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16 pages, 1051 KB  
Article
High-Intensity Interval and Aerobic Training Alleviate Cardiac Pathology, Apoptosis, and Atrial Fibrillation in Rats with Chronic Kidney Disease: The Roles of FGF23 and Klotho
by Sina Rokhsati, Nazanin Shahsavari, Shahram Rabbani, Katsuhiko Suzuki and Kayvan Khoramipour
Biomolecules 2026, 16(4), 513; https://doi.org/10.3390/biom16040513 - 30 Mar 2026
Abstract
Chronic kidney disease (CKD) leads to metabolic and cardiovascular complications, and the dysregulation of key biomolecules, namely fibroblast growth factor 23 (FGF23) and Klotho, plays a central role. This study investigated the effects of high-intensity interval training (HIIT) and moderate aerobic training (AT) [...] Read more.
Chronic kidney disease (CKD) leads to metabolic and cardiovascular complications, and the dysregulation of key biomolecules, namely fibroblast growth factor 23 (FGF23) and Klotho, plays a central role. This study investigated the effects of high-intensity interval training (HIIT) and moderate aerobic training (AT) on FGF23, Klotho, mineral metabolism, apoptosis markers (BAX, Bcl2), and atrial fibrillation (AF) in a rat CKD model. The study used 35 Wistar rats randomly assigned to control (CTL), sham (SH), CKD, CKD + HIIT, and CKD + AT groups. CKD was induced by 5/6 nephrectomy surgery. Exercise interventions consisted of eight weeks of HIIT (80–100% of maximum speed, 24–54 min/week) or AT (45–55% of maximum speed, 40–60 min/week), conducted three times weekly on a treadmill. We measured heart weight, blood levels of FGF23, Klotho, and mineral metabolism markers, as well as the heart expression of apoptosis proteins (i.e., BAX, Bcl2) and atrial fibrillation (AF). Both exercise types reduced the heart weight and heart/body weight ratio; attenuated CKD-induced elevations in FGF23 and reductions in Klotho; improved blood levels of phosphate, PTH, and vitamin D; and modulated apoptotic markers by decreasing BAX and increasing Bcl2 levels. Exercise improved cardiac function and reduced the AF duration. These findings emphasize that exercise could be a helpful non-pharmacological intervention to ameliorate CKD-induced cardiovascular and metabolic disturbances through the modulation of the FGF23 and Klotho pathways. Full article
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30 pages, 2314 KB  
Review
Replacing Meat with Plant-Based Proteins: An Analysis of Nutritional, Sustainability and Acceptability Aspects
by Ileana Cocan, Monica Negrea, Ersilia Alexa, Calin Jianu, Gabriel Heghedus-Mindru and Mihaela Cazacu
Appl. Sci. 2026, 16(7), 3356; https://doi.org/10.3390/app16073356 - 30 Mar 2026
Abstract
As the world progresses towards more sustainable food systems, an increasing number of individuals are inclined to reduce meat consumption and transition to plant-based protein sources. Given the implications of climate change and escalating public health issues, plant-based protein sources appear to be [...] Read more.
As the world progresses towards more sustainable food systems, an increasing number of individuals are inclined to reduce meat consumption and transition to plant-based protein sources. Given the implications of climate change and escalating public health issues, plant-based protein sources appear to be a viable alternative; yet, this transition will be challenging to implement. Legumes, cereals, oilseeds, microalgae, and mycoprotein constitute the primary sources of plant-derived protein. Each possesses distinct functional attributes; yet, they also exhibit certain nutritional constraints. The restrictions mostly pertain to the composition of essential amino acids and the body’s efficacy in utilizing micronutrients such as iron, zinc, and vitamin B12. From an ecological perspective, plant-based proteins often exert a significantly lesser impact on the environment compared to conventional meat. This reduces greenhouse gas emissions and optimizes resource utilization. Recent technological advancements, including fermentation methods, shear cell structuring, and high-moisture extrusion, have significantly improved the texture and flavor of plant-based products. However, consumer perceptions of the sensory attributes of these products significantly influence their acceptance. Current research priorities include improving protein digestibility, mitigating antinutritional factors, reducing salt content, and generating robust long-term data on health effects/health benefits. Ultimately, replacing meat with plant-based proteins involves not only scientific and nutritional considerations but also requires significant cultural and societal transformations to establish a more balanced and sustainable food system. Full article
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14 pages, 1356 KB  
Article
Vitamin D Status and Health Indicators in the Malagasy Population: A Pilot Study
by Milos Chudy, Petra Macounova, Nikol Gottfriedova, Adela Novotna, Klara Jaresova, Hana Tomaskova, Rastislav Madar and Marek Buzga
Healthcare 2026, 14(7), 887; https://doi.org/10.3390/healthcare14070887 - 30 Mar 2026
Abstract
Background: Vitamin D plays an important role in overall health. This study aimed to conduct a pilot screening of serum vitamin D levels in a Malagasy cohort and to compare vitamin D status groups with selected health indicators. Methods: A cross-sectional observational pilot [...] Read more.
Background: Vitamin D plays an important role in overall health. This study aimed to conduct a pilot screening of serum vitamin D levels in a Malagasy cohort and to compare vitamin D status groups with selected health indicators. Methods: A cross-sectional observational pilot study was performed in two geographically distinct regions of Madagascar—a coastal area and an inland area. In total, 150 individuals underwent a single health screening, including semi-quantitative assessment of serum 25-hydroxyvitamin D, as well as evaluation of glycemic and cholesterol levels, blood pressure, anthropometric parameters, and a brief personal and lifestyle questionnaire. Results: A total of 148 participants (aged 18–88 years) were analyzed. 45.9% of participants had low serum vitamin D levels (<75 nmol/L). Lower vitamin D levels and higher total cholesterol were observed in the coastal group compared to the inland group (p < 0.05). No significant differences were found for most other examined health indicators. In multivariable analysis, age was identified as an important determinant of several outcomes. Vitamin D status did not remain an independent predictor; however, a trend toward an independent association with hypercholesterolemia was observed (p = 0.07), while the association with hyperglycemia was less pronounced (p = 0.11). Conclusions: A substantial proportion of participants exhibited low vitamin D levels despite favorable geographic conditions. The results suggest a potential relationship between vitamin D status and lipid metabolism, although this association did not reach statistical significance after adjustment. These findings provide initial insight into vitamin D status and its potential associations in this setting and may inform future research and public health monitoring. Full article
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22 pages, 1080 KB  
Article
Interpretable Machine Learning to Predict Metformin-Induced Vitamin B12 Deficiency: Association with Glycemic Control and Neuropathic Symptoms
by Yasmine Salhi, Meriem Yazidi, Amine Dhraief, Elyes Kamoun, Melika Chihaoui, Tamim Alsuliman and Layth Sliman
Metabolites 2026, 16(4), 227; https://doi.org/10.3390/metabo16040227 - 30 Mar 2026
Abstract
Background/Objectives: Vitamin B12 deficiency is a common but often underdiagnosed complication in patients with type 2 diabetes (T2D) undergoing long-term metformin therapy. Accurate early prediction could enable targeted screening and timely intervention. This study aimed to develop and interpret a machine learning model [...] Read more.
Background/Objectives: Vitamin B12 deficiency is a common but often underdiagnosed complication in patients with type 2 diabetes (T2D) undergoing long-term metformin therapy. Accurate early prediction could enable targeted screening and timely intervention. This study aimed to develop and interpret a machine learning model for predicting vitamin B12 deficiency in metformin-treated patients with T2D, using eXtreme Gradient Boosting (XGBoost). Methods: A retrospective cross-sectional study was conducted at a single endocrinology centre (La Rabta University Hospital, Tunis, Tunisia). Patients with T2D treated with metformin for at least three years were included (n = 257); those with conditions independently affecting vitamin B12 metabolism were excluded. Vitamin B12 deficiency was defined as a serum B12 level below 150 pmol/L or a borderline level (150–221 pmol/L) with concurrent hyperhomocysteinemia (>15 μmol/L). XGBoost was selected after comparison with Logistic Regression (L2), Random Forest, and Support Vector Machine on the same 5-fold stratified cross-validated pipeline. Hyperparameters were optimized via Bayesian search (100 iterations × 5-fold stratified cross-validation), with the Matthews correlation coefficient (MCC) as the primary optimization metric to account for class imbalance. Model interpretability was achieved using SHapley Additive exPlanations (SHAP). Discrimination and calibration were assessed on an independent test set using bootstrap 95% confidence intervals (2000 resamples). Results: Of 257 patients, 95 (37.0%) presented with vitamin B12 deficiency. On the independent test set (n = 52), the optimized XGBoost model achieved an ROC-AUC of 0.671 [95% CI: 0.514–0.818], sensitivity of 0.737 [95% CI: 0.533–0.938], specificity of 0.545 [95% CI: 0.375–0.710], MCC of 0.273 [95% CI: 0.018–0.517], and a Brier Score of 0.259. SHAP analysis identified HbA1c, microalbuminuria, autonomic neuropathy, BMI, DN4 score, and fasting glucose as the most influential predictors. Nonlinear SHAP interaction plots revealed an increased predicted risk in patients with low HbA1c combined with a high cumulative metformin dose. Conclusions: The XGBoost–SHAP framework provided interpretable predictions of vitamin B12 deficiency in patients with T2D on metformin, identifying key clinical profiles for targeted screening. External multi-centre validation is required before clinical deployment. Full article
(This article belongs to the Special Issue Metabolic Dysfunction in Diabetic Neuropathy)
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20 pages, 713 KB  
Review
Transdiagnostic Neurobiological and Nutritional Factors in Eating Disorders: Implications for Integrative Treatment Models
by Izabela Łucka, Ariadna Dobrzańska, Jolanta Góral-Półrola, Patrycja Leśnicka and Marta Kopańska
Nutrients 2026, 18(7), 1108; https://doi.org/10.3390/nu18071108 - 30 Mar 2026
Abstract
Eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED), are complex psychiatric conditions characterized by high morbidity and mortality. Increasing evidence suggests that beyond disorder-specific symptomatology, shared transdiagnostic mechanisms contribute to their onset and persistence. This narrative review [...] Read more.
Eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED), are complex psychiatric conditions characterized by high morbidity and mortality. Increasing evidence suggests that beyond disorder-specific symptomatology, shared transdiagnostic mechanisms contribute to their onset and persistence. This narrative review synthesizes current data on neurobiological and nutritional factors implicated in EDs, with particular emphasis on trait–state interactions and starvation-induced neuroadaptations. Predisposing vulnerabilities such as heightened anxiety, cognitive rigidity, and perfectionism appear to interact with state-dependent biological alterations induced by malnutrition. Chronic dietary restriction is associated with measurable alterations in serotonergic and dopaminergic systems, altered reward processing, and persistent activation of the hypothalamic–pituitary–adrenal (HPA) axis. Experimental studies suggest that acute tryptophan depletion may transiently reduce anxiety in individuals with anorexia nervosa, suggesting that, in some individuals, food restriction may function as a biologically reinforced strategy of affect regulation. Furthermore, disturbances in leptin and ghrelin signaling, along with widespread micronutrient deficiencies—including zinc, iron, selenium, and B vitamins—may exacerbate cognitive inflexibility, mood instability, and impaired decision-making. These metabolic and endocrine adaptations may contribute to a self-perpetuating cycle in which starvation-induced neurochemical changes reinforce restrictive or dysregulated eating behaviors. Importantly, several of these mechanisms extend beyond anorexia nervosa and may represent common transdiagnostic processes across eating disorders and related mental health conditions, including anxiety, depression, and addictive behaviors. Recognition of these biological and nutritional factors has significant implications for treatment. Nutritional rehabilitation should be conceptualized not solely as weight restoration, but as a neurobiological recalibration of stress regulation, reward sensitivity, and affective processing systems. An integrative treatment approach that combines behavioral stabilization with attention to underlying neurobiological and relational mechanisms may offer a more comprehensive framework for long-term recovery. Full article
15 pages, 3953 KB  
Article
Ameliorative Effects of Pumpkin Seed Protein Peptides on Dexamethasone-Treated Sarcopenia and Their Effects When Combined with Vitamin D
by Donghui Ma, Yuxin Liu, Jing Zhao and Quanhong Li
Foods 2026, 15(7), 1162; https://doi.org/10.3390/foods15071162 (registering DOI) - 30 Mar 2026
Abstract
Sarcopenia is a degenerative condition that imposes a substantial global public health burden, yet safe and effective interventions remain limited. Nutritional support is regarded as an important strategy to mitigate age-related muscle loss and improve physical function in older adults. Due to time [...] Read more.
Sarcopenia is a degenerative condition that imposes a substantial global public health burden, yet safe and effective interventions remain limited. Nutritional support is regarded as an important strategy to mitigate age-related muscle loss and improve physical function in older adults. Due to time and cost constraints, dexamethasone (DEX)-treated models are often used as an alternative to age-related sarcopenia models. This study investigated the effects of pumpkin seed protein peptides (PSPP) and vitamin D on DEX-treated mice. In vitro, PSPP attenuated senescence-associated phenotypes, reduced cellular injury, and partially alleviated DEX-treated myofibrillar atrophy, as evidenced by decreased Atrogin-1 and MuRF1 expression and increased MyoD expression. In vivo, PSPP and vitamin D, particularly in combination, ameliorated DEX-treated declines in muscle mass, grip strength, and endurance. Histological analyses further demonstrated improvements in myofibrillar architecture and muscle fiber cross-sectional area. In addition, each intervention was associated with increased ATP content, elevated interleukin-10 and insulin-like growth factor-1 levels, and reduced tumor necrosis factor-α and malondialdehyde levels. Collectively, these findings suggest that PSPP, either alone or combined with vitamin D, may alleviate DEX-treated sarcopenia, potentially through the modulation of mitochondrial homeostasis, attenuation of oxidative stress and inflammatory responses, and promotion of myogenic regeneration. Full article
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15 pages, 3964 KB  
Article
Assessment of the Immunohistochemical Expression of Vitamin D Receptor, β-Catenin, and Ki-67 in Urothelial Carcinoma: A Cross-Sectional Study from Egypt
by Marwa M. El-Mosely, Abdulkarim Hasan, Mohamed Tharwat, Ahmed Abdellatief, Reda Elhawary, Mahmoud Salem, Mostafa Fawzy, Dina Sakr, Salah-el-din Sayed O. Semary, Sabah Mohamed Sharaf, Heba Gamil, Ahmed Abdulwahab Bawahab, Dahlia Soleman A. Mirdad, Mohammed S. Abdelwahed and Mohamed Mahmoud Abdellah
Int. J. Transl. Med. 2026, 6(2), 14; https://doi.org/10.3390/ijtm6020014 - 30 Mar 2026
Abstract
Background: Conventional urothelial carcinoma (UC) requires accurate risk stratification, particularly differentiation between non-muscle-invasive (NMIBC) and muscle-invasive bladder cancer (MIBC) and between low- and high-grade tumors. This study evaluated immunohistochemical (IHC) expression of vitamin D receptor (VDR), β-catenin, and Ki-67 index in Egyptian patients [...] Read more.
Background: Conventional urothelial carcinoma (UC) requires accurate risk stratification, particularly differentiation between non-muscle-invasive (NMIBC) and muscle-invasive bladder cancer (MIBC) and between low- and high-grade tumors. This study evaluated immunohistochemical (IHC) expression of vitamin D receptor (VDR), β-catenin, and Ki-67 index in Egyptian patients with conventional UC. Methods: A cross-sectional study was conducted on 58 archived conventional UC cases diagnosed in 2023 at Al-Azhar University Hospitals. VDR positivity was defined as ≥10% cytoplasmic and/or nuclear tumor cell staining. Membranous β-catenin was considered preserved when >80% of tumor cell membranes were stained; otherwise, it was reduced. Nuclear β-catenin was considered positive when ≥5% of tumor nuclei were stained. Ki-67 was categorized as high using a ≥30% cutoff. Associations with grade, muscle invasion status, and lymphovascular invasion (LVI) were analyzed. Results: Mean age was 65.3 ± 9.3 years; 86.2% were males; 51.7% were MIBC. Compared with NMIBC, MIBC was significantly associated with high grade, non-papillary architecture, LVI, and high Ki-67. VDR positivity was detected in 82.7% of cases and showed no significant association with grade, muscle invasion, or LVI. Preserved membranous β-catenin was seen in 34.5% and was significantly associated with tumor grade but not with muscle invasion or LVI; nuclear β-catenin was absent. High Ki-67 (60.3%) was significantly associated with high grade and MIBC, with no association with age, sex, or LVI. Conclusions: In Egyptian conventional UC, Ki-67 was a significant marker for aggressive clinicopathologic features, while VDR lacked discriminatory associations and β-catenin findings were mainly grade-related. Full article
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13 pages, 542 KB  
Article
Independent Predictors of Hungry Bone Syndrome After Parathyroidectomy for Primary Hyperparathyroidism: Insights from a Large Cohort Study
by Ibrahim Kilinc, Mustafa Oruc, Furkan Savas, Alparslan Ertenlice and Serap Ulusoy
Diagnostics 2026, 16(7), 1041; https://doi.org/10.3390/diagnostics16071041 - 30 Mar 2026
Abstract
Background/Objectives: Hungry bone syndrome (HBS) is a clinically significant metabolic complication following parathyroidectomy for primary hyperparathyroidism (PHPT), characterized by profound and prolonged hypocalcemia resulting from rapid skeletal remineralization. Although multiple risk factors have been proposed, published data remain inconsistent regarding the most [...] Read more.
Background/Objectives: Hungry bone syndrome (HBS) is a clinically significant metabolic complication following parathyroidectomy for primary hyperparathyroidism (PHPT), characterized by profound and prolonged hypocalcemia resulting from rapid skeletal remineralization. Although multiple risk factors have been proposed, published data remain inconsistent regarding the most reliable predictors. This study aimed to evaluate potential risk factors associated with the development of HBS and to clarify controversial findings reported in the literature. Methods: Patients who underwent surgery for PHPT between January 2019 and May 2025 were retrospectively analyzed. Individuals who developed HBS were compared with those who did not in terms of clinical, biochemical, and surgical parameters. Results: HBS occurred in 4.7% of patients. Those in the HBS group exhibited significantly higher preoperative serum calcium, parathyroid hormone, alkaline phosphatase (ALP), and Ca/P ratio, while phosphate, vitamin D, and T-scores were significantly lower. Postoperative day 1 calcium levels were also markedly reduced. Multivariate analysis identified increased ALP, low T-score, concomitant thyroid surgery, and decreased postoperative day 1 calcium as independent predictors. A postoperative day 1 calcium cutoff of 8.6 mg/dL demonstrated strong predictive accuracy. Conclusions: HBS is more commonly observed in patients with low bone density and high bone turnover. Patients with these risk factors should be considered high-risk and closely monitored in the early postoperative period to enable prompt intervention and prevent severe complications. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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17 pages, 299 KB  
Article
Eating Behaviors and Energy and Nutrient Intakes in Children with Autism Spectrum Disorder with and Without Sensory Integration Difficulties
by Gözde Ede İleri, Yeliz Serin, Pelin Akın, Yusuf Ataş and Sude Çınar
Children 2026, 13(4), 478; https://doi.org/10.3390/children13040478 (registering DOI) - 30 Mar 2026
Abstract
Background/Objectives: Sensory processing disorders (SID) are common in children with autism spectrum disorder (ASD) and can influence children’s eating behaviors. Evaluating the nutritional status of children with ASD is crucial for families or caregivers to manage their feeding. Therefore, this study aimed [...] Read more.
Background/Objectives: Sensory processing disorders (SID) are common in children with autism spectrum disorder (ASD) and can influence children’s eating behaviors. Evaluating the nutritional status of children with ASD is crucial for families or caregivers to manage their feeding. Therefore, this study aimed to compare the eating behaviors and dietary intake between children with ASD and children with ASD + SID. Methods: This cross-sectional study included 72 children with ASD aged 6–15 years, of whom 36 also had SID. Sociodemographic information and dietary habits of children were collected. The children’s body weight and height were measured. Children’s eating behaviors were assessed using the Children’s Eating Behavior Scale. Dietary intake was obtained using 3-day food consumption records. Results: The rate of overweight was higher in children with ASD compared to children with ASD + SID, but there was no statistically significant difference between the groups (p > 0.05). Children with ASD + SID were more likely to skip main meals than children with ASD (p < 0.05). Children with ASD + SID had significantly lower dietary reference intake levels of energy, macronutrients, fiber, PUFAs, vitamin E, B1, B6, folate, potassium, calcium, magnesium, phosphorus, and iron compared to children with ASD (p < 0.05). Increased scores on the drinking passion subscale were identified as a risk factor for SID (OR = 2.15, 95% CI [1.30, 4.30], p = 0.005). Conclusions: The higher frequency of skipping main meals, significantly lower energy and nutrient intake in the ASD + SID group indicates that these children are at higher nutritional risk. Incorporating sensory-based assessments and interventions into nutritional management may be crucial. Full article
(This article belongs to the Section Pediatric Neurology & Neurodevelopmental Disorders)
13 pages, 540 KB  
Article
Dietary Supplements Use Among Individuals over 60 Years of Age in Poland
by Sonia Woch, Łukasz Wierucki, Krzysztof Flis, Małgorzata Sznitowska, Emilia Błeszyńska-Marunowska, Tomasz Zdrojewski and Piotr Bandosz
Nutrients 2026, 18(7), 1099; https://doi.org/10.3390/nu18071099 - 30 Mar 2026
Abstract
Background/Objectives: Dietary supplements (DSs) are widely available on the pharmaceutical market. Their consumption frequency has been observed to increase over the years, especially with age. To the best of our knowledge, this is the first study in Poland and Central-Eastern Europe to analyze [...] Read more.
Background/Objectives: Dietary supplements (DSs) are widely available on the pharmaceutical market. Their consumption frequency has been observed to increase over the years, especially with age. To the best of our knowledge, this is the first study in Poland and Central-Eastern Europe to analyze the use of dietary supplements (DSs) based on a nationally representative, random sample of the elderly population. Methods: We examined 5987 individuals aged 60 years and older to assess the prevalence and types of DSs they use, with particular attention to socio-economic factors associated with their consumption. It also aimed to determine whose recommendations were followed when choosing supplements. Results: The percentage of individuals taking any DSs was 32.1% (95% CI: 29.8–34.4), with a higher proportion among women (38.7% (95% CI: 35.7–41.7)) compared to men (22.8% (95% CI: 20.6–25.1)). A multivariable analysis showed that DSs were more likely to be used by individuals with higher education (Prevalence Ratio (PR) 1.74 (95% CI: 1.47–2.06) for individuals with higher education vs. those with primary education). A link between age and DSs consumption was also observed, with the highest consumption rates found among those in their 80s (PR 1.46 (95% CI: 1.30–1.63) vs. the 60–69 age group). The most commonly used ingredients were vitamins, taken by 76.2% (95% CI: 73.6–78.9) of respondents, minerals (55.9% (95% CI: 52.8–59)), and plant-based preparations (45.0% (95% CI: 42–48)). Although DSs were most often used based on a doctor’s recommendation (58.5% (95% CI: 54.5–62.6)), over a third of patients initiated their use independently. Conclusions: This significant proportion of individuals taking dietary supplements in Poland, often without consultation with healthcare professionals, suggests that these products may be used in the absence of objective indications, which may be associated with adverse effects and potential drug–supplement interactions. This represents an important implication for clinicians, who should always extend the medical history to include information on DSs use. The findings also highlight the need to strengthen regulatory frameworks to ensure the safe use of these products and to optimally protect the health of older adults. Full article
(This article belongs to the Section Geriatric Nutrition)
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17 pages, 1338 KB  
Review
Vitamin B12 Deficiency in the Diagnostic Work-Up of Global Developmental Delay: A Treatable and Time-Sensitive Condition
by Rouzha Pancheva, Maria Dzhogova, Lyubomir Dimitrov, Miglena Nikolova, Galya Mihaylova, Veselina Panayotova, Diana A. Dobreva, Katya Peycheva, Bistra Galunska and Albena Merdzhanova
Nutrients 2026, 18(7), 1098; https://doi.org/10.3390/nu18071098 - 29 Mar 2026
Abstract
Background: Vitamin B12 deficiency is a recognized but frequently under-integrated cause of global developmental delay (GDD) in infancy and early childhood. Early diagnosis is critical because neurological impairment may be partially or completely reversible with timely treatment. Objective: This narrative review aims to [...] Read more.
Background: Vitamin B12 deficiency is a recognized but frequently under-integrated cause of global developmental delay (GDD) in infancy and early childhood. Early diagnosis is critical because neurological impairment may be partially or completely reversible with timely treatment. Objective: This narrative review aims to synthesize current evidence on the role of vitamin B12 deficiency in the diagnostic evaluation of GDD, with a focus on clinical phenotype, risk factors, biomarkers, treatment outcomes, and practical integration into contemporary diagnostic algorithms. Methods: A structured, non-systematic search of PubMed/MEDLINE, Embase, and Web of Science was performed to identify clinical studies, case series, reviews, and guideline documents addressing pediatric vitamin B12 deficiency and neurodevelopmental delay. Results: Vitamin B12 deficiency in early childhood is most commonly associated with maternal deficiency and exclusive breastfeeding without adequate supplementation. Evidence from recent clinical and observational studies indicates that vitamin B12 deficiency may present with nonspecific neurological symptoms, including developmental regression, hypotonia, and feeding difficulties. Incorporating vitamin B12 assessment—using serum vitamin B12, holotranscobalamin, methylmalonic acid, and homocysteine—into early diagnostic algorithms for GDD may facilitate timely identification of a treatable cause of neurodevelopmental impairment. The proposed diagnostic framework emphasizes early biochemical evaluation in infants with unexplained developmental delay, thereby supporting prompt treatment during a critical window of neurological reversibility. Conclusions: Targeted assessment of vitamin B12 status in children with GDD, together with evaluation of maternal status, represents a clinically relevant approach to identifying a potentially preventable and treatable cause of neurodevelopmental impairment. Integration of functional biomarkers into diagnostic pathways and the development of pediatric-specific reference standards are key priorities for future research and clinical practice. Full article
(This article belongs to the Special Issue Micronutrients Intake and Physiological-Disease-Related Outcomes)
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27 pages, 1412 KB  
Article
Apple Pomace as a Source of Valuable Phenolics: From Drying Kinetics to Optimization of Ultrasound-Assisted Extraction Using Conventional and Alternative Solvents
by Silviu Măntăilă, Nicoleta Balan, Ștefania Adelina Milea, Oana Viorela Nistor, Doina Georgeta Andronoiu, Gabriel Dănuț Mocanu, Gabriela Râpeanu and Nicoleta Stănciuc
Antioxidants 2026, 15(4), 429; https://doi.org/10.3390/antiox15040429 (registering DOI) - 29 Mar 2026
Abstract
Industrial processing of apple to obtain products like juice or cider generates a significant amount of pomace, which represents 25–30% of the fresh fruit mass. Different technologies are needed to valorize apple pomace (AP), considering its significant amount of high-value compounds, such as [...] Read more.
Industrial processing of apple to obtain products like juice or cider generates a significant amount of pomace, which represents 25–30% of the fresh fruit mass. Different technologies are needed to valorize apple pomace (AP), considering its significant amount of high-value compounds, such as fiber, vitamins, and polyphenols. Hot-air convection (CA) and infrared (IR) drying are widely used methods for preserving polyphenols from by-products, such as apple pomace (AP), while also extending their shelf life. This study aimed to evaluate the influence of CA and IR drying on drying kinetics, color parameters, and the preservation of polyphenolic compounds, as well as to identify a sustainable extraction approach. Both drying methods significantly affected the color characteristics and content of polyphenols with high antioxidant activity. A significant impact was noticed at higher temperatures, which may be associated with the partial inactivation of browning enzymes. IR drying resulted in a shorter drying time and lower specific energy consumption compared to CA. Furthermore, the assessment of solvent efficiency in ultrasound-assisted extraction (UAE) indicated that the natural deep eutectic solvent (NaDES) composed of choline chloride and glycerol (1:1 molar ratio) provided superior recovery of phenolic compounds with high antioxidant activity compared to conventional solvents and the other NaDES analyzed. Optimization of UAE conditions using this polyol-based NaDES allowed for achieving an extract characterized by a polyphenolic profile dominated by flavan-3-ols (catechin and epigallocatechin), followed by phenolic acids, mainly chlorogenic acid. These results confirm the potential of AP as a valuable source of bioactive compounds and of polyol-based NaDESs as a sustainable and efficient alternative for their recovery. Full article
22 pages, 1565 KB  
Article
Protective Effects of Vitamin D Against Doxorubicin Chemotherapy–Induced Hepatotoxicity in Wistar Albino Rats: Evidence from 99mTc-Pyrophosphate Scintigraphy and Oxidative–Inflammatory Pathways
by Murat Kalın, Haluk Kerim Karakullukcu, Mina Karakullukcu, Aylin Arslan, Serdar Savaş Gül, Reyhan Toyran, Ömer Faruk Özkan, Gülçin Ercan and Hatice Aygun
Nutrients 2026, 18(7), 1097; https://doi.org/10.3390/nu18071097 - 29 Mar 2026
Abstract
Objectives: Doxorubicin, a widely used chemotherapeutic agent, is known to induce hepatotoxicity through oxidative stress and inflammatory pathways. Vitamin D has been reported to exert antioxidant and immunomodulatory effects; however, its potential protective role in doxorubicin-induced liver injury remains insufficiently characterized. Materials and [...] Read more.
Objectives: Doxorubicin, a widely used chemotherapeutic agent, is known to induce hepatotoxicity through oxidative stress and inflammatory pathways. Vitamin D has been reported to exert antioxidant and immunomodulatory effects; however, its potential protective role in doxorubicin-induced liver injury remains insufficiently characterized. Materials and Methods: Adult male Wistar albino rats were randomly assigned to six groups (n = 7): Control, Vitamin D (5000 IU/kg), Vitamin D (60,000 IU/kg), Doxorubicin, DOX + Vitamin D (5000 IU/kg), and DOX + Vitamin D (60,000 IU/kg). Vitamin D3 (cholecalciferol) was administered orally either as a daily dose (5000 IU/kg for 12 days) or as a single bolus dose (60,000 IU/kg). Doxorubicin (6 mg/kg/day, cumulative dose 18 mg/kg) was administered intraperitoneally on days 10–12. Hepatic injury was evaluated using 99mTc-pyrophosphate (99mTc-PYP) scintigraphy, serum liver enzymes (AST, ALT, LDH, total bilirubin), renal markers (BUN, creatinine), calcium and 25-hydroxyvitamin D [25(OH)D], oxidative stress parameters (MDA, TOS, TAS, GSH, SOD, Nrf2), and inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-10). Results: Doxorubicin markedly increased hepatic 99mTc-PYP uptake and significantly elevated AST, ALT, LDH, bilirubin, MDA, TOS, TNF-α, IL-6, and IL-1β levels while reducing Nrf2, GSH, SOD, TAS, and IL-10 (all p < 0.001). Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D [25(OH)D] levels compared with controls (32.3 ± 2.7 vs. 74.1 ± 3.8 and 69.3 ± 3.2 ng/mL for the 5000 and 60,000 IU/kg groups, respectively; p < 0.001) and attenuated DOX-induced hepatic injury, as indicated by reduced radiotracer uptake and improved oxidative and inflammatory markers. Vitamin D also mitigated DOX-associated increases in renal injury markers (BUN and creatinine) without inducing hypercalcemia. No significant differences were observed between the two vitamin D dosing regimens in most outcome measures. Conclusion: Vitamin D supplementation exerted protective effects against doxorubicin-induced liver injury, likely through modulation of oxidative stress and inflammatory pathways. Additionally, 99mTc-PYP scintigraphy may serve as a useful imaging tool for detecting acute hepatocellular injury and evaluating therapeutic responses. Full article
(This article belongs to the Section Micronutrients and Human Health)
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27 pages, 690 KB  
Review
Vitamin D: Nutritional Programming During the First 1000 Days of Life
by Costanza Sortino, Maurizio Carta, Cristina Bonacasa, Eva Candela, Veronica Notarbartolo, Laura Maria Sollena and Mario Giuffrè
Nutrients 2026, 18(7), 1096; https://doi.org/10.3390/nu18071096 - 29 Mar 2026
Abstract
Background: The first 1000 days of life represent a critical window for developmental programming, during which specific nutritional exposures, such as vitamin D levels, may influence long-term health trajectories. Vitamin D plays a central role in skeletal development, but increasing evidence also supports [...] Read more.
Background: The first 1000 days of life represent a critical window for developmental programming, during which specific nutritional exposures, such as vitamin D levels, may influence long-term health trajectories. Vitamin D plays a central role in skeletal development, but increasing evidence also supports its possible involvement in immune, metabolic, and neurodevelopmental processes during early life. In this narrative review, we summarize current evidence on the biological functions of vitamin D across the first 1000 days, focusing on its roles in skeletal, immune, metabolic, and neurodevelopmental processes, and its potential role as a programming factor. Methods: We conducted our research using the PubMed, Scopus, and Cochrane databases. We included systematic reviews, randomized controlled trials, and high-quality observational studies published from 2015 onward, focusing on pregnancy, neonatal life, and early childhood. Results: Vitamin D acts through placental, epigenetic, skeletal, immune, metabolic, and neurodevelopmental pathways that are particularly active during early development. Low maternal or early-life vitamin D status has been associated with adverse birth outcomes and impaired bone health. It has also been linked to increased susceptibility to infections and allergic diseases, altered metabolic trajectories, and mild neurodevelopmental differences. Evidence from supplementation trials remains heterogeneous, with benefits appearing more consistent in populations with baseline deficiency. Conclusions: Vitamin D fulfills several biological plausibility criteria for a potential early-life programming factor, although current human evidence remains heterogeneous. Full article
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24 pages, 1740 KB  
Review
A Narrative Review on Pseudocereals and Cardiometabolic Health: Biological Mechanisms and Evidence from Human Studies
by Yesim Oztekin and Zehra Buyuktuncer
Nutrients 2026, 18(7), 1093; https://doi.org/10.3390/nu18071093 - 29 Mar 2026
Abstract
Background/Objectives: Demand for functional foods is growing due to the desire to prevent cardiometabolic disorders. Pseudocereals, particularly quinoa, buckwheat, and amaranth, stand out for their functional properties related to cardiometabolic health. The dietary fiber, plant proteins, vitamins, minerals, and phytochemicals in pseudocereals [...] Read more.
Background/Objectives: Demand for functional foods is growing due to the desire to prevent cardiometabolic disorders. Pseudocereals, particularly quinoa, buckwheat, and amaranth, stand out for their functional properties related to cardiometabolic health. The dietary fiber, plant proteins, vitamins, minerals, and phytochemicals in pseudocereals primarily help to regulate glycemic response and lipid profile, as well as blood pressure. The aim of this review is to briefly explain the role of pseudocereals in biological mechanisms underlying cardiometabolic effects and evaluate the findings of human studies. Methods: The biological mechanisms that emphasize potential cardiometabolic effects of pseudocereals were summarized based on preclinical studies. Human studies were searched on Web of Science, PubMed, and ScienceDirect between June and December 2025. Findings of human studies on potential cardiometabolic health benefits of pseudocereals, including their anti-hyperlipidemic, anti-hyperglycemic, anti-obesity, and anti-hypertensive effects, are discussed. Results: The revealed mechanisms in preclinical studies and current outcomes of thirty-three human studies included in this review indicated that pseudocereals, especially quinoa and buckwheat, might be a part of healthy nutrition to assist the prevention and management of cardiometabolic disorders. In human studies, the most notable improvements were reported in plasma triglyceride and total cholesterol levels. Nevertheless, the number of human studies is limited, and existing studies have methodological variations to state cumulative and evidence-based consumption recommendations. Conclusions: Despite the potential protective effects of pseudocereals on cardiometabolic health, well-designed, controlled human studies are needed to elucidate the outcomes and provide clear evidence of the role of pseudocereals in relation to cardiometabolic effects. Full article
(This article belongs to the Special Issue Featured Papers on Dietary Carbohydrates and Human Health)
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