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35 pages, 6389 KiB  
Article
Towards Sustainable Construction: Experimental and Machine Learning-Based Analysis of Wastewater-Integrated Concrete Pavers
by Nosheen Blouch, Syed Noman Hussain Kazmi, Mohamed Metwaly, Nijah Akram, Jianchun Mi and Muhammad Farhan Hanif
Sustainability 2025, 17(15), 6811; https://doi.org/10.3390/su17156811 - 27 Jul 2025
Viewed by 389
Abstract
The escalating global demand for fresh water, driven by urbanization and industrial growth, underscores the need for sustainable water management, particularly in the water-intensive construction sector. Although prior studies have primarily concentrated on treated wastewater, the practical viability of utilizing untreated wastewater has [...] Read more.
The escalating global demand for fresh water, driven by urbanization and industrial growth, underscores the need for sustainable water management, particularly in the water-intensive construction sector. Although prior studies have primarily concentrated on treated wastewater, the practical viability of utilizing untreated wastewater has not been thoroughly investigated—especially in developing nations where treatment expenses frequently impede actual implementation, even for non-structural uses. While prior research has focused on treated wastewater, the potential of untreated or partially treated wastewater from diverse industrial sources remains underexplored. This study investigates the feasibility of incorporating wastewater from textile, sugar mill, service station, sewage, and fertilizer industries into concrete paver block production. The novelty lies in a dual approach, combining experimental analysis with XGBoost-based machine learning (ML) models to predict the impact of key physicochemical parameters—such as Biochemical Oxygen Demand (BOD), Chemical Oxygen Demand (COD), and Hardness—on mechanical properties like compressive strength (CS), water absorption (WA), ultrasonic pulse velocity (UPV), and dynamic modulus of elasticity (DME). The ML models showed high predictive accuracy for CS (R2 = 0.92) and UPV (R2 = 0.97 direct, 0.99 indirect), aligning closely with experimental data. Notably, concrete pavers produced with textile (CP-TXW) and sugar mill wastewater (CP-SUW) attained 28-day compressive strengths of 47.95 MPa and exceeding 48 MPa, respectively, conforming to ASTM C936 standards and demonstrating the potential to substitute fresh water for non-structural applications. These findings demonstrate the viability of using untreated wastewater in concrete production with minimal treatment, offering a cost-effective, sustainable solution that reduces fresh water dependency while supporting environmentally responsible construction practices aligned with SDG 6 (Clean Water and Sanitation) and SDG 12 (Responsible Consumption and Production). Additionally, the model serves as a practical screening tool for identifying and prioritizing viable wastewater sources in concrete production, complementing mandatory laboratory testing in industrial applications. Full article
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19 pages, 10094 KiB  
Article
Effects of Exogenous Plant Hormones on Agronomic Traits and Physiological Responses of Elymus sibiricus
by Qi Yuan, Juan Qi, Wenhui Liu, Wangyi Du and Mingjie Li
Agriculture 2025, 15(13), 1407; https://doi.org/10.3390/agriculture15131407 - 30 Jun 2025
Viewed by 366
Abstract
As key endogenous signal molecules regulating plant growth processes, plant hormones have significant applications in forage breeding. The experiment used ‘Elymus sibiricus Qingmu No. 2’ as the test material, and the effects of foliar applied phytohormones of gibberellin (GA3: 50, [...] Read more.
As key endogenous signal molecules regulating plant growth processes, plant hormones have significant applications in forage breeding. The experiment used ‘Elymus sibiricus Qingmu No. 2’ as the test material, and the effects of foliar applied phytohormones of gibberellin (GA3: 50, 100, 200, and 300 mg/L), cytokinin (6-BA: 1, 10, 100, and 150 mg/L), epibrassinolide (EBR: 0.01, 0.1, 1, and 10 mg/L), zeatin (ZT: 1, 10, 20, and 100 mg/L), and auxin (IAA: 10, 50, 100, and 150 mg/L) on growth and physiological responses in Elymus sibiricus were investigated. The results indicated that GA3 at 200 mg/L significantly enhanced biomass by 38.19%, plant height by 75.11%, and leaf area by 40.58% compared to controls. IAA (150 mg/L) specifically increased stem diameter by 38.25%, while 6-BA (100 mg/L) elevated chlorophyll content and antioxidant enzyme activities, indicating dual photoprotective and stress-mitigating roles. EBR (1 mg/L) and ZT (20 mg/L) moderately enhanced growth metrics. All treatments universally boosted stress tolerance via soluble sugar/protein accumulation and antioxidant system activation. Through comprehensive analysis, we recommend GA3 (200 mg/L) for effective grassland improvement, propose synergistic combinations of 6-BA and IAA to overcome morphological limitations, and highlight ultra-low EBR (0.01–0.1 mg/L) as a priority for future research. Full article
(This article belongs to the Section Crop Production)
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16 pages, 1472 KiB  
Article
Valorization of Underused Biomass of Acacia dealbata and Acacia melanoxylon Through Vermicomposting as an Alternative Substrate for Cucumber Production
by Maria C. Morais, Elisabete Nascimento-Gonçalves, Tiago Azevedo, Henda Lopes, Helena Ferreira, Ana M. Coimbra, Berta Gonçalves, João R. Sousa, Marta Roboredo and Paula A. Oliveira
Recycling 2025, 10(3), 120; https://doi.org/10.3390/recycling10030120 - 17 Jun 2025
Viewed by 328
Abstract
Invasive alien species are one of the main threats to global biodiversity, and pose significant management challenges in several areas outside their natural range. In southern Mediterranean Europe, the invasion of Acacia species is particularly severe and its control requires costly and often [...] Read more.
Invasive alien species are one of the main threats to global biodiversity, and pose significant management challenges in several areas outside their natural range. In southern Mediterranean Europe, the invasion of Acacia species is particularly severe and its control requires costly and often ineffective actions. The use of vermicompost derived from these species to replace peat-based substrates in horticulture offers a promising alternative to mitigate their economic and environmental impacts while enhancing the sustainability of their control. This study explored the potential of vermicompost produced from the fresh aboveground waste biomass (leaves + stems + flowers) of Acacia dealbata and Acacia melanoxylon (75:25 w/w), two of the most aggressive Acacia species in the Mediterranean, using Eisenia fetida over twelve weeks. In essence, this study aimed to evaluate the quality of the produced vermicompost and its suitability as a partial substitute for potting substrate in the production of cucumber (Cucumis sativus) seedlings for transplant. Four substrate mixtures containing 0%, 10%, 30%, and 50% of Acacia vermicompost (w/w), combined with commercial peat-based potting substrate and perlite (20%) were tested in polystyrene seedling trays. Seedling emergence, growth, and leaf biochemical parameters (photosynthetic pigments, phenolics, soluble sugars and starch, and total thiobarbituric acid-reactive substances—TBARSs) were evaluated. The results showed that the addition of Acacia vermicompost to the commercial substrate did not affect its germination but significantly enhanced seedling growth, particularly in mixtures containing 30% and 50% Acacia vermicompost. In addition, the absence of accumulation of TBARSs also reflected the superiority of these two treatments. These findings suggest that vermicompost derived from A. dealbata and A. melanoxylon biomass can be a viable peat-based substrate alternative for horticultural production, with the dual benefit of promoting sustainable agricultural practices and contributing to invasive species management. Full article
(This article belongs to the Special Issue Biomass Revival: Rethinking Waste Recycling for a Greener Future)
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15 pages, 2090 KiB  
Article
Assessment of the Curative Anti-Glycation Properties of a Novel Injectable Formulation Combining Dual-Weight Hyaluronic Acid (Low- and Mid/High-Molecular Weight) with Trehalose on Human Skin Ex Vivo
by Robert Chmielewski, Agata Lebiedowska and Wioletta Barańska-Rybak
Int. J. Mol. Sci. 2025, 26(10), 4747; https://doi.org/10.3390/ijms26104747 - 15 May 2025
Viewed by 632
Abstract
Glycation influences skin aging through non-enzymatic reactions between reducing sugars and proteins, forming advanced glycation end-products (AGEs) that accelerate skin deterioration. This study evaluates the curative anti-glycation effects of an injectable formulation combining dual-molecular-weight hyaluronic acid (low and mid/high) with trehalose in methylglyoxal-induced [...] Read more.
Glycation influences skin aging through non-enzymatic reactions between reducing sugars and proteins, forming advanced glycation end-products (AGEs) that accelerate skin deterioration. This study evaluates the curative anti-glycation effects of an injectable formulation combining dual-molecular-weight hyaluronic acid (low and mid/high) with trehalose in methylglyoxal-induced glycation in human skin explants. Thirty-six human skin explants were allocated across five experimental groups in a 12-day study. Glycation was induced using methylglyoxal (500 μM) on days 1 and 4, followed by curative product administration on day 5. CML (Nε-(carboxymethyl)lysine) immunohistochemistry was performed to assess glycation levels in the reticular dermis at days 6, 8, and 12, with quantitative analysis conducted through standardized image analysis. The formulation significantly reduced CML formation by 60% on day 6 compared to untreated controls (p < 0.001). Under methylglyoxal-induced glycation stress the product showed sustained curative effects, with CML reductions of 69% on day 6 (p = 0.008), 68% on day 8 (p = 0.012), and 61% on day 12 (p = 0.033) compared to methylglyoxal treatment alone. Cell viability remained unaffected throughout the study period across all experimental conditions. The tested injectable formulation exhibits significant and sustained curative anti-glycation properties in human skin explants for 12 days, effectively counteracting methylglyoxal-induced glycation damage without affecting cell viability. These findings advance anti-aging skin interventions, offering a novel approach to address glycation-induced skin damage with potential applications in clinical dermatology and aesthetic medicine. Full article
(This article belongs to the Special Issue Molecular Mechanisms for Skin Protection and Aging)
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12 pages, 1151 KiB  
Communication
Production of α-Glycerylphosphorylcholine in Fermented Roots, Tubers, and Fruits
by Timothy J. Tse, Farley Chicilo, Daniel J. Wiens, Jianheng Shen, Javier Anleu Alegria, Young Jun Kim, Ji Youn Hong, Jae Kyeom Kim, Eui-Cheol Shin, Martin J. T. Reaney and Youn Young Shim
Foods 2024, 13(19), 3085; https://doi.org/10.3390/foods13193085 - 27 Sep 2024
Cited by 3 | Viewed by 1520
Abstract
Vegetables and fruits, high in starch and sugars, are promising substrates for bioethanol production, but can also yield valuable nootropic compounds, such as α-glycerylphosphorylcholine (α-GPC). This compound is a known cognitive enhancer that works by increasing the release of acetylcholine, a neurotransmitter essential [...] Read more.
Vegetables and fruits, high in starch and sugars, are promising substrates for bioethanol production, but can also yield valuable nootropic compounds, such as α-glycerylphosphorylcholine (α-GPC). This compound is a known cognitive enhancer that works by increasing the release of acetylcholine, a neurotransmitter essential for learning and memory. In this study, select root and tuber crops, as well as fruits, were subjected to Saccharomyces cerevisiae fermentation to observe the co-production of ethanol and α-GPC. The ethanol yields from these substrates were comparable to those from wheat (var. AC Andrew), ranging from 30.44 g/L (beet) to 70.04 g/L (lotus root). Aside from ethanol, α-GPC was also produced, with purple top turnip yielding 0.91 g/L, the second highest concentration after wheat (used as a reference), which produced 1.25 g/L. Although α-GPC yields in the tested substrates were lower than those from cereal grains (e.g., wheat and barley), a noteworthy observation was the production of methanol in many of these substrates. Methanol was detected in all feedstocks except wheat, with concentrations ranging from 0.10 g/L (cassava) to 1.69 g/L (purple top turnip). A linear regression analysis revealed a strong correlation between methanol and α-GPC content (R2 = 0.876; slope = 0.52), suggesting a potential link in their biosynthetic pathways. These feedstocks not only proved effective as substrates for bioethanol production, but also showed potential for generating value-added compounds such as α-GPC. This dual-purpose potential presents new market opportunities for producers by leveraging both biofuel and nootropic compound production. Furthermore, the observed relationship between methanol and α-GPC production warrants further investigation to elucidate the metabolic pathways involved. Full article
(This article belongs to the Special Issue Sustainable Uses and Applications of By-Products of the Food Industry)
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20 pages, 3712 KiB  
Article
Overexpression of SlALC Increases Drought and Salt Tolerance and Affects Fruit Dehiscence in Tomatoes
by Zihan Gao, Yuqing Tu, Changguang Liao, Pengyu Guo, Yanling Tian, Ying Zhou, Qiaoli Xie, Guoping Chen and Zongli Hu
Int. J. Mol. Sci. 2024, 25(17), 9433; https://doi.org/10.3390/ijms25179433 - 30 Aug 2024
Cited by 1 | Viewed by 1179
Abstract
The bHLH transcription factors are important plant regulators against abiotic stress and involved in plant growth and development. In this study, SlALC, a gene coding for a prototypical DNA-binding protein in the bHLH family, was isolated, and SlALC-overexpression tomato (SlALC [...] Read more.
The bHLH transcription factors are important plant regulators against abiotic stress and involved in plant growth and development. In this study, SlALC, a gene coding for a prototypical DNA-binding protein in the bHLH family, was isolated, and SlALC-overexpression tomato (SlALC-OE) plants were generated by Agrobacterium-mediated genetic transformation. SlALC transgenic lines manifested higher osmotic stress tolerance than the wild-type plants, estimated by higher relative water content and lower water loss rate, higher chlorophyll, reducing sugar, starch, proline, soluble protein contents, antioxidant enzyme activities, and lower MDA and reactive oxygen species contents in the leaves. In SlALC-OE lines, there were more significant alterations in the expression of genes associated with stress. Furthermore, SlALC-OE fruits were more vulnerable to dehiscence, with higher water content, reduced lignin content, SOD/POD/PAL enzyme activity, and lower phenolic compound concentrations, all of which corresponded to decreased expression of lignin biosynthetic genes. Moreover, the dual luciferase reporter test revealed that SlTAGL1 inhibits SlALC expression. This study revealed that SlALC may play a role in controlling plant tolerance to drought and salt stress, as well as fruit lignification, which influences fruit dehiscence. The findings of this study have established a foundation for tomato tolerance breeding and fruit quality improvement. Full article
(This article belongs to the Special Issue Advances in Tomato Breeding and Molecular Research)
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14 pages, 4035 KiB  
Article
Transcriptomic Analysis of Alfalfa Flowering and the Dual Roles of MsAP1 in Floral Organ Identity and Flowering Time
by Xu Jiang, Huiting Cui, Zhen Wang, Ruicai Long, Qingchuan Yang and Junmei Kang
Agronomy 2024, 14(8), 1741; https://doi.org/10.3390/agronomy14081741 - 8 Aug 2024
Viewed by 1370
Abstract
Flowering, the transition from the vegetative to the reproductive stage, is vital for reproductive success, affecting forage quality, the yield of aboveground biomass, and seed production in alfalfa. To explore the transcriptomic profile of alfalfa flowering transition, we compared gene expression between shoot [...] Read more.
Flowering, the transition from the vegetative to the reproductive stage, is vital for reproductive success, affecting forage quality, the yield of aboveground biomass, and seed production in alfalfa. To explore the transcriptomic profile of alfalfa flowering transition, we compared gene expression between shoot apices (SAs) at the vegetative stage and flower buds (FBs) at the reproductive stage by mRNA sequencing. A total of 3,409 DEGs were identified, and based on gene ontology (GO), 42.53% of the most enriched 15 processes were associated with plant reproduction, including growth phase transition and floral organ development. For the former category, 79.1% of DEGs showed higher expression levels in SA than FB, suggesting they were sequentially turned on and off at the two test stages. For the DEGs encoding the components of circadian rhythm, sugar metabolism, phytohormone signaling, and floral organ identity genes, 60.71% showed higher abundance in FB than SA. Among them, MsAP1, an APETALA1 (AP1) homolog of Arabidopsis thaliana, showed high expression in flower buds and co-expressed with genes related to flower organ development. Moreover, ectopic expression of MsAP1 in Arabidopsis resulted in dwarfism and early flowering under long-day conditions. The MsAP1-overexpression plant displayed morphological abnormalities including fused whorls, enlarged pistils, determinate inflorescence, and small pods. In addition, MsAP1 is localized in the nucleus and exhibits significant transcriptional activity. These findings revealed a transcriptional regulation network of alfalfa transition from juvenile phase to flowering and provided genetic evidence of the dual role of MsAP1 in flowering and floral organ development. Full article
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18 pages, 1302 KiB  
Review
Bridging the Gap: A Literature Review of Advancements in Obesity and Diabetes Mellitus Management
by Gheorghe Nicusor Pop, Felicia Manole, Florina Buleu, Alexandru Catalin Motofelea, Silviu Bircea, Daian Popa, Nadica Motofelea and Catalin Alexandru Pirvu
Appl. Sci. 2024, 14(15), 6565; https://doi.org/10.3390/app14156565 - 27 Jul 2024
Cited by 3 | Viewed by 3605
Abstract
This literature review explores advancements in obesity and diabetes mellitus diagnosis and treatment, highlighting recent innovations that promise more personalized and effective healthcare interventions. For obesity diagnosis, traditional methods like body mass index (BMI) calculations are now complemented by bioelectrical impedance analysis (BIA) [...] Read more.
This literature review explores advancements in obesity and diabetes mellitus diagnosis and treatment, highlighting recent innovations that promise more personalized and effective healthcare interventions. For obesity diagnosis, traditional methods like body mass index (BMI) calculations are now complemented by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA) scans, with emerging biomarkers from “omics” technologies. Diabetes diagnosis has advanced with standard hemoglobin A1c (HbA1c) testing supplemented by novel measures such as advanced glycation end products (AGEs) and autoantibodies, alongside the use of artificial intelligence to enhance diagnostic accuracy. Treatment options for obesity are expanding beyond traditional methods. Minimally invasive bariatric surgeries, endoscopic procedures, fecal microbiota transplants (FMTs), and pharmaceuticals like GLP-1 receptor agonists (semaglutide, tirzepatide) show promising results. Cognitive behavioral therapy (CBT) and prescription digital therapeutics (PDTs) are also valuable tools for weight management. Diabetes treatment is also undergoing a transformation. Ultra-long-acting insulins and innovative oral insulin delivery methods are on the horizon. SGLT2 inhibitors and GLP-1 receptor agonists are proving to be effective medications for blood sugar control. Continuous glucose monitoring (CGM) systems and closed-loop insulin delivery are revolutionizing diabetes management, while stem cell therapy holds promise for the future. By integrating advanced diagnostic tools with personalized treatment plans, obesity and diabetes care are entering a new era. This personalized approach empowers patients and paves the way for improved health outcomes and a better quality of life. Full article
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9 pages, 2842 KiB  
Article
A Rapid and Reliable Spectrofluorimetric Method to Measure the Urinary Lactulose/Mannitol Ratio for Dysbiosis Assessment
by Lorenzo Marino Cerrato, Elisabetta Schiano, Fortuna Iannuzzo, Gian Carlo Tenore, Vincenzo Summa, Maria Daglia, Ettore Novellino and Mariano Stornaiuolo
Biomedicines 2024, 12(7), 1557; https://doi.org/10.3390/biomedicines12071557 - 13 Jul 2024
Viewed by 1518
Abstract
Gut microbiota plays a crucial role in human health homeostasis, and the result of its alteration, known as dysbiosis, leads to several pathologies (e.g., inflammatory bowel disease, metabolic syndrome, and Crohn’s disease). Traditional methods used to assess dysbiosis include the dual sugar absorption [...] Read more.
Gut microbiota plays a crucial role in human health homeostasis, and the result of its alteration, known as dysbiosis, leads to several pathologies (e.g., inflammatory bowel disease, metabolic syndrome, and Crohn’s disease). Traditional methods used to assess dysbiosis include the dual sugar absorption test and the urinary lactulose/mannitol ratio (LMR) measurement using mass spectrometry. Despite its precision, this approach is costly and requires specialized equipment. Hence, we developed a rapid and reliable spectrofluorimetric method for measuring LMR in urine, offering a more accessible alternative. This spectrofluorimetric assay quantifies the fluorescence of nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH) produced during the enzymatic oxidation of mannitol and lactulose, respectively. The assay requires 100 µL of urine samples and detects LMR values lower (eubiosis) and higher (dysbiosis) than 0.05, ultimately being amenable to high-throughput screening and automatization, making it practical for clinical and research settings. A validation of the method demonstrated its high precision, accuracy, and robustness. Additionally, this study confirmed analyte stability under various storage conditions, ensuring reliable results even with delayed analysis. Overall, this spectrofluorimetric technique reduces costs, time, and the environmental impact associated with traditional mass spectrometry methods, making it a viable option for widespread use in the assessment of dysbiosis. Full article
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14 pages, 1584 KiB  
Article
In Vitro and In Silico Investigation of Polyacetylenes from Launaea capitata (Spreng.) Dandy as Potential COX-2, 5-LOX, and BchE Inhibitors
by Fatma M. Abdel Bar, Amira Mira, Ahmed I. Foudah, Manal A. Alossaimi, Shatha F. Alkanhal, Alanoud M. Aldaej and Mai H. ElNaggar
Molecules 2023, 28(8), 3526; https://doi.org/10.3390/molecules28083526 - 17 Apr 2023
Cited by 2 | Viewed by 2041
Abstract
Diverse secondary metabolites are biosynthesized by plants via various enzymatic cascades. These have the capacity to interact with various human receptors, particularly enzymes implicated in the etiology of several diseases. The n-hexane fraction of the whole plant extract of the wild edible [...] Read more.
Diverse secondary metabolites are biosynthesized by plants via various enzymatic cascades. These have the capacity to interact with various human receptors, particularly enzymes implicated in the etiology of several diseases. The n-hexane fraction of the whole plant extract of the wild edible plant, Launaea capitata (Spreng.) Dandy was purified by column chromatography. Five polyacetylene derivatives were identified, including (3S,8E)-deca-8-en-4,6-diyne-1,3-diol (1A), (3S)-deca-4,6,8-triyne-1,3-diol (1B), (3S)-(6E,12E)-tetradecadiene-8,10-diyne-1,3-diol (2), bidensyneoside (3), and (3S)-(6E,12E)-tetradecadiene-8,10-diyne-1-ol-3-O-β-D-glucopyranoside (4). These compounds were investigated for their in vitro inhibitory activity against enzymes involved in neuroinflammatory disorders, including cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and butyrylcholinesterase (BchE) enzymes. All isolates recorded weak–moderate activities against COX-2. However, the polyacetylene glycoside (4) showed dual inhibition against BchE (IC50 14.77 ± 1.55 μM) and 5-LOX (IC50 34.59 ± 4.26 μM). Molecular docking experiments were conducted to explain these results, which showed that compound 4 exhibited greater binding affinity to 5-LOX (−8.132 kcal/mol) compared to the cocrystallized ligand (−6.218 kcal/mol). Similarly, 4 showed a good binding affinity to BchE (−7.305 kcal/mol), which was comparable to the cocrystallized ligand (−8.049 kcal/mol). Simultaneous docking was used to study the combinatorial affinity of the unresolved mixture 1A/1B to the active sites of the tested enzymes. Generally, the individual molecules showed lower docking scores against all the investigated targets compared to their combination, which was consistent with the in vitro results. This study demonstrated that the presence of a sugar moiety (in 3 and 4) resulted in dual inhibition of 5-LOX and BchE enzymes compared to their free polyacetylenes analogs. Thus, polyacetylene glycosides could be suggested as potential leads for developing new inhibitors against the enzymes involved in neuroinflammation. Full article
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20 pages, 5031 KiB  
Article
Exploring Mannosylpurines as Copper Chelators and Cholinesterase Inhibitors with Potential for Alzheimer’s Disease
by Ignazio Schino, Mariangela Cantore, Modesto de Candia, Cosimo D. Altomare, Catarina Maria, João Barros, Vasco Cachatra, Patrícia Calado, Karina Shimizu, Adilson A. Freitas, Maria C. Oliveira, Maria J. Ferreira, José N. C. Lopes, Nicola A. Colabufo and Amélia P. Rauter
Pharmaceuticals 2023, 16(1), 54; https://doi.org/10.3390/ph16010054 - 30 Dec 2022
Cited by 3 | Viewed by 2887
Abstract
Alzheimer’s Disease (AD) is characterized by a progressive cholinergic neurotransmission imbalance, with a decrease of acetylcholinesterase (AChE) activity followed by a significant increase of butyrylcholinesterase (BChE) in the later AD stages. BChE activity is also crucial for the development of Aβ plaques, the [...] Read more.
Alzheimer’s Disease (AD) is characterized by a progressive cholinergic neurotransmission imbalance, with a decrease of acetylcholinesterase (AChE) activity followed by a significant increase of butyrylcholinesterase (BChE) in the later AD stages. BChE activity is also crucial for the development of Aβ plaques, the main hallmarks of this pathology. Moreover, systemic copper dyshomeostasis alters neurotransmission leading to AD. In the search for structures targeting both events, a set of novel 6-benzamide purine nucleosides was synthesized, differing in glycone configuration and N7/N9 linkage to the purine. Their AChE/BChE inhibitory activity and metal ion chelating properties were evaluated. Selectivity for human BChE inhibition required N9-linked 6-deoxy-α-d-mannosylpurine structure, while all three tested β-d-derivatives appeared as non-selective inhibitors. The N9-linked l-nucleosides were cholinesterase inhibitors except the one embodying either the acetylated sugar or the N-benzyl-protected nucleobase. These findings highlight that sugar-enriched molecular entities can tune bioactivity and selectivity against cholinesterases. In addition, selective copper chelating properties over zinc, aluminum, and iron were found for the benzyl and acetyl-protected 6-deoxy-α-l-mannosyl N9-linked purine nucleosides. Computational studies highlight molecular conformations and the chelating molecular site. The first dual target compounds were disclosed with the perspective of generating drug candidates by improving water solubility. Full article
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13 pages, 600 KiB  
Systematic Review
A Systematic Review of the Influence of Bovine Colostrum Supplementation on Leaky Gut Syndrome in Athletes: Diagnostic Biomarkers and Future Directions
by Hanna Dziewiecka, Harpal S. Buttar, Anna Kasperska, Joanna Ostapiuk-Karolczuk, Małgorzata Domagalska, Justyna Cichoń and Anna Skarpańska-Stejnborn
Nutrients 2022, 14(12), 2512; https://doi.org/10.3390/nu14122512 - 17 Jun 2022
Cited by 11 | Viewed by 7828
Abstract
Background: Bovine colostrum (BC) contains a myriad of bioactive molecules that are renowned for possessing unique medicinal benefits in children and adults, and BC supplements are considered safe and cost-effective options to manage/prevent the incidence of upper respiratory tract infections and gut-related problems [...] Read more.
Background: Bovine colostrum (BC) contains a myriad of bioactive molecules that are renowned for possessing unique medicinal benefits in children and adults, and BC supplements are considered safe and cost-effective options to manage/prevent the incidence of upper respiratory tract infections and gut-related problems in athletes. In this review, we will try to answer the question: How will BC supplementation ameliorate gut permeability problems among athletes? Methods: Literature searches were performed using PRISMA guidance to identify studies assessing the influence of BC supplements on gut permeability. Studies were selected using four databases: PubMed, Web of Science, Scopus, and EBSCO, and a total number of 60 articles were retrieved by using appropriate keywords. Results: Nine studies were selected that met the eligibility criteria for this review. The data analysis revealed that vigorous exercise profoundly increases intestinal permeability, and BC supplementation helps to reverse gut permeability in athletes. Conclusion: BC supplementation may be highly beneficial in improving gut permeability in athletes. However, well-designed, placebo-controlled, and randomized studies are needed to evaluate the long-term safety and efficacy and to determine the optimal dose schedules of BC supplementation in high-performance athletes. Full article
(This article belongs to the Special Issue Nutritional Intervention for Competitive Athletes)
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12 pages, 2361 KiB  
Article
A Simple, Robust, and Convenient HPLC Assay for Urinary Lactulose and Mannitol in the Dual Sugar Absorption Test
by Ivana R. Sequeira, Marlena C. Kruger, Roger D. Hurst and Roger G. Lentle
Molecules 2022, 27(9), 2677; https://doi.org/10.3390/molecules27092677 - 21 Apr 2022
Cited by 8 | Viewed by 3193
Abstract
Background: Heterogeneous laborious analytical methodologies for the determination of urinary lactulose and mannitol limit their utility in intestinal permeability testing. Methods: We developed an assay using a Shimadzu HPLC system, an Aminex HPX87C column, and refractive index detection. The test was calibrated using [...] Read more.
Background: Heterogeneous laborious analytical methodologies for the determination of urinary lactulose and mannitol limit their utility in intestinal permeability testing. Methods: We developed an assay using a Shimadzu HPLC system, an Aminex HPX87C column, and refractive index detection. The test was calibrated using a series of dilutions from standard stock solutions of lactulose and mannitol ‘spiked’ into urine samples. The utility to quantify urinary excretion during the dual sugar absorption test over 6 h was also determined. Results: Lactulose and mannitol were eluted isocratically at 5.7 and 10.1 min, respectively, with water as a mobile phase at a flow rate of 0.3 mL min−1, 858 psi, 60 °C. The calibration curves for both sugars were linear up to 500 µg mL−1 with a limit of detection in standard solutions at 4 µg mL−1 and in ‘spiked’ urine samples at 15 µg mL−1. The intra-assay and inter-assay CVs were between 2.0–5.1% and 2.0–5.1% for lactulose and 2.5–4.4% and 2.8–3.9% for mannitol. The urinary profiles of the 6 h absorption of lactulose and mannitol showed similar peak-retention times to standard solutions and were well-resolved at 5.9 and 10.4 min, respectively. Conclusions: The assay was easy to automate, using commonly available equipment and convenient requiring no prior laborious sample derivatization. The simplicity, reproducibility, and robustness of this assay facilitates its use in routine clinical settings for the quantification of intestinal permeability. Full article
(This article belongs to the Section Analytical Chemistry)
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15 pages, 3852 KiB  
Article
Plasma Metabolic and Lipidomic Fingerprinting of Individuals with Increased Intestinal Permeability
by Rohan M. Shah, Snehal R. Jadhav, Laura Phan, Kelton Tremellen, Cuong D. Tran and David J. Beale
Metabolites 2022, 12(4), 302; https://doi.org/10.3390/metabo12040302 - 29 Mar 2022
Cited by 7 | Viewed by 2838
Abstract
The dual-sugar intestinal permeability test is a commonly used test to assess changes in gut barrier function. However, it does not identify functional changes and the exact mechanism of damage caused by the increased intestinal permeability. This study aims to explore the application [...] Read more.
The dual-sugar intestinal permeability test is a commonly used test to assess changes in gut barrier function. However, it does not identify functional changes and the exact mechanism of damage caused by the increased intestinal permeability. This study aims to explore the application of untargeted metabolomics and lipidomics to identify markers of increased intestinal permeability. Fifty fasting male participants (18–50 years) attended a single visit to conduct the following procedures: assessment of anthropometric measures, assessment of gastrointestinal symptoms, intestinal permeability test, and assessment of blood samples 90 min post-administration of the intestinal permeability test. Rhamnose and lactulose were analysed using gas chromatography-mass spectrometry (GC-MS). Untargeted polar metabolites and lipidomics were assessed by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF MS). There was an elevated lactulose/rhamnose ratio in 27 subjects, indicating increased permeability compared to the remaining 23 control subjects. There were no significant differences between groups in characteristics such as age, body mass index (BMI), weight, height, and waist conference. Fourteen metabolites from the targeted metabolomics data were identified as statistically significant in the plasma samples from intestinal permeability subjects. The untargeted metabolomics and lipidomics analyses yielded fifteen and fifty-one statistically significant features, respectively. Individuals with slightly elevated intestinal permeability had altered energy, nucleotide, and amino acid metabolism, in addition to increased glutamine levels. Whether these biomarkers may be used to predict the early onset of leaky gut warrants further investigation. Full article
(This article belongs to the Section Nutrition and Metabolism)
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12 pages, 3275 KiB  
Case Report
Management of HER2-Positive Breast Cancer for a Young Patient with Visceral Crisis—The Adjuvant Role of Lifestyle Changes
by Larisa Maria Badau, Andrei Dorin Ciocoiu, Cristina Marinela Oprean, Nusa Alina Segarceanu, Adelina Gheju and Brigitha Vlaicu
Curr. Oncol. 2022, 29(3), 1890-1901; https://doi.org/10.3390/curroncol29030154 - 10 Mar 2022
Cited by 2 | Viewed by 5655
Abstract
The safety profile and effectiveness of existing anti-HER2-targeted therapies have not been evaluated in patients with breast cancer and visceral crisis. We report the case of a 26-year-old woman who was diagnosed with advanced HER2-positive breast cancer and initially treated with curative intent [...] Read more.
The safety profile and effectiveness of existing anti-HER2-targeted therapies have not been evaluated in patients with breast cancer and visceral crisis. We report the case of a 26-year-old woman who was diagnosed with advanced HER2-positive breast cancer and initially treated with curative intent therapy in a neoadjuvant setting, using Trastuzumab and Pertuzumab in combination with Docetaxel; her cancer recurred two years later, with liver metastases and pulmonary lymphangitic carcinomatosis, causing visceral crisis. Furthermore, the patient’s clinical status worsened when she developed respiratory failure, hepatomegaly and a severe hepatocytolysis. Since the patient was free of disease more than six months, we started with Paclitaxel half dose because of the hepatic dysfunction, and we gradually reintroduced Trastuzumab and then Pertuzumab. In the meantime, the patient changed her lifestyle by increasing her consumption of fresh fruits and vegetables and fiber and reducing her intake of processed meat, dairy and sugar. As a result, the patient showed a significant improvement in her respiratory symptoms and liver tests in less than two months. Imaging reevaluation showed partial remission of liver metastases and pulmonary lymphangitic carcinomatosis. She underwent seven months of dual anti-HER2 blockade before relapsing cerebrally. Our results suggest that the sequential combination therapy with Trastuzumab, Pertuzumab and Paclitaxel presented in this study, associated with a healthy lifestyle, may be a good management for recurrent HER2-positive breast cancer with pulmonary visceral crisis and severe liver dysfunction. Full article
(This article belongs to the Topic Immunotherapy and Targeted Therapy in Breast Cancer)
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