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Search Results (1,141)

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36 pages, 2396 KB  
Review
The Photosynthetic Complexes of Thylakoid Membranes of Photoautotrophs and a Quartet of Their Polar Lipids
by Anatoly Zhukov and Vadim Volkov
Int. J. Mol. Sci. 2025, 26(20), 9869; https://doi.org/10.3390/ijms26209869 - 10 Oct 2025
Abstract
The important function of polar lipids in the biochemical chains of photosynthesis, the outstanding biochemical process on our planet, has been mentioned in many publications. Over the last several years, apart from the known function of lipids in creating a matrix for photosynthetic [...] Read more.
The important function of polar lipids in the biochemical chains of photosynthesis, the outstanding biochemical process on our planet, has been mentioned in many publications. Over the last several years, apart from the known function of lipids in creating a matrix for photosynthetic complexes, most attention has been paid to the role of lipids in building up and functioning of the photosynthetic complexes. The lipid molecules are found inside the complexes of photosystem II (PSII), photosystem I (PSI), and cytochrome b6f (Cyt b6f) together with other cofactors that accompany proteins and chlorophyll molecules. Super complexes PSII-light-harvesting complex II (PSII-LHCII) and PSI-light-harvesting complex I (PSI-LHCI) also include lipid molecules; part of the lipid molecules is located at the borders between the separate monomers of the complexes. Our interest is in the exact localization of lipid molecules inside the monomers: what are the protein subunits with the lipid molecules in between and how do the lipids contact directly with the amino acids of the proteins? The photosystems include very few classes of all the polar lipids, three groups of glyceroglycolipids, and one group of glycerophospholipids make up the quartet of polar lipids. What are the reasons they have been selected for the role? There are no doubts that the polar heads and the fatty acids chains of these lipids are taking part in the processes of photosynthesis. However, what are the distinct roles for each of them? The advantages and disadvantages of the head groups of lipids from thylakoid membranes and those lipids that for various reasons could not take their place are discussed. Attention is focused on those bound fatty acids that predominate or are characteristic for each class of thylakoid lipids. Emphasis is also placed on the content of each of the four lipids in all photosynthetic complexes, as well as on contacts of head groups and acyl chains of lipids with specific proteins, transmembrane chains, and their amino acids. This article is devoted to the search for answers to the questions posed. Full article
17 pages, 4029 KB  
Article
Exploring the Mechanisms of n-Butanol Extract from Tibetan Medicine Biebersteinia heterostemon in Improving Type 2 Diabetes Based on Network Pharmacology and Cellular Experiments
by Shengwen Chen, Mengting Zeng, Xiuxiu Shen and Benyin Zhang
Int. J. Mol. Sci. 2025, 26(20), 9866; https://doi.org/10.3390/ijms26209866 - 10 Oct 2025
Abstract
An integrative approach combining network pharmacology, molecular docking, and cellular assays was used to elucidate the potential mechanisms by which the n-butanol extract of Biebersteinia heterostemon ameliorates type 2 diabetes mellitus (T2DM). Chemical constituents of the n-butanol extract were identified via [...] Read more.
An integrative approach combining network pharmacology, molecular docking, and cellular assays was used to elucidate the potential mechanisms by which the n-butanol extract of Biebersteinia heterostemon ameliorates type 2 diabetes mellitus (T2DM). Chemical constituents of the n-butanol extract were identified via ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry. Active compounds and T2DM-related targets were retrieved from public databases, and intersecting targets were identified. Protein–protein interaction (PPI) networks were constructed using the STRING database, while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed via the DAVID database. A comprehensive “drug–compound–target–disease–pathway” network was established, and molecular docking was conducted to evaluate binding affinities of key compounds to core targets. Functional validation was performed in insulin-resistant cell models. Network pharmacology analysis identified 37 active constituents within the extract and 222 overlapping targets associated with T2DM. GO enrichment indicated involvement in protein phosphorylation, MAPK cascade activation, and negative regulation of apoptosis. Key signaling pathways included PI3K/AKT and lipid and atherosclerosis pathways. Molecular docking revealed strong binding affinities (binding energies ≤ −9.3 kcal·mol−1) between core compounds—such as cheilanthifoline, glabridin, acetylcorynoline, skullcapflavone II, liquiritigenin, and dinatin—and pivotal targets including GAPDH, AKT1, TNF, SRC, EGFR, and PPARγ. In vitro experiments demonstrated that the extract significantly enhanced glucose uptake and glycogen synthesis in insulin-resistant cells, while suppressing oxidative stress and the expression of pro-inflammatory mediators such as TNF-α, MMP9, and IL-6. Collectively, B. heterostemon shows potential as an effective intervention for T2DM by targeting key molecular pathways, improving insulin sensitivity, and mitigating oxidative stress and inflammation in insulin-resistant cells. Full article
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17 pages, 306 KB  
Article
A Combined Physical Activity and Multi-Micronutrient Supplementation Intervention in South African Primary Schools: Effects on Physical Activity, Fitness, and Cardiovascular Disease Risk Factors
by Siphesihle Nqweniso, Cheryl Walter, Rosa du Randt, Larissa Adams, Johanna Beckmann, Danielle Dolley, Nandi Joubert, Kurt Z. Long, Ivan Müller, Uwe Pühse, Harald Seelig, Peter Steinmann, Jürg Utzinger, Christin Lang and Markus Gerber
Children 2025, 12(10), 1352; https://doi.org/10.3390/children12101352 - 9 Oct 2025
Abstract
Background/Objectives: Declining physical activity (PA) and cardiorespiratory fitness (CRF) in children are global public health concerns, particularly in populations experiencing urbanization and economic transition. This study investigated the effects of a school-based intervention on PA, CRF, and cardiovascular disease (CVD) risk factors [...] Read more.
Background/Objectives: Declining physical activity (PA) and cardiorespiratory fitness (CRF) in children are global public health concerns, particularly in populations experiencing urbanization and economic transition. This study investigated the effects of a school-based intervention on PA, CRF, and cardiovascular disease (CVD) risk factors in children aged 6–12 years from marginalized communities in Gqeberha, South Africa. Methods: A cluster randomized controlled trial was conducted in four schools, with participants randomly assigned to one of the following four arms: (i) PA and multi-micronutrient supplementation (MMNS); (ii) PA and placebo; (iii) MMNS; or (iv) placebo (control). A total of 1151 children were assessed at baseline (T1), 1003 at post-intervention (T2), and 549 at follow-up (T3). PA was measured using accelerometers. Secondary outcomes included CRF (20 m shuttle-run) and CVD risk factors (i.e., anthropometry, blood pressure, glycated hemoglobin [HbA1c], and lipid profile). Mixed linear models adjusted for baseline characteristics were used. Results: None of the interventions significantly improved daily PA. From T1 to T2, the MMNS arm significantly increased CRF, while PA + MMNS reduced HbA1c. However, MMNS alone increased triglycerides, and PA + placebo increased low-density lipoprotein (LDL). From post-intervention (T2) to follow-up (T3), the MMNS arms significantly reduced blood pressure. Yet, the PA + MMNS arm increased body fat percentage and decreased high-density lipoprotein (HDL). Conclusions: While MMNS showed promise for improving fitness and blood pressure and PA + MMNS reduced HbA1c, adverse metabolic changes emerged. The results should be interpreted with caution due to the short intervention span and COVID-19 disruptions during the second year of the intervention. Full article
(This article belongs to the Section Global Pediatric Health)
14 pages, 3947 KB  
Article
Characterization of Rhesus Macaque Embryonic Stem Cells in Primed and Naïve-like Cell States of Pluripotency Using Fourier Transform Infrared (FTIR) Microspectroscopy
by Jittanun Srisutush, Worawalan Samruan, Preeyanan Anwised, Anaïs Amzal, Cloé Rognard, Pierre Savatier, Irene Aksoy, Kanjana Thumanu and Rangsun Parnpai
Int. J. Mol. Sci. 2025, 26(19), 9514; https://doi.org/10.3390/ijms26199514 - 29 Sep 2025
Viewed by 475
Abstract
We evaluated the potential of Fourier-transform infrared (FTIR) microspectroscopy for non-invasive biochemical profiling of rhesus macaque embryonic stem cells (rhESCs) cultured in either conventional FGF2/KOSR medium or a novel formulation, ALGöX. Cells from both conditions were analyzed by immunocytochemistry, RNA sequencing, and high-resolution [...] Read more.
We evaluated the potential of Fourier-transform infrared (FTIR) microspectroscopy for non-invasive biochemical profiling of rhesus macaque embryonic stem cells (rhESCs) cultured in either conventional FGF2/KOSR medium or a novel formulation, ALGöX. Cells from both conditions were analyzed by immunocytochemistry, RNA sequencing, and high-resolution FTIR profiling. Molecular marker expression patterns and transcriptional profiles revealed that rhESCs maintained in FGF2/KOSR were in the primed pluripotent state, whereas those cultured in ALGöX adopted a naïve-like state. FTIR spectra showed consistent differences in protein, lipid, and nucleic acid signatures, with ALGöX-cultured cells displaying higher amide I/II and nucleic acid absorbance and FGF2/KOSR-cultured cells exhibiting stronger lipid-associated bands. Principal component analysis (PCA) separated the two groups along PC−1 (64% variance), and partial least squares discriminant analysis (PLS-DA) classified samples with 100% specificity and 100% sensitivity. These findings demonstrate that FTIR microspectroscopy can reliably discriminate pluripotent state–specific biochemical features in non-human primate PSCs, providing a rapid and label-free approach for monitoring stem cell identity and quality. Full article
(This article belongs to the Section Molecular Biology)
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15 pages, 2072 KB  
Review
Angiotensin-Converting Enzyme Inhibitors and Metabolic Aging: A Drosophila Perspective
by Denise Vecchie’, Victoria G. Faber, Patricia Jumbo-Lucioni, Robert R. H. Anholt, Trudy F. C. Mackay and Maria De Luca
Biomolecules 2025, 15(10), 1378; https://doi.org/10.3390/biom15101378 - 28 Sep 2025
Viewed by 366
Abstract
Aging is characterized by a progressive decline in physiological function that impairs performance and increases vulnerability to disease and mortality. Delaying this deterioration is key to promoting healthy aging. Age-associated functional decline is closely linked to alterations in intermediary metabolism, including disrupted lipid [...] Read more.
Aging is characterized by a progressive decline in physiological function that impairs performance and increases vulnerability to disease and mortality. Delaying this deterioration is key to promoting healthy aging. Age-associated functional decline is closely linked to alterations in intermediary metabolism, including disrupted lipid metabolism and impaired mitochondrial function. Counteracting these metabolic changes, particularly those affecting basal metabolic rate and energy utilization, may be a feasible strategy to extend healthspan. The Renin-Angiotensin System (RAS), which controls blood pressure through Angiotensin II, an octapeptide hormone generated from Angiotensin I by Angiotensin-Converting Enzyme (ACE), has been identified as a potential target for aging therapies. ACE inhibitors, such as the commonly prescribed vasodilator lisinopril, have been shown to exert beneficial effects on healthspan. Disentangling their systemic effects from direct cellular actions on intermediary metabolism is challenging in humans but can be pursued in model organisms. Drosophila melanogaster expresses two ortholog of mammalian ACE, Ance and Acer, which have diverged to acquire different functions. Since fundamental cellular processes are evolutionarily conserved and flies have an open circulatory system, Drosophila provides a versatile model for translational studies on ACE inhibition and aging. Recent studies in Drosophila reveal sex-, age-, and genetic background-specific effects of lisinopril on metabolic rates and aging-related organismal phenotypes. Integrating preclinical findings from Drosophila with clinical studies will be essential to define the therapeutic potential of RAS inhibition in extending lifespan and delaying aging. Full article
(This article belongs to the Special Issue Drosophila as a Model System to Study Metabolism)
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18 pages, 6403 KB  
Article
Tannic Acid/Fe(III)-Coated Curcumin Self-Assembled Nanoparticles for Combination Therapy to Treat Triple-Negative Breast Cancer
by Jialing Li, Ning Han, Mingyue Ruan, Hongmei Wei, Yunan Dong, Haitong Zhang, Zishuo Guo, Shouying Du and Pengyue Li
Pharmaceutics 2025, 17(10), 1257; https://doi.org/10.3390/pharmaceutics17101257 - 25 Sep 2025
Viewed by 450
Abstract
Background/Objectives: Triple-negative breast cancer (TNBC) exhibits pronounced biological heterogeneity, aggressive behavior, and a high risk of recurrence and metastasis. The conventional treatments for TNBC have notable limitations: surgical resection may leave residual tumor cells; chemotherapy (CT) frequently induces systemic toxicity and drug resistance; [...] Read more.
Background/Objectives: Triple-negative breast cancer (TNBC) exhibits pronounced biological heterogeneity, aggressive behavior, and a high risk of recurrence and metastasis. The conventional treatments for TNBC have notable limitations: surgical resection may leave residual tumor cells; chemotherapy (CT) frequently induces systemic toxicity and drug resistance; and radiotherapy damages surrounding organs and compromises the patients’ immune function. Methods: Herein, we designed a carrier-free nanodrug delivery system composed of self-assembled Curcumin nanoparticles (NPs) coated with a tannic acid (TA)/Fe(III) network (denoted as CUR@TA-Fe(III) NPs). We systematically evaluated the in vitro cytotoxicity and photothermal–ferroptosis synergistic therapeutic efficacy of CUR@TA-Fe(III) NPs in 4T1 breast cancer cells, as well as the in vivo antitumor activity using 4T1 tumor-bearing mouse models. Results: CUR@TA-Fe(III) NPs had high drug loading efficiency (LE) of 27.99%, good dispersion stability, and photothermal properties. Curcumin could inhibit the growth of 4T1 cancer cells, while TA-Fe(III) efficiently converted light energy into heat upon exposure to near-infrared (NIR) light, leading to direct thermal ablation of 4T1 cells. Additionally, TA-Fe(III) could supply Fe(II) via TA, increase intracellular Fe(II) content, and generate reactive oxygen species (ROS) through the Fenton reaction, in turn inducing lipid peroxidation (LPO), a decrease in mitochondrial membrane potential (MMP), and glutathione depletion, eventually triggering ferroptosis. Conclusions: This treatment strategy, which integrates CT, PTT, and ferroptosis, is expected to overcome the limitations of traditional single-treatment methods and provide a more effective method for the treatment of TNBC. Full article
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11 pages, 739 KB  
Article
Influences of Chloride Salts on Enzymatic Activity, Lipid Oxidation and Volatile Compounds of Reduced-Sodium Salt Pastırma
by Barış Yalınkılıç, Fatma Yağmur Hazar Suncak, Güzin Kaban, Muhammet İrfan Aksu and Mükerrem Kaya
Appl. Sci. 2025, 15(19), 10390; https://doi.org/10.3390/app151910390 - 24 Sep 2025
Viewed by 334
Abstract
The study investigated the effects of chloride salts (control: 100% NaCl, salt mixture I: NaCl/KCl (50/50), salt mixture II: NaCl/KCl/CaCl2 (40/40/20), salt mixture III: NaCl/KCl/CaCl2/MgCl2 (30/40/20/10)) on enzymatic activity, lipid oxidation, and volatile compounds in reduced-sodium salt pastırma, a [...] Read more.
The study investigated the effects of chloride salts (control: 100% NaCl, salt mixture I: NaCl/KCl (50/50), salt mixture II: NaCl/KCl/CaCl2 (40/40/20), salt mixture III: NaCl/KCl/CaCl2/MgCl2 (30/40/20/10)) on enzymatic activity, lipid oxidation, and volatile compounds in reduced-sodium salt pastırma, a Turkish dry-cured meat product. Lipid oxidation and instrumental color values were not affected by different salt mixtures. Salt mixtures II and III decreased pH value (p < 0.05). However, the mean pH value did not fall below 5.5 in any sample. The salt mixture treatment had significant effect on water activity, cathepsin B, and cathepsin B + L. In contrast, aw value was under 0.90 in all treatments. The highest mean values for cathepsin B and B + L were determined in the control group with 11.69 ± 2.73 and 85.82 ± 12.65 U g−1 × 10−3 dry matter, respectively. The closest correlation for lipolytic enzyme activities was determined by the mixture II and III groups, while a closer correlation was observed between salt mixtures I and III in terms of proteolytic enzyme activities. With regard to volatile compounds, there was a closer relationship between the control and salt mixture I. As a result, it can be concluded that salt mixture I in reduced-sodium salt pastırma showed closer results to the control group. Full article
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10 pages, 547 KB  
Article
Periodontitis, Dyslipidemia and Rheumatoid Arthritis: An Additive Model of Cardiovascular Risk
by Marco Bonilla, Enrique Raya-Álvarez, Manuel Bravo, Eva Rosel and Francisco Mesa
J. Clin. Med. 2025, 14(19), 6722; https://doi.org/10.3390/jcm14196722 - 23 Sep 2025
Viewed by 278
Abstract
Background: Rheumatoid arthritis and periodontitis are chronic inflammatory diseases linked to systemic complications, including increased cardiovascular risk. The impact of glycemia, lipid profile and atherogenic cardiovascular risk indices in patients with rheumatoid arthritis (RA) and periodontitis, compared to controls, has not yet [...] Read more.
Background: Rheumatoid arthritis and periodontitis are chronic inflammatory diseases linked to systemic complications, including increased cardiovascular risk. The impact of glycemia, lipid profile and atherogenic cardiovascular risk indices in patients with rheumatoid arthritis (RA) and periodontitis, compared to controls, has not yet been evaluated. We aimed to analyze whether periodontitis acts as an aggravating factor in this relationship. Methods: In a case–control study, we assessed biochemical, RA-related markers and four atherogenic indices (Atherogenic Index of Plasma, Castelli Risk Index I, Castelli Risk Index II, and Triglyceride–Glucose Index). Periodontitis was evaluated using a gingival inflammation index (BOP) and a periodontal severity index (PIRIM). Multiple linear regression models were used to analyze whether periodontitis had a differential effect in RA cases versus controls. Results: A total of 46 participants were included (32 RA cases, 14 controls). Periodontitis was more prevalent among cases (62.5% vs. 28.5%). BOP was significantly higher in RA patients (p < 0.001) and associated with LDLC (p = 0.031). Both BOP and PIRIM correlated with higher CRI-1 and CRI-2 values across groups. PIRIM was also linked to increased LDLC (p = 0.018) and decreased HDLC (p = 0.003). Conclusions: RA and periodontitis appear to interact synergistically and are associated with a more atherogenic profile. These findings highlight periodontal health as a potentially modifiable factor in reducing cardiovascular risk in RA patients. Full article
(This article belongs to the Section Cardiovascular Medicine)
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16 pages, 489 KB  
Article
Lipid Profile, Obesity Indicators and Cardiometabolic Risk Factors in School-Aged Children and Adolescents: Sex-Specific Associations
by Rafał Baran, Joanna Baran, Justyna Leszczak, Anna Bartosiewicz and Justyna Wyszyńska
J. Clin. Med. 2025, 14(18), 6677; https://doi.org/10.3390/jcm14186677 - 22 Sep 2025
Viewed by 746
Abstract
Background: Childhood obesity and cardiometabolic disturbances are growing global health concerns. This study aimed to assess the prevalence of excess body weight, body fat, and selected cardiometabolic risk factors in school-aged children and adolescents, focusing on sex- and age-related differences. Methods: [...] Read more.
Background: Childhood obesity and cardiometabolic disturbances are growing global health concerns. This study aimed to assess the prevalence of excess body weight, body fat, and selected cardiometabolic risk factors in school-aged children and adolescents, focusing on sex- and age-related differences. Methods: A cross-sectional study was conducted among 318 Polish participants aged 6–17 years, including 169 children (6–12 years) and 149 adolescents (13–17 years). Anthropometric, blood pressure (BP), and fasting blood lipid and glucose measurements were collected and analyzed by age group (children 6–12 years; adolescents 13–17 years) and sex. Results: The prevalence of overweight and obesity was 18.5% (BMI-based) and 26.1% (body fat-based). Abdominal obesity and stage I–II hypertension were observed in 24.5% and 23.6% of participants, respectively. Children had higher rates of excess body fat, abdominal obesity, elevated BP, and lipid abnormalities than adolescents. Among adolescents, girls more frequently presented with borderline/high total cholesterol and Low-Density Lipoprotein (LDL cholesterol) and borderline/low High-Density Lipoprotein (HDL cholesterol), while boys more often had elevated BP. In girls, elevated triglycerides (TGs) were independently associated with abdominal obesity (odds ratio (OR) = 2.36, p = 0.015) and hypertension (OR = 2.47, p = 0.023); no such associations were observed in boys. Conclusions: Cardiometabolic risk factors may appear early in life and differ by age and sex. Routine screening and early interventions, particularly targeting lipid abnormalities in girls, are essential to prevent long-term health consequences. Full article
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14 pages, 593 KB  
Article
BAN Score and Distinct Early Cardiometabolic Risk Signatures in a Non-Diabetic Population: A Cross-Sectional Analysis
by Yazeed Alshuweishi, Noha A. Alshuwayer, Lama Izziddeen, Arwa Abudawood, Dalal Alfayez and Ahmed M. Basudan
Healthcare 2025, 13(18), 2384; https://doi.org/10.3390/healthcare13182384 - 22 Sep 2025
Viewed by 438
Abstract
Background: The BMI–albumin–neutrophil-to-lymphocyte (BAN) score integrates adiposity, nutritional status, and systemic inflammation, but its role in detecting early cardiometabolic changes remains unclear. This study examined associations of the BAN score with vascular, glycemic, and lipid markers in non-diabetic adults. Methods: This retrospective cross-sectional [...] Read more.
Background: The BMI–albumin–neutrophil-to-lymphocyte (BAN) score integrates adiposity, nutritional status, and systemic inflammation, but its role in detecting early cardiometabolic changes remains unclear. This study examined associations of the BAN score with vascular, glycemic, and lipid markers in non-diabetic adults. Methods: This retrospective cross-sectional study included 162 non-diabetic subjects. Associations between the BAN score and vascular, glycemic, and lipid parameters were examined using Spearman’s correlation, ROC analysis, and regression models adjusted for age, sex, smoking status, and medication use. Results: Patients had a median age of 37 years, 72.8% were female, with median BMI 33 kg/m2, albumin 4.4 g/dL, and NLR 1.3. Higher BAN scores correlated with systolic blood pressure (SBP) (r = 0.23, p < 0.01), pulse pressure (PP) (r = 0.26, p < 0.001), and HbA1c (r = 0.22, p < 0.01). Compared with the lowest tertile, higher BAN tertiles showed significantly elevated SBP, PP, and HbA1c (p < 0.01). In adjusted models, each one-unit increase in BAN score was associated with higher SBP (β = 1.01, p = 0.037), PP (β = 0.66, p = 0.006), and HbA1c (β = 1.85, p = 0.008). No associations were found with the atherogenic index of plasma (AIP), Castelli risk index I (CRI-I), or Castelli risk index II (CRI-II). ROC analysis showed moderate discriminative ability for hypertension (AUC = 0.66) and HbA1c (AUC = 0.65). Conclusions: The BAN score is associated with a distinctive early cardiometabolic risk, particularly elevated SBP, widened PP, and early glycemic alterations. Further research should define the BAN score’s mechanisms and preventive utility. Full article
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15 pages, 1673 KB  
Article
Development of Organic Sourdough Bread with Paste from Germinated Seeds
by Alberto Akiki, Yasmin Muhammed Refaie Muhammed, Fabio Minervini and Ivana Cavoski
Foods 2025, 14(18), 3263; https://doi.org/10.3390/foods14183263 - 20 Sep 2025
Viewed by 1378
Abstract
This study aimed to (i) investigate the effect of using grape water in the production of traditional sourdough; (ii) select seeds for use in laboratory-scale sourdough bread production; and (iii) assess the effect of incorporating fresh germinated seeds into recipe of organic sourdough [...] Read more.
This study aimed to (i) investigate the effect of using grape water in the production of traditional sourdough; (ii) select seeds for use in laboratory-scale sourdough bread production; and (iii) assess the effect of incorporating fresh germinated seeds into recipe of organic sourdough bread on nutritional, technological, and sensory properties. The pH of both control (CSD, flour only) and boosted (BSD, supplemented with “grape water”) sourdough fell below 4.5 by day 3. After 10 days of back-slopping and fermentation, both sourdoughs harbored 9 log CFU/g of lactic acid bacteria, whereas yeast cell density in the CSD was 1 log cycle higher. Based on their high germination rates (~90%), lentil and wheat seeds were selected as additional ingredients (5%). Bread with germinated lentils (GL) and bread with germinated wheat (GW) were compared with control bread (without seeds). GL and GW breads showed gas cell areas of 28.6% and 18.1%, respectively, which were higher than the control. In addition, GL and GW received higher scores for taste (8.6) and softness (5.6), respectively. Additionally, GL contained more proteins (9.9%) and fewer lipids (0.3%) than the two other bread types, in addition to being potentially labeled as a “source of fiber”. Full article
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19 pages, 1268 KB  
Article
Sex- and Ethnic-Specific Associations of Serum Lipids with Risk of 12 Cancers: Findings from 506,381 Adults in Two Large Cohorts
by Minh Nguyen Thien, Ji Woo Baek, Yeun Soo Yang and Sun Ha Jee
Antioxidants 2025, 14(9), 1135; https://doi.org/10.3390/antiox14091135 - 19 Sep 2025
Viewed by 499
Abstract
The contribution of serum lipids to carcinogenesis, including their effects on inflammation and oxidative stress, remains debated due to inconsistent evidence across populations. This study aimed to elucidate sex- and ethnic-specific associations between serum lipid indices and the risk of 12 common cancers [...] Read more.
The contribution of serum lipids to carcinogenesis, including their effects on inflammation and oxidative stress, remains debated due to inconsistent evidence across populations. This study aimed to elucidate sex- and ethnic-specific associations between serum lipid indices and the risk of 12 common cancers in two large, distinct populations. We conducted a pooled analysis of 506,381 participants from the UK Biobank (UKB) and the Korean Cancer Prevention Study-II (KCPS-II) cohort, with median follow-ups of 12.0 and 13.0 years, respectively. Multivariable-adjusted Cox hazards models were used to estimate hazard ratios (HRs) for the association between baseline lipids and cancer incidence. In the UKB, a one-standard deviation (1-SD) increase in HDL-C was associated with a decreased overall cancer risk (HR 0.982, 95% CI: 0.969–0.995); meanwhile, a 1-SD increase in LDL-C was associated with an increased risk (HR 1.021, 1.009–1.034); higher HDL-C was linked to an increased risk of cervical cancer (HR 1.167, 1.019–1.337) and prostate cancer (HR 1.025, 1.001–1.049). These associations were not significant in the KCPS-II. The association between serum lipids and cancer risk is substantially modified by sex and ethnicity, suggesting that universal lipid-based prevention strategies may be inappropriate and underscoring the need for population-specific research. Full article
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13 pages, 2135 KB  
Article
Thymoquinone Versus Metformin in Letrozole-Induced PCOS: Comparative Insights into Metabolic, Hormonal, and Ovarian Outcomes
by Onder Ercan, Recep Dokuyucu, Ergun Yuksel and Tumay Ozgur
J. Clin. Med. 2025, 14(18), 6561; https://doi.org/10.3390/jcm14186561 - 18 Sep 2025
Viewed by 361
Abstract
Objectives: This study aimed to evaluate the effects of thymoquinone (TMQ) on metabolic, hormonal, and ovarian dysfunctions in a letrozole-induced polycystic ovary syndrome (PCOS) rat model and compare its efficacy with metformin, which is widely recognized as the first-line pharmacological treatment for [...] Read more.
Objectives: This study aimed to evaluate the effects of thymoquinone (TMQ) on metabolic, hormonal, and ovarian dysfunctions in a letrozole-induced polycystic ovary syndrome (PCOS) rat model and compare its efficacy with metformin, which is widely recognized as the first-line pharmacological treatment for PCOS. Methods: Thirty-two female Wistar Albino rats were randomly assigned into four groups: control (I), PCOS (II), PCOS + metformin (III), and PCOS + Thymoquinone (IV). PCOS was induced using 1 mg/kg/day letrozole for 21 days, followed by treatment with either metformin (500 mg/kg/day) or thymoquinone (50 mg/kg/day) for 30 days. Metabolic (glucose, insulin, HOMA-IR, lipid profile), hormonal (estrone, estradiol, testosterone, androstenedione), and histopathological parameters were assessed. Results: PCOS induction resulted in significant metabolic, hormonal, and ovarian dysfunctions. Final body weight was significantly higher in PCOS (309.0 ± 7.5 g) vs. control (275.3 ± 8.2 g, p < 0.001), but reduced by metformin (294.0 ± 7.4 g, p < 0.01) and thymoquinone (305.7 ± 7.5 g, p < 0.01). Glucose levels were significantly elevated in PCOS (341.8 ± 16.8 mg/dL) vs. control (260.0 ± 15.8 mg/dL, p < 0.01), while metformin (290.2 ± 19.7 mg/dL, p < 0.05) and thymoquinone (320.3 ± 13.7 mg/dL, p < 0.05) reduced glucose levels. Insulin and HOMA-IR were significantly increased in PCOS (p < 0.001), but reduced by both treatments (p < 0.01). Lipid profile improvements were observed, with significant reductions in TG and LDL-C and increases in HDL-C in both treatment groups (p < 0.05–0.01). PCOS induced hyperandrogenism, with increased testosterone and androstenedione (p < 0.05), and a decreased E2/E1 ratio (p < 0.001), which were significantly improved by metformin and thymoquinone (p < 0.01). Ovarian histopathology showed increased cystic and atretic follicles and reduced corpus luteum in PCOS (p < 0.05–0.01), which were significantly improved by both treatments. Conclusions: TMQ exerts metabolic, hormonal, and ovarian protective effects comparable to metformin, supporting its potential as a natural therapeutic alternative for PCOS management. Given that metformin is already established as a first-line pharmacological therapy, our findings suggest that TMQ may provide a promising complementary or alternative approach. Further clinical studies are warranted to evaluate its safety and efficacy in human PCOS patients. Full article
(This article belongs to the Special Issue New Challenges and Perspectives in Polycystic Ovary Syndrome)
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41 pages, 2093 KB  
Review
Cracking the Blood–Brain Barrier Code: Rational Nanomaterial Design for Next-Generation Neurological Therapies
by Lucio Nájera-Maldonado, Mariana Parra-González, Esperanza Peralta-Cuevas, Ashley J. Gutierrez-Onofre, Igor Garcia-Atutxa and Francisca Villanueva-Flores
Pharmaceutics 2025, 17(9), 1169; https://doi.org/10.3390/pharmaceutics17091169 - 6 Sep 2025
Viewed by 1489
Abstract
This review provides a mechanistic framework to strategically design nanoparticles capable of efficiently crossing the blood–brain barrier (BBB), a critical limitation in neurological treatments. We systematically analyze nanoparticle–BBB transport mechanisms, including receptor-mediated transcytosis, adsorptive-mediated transcytosis, and transient barrier modulation. Essential nanoparticle parameters (size, [...] Read more.
This review provides a mechanistic framework to strategically design nanoparticles capable of efficiently crossing the blood–brain barrier (BBB), a critical limitation in neurological treatments. We systematically analyze nanoparticle–BBB transport mechanisms, including receptor-mediated transcytosis, adsorptive-mediated transcytosis, and transient barrier modulation. Essential nanoparticle parameters (size, shape, stiffness, surface charge, and biofunctionalization) are evaluated for their role in enhancing brain targeting. For instance, receptor-targeted nanoparticles can significantly enhance brain uptake, achieving levels of up to 17.2% injected dose per gram (ID/g) in preclinical glioma models. Additionally, validated preclinical models (human-derived in vitro systems, rodents, and non-human primates) and advanced imaging techniques crucial for assessing nanoparticle performance are discussed. Distinct from prior BBB nanocarrier reviews that primarily catalogue mechanisms, this work (i) derives quantitative ‘design windows’ (size 10–100 nm, aspect ratio ~2–5, near-neutral ζ) linked to transcytosis efficiency, (ii) cross-walks human-relevant in vitro/in vivo models (including TEER thresholds and NHP evidence) into a translational decision guide, and (iii) integrates regulatory/toxicology readiness (ISO 10993-4, FDA/EMA, ICH) into practical checklists. We also curate recent (2020–2025) %ID/g brain-uptake data across lipidic, polymeric, protein, inorganic, and hybrid vectors to provide actionable, evidence-based rules for BBB design. Full article
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Article
Cubebin Attenuates Methamphetamine-Induced Neurotoxicity Through CREB/BDNF/Caspase-3 Signaling: In Vivo and In Silico Study
by Sattam Khulaif Alenezi, Khalid Saad Alharbi, Tariq G. Alsahli, Muhammad Afzal, Reem ALQahtani, Samiyah Alshehri, Imran Kazmi and Nadeem Sayyed
Medicina 2025, 61(9), 1567; https://doi.org/10.3390/medicina61091567 - 31 Aug 2025
Viewed by 534
Abstract
Background and Objectives: Methamphetamine (METH) is a potent psychostimulant known to induce neurotoxicity and neurodegeneration, leading to cognitive impairment. This study aimed to explore cubebin’s potential neuroprotective effects against METH-induced cognitive deficits by investigating its ability to suppress lipid peroxidation and pro-inflammatory markers [...] Read more.
Background and Objectives: Methamphetamine (METH) is a potent psychostimulant known to induce neurotoxicity and neurodegeneration, leading to cognitive impairment. This study aimed to explore cubebin’s potential neuroprotective effects against METH-induced cognitive deficits by investigating its ability to suppress lipid peroxidation and pro-inflammatory markers and modulate neurotransmitter levels. Material and Methods: A total of 30 rats were taken and randomly grouped into five groups: group I—control; group II—METH 100 mg/kg/i.p.; group III—METH + cubebin (10 mg/kg/p.o.); group IV—METH + cubebin (20 mg/kg/p.o.); and group V—cubebin per os at 20 mg/kg. After a 14-day oral regimen, behavioral activities were assessed utilizing the Morris water maze (MWM). Biochemical analysis included neurotransmitters, including dopamine (DA), norepinephrine (NE), and gamma-aminobutyric acid (GABA); oxidative stress markers (malondialdehyde (MDA); nitric oxide (NO), catalase (CAT), reduced glutathione (GSH)); inflammatory cytokines [interleukin (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)]; neurotrophic factors (BDNF, CREB); and apoptotic markers (caspase-3 and caspase-9). Furthermore, molecular docking and simulation studies were conducted. Results: Treatment with cubebin led to a marked reduction in latency during the MWM task. It significantly modulated the oxidative stress markers (SOD, GSH, CAT, MDA, and NO), inflammatory cytokines (IL-6, IL-1β, TNF-α), neurotrophic factors (CREB, BDNF), apoptotic markers (NFkB, caspase-3, caspase-9), and neurotransmitters (NE, DA, and GABA) in METH-induced memory-impaired rats. The results of molecular dynamics simulation (MDS) provided insight into the mechanisms that associate proteins CREB, BDNF, and caspase-3 in conformational dynamics upon binding to cubebin. Conclusions: In conclusion, cubebin administration improved cognitive function in rats by modulating antioxidant enzyme activity, reducing pro-inflammatory cytokines, and regulating neurotransmitter levels, demonstrating its potential neuroprotective effects against MA-induced neurodegeneration. Full article
(This article belongs to the Section Pharmacology)
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