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14 pages, 883 KB  
Article
Liver Fibrosis as a Predictor of Cardiovascular Risk in Patients with Severe Obesity
by Alina N. Saidi, Willy B. Theel, Vivian D. de Jong, Stefanie R. van Mil, Aart-Jan van der Lely, Diederick E. Grobbee, Jan Apers, Ellen van der Zwan-van Beek and Manuel Castro Cabezas
J. Clin. Med. 2025, 14(23), 8532; https://doi.org/10.3390/jcm14238532 - 1 Dec 2025
Viewed by 468
Abstract
Background: Obesity is a substantial global health issue associated with increased risk of cardiovascular disease (CVD) and metabolic dysfunction-associated steatotic liver disease (MASLD). Despite the known link between obesity, CVD and MASLD, it remains unknown which factors contribute to higher cardiovascular (CV) risk [...] Read more.
Background: Obesity is a substantial global health issue associated with increased risk of cardiovascular disease (CVD) and metabolic dysfunction-associated steatotic liver disease (MASLD). Despite the known link between obesity, CVD and MASLD, it remains unknown which factors contribute to higher cardiovascular (CV) risk in patients with obesity-induced liver fibrosis. Liver fibrosis, assessed by the Fibrosis-4 (FIB-4) index, may help to identify patients with obesity at increased CV risk. Methods: Patients with severe obesity (Body Mass Index (BMI) ≥ 40 kg/m2) scheduled for bariatric surgery were subdivided into FIB-4 categories. Systemic leukocyte activation markers were measured by flow cytometry. Additionally, markers of vascular damage, namely the carotid intima media thickness (cIMT) and pulse wave velocity (PWV), were included. Results: The cohort predominantly consisted of women (74%) with an average age of 41 years and mean BMI of 42.7 kg/m2. Patients with an elevated FIB-4 (≥1.3) had higher systolic (146 ± 16 vs. 139 ± 15, p = 0.002) and diastolic blood pressure (91 ± 13 vs. 83 ± 12, p = 0.002), increased cIMT (0.66 ± 0.11 vs. 0.55 ± 0.10, p < 0.001), and higher PWV (8.2 ± 0.9 vs. 6.8 ± 1.1, p < 0.001) compared to those with a low FIB-4 (<1.3). Additionally, patients with a high FIB-4 tended to show increased expression of CD66b on granulocytes. Conclusions: Patients with severe obesity who were at risk of liver fibrosis showed greater signs of vascular damage, insulin resistance, and systemic inflammation. This suggests that liver fibrosis can be a useful marker for identifying patients with obesity at high CV risk. Full article
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16 pages, 411 KB  
Article
The Influence of Berberine on Vascular Function Parameters, Among Them VEGF, in Individuals with MAFLD: A Double-Blind, Randomized, Placebo-Controlled Trial
by Anna Koperska, Ewa Miller-Kasprzak, Agnieszka Seraszek-Jaros, Katarzyna Musialik, Paweł Bogdański and Monika Szulińska
Nutrients 2025, 17(22), 3585; https://doi.org/10.3390/nu17223585 - 16 Nov 2025
Viewed by 1473
Abstract
Background: Metabolically Associated Fatty Liver Disease (MAFLD) is a prevalent liver disorder closely tied to metabolic dysfunction, insulin resistance, and chronic low-grade inflammation. Vascular Endothelial Growth Factor (VEGF) may have a dual interesting role in MAFLD pathophysiology—supporting vascular repair in early stages, but [...] Read more.
Background: Metabolically Associated Fatty Liver Disease (MAFLD) is a prevalent liver disorder closely tied to metabolic dysfunction, insulin resistance, and chronic low-grade inflammation. Vascular Endothelial Growth Factor (VEGF) may have a dual interesting role in MAFLD pathophysiology—supporting vascular repair in early stages, but potentially contributing to fibrosis in later stages. In this study, berberine (BBR), a plant-derived isoquinoline alkaloid, exhibits multiple beneficial properties, including anti-inflammatory, antioxidant, and endothelial-protective effects, on the study group, perhaps by influencing VEGF concentration. Objective: This study aimed to investigate the effectiveness of BBR in addressing vascular function parameters linked to MAFLD, particularly its impact on serum VEGF levels and arterial stiffness. Methods: This randomized, double-blind, placebo-controlled clinical trial enrolled seventy individuals with MAFLD who were overweight or obese. Participants were randomly assigned in a 1:1 ratio to receive either BBR (1500 mg/day) or a placebo orally for 12 weeks. The following parameters were assessed pre- and post-intervention: VEGF, brachial SBP (Systolic Blood Pressure)/DBP (Diastolic Blood Pressure), MAP (Mean Arterial Pressure), AIx (Augmentation Index), AP (Aortic Pressure), number of waveforms, Pulse Pressure (PP), PWV (Pulse Wave Velocity), and PWA-SP/PWA-DP (Pulse Wave Analysis Systolic/Diastolic Pressure). The results for the metabolic parameters—FLI (Fatty Liver Index)—and anthropometric parameters—BMI (Body Mass Index), fat mass corp—and laboratory parameters, among them, hsCRP (high-sensitivity C-reactive protein), were published by us earlier. Results: In the BBR-treated cohort, VEGF concentrations demonstrated a statistically significant increase following the intervention, rising from a baseline mean of 456.23 ± 307.61 pg/mL to 561.22 ± 389.77 pg/mL (p < 0.0001). In the BBR group, a significant reduction in PWA-SP was observed after 12 weeks of supplementation (134.85 ± 16.26 vs. 124.46 ± 13.47 mmHg, p < 0.0001). No statistically significant differences were observed in the parameters determining arterial stiffness in the BBR and placebo groups. In the BBR group, delta VEGF correlated negatively with delta FLI; no such associations were observed in the placebo group. Changes in PWV were consistent and significantly correlated with changes in brachial SBP/DBP, PWA-SP, PWA-DP, and MAP. No serious adverse events were reported, and BBR was well tolerated. Conclusions: BBR appears to be a safe and promising adjunct in MAFLD therapy, potentially exerting reparative effects through VEGF modulation and vascular support. Further research is warranted to confirm its long-term impact and elucidate underlying protective mechanisms. Full article
(This article belongs to the Special Issue Botanicals and Nutritional Approaches in Metabolic Disorders)
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16 pages, 2355 KB  
Article
Investigating the Metabolic Benefits of Magnetic Mitohormesis in Patients with Type 2 Diabetes Mellitus
by Fan Shuen Tseng, Gek Hsiang Lim, Yong Mong Bee, Phong Ching Lee, Yee Kit Tai, Alfredo Franco-Obregón and Hong Chang Tan
J. Clin. Med. 2025, 14(18), 6413; https://doi.org/10.3390/jcm14186413 - 11 Sep 2025
Cited by 1 | Viewed by 3203
Abstract
Background/Objectives: Exercise is a key pillar in the management of type 2 diabetes mellitus (T2DM), but adherence rates to physical activity are poor. Pulsed electromagnetic field (PEMF) therapy, termed magnetic mitohormesis (MM), has been shown in preclinical and early human studies to [...] Read more.
Background/Objectives: Exercise is a key pillar in the management of type 2 diabetes mellitus (T2DM), but adherence rates to physical activity are poor. Pulsed electromagnetic field (PEMF) therapy, termed magnetic mitohormesis (MM), has been shown in preclinical and early human studies to mimic the metabolic benefits of exercise without physical strain. However, its effects on glycemic control remain unknown. We evaluate the metabolic benefits of MM in patients with suboptimally-controlled T2DM. Methods: An exploratory study was conducted in 40 adults with T2DM (glycated hemoglobin, HbA1c 7.0–10.0%). MM treatment comprised 12 sessions organized weekly, where low-dose PEMF was delivered to alternate legs for 10 min per visit. Metabolic assessments—anthropometry, HbA1c, fasting glucose and insulin resistance (measured by Homeostatic Model Assessment for Insulin Resistance, HOMA-IR)—were measured at baseline and post-treatment. Subgroup analysis was performed to compare the effects of MM on patients with and without central obesity (defined as waist-to-hip ratio ≥ 1.0). Results: Participants had a mean age of 59.4 years and HbA1c of 8.1%. MM treatment was well tolerated with no adverse events, and 77.5% of patients completed all 12 sessions. There were no significant changes in HbA1c, fasting glucose or HOMA-IR for the overall cohort. However, in patients with central obesity, 88.9% showed a reduction in HbA1c post-treatment compared to 32.3% without central obesity (p < 0.01), and mean HbA1c decreased from 7.5% to 7.1% (p < 0.01). Conclusions: Our findings suggest that MM is safe and well-tolerated in T2DM patients and may confer a preferential benefit for individuals with greater central obesity. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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14 pages, 535 KB  
Article
Effects of 12 Weeks of Calanus Oil Supplementation on Cardiac Diastolic Function in Obese and Prediabetic Women—A Pilot Study
by Felix Kerlikowsky, Fabian Spahiu, Eric J. Stöhr, Sina Junge, Wiebke Jonas, Edda van de Flierdt, Jan Philipp Schuchardt and Andreas Hahn
Metabolites 2025, 15(9), 596; https://doi.org/10.3390/metabo15090596 - 8 Sep 2025
Viewed by 1266
Abstract
Background/Objectives: In early-stage diabetes, diastolic dysfunction is an initial indicator of heart failure and is linked to altered glucose metabolism, including in prediabetes. Based on initial evidence that Calanus oil, derived from Calanus finmarchicus, which is rich in omega-3 polyunsaturated fatty acids [...] Read more.
Background/Objectives: In early-stage diabetes, diastolic dysfunction is an initial indicator of heart failure and is linked to altered glucose metabolism, including in prediabetes. Based on initial evidence that Calanus oil, derived from Calanus finmarchicus, which is rich in omega-3 polyunsaturated fatty acids and other bioactive compounds, benefits metabolic and cardiorespiratory health, this proof-of-principle study aimed to assess whether Calanus oil improves diastolic function in prediabetic women. Methods: Twenty middle-aged, obese women with prediabetes and no history of cardiac complications were enrolled and received 4 g/day of Calanus oil, providing 276 mg EPA + 256 mg DHA, for 12 weeks. Systolic and diastolic cardiac function, including the E/A ratio (E/A), was assessed by echocardiography. In addition, central blood pressure (BP) and pulse wave velocity (PWV) were analyzed by oscillometry. Metabolic health was evaluated using composite markers, including the metabolic syndrome severity score (Met-S score) and the triacylglycerol glucose–waist-to-height ratio (TyG-WHtR). Results: E/A was significantly improved (p = 0.023) following 12 weeks of Calanus oil supplementation. Furthermore, a significant improvement in metabolic health, indicated by a reduced Met-S score and a lower TyG-WHtR, was noticed (p < 0.001, respectively), reflecting decreased metabolic syndrome severity and enhanced insulin sensitivity. In addition, a significant reduction in diastolic BP, resting heart rate (p = 0.047), but not PWV or systolic BP (all p > 0.05) was observed. The improvement in E/A was associated with improved insulin sensitivity, as reflected by a decrease in the TyG-WHtR (p = 0.014). Conclusions: These exploratory findings suggest that Calanus oil supplementation in pre-diabetic women might improve central diastolic haemodynamics, accompanied by an overall improvement in metabolic health. However, the absence of a placebo control group limits definitive conclusions. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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20 pages, 576 KB  
Article
Effectiveness of a Physiotherapy Stress-Management Protocol on Cardiorespiratory, Metabolic and Psychological Indicators of Children and Adolescents with Morbid Obesity
by Pelagia Tsakona, Alexandra Hristara-Papadopoulou, Thomas Apostolou, Ourania Papadopoulou, Ioannis Kitsatis, Eleni G. Paschalidou, Christos Tzimos, Maria G. Grammatikopoulou and Kyriaki Tsiroukidou
Children 2025, 12(8), 1010; https://doi.org/10.3390/children12081010 - 31 Jul 2025
Viewed by 1672
Abstract
Background: Chronic stress in childhood and adolescence leads to excessive cortisol secretion, adipokines production and obesity with all the negative mental and physical effects on the health of individuals and adulthood. Objectives: The aim of the present non-randomized controlled trial was to investigate [...] Read more.
Background: Chronic stress in childhood and adolescence leads to excessive cortisol secretion, adipokines production and obesity with all the negative mental and physical effects on the health of individuals and adulthood. Objectives: The aim of the present non-randomized controlled trial was to investigate the effect of a stress management protocol with diaphragmatic breathing (DB) and physiotherapy exercise on stress, body composition, cardiorespiratory and metabolic markers of children and adolescents with morbid obesity. Methods: The study included 31 children and adolescents (5–18 years old) with morbid obesity (22 in the intervention arm and 9 controls). All participants completed anxiety questionnaires and a self-perception scale. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), blood pressure (BP) and SpO2 were measured. Fasting glucose, uric acid, triglycerides, HbA1c, (AST/SGOT), (ALT/SGPT), HDL, LDL, insulin, ACTH, cortisol, HOMA-IR, 17-OH, S-DHEA, SHBG were assessed, and anthropometric measurements were also performed. Results: In the intervention group, 4 months after the treatment, an improvement was noted in the BMI, BMI z-score, waist-to-height ratio, FEV1, SpO2, pulse and systolic BP. HDL increased, ALT/SGPT and insulin resistance improved. Positive changes were observed in temporary and permanent stress and self-esteem of children in the intervention group, including anxiety, self-perception, physical appearance, etc. Conclusions: A combined exercise and DB protocol has a positive effect on stress, by improving body composition, reducing insulin resistance, and ameliorating physical and mental health and quality of life of pediatric patients with morbid obesity. Full article
(This article belongs to the Special Issue Childhood Obesity: Prevention, Intervention and Treatment)
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14 pages, 2340 KB  
Article
Oral Administration of 5-Aminolevulinic Acid Does Not Ameliorate Autoimmune Diabetes in NOD Mice
by Shinpei Nishikido, Satoru Akazawa, Tetsuro Niri, Shin-Ichi Inoue, Katsuya Matsuda, Taiki Aoshi, Masahiro Nakashima, Ai Haraguchi, Ichiro Horie, Masakazu Kobayashi, Minoru Okita, Atsushi Kawakami and Norio Abiru
Diabetology 2025, 6(7), 62; https://doi.org/10.3390/diabetology6070062 - 1 Jul 2025
Viewed by 875
Abstract
Background/Objectives: 5-Aminolevulinic acid (5-ALA) is a biosynthetic precursor of heme that induces heme oxygenase-1 (HO-1). Therapeutic induction of HO-1 has shown effectiveness in various autoimmune disease models, including type 1 diabetes (T1D). However, the efficacy of 5-ALA as an HO-1 inducer in [...] Read more.
Background/Objectives: 5-Aminolevulinic acid (5-ALA) is a biosynthetic precursor of heme that induces heme oxygenase-1 (HO-1). Therapeutic induction of HO-1 has shown effectiveness in various autoimmune disease models, including type 1 diabetes (T1D). However, the efficacy of 5-ALA as an HO-1 inducer in T1D models remains unexplored. This study aimed to investigate the therapeutic efficacy of oral 5-ALA administration in preventing autoimmune diabetes development in nonobese diabetic (NOD) mice. Methods: We evaluated diabetes incidence, levels of insulin autoantibody, and severity of insulitis in 5-ALA-treated and control NOD mice. HO-1 expression of dendritic cells in the pancreatic islets and spleen of 5-ALA-treated NOD mice was measured. The IFN-γ/IL-17 of islet-infiltrating T cells and IL-10/IL-12 productions of dendritic cells in the spleen of 5-ALA-treated NOD mice were assessed. We stimulated islet antigen-specific CD4+ T cells with islet antigen-pulsed dendritic cells in the presence of 5-ALA and examined the proliferation of the T cells. Finally, we adoptively transferred islet antigen-specific CD4+ T cells into 5-ALA-treated, immunodeficient NOD-Rag1 knockout mice, and diabetes incidence in recipients was determined. Results: Oral 5-ALA treatment did not significantly impact diabetes incidence, levels of insulin autoantibody, and insulitis. No significant difference was observed in HO-1 expression in dendritic cells and cytokine production of T cells and dendritic cells. Similarly, there was no significant difference in the proliferation of islet antigen-specific CD4+ T cells in vitro and diabetes induction in transfer experiments. Conclusions: Oral administration of 5-ALA has a limited effect on suppressing the development of autoimmune diabetes in NOD mice. Full article
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8 pages, 2259 KB  
Case Report
Successful Management of a Pancreatic Abscess in a Dog with Juvenile Diabetes Mellitus Through Ultrasound-Guided Drainage and Medical Therapy
by Alexandra Daravigka, Stefanos Ninis, Panagiotis Bourdekas, Alexandros O. Konstantinidis, Argyrios Ginoudis, Katerina K. Adamama-Moraitou, Maria Lyraki and Nektarios Soubasis
Vet. Sci. 2025, 12(7), 604; https://doi.org/10.3390/vetsci12070604 - 20 Jun 2025
Viewed by 2740
Abstract
A five-month-old female mixed-breed dog presented with a two-week history of polyuria, polydipsia, and vomiting. Clinical examination revealed poor body condition, growth retardation, pale oral mucous membranes, weak pulse, and prolonged capillary refill time. Laboratory findings included neutrophilic leukocytosis with a regenerative left [...] Read more.
A five-month-old female mixed-breed dog presented with a two-week history of polyuria, polydipsia, and vomiting. Clinical examination revealed poor body condition, growth retardation, pale oral mucous membranes, weak pulse, and prolonged capillary refill time. Laboratory findings included neutrophilic leukocytosis with a regenerative left shift, fasting hyperglycemia, elevated fructosamine, glycated hemoglobin, and β-hydroxybutyrate concentrations, while the acid–base balance remained normal. Canine-specific pancreatic lipase and trypsin-like immunoreactivity concentrations ruled out an underlying pancreatitis or exocrine pancreatic insufficiency, respectively. Urinalysis showed glycosuria and ketonuria. Supportive care included antibiotics and regular insulin administration. Abdominal ultrasonography identified a pancreatic cavity with a thick wall and mixed echogenic fluid. Ultrasound-guided drainage was performed without complications. Cytology confirmed a pancreatic abscess with pyogranulomatous inflammation, though the culture results were negative. The dog was discharged with intermediate-acting lente insulin. Follow-up ultrasonographic evaluations at 7, 14, and 21 days and 5 months post-drainage showed no recurrence. The diabetes remained well-controlled one year post-discharge. This case report describes the successful management of a dog with juvenile diabetes mellitus complicated by a pancreatic abscess, highlighting the effectiveness of percutaneous ultrasound-guided drainage combined with medical therapy. Full article
(This article belongs to the Section Veterinary Internal Medicine)
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20 pages, 751 KB  
Article
Crosstalk Between Metabolic Biomarkers and Pulse Wave Analysis in Hypertensive Patients
by Mirela Baba, Mihaela Ioana Maris, Adina Bucur, Daniela Jianu, Simina Mariana Moroz, Dana Stoian, Constantin Tudor Luca and Ioana Mozos
Biomedicines 2025, 13(7), 1514; https://doi.org/10.3390/biomedicines13071514 - 20 Jun 2025
Cited by 1 | Viewed by 1288
Abstract
Background/Objectives: Hypertension is strongly linked to changes in vascular function and lipid metabolism. This study aimed to examine the relationship between lipid profiles, various metabolic biomarkers, and pulse wave analysis in patients with hypertension. Methods: A group of 66 hypertensive patients, aged 64 [...] Read more.
Background/Objectives: Hypertension is strongly linked to changes in vascular function and lipid metabolism. This study aimed to examine the relationship between lipid profiles, various metabolic biomarkers, and pulse wave analysis in patients with hypertension. Methods: A group of 66 hypertensive patients, aged 64 ± 10 years, participated in pulse wave analysis utilizing an oscillometric device. Multiple lipid serum biomarkers were assessed, such as total cholesterol (TC), triglycerides (TG), and non-HDL cholesterol (non-HDL). Lipid balance index (LBI) was determined by considering TG, LDL, HDL levels, and lipid-lowering medications. Results: Notable correlations were observed for SBP, DBP, and early vascular aging (EVA) with lipid biomarkers. In addition to serum lipids, metabolic syndrome, insulin resistance, and non-alcoholic fatty liver disease (NAFLD) were significantly linked to pulse wave analysis variables. Multiple regression analysis showed that only TC continued to have a significant association with DBP. Conclusions: Total cholesterol, triglycerides, non-HDL cholesterol, and lipid balance index provide information about systolic and diastolic blood pressure, as well as early vascular aging in hypertensive patients. LBI offers valuable vascular insights in hypertensive individuals with cardiovascular risk factors, early vascular aging, insulin resistance, and NAFLD. The connection between metabolic biomarkers and pulse wave measurements in individuals with hypertension offers a comprehensive method for the early identification of vascular injury and could enhance the prediction of major cardiovascular events. Full article
(This article belongs to the Special Issue Lipids and Lipid Metabolism in Cardiovascular Health and Disease)
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30 pages, 15481 KB  
Article
Effects of 12 Weeks of Chromium, Phyllanthus emblica Fruit Extract, and Shilajit Supplementation on Markers of Cardiometabolic Health, Fitness, and Weight Loss in Men and Women with Risk Factors to Metabolic Syndrome Initiating an Exercise and Diet Intervention: A Randomized Double-Blind, Placebo-Controlled Trial
by Victoria Martinez, Kay McAngus, Broderick L. Dickerson, Megan Leonard, Elena Chavez, Jisun Chun, Megan Lewis, Dante Xing, Drew E. Gonzalez, Choongsung Yoo, Joungbo Ko, Heather Rhodes, Hudson Lee, Ryan J. Sowinski, Christopher J. Rasmussen and Richard B. Kreider
Nutrients 2025, 17(12), 2042; https://doi.org/10.3390/nu17122042 - 19 Jun 2025
Viewed by 11042
Abstract
Background: Exercise and nutritional interventions are often recommended to help manage risk related to metabolic syndrome (MetSyn). The co-ingestion of Phyllanthus emblica (PE) with trivalent chromium (Cr) has been purported to improve the bioavailability of chromium and enhance endothelial function, reduce platelet aggregation, [...] Read more.
Background: Exercise and nutritional interventions are often recommended to help manage risk related to metabolic syndrome (MetSyn). The co-ingestion of Phyllanthus emblica (PE) with trivalent chromium (Cr) has been purported to improve the bioavailability of chromium and enhance endothelial function, reduce platelet aggregation, and help manage blood glucose as well as lipid levels. Shilajit (SJ) has been reported to have anti-inflammatory, adaptogenic, immunomodulatory, and lipid-lowering properties. This study evaluated whether dietary supplementation with Cr, PE, and SJ, or PE alone, during an exercise and diet intervention may help individuals with risk factors to MetSyn experience greater benefits. Methods: In total, 166 sedentary men and women with at least two markers of metabolic syndrome participated in a randomized, placebo-controlled, parallel-arm, and repeated-measure intervention study, of which 109 completed the study (48.6 ± 10 yrs., 34.2 ± 6 kg/m2, 41.3 ± 7% fat). All volunteers participated in a 12-week exercise program (supervised resistance and endurance exercise 3 days/week with walking 10,000 steps/day on non-training days) and were instructed to reduce energy intake by −5 kcals/kg/d. Participants were matched by age, sex, BMI, and body mass for the double-blind and randomized supplementation of a placebo (PLA), 500 mg of PE (PE-500), 1000 mg/d of PE (PE-1000), 400 µg of trivalent chromium (Cr) with 6 mg of PE and 6 mg of SJ (Cr-400), or 800 µg of trivalent chromium with 12 mg of PE and 12 mg of SJ (Cr-800) once a day for 12 weeks. Data were obtained at 0, 6, and 12 weeks of supplementation, and analyzed using general linear model multivariate and univariate analyses with repeated measures, pairwise comparisons, and mean changes from the baseline with 95% confidence intervals (CIs). Results: Compared to PLA responses, there was some evidence (p < 0.05 or approaching significance, p > 0.05 to p < 0.10) that PE and/or Cr with PE and SJ supplementation improved pulse wave velocity, flow-mediated dilation, platelet aggregation, insulin sensitivity, and blood lipid profiles while promoting more optimal changes in body composition, strength, and aerobic capacity. Differences among groups were more consistently seen at 6 weeks rather than 12 weeks. While some benefits were seen at both dosages, greater benefits were more consistently observed with PE-1000 and Cr-800 ingestion. Conclusions: The results suggest that PE and Cr with PE and SJ supplementation may enhance some exercise- and diet-induced changes in markers of health in overweight individuals with at least two risk factors to MetSyn. Registered clinical trial #NCT06641596. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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26 pages, 3242 KB  
Article
Differential Association Between Ten Indices of Insulin Resistance and End-Organ Damage in a Community of African Ancestry in Africa
by Angela J. Woodiwiss, Gavin R. Norton, Carlos D. Libhaber, Pinhas Sareli and Patrick H. C. Dessein
J. Clin. Med. 2025, 14(8), 2703; https://doi.org/10.3390/jcm14082703 - 15 Apr 2025
Cited by 1 | Viewed by 1523
Abstract
Objective: Various insulin resistance (IR) indices have been developed to assess cardiovascular (CVS) risk. We compared the association between ten IR indices and cardiac, renal, and vascular end-organ measures in a predominantly young (age 45.0 ± 18.3 years) South African Black population. Methods: [...] Read more.
Objective: Various insulin resistance (IR) indices have been developed to assess cardiovascular (CVS) risk. We compared the association between ten IR indices and cardiac, renal, and vascular end-organ measures in a predominantly young (age 45.0 ± 18.3 years) South African Black population. Methods: We assessed the relationships between ten IR indices (homeostatic model assessment for IR [HOMA-IR], quantitative insulin sensitivity check index [QUICKI], metabolic score for IR [METS-IR], triglyceride–glucose index [TyG], TyG–body mass index [TyG-BMI], TyG–waist circumference [TyG-WC], TyG–waist-to-height ratio [TyG-WHtR], triglyceride to high-density cholesterol concentration [TyG-HDL], lipid accumulation product [LAP], visceral adiposity index [VAI]) and end-organ measures in 779 community participants of African ancestry. Results: HOMA-IR and QUICKI were the only IR indices consistently associated with end-organ measures (left ventricular [LV] mass index, p ≤ 0.005; LV relative wall thickness, p < 0.0001; early-to-late mitral velocity, p ≤ 0.01; E/e’, p ≤ 0.002; e’, p < 0.0001; pulse wave velocity, p = 0.036 (HOMA-IR only); glomerular filtration rate [GFR], p < 0.0001), independent of confounders. Furthermore, HOMA-IR was consistently higher, and QUICKI lower, in those with compared to those without end-organ damage (LV hypertrophy [p ≤ 0.03], concentric LV [p < 0.03], and reduced GFR [p ≤ 0.008]), independent of confounders. Importantly, the associations between HOMA-IR or QUICKI and end-organ measures were independent of additional CVS risk factors, including adiposity measures, and were replicated in the participants without diabetes mellitus (n = 669) and in the participants without high blood pressure (n = 505). Conclusions: In a predominantly young community of African ancestry, of ten recommended IR indices, only HOMA-IR and QUICKI were consistently associated with end-organ damage independent of CVS risk factors. Full article
(This article belongs to the Section Cardiovascular Medicine)
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10 pages, 729 KB  
Article
Carboxylated Osteocalcin as an Independent Predictor of Mean Arterial Pressure and the Atherogenic Index in Adults
by José Rafael Villafán-Bernal, Jorge David Rivas-Carrillo, Iris Paola Guzmán-Guzmán, Jose Luis Frias-Cabrera, Edgar Alfonso Rivera-León, Raigam Jafet Martinez-Portilla and Sergio Sánchez-Enríquez
Int. J. Mol. Sci. 2025, 26(4), 1733; https://doi.org/10.3390/ijms26041733 - 18 Feb 2025
Cited by 1 | Viewed by 1214
Abstract
Bone-derived proteins, including carboxylated osteocalcin (cOC), are thought to play a role in cardiovascular and metabolic health. cOC is recognized for its strong affinity for calcium hydroxyapatite and its possible involvement in vascular calcification and lipid metabolism. Although the undercarboxylated form of osteocalcin [...] Read more.
Bone-derived proteins, including carboxylated osteocalcin (cOC), are thought to play a role in cardiovascular and metabolic health. cOC is recognized for its strong affinity for calcium hydroxyapatite and its possible involvement in vascular calcification and lipid metabolism. Although the undercarboxylated form of osteocalcin (ucOC) has been widely researched, the connections between cOC and cardiovascular risk markers, such as mean arterial pressure (MAP), pulse pressure (PP), and the atherogenic index, are still not well understood. This cross-sectional study comprised 81 adults from Western Mexico; selection was based on rigorous inclusion criteria. Participants underwent various measurements, including anthropometric, biochemical, and cardiovascular assessments, such as the body mass index (BMI), body fat percentage, serum glucose, insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), lipid profile, creatinine, blood pressure parameters, and the atherogenic index. Serum cOC levels were determined using an enzyme-linked immunosorbent assay (ELISA). The study examined the relationships between cOC and cardiovascular/metabolic markers using inferential statistics and correlation coefficients. Multivariate linear analysis was performed to identify factors independently associated with the serum levels of cOC. Multivariate analysis revealed that MAP (B coefficient: 0.138, 95% CI: 0.028–0.247, p = 0.015) and the atherogenic index (B coefficient: 0.599, 95% CI: −0.039–1.161, p = 0.037) are independent predictors of cOC levels. A positive correlation was observed between cOC, PP, the atherogenic index, and HbA1, as well as an inverse correlation between cOC and HDL-c among the participants. Additionally, PP was positively correlated with HOMA-IR. Participants with elevated cOC levels showed higher MAP and atherogenic index values, indicating a potential connection between cOC and cardiovascular risk. cOC is independently associated with MAP and the atherogenic index, suggesting it may play a role in vascular remodeling and lipid metabolism. These results emphasize the importance of the bone–vascular axis in cardiovascular health and indicate that cOC might be a useful biomarker for assessing cardiovascular risk. Additional research is necessary to confirm these findings in larger, long-term studies and to investigate the mechanisms that connect cOC with cardiovascular outcomes. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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19 pages, 1622 KB  
Article
Saponins Effect on Human Insulin Amyloid Aggregation
by Eleonora Mari, Silvia Vilasi, Paolo Moretti, Maria Rosalia Mangione, Giorgia Giorgini, Roberta Galeazzi and Maria Grazia Ortore
Biomolecules 2025, 15(1), 40; https://doi.org/10.3390/biom15010040 - 31 Dec 2024
Cited by 1 | Viewed by 2245
Abstract
The misfolding and amyloid aggregation of proteins have been attracting scientific interest for a few decades, due to their link with several diseases, particularly neurodegenerative diseases. Proteins can assemble and result in insoluble aggregates that, together with intermediate oligomeric species, modify the extracellular [...] Read more.
The misfolding and amyloid aggregation of proteins have been attracting scientific interest for a few decades, due to their link with several diseases, particularly neurodegenerative diseases. Proteins can assemble and result in insoluble aggregates that, together with intermediate oligomeric species, modify the extracellular environment. Many efforts have been and are devoted to the search for cosolvents and cosolutes able to interfere with amyloid aggregation. In this work, we intensively study the effect of saponins, bioactive compounds, on human insulin aggregation. To monitor the kinetic of amyloid aggregation following secondary structure changes, we perform fluorescence and UV-Visible absorption spectroscopies, using Thioflavin T and Congo Red as amyloid specific probes, and Circular Dichroism. To study the overall structural features and size of aggregates, we perform Synchrotron Small-Angle X-ray Scattering and Dynamic Light Scattering experiments. The morphology of the aggregates was assessed by Atomic Force Microscopy. To deepen the understanding of the saponins interaction with insulin, a Molecular Dynamics investigation is performed, too. The reported data demonstrate that saponins interfere with the amyloid aggregation by inducing a strong inhibition on the formation of insulin fibrils, likely through specific interactions with insulin monomers. A dose-dependent effect is evident, and amyloid inhibition is already clear when saponins are just 0.01% w/w in solution. We suggest that saponins, which are natural metabolites present in a wide range of foods ranging from grains, pulses, and green leaves to sea stars and cucumbers, can be promising metabolites to inhibit human insulin aggregation. This basic research work can pave the way to further investigations concerning insulin amyloidosis, suggesting the use of saponins as amyloid inhibitors and/or stabilizing agents in solution. Full article
(This article belongs to the Collection Feature Papers in Molecular Structure and Dynamics)
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12 pages, 8031 KB  
Article
Localized In Vivo Electro Gene Therapy (LiveGT)-Mediated Skeletal Muscle Protein Factory Reprogramming
by Jacob Hensley, Michael Francis, Alex Otten, Nadezhda Korostyleva, Tina Gagliardo and Anna Bulysheva
Appl. Sci. 2024, 14(23), 11298; https://doi.org/10.3390/app142311298 - 4 Dec 2024
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Abstract
Gene electrotransfer (GET) has gained significant momentum as a non-viral gene delivery method for various clinical applications, primarily in the cancer immunotherapy and vaccine development space. Preclinical studies have demonstrated exogenous gene delivery and expression in various tissues, including the liver, skin, cardiac [...] Read more.
Gene electrotransfer (GET) has gained significant momentum as a non-viral gene delivery method for various clinical applications, primarily in the cancer immunotherapy and vaccine development space. Preclinical studies have demonstrated exogenous gene delivery and expression in various tissues, including the liver, skin, cardiac muscle, and skeletal muscle. However, protein replacement applications of this technology have yet to be fully actuated. Plasmid DNA skeletal muscle delivery has been shown to maintain expression for up to 18 months. In the current study, we evaluated localized skeletal muscle delivery for protein replacement applications. We developed localized in vivo electro gene therapy (liveGT) protocols utilizing mono- and biphasic pulse sequences for localized pulse delivery directly to skeletal muscle with a custom monopolar platinum electrode. Plasmid DNA encoding human insulin and human glucokinase were chosen for this study to evaluate the liveGT platform for protein replacement potential. Initial in vitro GET was performed in mouse myoblasts to evaluate human insulin and glucokinase co-delivery. This was followed by liveGT-mediated reporter gene delivery in the skeletal muscle of Sprague–Dawley rats for pulse sequence selection. Protein replacement potential was evaluated in healthy (non-diabetic) rats with liveGT-mediated human insulin and glucokinase co-delivery to skeletal muscle. Human and rat insulin levels were measured via ELISA over the course of 3 months. Fed-state blood glucose measurements were monitored in correlation with serum human insulin levels. LiveGT-mediated skeletal muscle reprogramming successfully produced physiological levels of human insulin in serum over the course of 3 months. Hypo- and hyperglycemic events were not observed. Therefore, liveGT is a safe and viable platform for potential protein replacement therapies. Full article
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19 pages, 4657 KB  
Article
Distinct Genomic Expression Signatures after Low-Force Electrically Induced Exercises in Persons with Spinal Cord Injury
by Michael A. Petrie, Manish Suneja and Richard K. Shields
Int. J. Mol. Sci. 2024, 25(18), 10189; https://doi.org/10.3390/ijms251810189 - 23 Sep 2024
Cited by 1 | Viewed by 1859
Abstract
People with a spinal cord injury are at an increased risk of metabolic dysfunction due to skeletal muscle atrophy and the transition of paralyzed muscle to a glycolytic, insulin-resistant phenotype. Providing doses of exercise through electrical muscle stimulation may provide a therapeutic intervention [...] Read more.
People with a spinal cord injury are at an increased risk of metabolic dysfunction due to skeletal muscle atrophy and the transition of paralyzed muscle to a glycolytic, insulin-resistant phenotype. Providing doses of exercise through electrical muscle stimulation may provide a therapeutic intervention to help restore metabolic function for people with a spinal cord injury, but high-frequency and high-force electrically induced muscle contractions increase fracture risk for the underlying osteoporotic skeletal system. Therefore, we investigated the acute molecular responses after a session of either a 3 Hz or 1 Hz electrically induced exercise program. Ten people with a complete spinal cord injury completed a 1 h (3 Hz) or 3 h (1 Hz) unilateral electrically induced exercise session prior to a skeletal muscle biopsy of the vastus lateralis. The number of pulses was held constant. Tissue samples were analyzed for genomic and epigenomic expression profiles. There was a strong acute response after the 3 Hz exercise leading to the upregulation of early response genes (NR4A3, PGC-1α, ABRA, IRS2, EGR1, ANKRD1, and MYC), which have prominent roles in regulating molecular pathways that control mitochondrial biogenesis, contractile protein synthesis, and metabolism. Additionally, these genes, and others, contributed to the enrichment of pathways associated with signal transduction, cellular response to stimuli, gene expression, and metabolism. While there were similar trends observed after the 1 Hz exercise, the magnitude of gene expression changes did not reach our significance thresholds, despite a constant number of stimuli delivered. There were also no robust acute changes in muscle methylation after either form of exercise. Taken together, this study supports that a dose of low-force electrically induced exercise for 1 h using a 3 Hz stimulation frequency is suitable to trigger an acute genomic response in people with chronic paralysis, consistent with an expression signature thought to improve the metabolic and contractile phenotype of paralyzed muscle, if performed on a regular basis. Full article
(This article belongs to the Special Issue Molecular Insights into the Role of Exercise in Disease and Health)
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18 pages, 1125 KB  
Article
Relationship between the Mediterranean Diet and Vascular Function in Subjects with and without Increased Insulin Resistance
by Marta Gómez-Sánchez, Leticia Gómez-Sánchez, Rocío Llamas-Ramos, Emiliano Rodríguez-Sánchez, Luis García-Ortiz, Ruth Martí-Lluch, María Cortés Rodríguez, Inés Llamas-Ramos and Manuel A. Gómez-Marcos
Nutrients 2024, 16(18), 3106; https://doi.org/10.3390/nu16183106 - 14 Sep 2024
Cited by 3 | Viewed by 2348
Abstract
(1) The main aim of this study was to analyze the relationship of the Mediterranean diet (MD) with vascular function in participants with and without increased insulin resistance (IR) in the Spanish population. A secondary aim was to study differences by gender. (2) [...] Read more.
(1) The main aim of this study was to analyze the relationship of the Mediterranean diet (MD) with vascular function in participants with and without increased insulin resistance (IR) in the Spanish population. A secondary aim was to study differences by gender. (2) Methods: Data were analyzed from 3401 subjects in the EVA, MARK, and EVIDENT studies (mean age = 60 years and 57% men). IR was evaluated with the triglyceride and glucose index (TyG index). TyG index = Ln [(fasting triglyceride mg/dL × fasting glucose mg/dL)/2]. The MD was measured against the MEDAS questionnaire, with the 14 items used in the PREDIMED study. Vascular stiffness was estimated with the brachial–ankle pulse wave velocity (baPWV) and the cardio ankle vascular index (CAVI) using the Vasera VS-1500®. (3) Results: The mean MEDAS value was 5.82 ± 2.03; (men: 5.66 ± 2.06; women: 6.04 ± 1.99; p < 0.001). MD adherence was 36.8% (men: 34.2%; women: 40.3%; p < 0.001). The mean baPWV value was 14.39 ± 2.78; (men: 14.50 ± 2.65; women: 14.25 ± 2.93; p = 0.005). A baPWV value ≥ 14.5 m/s was found in 43.4% (men: 43.6%; women: 40.0%; p = 0.727). The mean CAVI value was 8.59 ± 1.28; (men: 8.75 ± 1.28; women: 8.37 ± 1.26; p < 0.001). CAVI values ≥ 9 were present in 39.0% (men: 44.4%; women: 31.7%; p < 0.001). The mean value of the TGC/G index was 10.93 ± 1.39; (men: 11.08 ± 1.33; women: 10.73 ± 1.43; p < 0.001). IR was found in 49.9%. The average value of the MD score value was negatively associated with baPWV and CAVI in all groups analyzed (<0.05), except in the group of women with insulin resistance. (4) Conclusions: The results suggest that MD adherence is negatively associated with the vascular stiffness parameters analyzed in all the groups studied except the group of women with insulin resistance. Full article
(This article belongs to the Special Issue Diet, Obesity and Type 2 Diabetes in Cardiovascular Disease)
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