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21 pages, 4266 KB  
Article
Traffic-Related Emissions Induce Angiotensin II-Dependent Oxidative Stress in the Hippocampus of ApoE-Null Male Mice
by Tyler D. Armstrong, Usa Suwannasual, Analana Stanley, Bailee Johnson, Victoria L. Youngblood, Isabella Santiago, Mickaela Cook, Sophia M. Giasolli and Amie K. Lund
Antioxidants 2026, 15(2), 161; https://doi.org/10.3390/antiox15020161 - 25 Jan 2026
Abstract
Traffic-related air pollution (TRAP) is known to contribute to oxidative stress in the central nervous system (CNS) and has been linked to increased risk of Alzheimer’s disease (AD). Alterations in the renin–angiotensin system (RAS), specifically increased angiotensin II (Ang II) signaling via the [...] Read more.
Traffic-related air pollution (TRAP) is known to contribute to oxidative stress in the central nervous system (CNS) and has been linked to increased risk of Alzheimer’s disease (AD). Alterations in the renin–angiotensin system (RAS), specifically increased angiotensin II (Ang II) signaling via the angiotensin II type 1 (AT1) receptor, are implicated in increased oxidative stress in the CNS via activation of NADPH oxidase (NOX). As exposure to TRAP may further elevate AD risk, we investigated whether exposure to inhaled mixed gasoline and diesel vehicle emissions (MVE) promotes RAS-dependent expression of factors that contribute to AD pathophysiology in an apolipoprotein E-deficient (ApoE−/−) mouse model. Male ApoE−/− mice (6–8 weeks old) on a high-fat diet were treated with either an ACE inhibitor (captopril, 4 mg/kg/day) or water and exposed to filtered air (FA) or MVE (200 µg PM/m3) for 30 days. MVE exposure elevated plasma Ang II, inflammation, and oxidative stress in the hippocampus, associated with increased levels of Aph-1 homolog B (APH1B), a gamma-secretase subunit, and beta-secretase 1 (BACE1), involved in Aβ production. Each of these endpoints was normalized with ACEi treatment. These findings indicate that TRAP exposure in ApoE−/− mice drives a RAS- and NOX-dependent oxidative and inflammatory response and shifts Aβ processing towards an amyloidogenic profile before overt Aβ deposition, suggesting a potential therapeutic approach for air pollution-induced AD risk. Full article
(This article belongs to the Special Issue Oxidative Stress Induced by Air Pollution, 3rd Edition)
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21 pages, 11727 KB  
Article
Dietary Supplementation of Concentrate Improves Lactation Performance and Immune Function in Grazing Lactating Yaks Through Changes in Rumen Microbial Population and Metabolites
by Lu Sun, Xun Wang, Hao Wang, Zhanhong Cui, Shatuo Chai, Shujie Liu and Shiheng Tao
Microorganisms 2026, 14(2), 278; https://doi.org/10.3390/microorganisms14020278 - 24 Jan 2026
Viewed by 58
Abstract
Grazing yaks often face protein deficiency due to low-quality pasture, which limits milk production. This study aimed to investigate the effects of varying protein levels in concentrate supplementation on lactational performance, immune function, and rumen microbial and metabolites in grazing lactating yaks. Thirty-six [...] Read more.
Grazing yaks often face protein deficiency due to low-quality pasture, which limits milk production. This study aimed to investigate the effects of varying protein levels in concentrate supplementation on lactational performance, immune function, and rumen microbial and metabolites in grazing lactating yaks. Thirty-six lactating Qinghai Plateau yaks (172.78 ± 11.70 kg) were assigned to four treatments for 70 d (10 d adaptation + 60 d trial): grazing only (CON) or grazing plus 1.50 kg/d concentrate containing 15.09% (CP15), 17.00% (CP17), or 18.98% CP (CP19). Concentrate supplementation significantly increased average daily gain (ADG; 0.22 vs. 0.72–0.90 kg/d; p < 0.001) and milk yield (622.18 vs. 1094.25–1385.73 g/d; p < 0.001), and milk yield showed a linear increase with higher dietary protein levels (p < 0.001). Milk protein yield (29.99 vs. 56.00–68.60 g/d; p < 0.001) and milk lactose yield (40.71 vs. 79.85–93.53 g/d; p < 0.001) were also increased. Milk composition, including fat, protein, and lactose, also improved across supplementation groups, with the greatest enhancement observed at the CP17 group (p < 0.05). Rumen pH and volatile fatty acids did not differ between treatments, while microbial protein increased with supplementation (10.88 vs. 12.72–15.00 mg/dL; p = 0.041) and showed a linear response to dietary CP level (p = 0.033). Concentrate supplementation significantly altered the rumen microbial structure (ANOSIM, p = 0.036), enriching Succinivibrionaceae_UCG-002, Fibrobacter, Ruminobacter, and Succinimonas and reducing Saccharofermentans in CP17 yaks (p < 0.05). Untargeted metabolomics further indicated a marked shift in the ruminal metabolite profile. Compared with CON, CP17 yaks exhibited higher levels of calcium propionate, 2-nitrofuran, curvulalide, and 2,5-dihydroxybenzoic acid, but lower levels of 4-pyridoxic acid, L-carnitine, bitocholic acid, and taurodehydrocholic acid. Pathway enrichment analysis identified vitamin B6 metabolism as significantly enriched. Collectively, these findings suggest that moderate protein concentrate supplementation (CP17) may enhance lactation performance by modulating rumen microbiota and metabolism in lactating yaks. Full article
(This article belongs to the Section Veterinary Microbiology)
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20 pages, 1685 KB  
Article
Nutritional and Antioxidant Profile of Brown Eragrostis tef (Zucc.) Trotter Flour in Blends with Glycine max (L.) Merr. Flour
by Shewangzaw Addisu Mekuria, Kamil Czwartkowski and Joanna Harasym
Molecules 2026, 31(2), 365; https://doi.org/10.3390/molecules31020365 - 20 Jan 2026
Viewed by 214
Abstract
The still-growing demand for nutritious gluten-free products necessitates the development of a composite flour that addresses the nutritional deficiencies common in conventional gluten-free formulations. This study aimed to comprehensively characterize brown teff (Eragrostis tef (Zucc.) Trotter) and soybean (Glycine max (L.) [...] Read more.
The still-growing demand for nutritious gluten-free products necessitates the development of a composite flour that addresses the nutritional deficiencies common in conventional gluten-free formulations. This study aimed to comprehensively characterize brown teff (Eragrostis tef (Zucc.) Trotter) and soybean (Glycine max (L.) Merr.) composite flours at 0%, 10%, 20%, 30%, and 40% soybean inclusion levels (w/w) to establish evidence-based formulation guidelines for future products. Proximate composition, antioxidant properties (total polyphenol content—TPC, antioxidant capacity vs. 2,2-diphenyl-1-picrylhydrazyl radical—DPPH and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radical—ABTS, ferric reducing antioxidant power—FRAP), particle size distribution, pasting properties, color characteristics, and molecular fingerprints (Fourier transform infrared spectroscopy—FTIR) were evaluated. A principal component analysis (PCA) was employed to identify compositional–functional relationships. Soybean inclusion significantly enhanced protein content from 9.93% (pure teff) to 23.07% (60:40 blend, dry matter), fat from 2.14% to 10.47%, and fiber from 3.43% to 6.72%. The antioxidant capacity increased proportionally with soybean content, with a 40% inclusion yielding FRAP values of 5.19 mg FeSO4/g DM and TPC of 3.44 mg GAE/g DM. However, pasting viscosity decreased notably from 12,198.00 mPa·s (pure teff) to 129.00 mPa·s (60:40 blend), indicating a reduced gel-forming capacity caused by soybean addition. PCA revealed that nutritional composition (PC1: 70.6% variance) and pasting properties (PC2: 21.0% variance) vary independently, suggesting non-additive functional behavior in blends. Brown teff–soybean blends at a 20–30% soybean inclusion optimize the balance between protein enhancement, antioxidant preservation, and the maintenance of functional properties suitable for traditional applications, providing a nutritionally superior alternative for gluten-free product development. Full article
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20 pages, 1683 KB  
Article
Effects of Rosmarinic Acid and Sinapic Acid on the Skeletal System in Ovariectomized Rats
by Maria Zych, Radosław Wolan, Agnieszka Włodarczyk, Piotr Londzin, Weronika Borymska, Ilona Kaczmarczyk-Żebrowska and Joanna Folwarczna
Nutrients 2026, 18(2), 301; https://doi.org/10.3390/nu18020301 - 18 Jan 2026
Viewed by 284
Abstract
Background/Objectives: It is believed that some polyphenols, including phenolic acids, may counteract estrogen deficiency-induced bone loss, decreasing oxidative stress. Moreover, some phenolic acids—among others, rosmarinic acid and sinapic acid—have been reported to increase the serum estradiol concentration in rats. The study aimed [...] Read more.
Background/Objectives: It is believed that some polyphenols, including phenolic acids, may counteract estrogen deficiency-induced bone loss, decreasing oxidative stress. Moreover, some phenolic acids—among others, rosmarinic acid and sinapic acid—have been reported to increase the serum estradiol concentration in rats. The study aimed to investigate the impact of rosmarinic acid and sinapic acid on the skeletal system of rats with estrogen deficiency induced by bilateral ovariectomy. Methods: The study was carried out on mature female rats, divided into sham-operated control rats, ovariectomized (OVX) control rats, and OVX rats treated with estradiol (0.2 mg/kg; positive control), rosmarinic acid (10 and 50 mg/kg), or sinapic acid (5 and 25 mg/kg). The compounds were administered orally for 4 weeks. Serum bone turnover markers, bone mass, mineral and calcium content, macrometric and histomorphometric parameters, as well as mechanical properties were examined. Results: Estrogen deficiency induced osteoporotic changes in ovariectomized control rats, which were slightly counteracted by the administration of estradiol. The phenolic acids slightly counteracted some changes caused by estrogen deficiency, but their administration at higher doses led to further worsening of cancellous bone quality. Conclusions: The results demonstrated that administration of high doses of rosmarinic acid or sinapic acid slightly unfavorably affected the rats’ skeletal system under conditions of estrogen deficiency. Full article
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24 pages, 3083 KB  
Article
Altered Magnesium Environments Restrict Colorectal HT-29 Spheroid Growth by Disturbing Cellular Mg2+ Homeostasis
by Nattida Kampuang, Pongsakorn Lapchock, Tanida Treerattanakulporn, Phossawee Kongkaew, Siriporn Chamniansawat and Narongrit Thongon
Int. J. Mol. Sci. 2026, 27(2), 834; https://doi.org/10.3390/ijms27020834 - 14 Jan 2026
Viewed by 125
Abstract
Dysregulated magnesium (Mg2+) homeostasis contributes to colorectal cancer (CRC), yet its context-dependent function within the tumor microenvironment remains unresolved. This study aimed to determine how sustained low and high extracellular Mg2+ environments affect CRC spheroid (SP) growth and Mg2+ [...] Read more.
Dysregulated magnesium (Mg2+) homeostasis contributes to colorectal cancer (CRC), yet its context-dependent function within the tumor microenvironment remains unresolved. This study aimed to determine how sustained low and high extracellular Mg2+ environments affect CRC spheroid (SP) growth and Mg2+ homeostasis using HT-29 SPs. We analyzed Mg2+ flux, the expression of Mg2+ transporters (e.g., Transient Receptor Potential Melastatin (TRPM) 6), viability, apoptotic and autophagic markers, and phospho-/oxidoproteomic alterations. Both Mg2+ extremes destabilized SP architecture, reduced viability, and induced apoptosis and autophagy, with SPs displaying heightened vulnerability relative to 2D cultures. Mg2+ stress impaired Mg2+ influx and eliminated adaptive transporter regulation in SPs. Loss of membrane TRPM6/7 heterodimers, driven by altered phosphorylation (e.g., TRPM6 Serine 141, Serine 1252, Threonine 1851) and elevated oxidation (e.g., Methionine 1755), suppressed channel activity. High Mg2+ caused profound metabolic failure despite increased total Mg2+, reflecting functional Mg2+ deficiency. CRC spheroids are acutely susceptible to Mg2+ imbalance due to collapsed transporter homeostasis and post-translational inhibition of Mg2+ channels. These findings reveal a targetable metabolic vulnerability and support the therapeutic potential of localized Mg2+ modulation in CRC. Full article
(This article belongs to the Special Issue The Role of Mg Homeostasis in Disease: 2nd Edition)
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15 pages, 531 KB  
Article
Disrupted Vitamin D Metabolism in Hepatocellular Carcinoma: Free and Bioavailable 25(OH)D as Novel Biomarkers of Hepatic Reserve and Clinical Risk
by Joško Osredkar, Matej Rakusa, Aleš Jerin, Borut Štabuc, Martin Zaplotnik, Saša Štupar and Darko Siuka
Molecules 2026, 31(2), 273; https://doi.org/10.3390/molecules31020273 - 13 Jan 2026
Viewed by 214
Abstract
Background: Although total 25-hydroxyvitamin D (25(OH)D) measurements may not accurately reflect functional vitamin D status, vitamin D deficiency is common in hepatocellular carcinoma (HCC). The contribution of altered vitamin D-binding protein (VDBP) and albumin to impaired bioavailability is poorly characterized in liver cancer. [...] Read more.
Background: Although total 25-hydroxyvitamin D (25(OH)D) measurements may not accurately reflect functional vitamin D status, vitamin D deficiency is common in hepatocellular carcinoma (HCC). The contribution of altered vitamin D-binding protein (VDBP) and albumin to impaired bioavailability is poorly characterized in liver cancer. Methods: We measured total, free, and bioavailable 25(OH)D, VDBP, and albumin in 46 HCC patients and 87 healthy controls during winter and summer. Correlations with Child–Pugh score, Barcelona Clinic Liver Cancer (BCLC) stage, and disease aetiology were evaluated. Results: HCC patients exhibited significantly lower VDBP (177.3 ± 237.0 vs. 239.9 ± 141.9 mg/L, p < 0.001) and albumin (35.9 ± 5.4 vs. 48.0 ± 3.9 g/L, p < 0.001) compared to winter controls. Total 25(OH)D was lower in HCC (39.3 ± 22.1 nmol/L) versus summer controls (75.0 ± 22.8 nmol/L, p < 0.001) but comparable to winter controls (p = 0.061). HCC patients lacked seasonal variation in vitamin D fractions, unlike the controls. VDBP negatively correlated with free (ρ = −0.606, p < 0.001) and bioavailable 25(OH)D (ρ = −0.541, p < 0.001). Child–Pugh score correlated positively with BCLC stage (ρ = 0.378, p = 0.012) and inversely with albumin (ρ = −0.565, p < 0.001). Conclusions: Free and bioavailable vitamin D are profoundly compromised in HCC, reflecting impaired hepatic synthetic function and systemic inflammation. These fractions may serve as novel metabolic biomarkers superior to total 25(OH)D for assessing vitamin D deficiency and guiding individualized supplementation strategies in patients with liver cancer. Full article
(This article belongs to the Special Issue Novel Metabolism-Related Biomarkers in Cancer)
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20 pages, 347 KB  
Article
Vitamin D Deficiency Mediates the Link Between Dietary Patterns, Inflammatory Biomarkers, and Iron Status Indicators (Ferritin and Hemoglobin) in Metabolic Syndrome
by Salma I. Cortes-Álvarez, Iván Delgado-Enciso, Gustavo A. Hernández-Fuentes, José Guzmán-Esquivel, Janet Diaz-Martinez, Alejandrina Rodríguez-Hernández, Margarita L. Martinez-Fierro, Iram P. Rodríguez-Sánchez, Valery Melnikov, Yunue Flores-Ruelas, Idalia Garza-Veloz, Miriam De la Cruz-Ruiz, Ángel A. Ramos-Organillo and Carmen A. Sánchez-Ramírez
Nutrients 2026, 18(2), 224; https://doi.org/10.3390/nu18020224 - 10 Jan 2026
Viewed by 518
Abstract
Background/Objectives: Chronic low-grade inflammation and nutritional deficiencies, particularly vitamin D deficiency, have emerged as important contributors to Metabolic syndrome (MetS) pathogenesis but remain underexplored. This study aimed to comprehensively evaluate the associations between dietary intake, vitamin D status, and inflammatory biomarkers (high-sensitivity [...] Read more.
Background/Objectives: Chronic low-grade inflammation and nutritional deficiencies, particularly vitamin D deficiency, have emerged as important contributors to Metabolic syndrome (MetS) pathogenesis but remain underexplored. This study aimed to comprehensively evaluate the associations between dietary intake, vitamin D status, and inflammatory biomarkers (high-sensitivity C-reactive protein -CRP- and ferritin) in patients with MetS. Methods: A cross-sectional observational study was conducted on 141 adult MetS patients at a Mexican hospital. Clinical, anthropometric, dietary (using a validated food frequency questionnaire), and biochemical data including serum 25-hydroxyvitamin D, CRP, ferritin, and neutrophil-to-lymphocyte ratio (NLR) were collected. Vitamin D deficiency was defined as serum 25(OH)D < 20 ng/mL, and high inflammation as CRP ≥ 3 mg/L. Logistic regression models adjusted for confounders were used to analyze associations. Mediation analysis assessed whether vitamin D deficiency mediated the link between dietary intake and high CRP or ferritin. Results: Patients with elevated CRP had significantly lower serum vitamin D levels (14.0 ± 5.1 vs. 22.1 ± 7.0 ng/mL; p < 0.001). Multivariable analysis showed vitamin D deficiency (adjusted OR 7.1; 95% CI 2.5–19.4; p < 0.001) and hyperferritinemia (ferritin ≥ 200 μg/L; aOR 8.0, 95% CI 3.5–18.2, p < 0.001) as predictors of high CRP. Conversely, hyperferritinemia was predicted by vitamin D deficiency (aOR 24.69; 95% CI 3.76–162.16; p = 0.001), elevated CRP (aOR 5.06; p = 0.014), Hb (aOR 63.23; p < 0.001), and inversely by grade 2 obesity (aOR 0.11; 95% CI 0.02–0.60; p = 0.03), confirming bidirectional CRP-ferritin associations and hyperferritinemia as an inflammation marker rather than iron overload indicator. Although Hb > 14.3 g/dL associated with hyperferritinemia, it did not independently predict CRP in multivariate analyses. Frequent consumption of vitamin D-rich foods (milk, fish, Manchego and Oaxaca cheese) was associated with lower inflammation. Mediation analysis confirmed that vitamin D deficiency mediated dietary intake-CRP and dietary intake-ferritin links (Sobel test p < 0.05). Conclusions: Vitamin D deficiency is a key mediator linking inadequate dietary vitamin D intake to systemic inflammation in MetS. Nutritional strategies emphasizing vitamin D repletion and consumption of vitamin D fortified foods may effectively reduce chronic inflammation and improve metabolic outcomes. Full article
20 pages, 2748 KB  
Article
Seasonal Variation in PM2.5 Composition Modulates Oxidative Stress and Neutrophilic Inflammation with Involvement of TLR4 Signaling
by Duo Wang, Zirui Zeng, Aya Nawata, Ryoko Baba, Ryuji Okazaki, Tomoaki Okuda and Yasuhiro Yoshida
Antioxidants 2026, 15(1), 89; https://doi.org/10.3390/antiox15010089 - 9 Jan 2026
Viewed by 289
Abstract
Seasonal fluctuations in the chemical composition of fine particulate matter (PM2.5) are known to influence its toxicological properties; however, their integrated biological effects remain incompletely understood. In this study, PM2.5 was continuously collected over two consecutive years at a single [...] Read more.
Seasonal fluctuations in the chemical composition of fine particulate matter (PM2.5) are known to influence its toxicological properties; however, their integrated biological effects remain incompletely understood. In this study, PM2.5 was continuously collected over two consecutive years at a single urban site in Japan and classified by season. The samples were comprehensively characterized for ionic species, metals, carbonaceous fractions, and polycyclic aromatic hydrocarbons (PAHs), and their pulmonary effects were evaluated in vivo following intratracheal administration in mice. Seasonal PM2.5 exhibited pronounced compositional differences, with higher levels of secondary inorganic aerosol components in summer and enrichment of PAHs and mineral-associated components in winter. These seasonal differences translated into distinct biological responses. Reactive oxygen species (ROS) production (1.6–2.7-fold increase) and bronchoalveolar lavage (BAL) neutrophil infiltration were strongly associated with PAH-rich PM2.5, whereas interleukin-1α (IL-1α) showed robust positive correlations with mineral components, including K+, Ca2+, and Mg2+, which were predominantly enriched in winter PM2.5. In contrast, secondary inorganic aerosol species displayed a limited capacity to induce IL-1α. Compared with summer samples, winter PM2.5 induced significantly higher levels of ROS production and IL-1α (approximately 1.5–2.6-fold increase). Using TLR2- and TLR4-deficient mice, we further demonstrated that PM2.5-induced increases in BAL cell counts, ROS, IL-6, and TNF-α were partially attenuated in TLR4 knockout mice, indicating a contributory but not exclusive role for TLR4 signaling in PM2.5-driven pulmonary inflammation. Collectively, these findings demonstrate that seasonal variations in PM2.5 composition, not particle mass alone, critically shape oxidative stress and innate immune responses in the lungs. In particular, winter PM2.5 enriched in mineral-associated components preferentially activates IL-1α-mediated alarmin pathways, underscoring the importance of the particle composition in determining seasonal air pollution toxicity. Full article
(This article belongs to the Special Issue Oxidative Stress Induced by Air Pollution, 2nd Edition)
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17 pages, 913 KB  
Article
Soil Fertility Status and Its Implications for Sustainable Cocoa Cultivation in Ghana and Togo
by Afi Amen Christèle Attiogbé, Udo Nehren, Sampson K. Agodzo, Emmanuel Quansah, Enoch Bessah, Seyni Salack, Essi Nadège Parkoo and Jean Mianikpo Sogbedji
Land 2026, 15(1), 127; https://doi.org/10.3390/land15010127 - 9 Jan 2026
Viewed by 370
Abstract
Soil fertility plays a crucial role in crop productivity, particularly in cocoa cultivation, which is highly dependent on soil quality that directly influences both productivity and sustainability. Understanding how to achieve and maintain soil fertility on cocoa farms is fundamental to sustaining higher [...] Read more.
Soil fertility plays a crucial role in crop productivity, particularly in cocoa cultivation, which is highly dependent on soil quality that directly influences both productivity and sustainability. Understanding how to achieve and maintain soil fertility on cocoa farms is fundamental to sustaining higher yields. Cocoa production in Ghana and Togo remains low, at 350–600 kg/ha, compared to the potential yield of over 1–3 tons per hectare. Given the growing demand for cocoa and limited arable land, adequate soil nutrients are essential to optimise productivity. Soil fertility indices (SFIs) have been widely used as soil metrics by integrating multiple physical, chemical, and biological soil properties. In this study, standard analytical methods were employed to evaluate the SFI through laboratory analyses of 49 surface soil samples collected at a depth of 0–30 cm with an auger. Eleven soil chemical indicators were analysed: pH (water), organic matter (OM), potassium (K), calcium (Ca), magnesium (Mg), available phosphorus (P), total nitrogen (N), cation exchange capacity (CEC), electrical conductivity (EC), and carbon-to-nitrogen ratio (C/N). Principal component analysis, followed by normalisation, was used to select a minimum dataset, which was then integrated into an additive SFI. Results indicated that N, Ca, Mg, CEC, and pH were within the optimal range for most surveyed locations (96%, 94%, 92%, 73%, and 63%, respectively), while OM and C/N were within the optimal range in approximately half of the study area. Available P, K, and C/N were highly deficient in 100%, 67%, and 96% of surveyed locations, respectively. Soil fertility varied significantly among locations (p = 0.007) and was generally low, ranging from 0.15 to 0.66. Only 20% of the soils in the study area were classified as adequately fertile for cocoa cultivation. Therefore, it is necessary to restore soil nutrient balance, especially the critically low levels of K and P, through appropriate management practices that improve fertility over time and help close the yield gap. Full article
(This article belongs to the Special Issue Feature Papers for "Land, Soil and Water" Section)
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34 pages, 8505 KB  
Article
Complex I Modulator BI4500 Reduces MASH by Limiting Oxidative Stress and Reprogramming Lipid Metabolism via AMPK in MCD Rats
by Laura Giuseppina Di Pasqua, Sofia Lotti, Michelangelo Trucchi, Giuseppina Palladini, Anna Cleta Croce, Francesca Protopapa, Fausto Feletti, Stefan G. Kauschke, Peng Sun, Mariapia Vairetti and Andrea Ferrigno
Antioxidants 2026, 15(1), 82; https://doi.org/10.3390/antiox15010082 - 8 Jan 2026
Viewed by 444
Abstract
Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a multifactorial liver disease in which mitochondrial dysfunction, oxidative stress, and inflammation play key roles in driving the progression toward metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC). Dysfunctional mitochondria generate excess reactive oxygen species (ROS), [...] Read more.
Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a multifactorial liver disease in which mitochondrial dysfunction, oxidative stress, and inflammation play key roles in driving the progression toward metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC). Dysfunctional mitochondria generate excess reactive oxygen species (ROS), impair antioxidant defenses, activate pro-inflammatory pathways and hepatic stellate cells, and perpetuate liver injury. Mitochondrial Complex I is a major ROS source, particularly under conditions of dysregulated energy metabolism. Since Complex I inhibition by metformin was shown to reduce ROS and activate the adenosine monophosphate-activated protein kinase (AMPK), this study aimed to evaluate whether a novel Complex I Modulator (CIM, BI4500) could attenuate oxidative stress, inflammation, and consequently reduce lipid accumulation and fibrosis in a methionine- and choline-deficient diet (MCD)-fed rat model of MASH. Methods: Rats were fed an MCD or an isocaloric control diet for six weeks. From week four, animals received daily oral treatment with CIM (10 mg/kg) or vehicle (Natrosol). At the endpoint, liver tissue was collected for histological, biochemical, and molecular analyses. Lipid droplet area, inflammatory infiltration, and collagen deposition were evaluated on tissue sections; total lipid content and oxidative stress markers were assessed in homogenates and isolated mitochondria. Molecular pathways related to oxidative stress, lipid metabolism, and fibrosis were assessed at protein and mRNA levels. Results: CIM treatment significantly reduced oxidative stress (ROS, lipid peroxidation, nitrogen species), promoting AMPK activation and metabolic reprogramming. This included increased expression of peroxisome proliferator-activated receptor alpha (PPAR-α) and its target genes, and decreased sterol regulatory element binding protein-1c (SREBP-1c)-driven lipogenesis. These changes halted fibrosis progression, as confirmed by Picro-Sirius Red staining and fibrosis markers. Conclusions: these findings indicate that Complex I modulation may represent a promising strategy to counteract MASLD progression toward MASH. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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14 pages, 775 KB  
Article
Tear Protein Alteration in Dogs with Keratoconjunctivitis Sicca
by Takuya Yogo, Kunihiko Terakado and Kinya Katayama
Animals 2026, 16(2), 160; https://doi.org/10.3390/ani16020160 - 6 Jan 2026
Viewed by 223
Abstract
Keratoconjunctivitis sicca (KCS) in dogs is an immune-mediated disorder characterized by aqueous tear deficiency, ocular surface inflammation, and risk of vision loss. Although tear quantity is routinely evaluated using the Schirmer tear test (STT), the accompanying qualitative alterations in tear protein composition remain [...] Read more.
Keratoconjunctivitis sicca (KCS) in dogs is an immune-mediated disorder characterized by aqueous tear deficiency, ocular surface inflammation, and risk of vision loss. Although tear quantity is routinely evaluated using the Schirmer tear test (STT), the accompanying qualitative alterations in tear protein composition remain poorly understood. In this exploratory study, we identified and characterized qualitatively differentially expressed tear proteins in samples collected from seven Beagle dogs with KCS and five healthy Beagles. Samples were collected using filter paper, extracted in phosphate-buffered saline, concentrated by trichloroacetic acid precipitation, and then separated via two-dimensional electrophoresis. Differential protein spots were identified by MALDI-TOF-MS-based peptide mass fingerprinting. Total protein concentrations were determined by measuring UV absorbance at 280 nm and were found to be significantly higher in dogs with KCS (30.7 ± 13.5 mg/mL) than in healthy dogs (11.5 ± 1.8 mg/mL, p < 0.05). Five proteins were identified as differentially expressed: serum albumin, lactotransferrin isoform 1, immunoglobulin gamma heavy chain C, major allergen Can f 1, and lysozyme C. High-molecular-weight proteins were upregulated in KCS, whereas low-molecular-weight proteins (<10 kDa, proline-rich protein-like components) were markedly reduced or absent. These compositional shifts suggest that KCS alters both the quantity and qualitative integrity of the tear proteosome, reflecting impaired tear film homeostasis and diminished ocular surface defense. The results support the potential utility of the tear proteome as a source of diagnostic and therapeutic biomarkers in canine KCS. Full article
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12 pages, 895 KB  
Article
Fetal Safety of Intravenous Ferric Carboxymaltose in Pregnancy: A Cardiotocography Study from a Tertiary Care Hospital in Italy
by Francesca Polese, Chiara Pesce, Giulia De Fusco, Gianni Tidore, Enza Coluccia, Raffaele Battista and Gianluca Gessoni
Hematol. Rep. 2026, 18(1), 7; https://doi.org/10.3390/hematolrep18010007 - 5 Jan 2026
Viewed by 702
Abstract
Background: Iron-deficient anemia (IDA) in pregnant women is a significant health issue globally. Oral iron supplementation is the primary treatment for IDA during pregnancy. For women who do not respond to or cannot tolerate oral iron treatment, intravenous (IV) iron preparations may offer [...] Read more.
Background: Iron-deficient anemia (IDA) in pregnant women is a significant health issue globally. Oral iron supplementation is the primary treatment for IDA during pregnancy. For women who do not respond to or cannot tolerate oral iron treatment, intravenous (IV) iron preparations may offer a viable therapeutic option in the third trimester of pregnancy. Ferric carboxymaltose (FCM; Ferinject®) is an IV iron preparation that allows rapid administration of high single doses of iron with a favorable safety profile. This study evaluated the potential impact of FCM therapy on fetal well-being by recording cardiotocography (CTG) before, during, and after iron infusions. Materials and Methods: We examined 105 women with IDA in the third trimester of pregnancy. During the initial evaluation, each patient was assessed for complete blood count, iron metabolism, B12, folates, hemoglobinopathies, CRP, kidney and liver function, and glucose levels. Each subject received intravenous ferric carboxymaltose (FCM), 500 mg. The study focused on the maternal and fetal safety of FCM infusion. The primary endpoint for maternal safety was the observation of adverse effects of iron infusion. For fetal safety, the primary endpoint was the assessment of CTG. Results: We considered 105 women, comprising 101 singleton and 4 twin pregnancies. The median hemoglobin (Hb) at initial observation was 95 g/L and 117 g/L post-therapy. Regarding maternal safety, side effects were observed during or after FCM infusion in four subjects; three cases involved local symptoms, while one case included nausea and skin rash. Concerning fetal safety, 100% of the cardiotocography records were deemed “normal” using the Dawes–Redman criteria. Conclusions: In conclusion, FCM proved effective in treating anemia in this clinically complex population of pregnant women in the third trimester and appeared safe in this cohort, though larger prospective studies are warranted. Full article
(This article belongs to the Special Issue Anaemia in Focus: Challenges and Solutions in Haematology)
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47 pages, 454 KB  
Article
Selenium (IV) and Sulphur (VI) as Elements Modifying Plant Quality: Content of Selenium and Sulphur Forms in Wheat
by Marzena S. Brodowska, Magdalena Kurzyna-Szklarek and Mirosław Wyszkowski
Molecules 2026, 31(1), 160; https://doi.org/10.3390/molecules31010160 - 1 Jan 2026
Viewed by 262
Abstract
In order to achieve high-quality yields, it is essential to provide plants with the necessary nutrients, including selenium (Se) and sulphur (S), to meet their nutritional requirements. This study aimed to determine the effect of selenium (0, 10 and 20 g Se ha [...] Read more.
In order to achieve high-quality yields, it is essential to provide plants with the necessary nutrients, including selenium (Se) and sulphur (S), to meet their nutritional requirements. This study aimed to determine the effect of selenium (0, 10 and 20 g Se ha−1) and the date of its application (in the tillering phase and in the stem elongation phase) and sulphur application (0, 15 and 30 kg S ha−1) on the content of selenium and various forms of sulphur (total sulphur, sulphate sulphur and organic sulphur) and the N:S ratio in winter spelt wheat and winter common wheat. The research hypothesis assumed that different doses of selenium and sulphur and the timing of their application would have a beneficial effect on the Se and S content in the grain and straw of spelt wheat and common wheat. Selenium fertilisation significantly increased the content of this element in the grain of spelt wheat and common wheat. The concentration of selenium was also influenced by the timing of its application in the plant growth environment. However, the dose of selenium and the timing of its application were not associated with significant changes in the content of both forms of sulphur in the tested plants. The experimental factors used did not contribute to the achievement of selenium levels toxic to humans and animals. The presence of sulphur in the growth environment of spelt wheat and common wheat was associated with an increase in the content of both total sulphur, sulphate sulphur and organic sulphur in their grain and straw, especially in spelt wheat straw by an average of 17%, 29% and 23%, respectively, and in common wheat straw by 26%, 18% and 57%, respectively. The sulphur content in the plant growth environment was not associated with a change in the selenium content in the grain of the tested plants. The results of our study suggest that the optimal dose of selenium for biofortification of humans and animals is 20 mg Se ha−1 on clay soil, applied during the stem elongation phase of spelt and common wheat. Biofortification of wheat with selenium and sulphur is a good method of supplementing deficiencies of this element in the human diet. Full article
(This article belongs to the Special Issue Green Chemistry and Molecular Tools in Agriculture)
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12 pages, 444 KB  
Article
Adjusting Iron Markers for Inflammation Reduces Misclassification of Iron Deficiency After Total Hip Arthroplasty
by Alexander Tham, Donald C. McMillan, Dinesh Talwar and Stephen T. McSorley
J. Clin. Med. 2026, 15(1), 259; https://doi.org/10.3390/jcm15010259 - 29 Dec 2025
Viewed by 237
Abstract
Background: Preoperative anemia is common among patients undergoing arthroplasty and is associated with increased transfusion requirements and worse outcomes. Current perioperative pathways rely on iron studies to guide intravenous iron supplementation, but systemic inflammation triggered by surgery profoundly alters iron markers, risking misclassification [...] Read more.
Background: Preoperative anemia is common among patients undergoing arthroplasty and is associated with increased transfusion requirements and worse outcomes. Current perioperative pathways rely on iron studies to guide intravenous iron supplementation, but systemic inflammation triggered by surgery profoundly alters iron markers, risking misclassification of iron deficiency. This study evaluated whether adjusting iron indices for inflammatory markers improves diagnostic accuracy after total hip arthroplasty (THA). Methods: In this prospective cohort study, 20 patients undergoing elective primary THA at a single center were enrolled. Patients with preoperative inflammation were excluded. Serum iron, transferrin, transferrin saturation (TSAT), CRP, and albumin were measured preoperatively and on postoperative days (PODs) 1, 2, 3, and 90. Serum iron was adjusted for systemic inflammation using a validated regression equation incorporating CRP and albumin, and adjusted TSAT was calculated accordingly. Absolute iron deficiency was defined as serum iron < 10 µmol/L, and functional iron deficiency was defined as TSAT < 20%. Comparisons were made using Wilcoxon’s signed-rank test and ANOVA. Results: In the 20 included patients, a pronounced systemic inflammatory response was observed, with CRP peaking on POD 2 (median, 162 mg/L) and albumin falling to 32 g/L on POD 1 (both p < 0.001). Unadjusted serum iron and TSAT fell sharply, with nearly all patients classified as iron-deficient in the first three postoperative days. Adjustment for CRP and albumin significantly attenuated these declines: on POD 2, median iron was 8.2 µmol/L adjusted versus 2.0 µmol/L unadjusted (p < 0.001), and TSAT was 19% versus 4% (p < 0.001). Misclassification of iron deficiency fell by 40–50% with adjustment, and by POD 90, adjusted indices approximated baseline values. Conclusions: Systemic inflammation after THA markedly suppresses iron indices, leading to widespread misclassification of iron deficiency. Adjustment for CRP and albumin reduces this misclassification and provides a more accurate assessment of perioperative iron status. These findings complement existing evidence supporting intravenous iron supplementation by highlighting a diagnostic refinement that could improve patient selection for therapy. Full article
(This article belongs to the Special Issue Hip Fracture and Surgery: Clinical Updates and Challenges)
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18 pages, 1037 KB  
Article
Magnesium and Zinc Are Associated with Sleep Quality in Saudi Adults: Evidence from a Cross-Sectional Study
by Sara Al-Musharaf, Madhawi M. Aldhwayan, Tagreed A. Mazi, Ohud Abujabir, Waad Alfawaz and Ghadeer S. Aljuraiban
Nutrients 2026, 18(1), 114; https://doi.org/10.3390/nu18010114 - 29 Dec 2025
Viewed by 742
Abstract
Background: Studies that examine magnesium (Mg), zinc (Zn), and copper (Cu) in relation to sleep in the Middle East and North Africa are limited. We aim to assess the associations between serum and dietary Mg, Zn, and Cu levels and sleep quality in [...] Read more.
Background: Studies that examine magnesium (Mg), zinc (Zn), and copper (Cu) in relation to sleep in the Middle East and North Africa are limited. We aim to assess the associations between serum and dietary Mg, Zn, and Cu levels and sleep quality in Saudi adults. Methods: A cross-sectional study was conducted among 1041 adults. Sleep quality was assessed using the Arabic Pittsburgh Sleep Quality Index (PSQI). Serum mineral levels were quantified biochemically, and dietary intake information was obtained. We utilized logistic regression to estimate the odds ratios for poor sleep (PSQI-P) in relation to serum and dietary indices in a crude model and after adjustment for confounders. Results: Serum Mg deficiency (<1.8 mg/dL) increased the odds of PSQI-P by 30% in the crude and age-adjusted models, with attenuation after further adjustment, suggesting partial mediation by lifestyle and metabolic factors. Mg deficiency was associated with PSQI-P (1.8-fold higher odds) after full adjustment. Dietary Mg levels below the DRI were independently associated with poor sleep across models. Higher serum Zn tertiles were associated with 40% lower odds of PSQI-P, and Zn deficiency (<80 µg/dL) demonstrated a three-fold independent increase in risk. Neither serum nor dietary intake levels of Cu demonstrated an association with sleep quality. Conclusion: In Saudi adults, serum and dietary Mg levels were associated with poor sleep, particularly in males, while the serum Zn concentration exhibited a modest inverse association at higher levels. Further longitudinal studies are warranted. Full article
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