the predictions of (<b>D</b>) oral toxicity site and CYP450-dependent metabolism site.</p>
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12 pages, 5757 KiB  
Article
Toxicity of Flonicamid to Diaphorina citri (Hemiptera: Liviidae) and Its Identification and Expression of Kir Channel Genes
by Jiangyue Zhu, Xinjing Wang, Yunfei Mo, Beibei Wu, Tuyong Yi and Zhongxia Yang
Insects 2024, 15(11), 900; https://doi.org/10.3390/insects15110900 (registering DOI) - 18 Nov 2024
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Abstract
Flonicamid is a selective insecticide effective against piercing–sucking insects. Although its molecular target has been identified in other species, the specific effects and detailed mechanism of action in Diaphorina citri Kuwayama remain poorly understood. In this study, we determined that the LC50 [...] Read more.
Flonicamid is a selective insecticide effective against piercing–sucking insects. Although its molecular target has been identified in other species, the specific effects and detailed mechanism of action in Diaphorina citri Kuwayama remain poorly understood. In this study, we determined that the LC50 of flonicamid for D. citri adults was 16.6 mg AI L−1 after 4 days of exposure. To explore the relevant mechanisms, the treatments with acetone and with 20 mg AI L−1 flonicamid for 96 h were collected as samples for RNA-Seq. The analysis of the transcriptomes revealed 345 differentially expressed genes (DEGs) in D. citri adults subjected to different treatments. Among these DEGs, we focused on the inward-rectifying potassium (Kir) channel genes, which have been extensively studied as potential targets of flonicamid. Three Kir subunit genes (Dckir1, Dckir2, Dckir3) in D. citri were successfully cloned and identified. Furthermore, the expression profiles of these DcKirs were investigated using RT-qPCR and showed that their expression significantly increased after D. citri eclosion to adulthood, particularly for DcKir3. The DcKirs were predominantly expressed in gut tissues, with DcKir1 and DcKir2 exhibiting high expression levels in the hindgut and midgut, respectively, while DcKir3 showing high expression in the midgut and Malpighian tubules. This study provides insights into the potential roles of Kir subunits in D. citri and enhances our understanding of the physiological effects of flonicamid in this pest. Full article
(This article belongs to the Special Issue Effects of Environment and Food Stress on Insect Population)
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<p>The toxicity of flonicamid on <span class="html-italic">D. citri</span> adults. (<b>A</b>) Survival curves of <span class="html-italic">D. citri</span> adults to different concentrations (2.5-40 mg AI L<sup>−1</sup>) of flonicamid for the first four days post treatment. (<b>B</b>) Changes in midgut and Malpighian tubules of <span class="html-italic">D. citri</span> adults after treatment with flonicamid. (<b>a</b>) The gut of <span class="html-italic">D. citri</span> adults treated with acetone. (<b>b</b>) The gut of <span class="html-italic">D. citri</span> adults treated with acetone and flonicamid (LC<sub>30</sub>). Tissue abbreviations: Malpighian tubules, Mt; foregut, Fg; midgut, Mg; and hindgut (Hg).</p>
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<p>DEGs in <span class="html-italic">D. citri</span> after being treated with 20 mg AI L<sup>−1</sup> flonicamid. (<b>A</b>) The volcano plots of DEGs identified from <span class="html-italic">D. citri</span> responsive to flonicamid treatments. Red spots: up-regulated DEGs; blue spots: down-regulated DEGs; gray spots: genes with no significant change in expression levels. (<b>B</b>) GO enrichment analysis of DEGs obtained from the comparison of flonicamid exposure and control group of <span class="html-italic">D. citri</span> adults. Red histograms: up-regulated DEGs; blue histograms: down-regulated DEGs. (<b>C</b>) The heat map indicates the DEGs related to ion channel activity after flonicamid exposure. A shift in color from red to blue indicates a change in the level of gene expression.</p>
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<p>Comparison of expression levels of <span class="html-italic">DcKirs</span> by RT-qPCR and RNA-Seq. β-actin was used as the reference gene for RT-qPCR normalization. The data are represented as the mean ± SEM (n = 3). mRNA expression levels for the selected genes were calculated using the 2<sup>−ΔΔCT</sup> method. Student’s <span class="html-italic">t</span> tests were performed for comparison with the control group, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Phylogenetic analysis, genomic structure and amino acid alignments of <span class="html-italic">DcKirs</span>. (<b>A</b>) Phylogenetic analysis of <span class="html-italic">Kirs</span> from <span class="html-italic">D. citri</span> and other species. The <span class="html-italic">DcKirs</span> are indicated with red color. Accession numbers are listed in <a href="#app1-insects-15-00900" class="html-app">Table S4</a>. (<b>B</b>) Genomic structures of <span class="html-italic">DcKirs</span>. The reds represent the exons, and the gray lines represent the original genomic scaffold sequences. (<b>C</b>) Amino acid alignments of <span class="html-italic">Kirs</span> from <span class="html-italic">D. citri</span>. The underlined lines consist of conserved domains, including the G-Loop, ion selectivity filter, pore helix, and transmembrane domains (TM1 and TM2).</p>
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<p>The expression patterns of <span class="html-italic">DcKirs</span> in different developmental stages (<b>A</b>–<b>C</b>) and tissues (<b>D</b>–<b>F</b>). Different developmental stages of <span class="html-italic">D.citri</span>, including eggs, 1st to 5th instar nymphs, and adults (1-day-old females and 1-day-old males). Different tissues are derived from 1-day-old adults. Tissue abbreviations: salivary gland, SG; midgut, MG; hindgut, HG; and Malpighian tubules, MT. Error bars indicate ± SEM of three biological repeats. The different letters on the column indicate significant differences (<span class="html-italic">p</span> &lt; 0.05; one-way ANOVA, LSD test).</p>
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16 pages, 847 KiB  
Review
The Mechanisms of Developing Fungicide Resistance in Fusarium graminearum Causing Fusarium Head Blight and Fungicide Resistance Management
by Malini Anudya Jayawardana and Wannakuwattewaduge Gerard Dilantha Fernando
Pathogens 2024, 13(11), 1012; https://doi.org/10.3390/pathogens13111012 - 18 Nov 2024
Viewed by 99
Abstract
Fusarium head blight (FHB), primarily caused by Fusarium graminearum, is one of the economically significant diseases in small grains. FHB causes severe damage to wheat production and grain quality. Several management strategies have been developed to control FHB, and chemical control through [...] Read more.
Fusarium head blight (FHB), primarily caused by Fusarium graminearum, is one of the economically significant diseases in small grains. FHB causes severe damage to wheat production and grain quality. Several management strategies have been developed to control FHB, and chemical control through fungicides plays a significant role. Although fungicides have effectively controlled F. graminearum in the field, the continuous exposure causes a selection pressure in the pathogen population towards fungicide resistance. Several studies have identified fungicide-resistant F. graminearum isolates and fungicide-resistance mechanisms. Although new fungicides with a new mode of action can be introduced into the market, developing a new fungicide is time-consuming, and extra efforts are needed for testing, approvals, and registrations. Therefore, it is essential to strategize the methods to delay the fungicide resistance. This review focuses on the impact of several fungicide applications currently used on FHB, focusing on Fusarium graminearum, the status of the fungicide sensitivity for fungicide classes, the resistance mechanisms against fungicides, and the mitigation strategies to delay the development of fungicide resistance in the pathogen population. Studying the fungicide resistance mechanisms and the mitigation strategies will be helpful in the future to use the available fungicides against F. graminearum without losing its effectiveness. Full article
(This article belongs to the Special Issue Current Research on Fusarium: 2nd Edition)
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<p>The fungicide resistance mechanisms developed in the pathogen. The diagram shows how the sensitive and fungicide-resistant isolates react in the presence of fungicides.</p>
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25 pages, 1793 KiB  
Review
Mesenchymal Stem Cells and Their Extracellular Vesicles Are a Promising Alternative to Antibiotics for Treating Sepsis
by Yu Jiang, Yunjuan Song, Qin Zeng and Bin Jiang
Bioengineering 2024, 11(11), 1160; https://doi.org/10.3390/bioengineering11111160 - 18 Nov 2024
Viewed by 278
Abstract
Sepsis is a life-threatening disease caused by the overwhelming response to pathogen infections. Currently, treatment options for sepsis are limited to broad-spectrum antibiotics and supportive care. However, the growing resistance of pathogens to common antibiotics complicates treatment efforts. Excessive immune response (i.e., cytokine [...] Read more.
Sepsis is a life-threatening disease caused by the overwhelming response to pathogen infections. Currently, treatment options for sepsis are limited to broad-spectrum antibiotics and supportive care. However, the growing resistance of pathogens to common antibiotics complicates treatment efforts. Excessive immune response (i.e., cytokine storm) can persist even after the infection is cleared. This overactive inflammatory response can severely damage multiple organ systems. Given these challenges, managing the excessive immune response is critical in controlling sepsis progression. Therefore, Mesenchymal stem cells (MSCs), with their immunomodulatory and antibacterial properties, have emerged as a promising option for adjunctive therapy in treating sepsis. Moreover, MSCs exhibit a favorable safety profile, as they are eventually eliminated by the host’s immune system within several months post-administration, resulting in minimal side effects and have not been linked to common antibiotic therapy drawbacks (i.e., antibiotic resistance). This review explores the potential of MSCs as a personalized therapy for sepsis treatment, clarifying their mechanisms of action and providing up-to-date technological advancements to enhance their protective efficacy for patients suffering from sepsis and its consequences. Full article
(This article belongs to the Special Issue Innovations in Regenerative Therapy: Cell and Cell-Free Approaches)
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<p>Illustration of the Progression Stages in Sepsis Development. The initial phase, Systemic Inflammatory Response Syndrome (SIRS), can originate from infections in organs such as the lungs and appendix. Subsequently, the dissemination of bacteria into the bloodstream triggers inflammation, characterized by the activation of T and B cells and the elevation of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α. This process is also associated with an increase in body temperature. As the infection advances, vascular thrombosis occurs, marking the transition to the second stage, severe sepsis. The onset of acute organ dysfunction distinguishes this stage. It can be identified in sepsis with accompanying hypotension (low blood pressure) or hypoperfusion (reduced blood flow through an organ). Without effective intervention, the condition may progress to the third stage, septic shock, characterized by a bacterial infection leading to low blood pressure, vasodilation, and organ failure.</p>
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<p>Overview of MSCs origins and their therapeutic role in sepsis. (<b>A</b>) MSCs are sourced from various bodily tissues, including bone marrow, adipose tissue, umbilical cord and its blood, dental pulp, and placenta. These cells adhere to 2D culture surfaces, exhibiting a fibroblast-like cell morphology. MSCs can undergo several rounds of expansion; however, only cells from early passages (e.g., up to 6 passages) are considered suitable for therapeutic applications. (<b>B</b>) MSCs can differentiate into various somatic cell types, such as muscle cells, osteocytes, chondrocytes, and adipocytes, contributing to tissue regeneration. MSCs exhibit immunomodulatory effects by inhibiting Th1/17 cells, M1 macrophages, natural killer cells, plasma cells, and neutrophils while promoting the activity of regulatory T cells, M2 macrophages, and dendritic cells. This modulation of the immune response, combined with the secretion of exosomes containing beneficial molecules, peptides, and microRNAs, enables MSCs to offer organ protection and prevent the progression of septic shock. * Indicates the donor samples.</p>
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<p>The role of MSCs in sepsis treatment: a promising therapeutic strategy. (<b>A</b>,<b>B</b>) MSCs offer a novel personalized approach to sepsis therapy, including autogenous or allogenous avenues, differing from traditional antibiotics, which solely target pathogens without addressing the inflammatory cascade or subsequent organ damage. MSCs have unique attributes that render them particularly efficacious in combating sepsis. They can produce antimicrobial peptides (AMPs) (<b>A</b>) and modulate immune responses (<b>B</b>), specifically by inhibiting the maturation of T and B cells and enhancing the proportion of regulatory T cells. This dual action facilitates infection control and diminishes the systemic inflammation that is a hallmark of sepsis. (<b>C</b>) Additionally, MSCs have an extraordinary ability to provide organ protection through trophic effects, halting the advancement to septic shock by maintaining organ function and fostering tissue repair and regeneration. Such trophic support significantly improves recovery chances for individuals experiencing septic shock. Eventually, all the MSCs are eliminated by the host immune system; the elapse from hours to weeks varies per the location in vivo, which promises a high safety profile. For the images labeled as “i” means before MSCs administration and “ii” means post-MSCs administration.</p>
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14 pages, 1958 KiB  
Review
Cinnamaldehyde in Focus: Antimicrobial Properties, Biosynthetic Pathway, and Industrial Applications
by Brandon Armando Jaramillo Jimenez, Fatima Awwad and Isabel Desgagné-Penix
Antibiotics 2024, 13(11), 1095; https://doi.org/10.3390/antibiotics13111095 - 18 Nov 2024
Viewed by 157
Abstract
Trans-cinnamaldehyde (TCA), a major bioactive compound derived from cinnamon (Cinnamomum spp.), has garnered significant attention for its diverse therapeutic properties. Its broad-spectrum antimicrobial activity, targeting both Gram-positive and Gram-negative bacteria as well as various fungi, positions TCA as a potent natural [...] Read more.
Trans-cinnamaldehyde (TCA), a major bioactive compound derived from cinnamon (Cinnamomum spp.), has garnered significant attention for its diverse therapeutic properties. Its broad-spectrum antimicrobial activity, targeting both Gram-positive and Gram-negative bacteria as well as various fungi, positions TCA as a potent natural antimicrobial agent. Beyond its antimicrobial effects, TCA demonstrates promising antidiabetic and anti-inflammatory activities, making it a valuable compound in medicinal and cosmetic applications. Recent studies have highlighted its role in disrupting microbial membranes, inhibiting biofilm formation, and modulating key metabolic pathways in pathogens. Furthermore, TCA has gained popularity in cosmetics due to its antimicrobial activity, antioxidant properties, and skin-friendly profile. This review provides a comprehensive overview of TCA’s antimicrobial potential, focusing on its mechanisms of action and its market and industrial applications. We also discuss the biosynthetic pathway of TCA, exploring both its natural production in cinnamon and advances in biotechnological production methods. As the demand for sustainable and natural antimicrobial agents grows, TCA emerges as a promising candidate for diverse applications. Finally, this review explores future directions for optimizing TCA production through metabolic engineering and synthetic biology approaches to meet industrial-scale demands. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Secondary Metabolites Produced in Nature)
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<p>The chemical structure of <span class="html-italic">trans</span>-cinnamaldehyde.</p>
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<p>Percentage of global natural cinnamaldehyde market, regional distribution, and expected reach in 2023. North America is the region that leads the TCA industry, followed by Europe and Asia. Adapted from Insights (2023).</p>
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<p>Schematic representation showing the potential inhibition mechanism of <span class="html-italic">trans</span>-cinnamaldehyde. TCA changes the cell membrane’s permeability and attacks the mitochondria, leading to the reactive oxygen species (ROS) and leakage of intracellular substances such as Na<sup>+</sup>, K<sup>+</sup>, and proteins. Adapted from [<a href="#B10-antibiotics-13-01095" class="html-bibr">10</a>,<a href="#B20-antibiotics-13-01095" class="html-bibr">20</a>,<a href="#B21-antibiotics-13-01095" class="html-bibr">21</a>]. Created in Biorender.</p>
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<p>Structure of <span class="html-italic">trans</span>-cinnamaldehyde Schiff base compounds.</p>
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<p>Proposed cinnamaldehyde biosynthetic pathway in microalgae. Black dotted lines show multiple enzymatic steps involved. Black arrows represent enzymatic, or transport steps supported by direct experimental evidence. Gray dashed arrows represent hypothesized steps. Enzyme abbreviations: CM, chorismate mutase; PPA-AT, prephenate aminotransferase; ADT, arogenate dehydratase; pCAT, plastidial cationic amino acid transporter; PDT, prephenate dehydratase; PPY-AT, phenylpyruvate aminotransferase; PAL, phenylalanine ammonia-lyase 4CL, 4-coumarate-CoA ligase; CCR, cinnamoyl CoA reductase. Adapted from [<a href="#B48-antibiotics-13-01095" class="html-bibr">48</a>,<a href="#B49-antibiotics-13-01095" class="html-bibr">49</a>,<a href="#B50-antibiotics-13-01095" class="html-bibr">50</a>,<a href="#B51-antibiotics-13-01095" class="html-bibr">51</a>,<a href="#B52-antibiotics-13-01095" class="html-bibr">52</a>]). Created in ChemDraw.</p>
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30 pages, 694 KiB  
Review
Activins and Inhibins in Cardiovascular Pathophysiology
by Wenyi Tang, Zhilin Gu, Jiuqi Guo, Mingzhi Lin, Hongqian Tao, Dalin Jia and Pengyu Jia
Biomolecules 2024, 14(11), 1462; https://doi.org/10.3390/biom14111462 - 18 Nov 2024
Viewed by 242
Abstract
Activins and inhibins, members of the transforming growth factor β (TGFβ) superfamily, were initially recognized for their opposing effects on the secretion of follicle-stimulating hormone. Subsequent research has demonstrated their broader biological roles across various tissue types. Primarily, activins and inhibins function through [...] Read more.
Activins and inhibins, members of the transforming growth factor β (TGFβ) superfamily, were initially recognized for their opposing effects on the secretion of follicle-stimulating hormone. Subsequent research has demonstrated their broader biological roles across various tissue types. Primarily, activins and inhibins function through the classical TGFβ SMAD signaling pathway, but studies suggest that they also act through other pathways, with their specific signaling being complex and context-dependent. Recent research has identified significant roles for activins and inhibins in the cardiovascular system. Their actions in other systems and their signaling pathways show strong correlations with the development and progression of cardiovascular diseases, indicating potential broader roles in the cardiovascular system. This review summarizes the progress in research on the biological functions and mechanisms of activins and inhibins and their signaling pathways in cardiovascular diseases, offering new insights for the prevention and treatment of cardiovascular diseases. Full article
(This article belongs to the Section Molecular Medicine)
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<p>Subunit structures, precursors, and mature forms of inhibins and activins. (<b>a</b>,<b>b</b>) Diagrammatic representation of human inhibin α and β subunit precursor structure, respectively. Polyarginine cleavage sites are shown with arrows. (<b>a</b>) α subunits consist of a 43-amino-acid prodomain, a 171-amino-acid αN domain, and a 134-amino-acid αC domain. N-glycosylation sites are shown at positions 146, 268, and 302. Amino acid 302 shows differential glycosylation. (<b>b</b>) βA subunits consist of a 290-amino-acid prodomain and a 116-amino-acid mature domain, with the N-glycosylation site shown at position 165. βB subunits consist of a 264-amino-acid prodomain and a 115-amino-acid mature domain, with the N-glycosylation site shown at position 93. (<b>c</b>) Precursor and mature inhibin dimers. Inhibins are heterodimers of α and β subunits. (<b>d</b>) Precursor and mature activin dimers. Activins are homodimers of two β subunits. The cysteine residues at position 95 of the α subunit, 80 of the βA subunit, and 79 of the βB subunit contribute to intermolecular disulfide bonds. The molecular masses of the dimers are indicated in kilodaltons.</p>
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10 pages, 1914 KiB  
Article
Nitric Oxide and Small and Intermediate Calcium-Activated Potassium Channels Mediate the Vasodilation Induced by Apigenin in the Resistance Vessels of Hypertensive Rats
by Lislaine Maria Klider, Maria Luiza Fidelis da Silva, Gustavo Ratti da Silva, João Ricardo Cray da Costa, Marcia Alessandra Arantes Marques, Emerson Luiz Botelho Lourenço, Francislaine Aparecida dos Reis Lívero, Jane Manfron and Arquimedes Gasparotto Junior
Molecules 2024, 29(22), 5425; https://doi.org/10.3390/molecules29225425 (registering DOI) - 18 Nov 2024
Viewed by 227
Abstract
Background: Apigenin (4′,5,7-trihydroxyflavone), a flavonoid with potential cardiovascular benefits, has unclear mechanisms of action. This study investigates its effects on vascular function in Spontaneously Hypertensive Rats (SHRs). Methods: Mesenteric vascular beds (MVBs) were isolated from SHRs and perfused with increasing doses of apigenin [...] Read more.
Background: Apigenin (4′,5,7-trihydroxyflavone), a flavonoid with potential cardiovascular benefits, has unclear mechanisms of action. This study investigates its effects on vascular function in Spontaneously Hypertensive Rats (SHRs). Methods: Mesenteric vascular beds (MVBs) were isolated from SHRs and perfused with increasing doses of apigenin after pre-contraction with phenylephrine. To explore the mechanisms, different MVBs were pre-perfused with antagonists and inhibitors, including indomethacin, L-NAME, and potassium channel blockers (tetraethylammonium, a non-specific potassium channel blocker; glibenclamide, an ATP-sensitive potassium channel blocker; 4-aminopyridine, a voltage-gated potassium channel blocker; charybdotoxin a selective intermediate-conductance calcium-activated potassium channel blocker; and apamin, a selective small-conductance calcium-activated potassium channel blocker). Results: Apigenin induced a dose-dependent reduction in perfusion pressure in MVBs with intact endothelium, an effect abolished by endothelium removal. L-NAME reduced apigenin-induced vasodilation by approximately 40%. The vasodilatory effect was blocked by potassium chloride and tetraethylammonium. The inhibition of small and intermediate calcium-activated potassium channels with charybdotoxin and apamin reduced apigenin-induced vasodilation by 50%, and a combination of these blockers with L-NAME completely inhibited the effect. Conclusions: Apigenin promotes vasodilation in resistance arteries through endothelial nitric oxide and calcium-activated potassium channels. These findings suggest that apigenin could have therapeutic potential in cardiovascular disease, warranting further clinical research. Full article
(This article belongs to the Special Issue Analyses and Applications of Phenolic Compounds in Food—2nd Edition)
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<p>Apigenin induces vasodilation in resistance arteries of rats. Molecular structure of apigenin (<b>A</b>). Effects of apigenin on the mesenteric vascular beds of WKY and SHRs (<b>B</b>,<b>C</b>). Typical representative record of the administration of acetylcholine (1 nmol) and apigenin (0.1, 0.3, and 1 µmol) in preparations of mesenteric vascular bed of SHRs (<b>D</b>). Values represent the mean ± standard error of the mean (<span class="html-italic">n</span> = 6 preparations). + <span class="html-italic">p</span> &lt; 0.05 compared with the previously administered dose. All experiments were performed in endothelium-intact preparations.</p>
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<p>The vasodilatory effects of apigenin are dependent on vascular endothelium and nitric oxide release. Vasodilatory action of apigenin in the presence (End+) and absence of endothelium (End-) are presented (<b>A</b>). Apigenin’s vasodilatory action was investigated in the presence of the nitric oxide synthase inhibitor (L-NAME) (<b>B</b>), regarding the formation of cGMP (<b>C</b>), or during the inhibition of the enzyme cyclooxygenase (indomethacin) (<b>D</b>). Values represent the mean ± standard error of the mean (<span class="html-italic">n</span> = 6 preparations). * <span class="html-italic">p</span> &lt; 0.05 compared with preparations in the presence of endothelium (<b>A</b>) or after treatment only with vehicle (<b>B</b>,<b>C</b>). + <span class="html-italic">p</span> &lt; 0.05 compared with the respective previous dose.</p>
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<p>The vasodilatory effects of apigenin depend on potassium channels. Apigenin’s vasodilatory action was investigated in the presence of 40 mM KCl (<b>A</b>), tetraethylammonium (TEA) (<b>B</b>), glibenclamide (<b>C</b>), 4-aminopyridine (4-AP) (<b>D</b>), charybdotoxin (ChTx) (<b>E</b>), or apamin (Apm) (<b>F</b>). The results show the mean ± S.E.M. of six preparations per group. * Indicate <span class="html-italic">p</span> &lt; 0.05 compared with the effects of apigenin on the vehicle group. + indicates <span class="html-italic">p</span> &lt; 0.05 compared with the respective previous dose. All experiments were performed in endothelium-intact preparations.</p>
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<p>The vasodilator effects of apigenin are dependent on the release of nitric oxide and the activation of potassium channels. Apigenin’s vasodilatory action was investigated in the presence of charybdotoxin (ChTx) plus apamin (Apm) (<b>A</b>), and charybdotoxin (ChTx) plus apamin (Apm) plus L-NAME (<b>B</b>). The results show the mean ± S.E.M. of six preparations per group. * Indicate <span class="html-italic">p</span> &lt; 0.05 compared with the effects of apigenin on the vehicle group. + indicates <span class="html-italic">p</span> &lt; 0.05 compared with the respective previous dose. All experiments were performed in endothelium-intact preparations.</p>
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15 pages, 499 KiB  
Communication
RNA-Seq Analysis of Pubertal Mammary Epithelial Cells Reveals Novel n-3 Polyunsaturated Fatty Acid Transcriptomic Changes in the fat-1 Mouse Model
by Connor D. C. Buchanan, Rahbika Ashraf, Lyn M. Hillyer, Wangshu Tu, Jing X. Kang, Sanjeena Subedi and David W. L. Ma
Nutrients 2024, 16(22), 3925; https://doi.org/10.3390/nu16223925 (registering DOI) - 17 Nov 2024
Viewed by 316
Abstract
Background: The early exposure of nutrients during pubertal mammary gland development may reduce the risk of developing breast cancer later in life. Anticancer n-3 polyunsaturated fatty acids (n-3 PUFA) are shown to modulate pubertal mammary gland development; however, the mechanisms [...] Read more.
Background: The early exposure of nutrients during pubertal mammary gland development may reduce the risk of developing breast cancer later in life. Anticancer n-3 polyunsaturated fatty acids (n-3 PUFA) are shown to modulate pubertal mammary gland development; however, the mechanisms of action remain unclear. Prior work focused on effects at the whole tissue level, and little is known at the cellular level, such as at the level of mammary epithelial cells (MECs), which are implicated in cancer development. Methods: This pilot study examined the effects of lifelong n-3 PUFA exposure on the transcriptome by RNA-Seq in the isolated MECs of pubertal (6–8-week-old) female fat-1 transgenic mice capable of de novo n-3 PUFA synthesis. edgeR and DESeq2 were used separately for the differential expression analysis of RNA sequencing data followed by the Benjamani–Hochberg procedure for multiple testing correction. Results: Nine genes were found concordant and significantly different (p ≤ 0.05) by both the DESeq2 and edgeR methods. These genes were associated with multiple pathways, suggesting that n-3 PUFA stimulates estrogen-related signaling (Mlltl0, Galr3, and Nrip1) and a glycolytic profile (Soga1, Pdpr, and Uso1) while offering protective effects for immune and DNA damage responses (Glpd1, Garre1, and Rpa1) in MECs during puberty. Conclusions: This pilot study highlights the utility of RNA-Seq to better understanding the mechanistic effects of specific nutrients such as n-3 PUFA in a cell-specific manner. Thus, further studies are warranted to investigate the cell-specific mechanisms by which n-3 PUFA influences pubertal mammary gland development and breast cancer risk later in life. Full article
(This article belongs to the Special Issue Nutrition and Gene Interaction)
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<p>Comparison of concordant and differentially expressed genes (<span class="html-italic">p</span> ≤ 0.05) across both <span class="html-italic">edgeR</span> and <span class="html-italic">DESeq2</span> in isolated mammary epithelial cells of 6- to 8-week-old female transgenic <span class="html-italic">fat-1</span> mice (<span class="html-italic">n</span> = 3) relative to WT mice (<span class="html-italic">n</span> = 3). Data are <span class="html-italic">DESeq2</span>. See methods and details in <a href="#nutrients-16-03925-t001" class="html-table">Table 1</a>.</p>
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