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12 pages, 418 KB  
Article
Integrated Evaluation of CPAP Therapy in Type 2 Diabetic Patients with Sleep Apnea: Quality of Life and Effects on Metabolic Function and Inflammation in Outpatient Care
by Petar Kalaydzhiev, Tsvetelina Velikova, Yanitsa Davidkova, Radostina Ilieva, Elena Kinova and Emilia Naseva
Diabetology 2025, 6(9), 87; https://doi.org/10.3390/diabetology6090087 - 1 Sep 2025
Viewed by 155
Abstract
Background. Type 2 diabetes mellitus (T2D) and moderate-to-severe obstructive sleep apnea (OSA) commonly coexist and exacerbate poor glycemic control, systemic inflammation, and diminished quality of life (QoL). Although continuous positive airway pressure (CPAP) therapy has demonstrated metabolic and anti-inflammatory benefits, its real-world [...] Read more.
Background. Type 2 diabetes mellitus (T2D) and moderate-to-severe obstructive sleep apnea (OSA) commonly coexist and exacerbate poor glycemic control, systemic inflammation, and diminished quality of life (QoL). Although continuous positive airway pressure (CPAP) therapy has demonstrated metabolic and anti-inflammatory benefits, its real-world impact in Bulgarian outpatient settings—where CPAP costs are borne entirely by patients—has not been characterized. Objectives. To evaluate the effects of six months of CPAP therapy on glycemic control (hemoglobin A1c [HbA1c]), systemic inflammation (high-sensitivity C-reactive protein [hsCRP]), body mass index (BMI), lipid profile (low-density lipoprotein [LDL]), QoL (Short Form 36 Physical Component Summary [SF-36 PCS] and Mental Component Summary [SF-36 MCS]), and survival among Bulgarian outpatients with T2D and moderate-to-severe OSA. Methods. In this prospective, multicenter cohort study conducted from January 2022 to July 2023, 142 adults with established T2D and OSA (apnea–hypopnea index [AHI] ≥ 15) were enrolled at three outpatient centers in Bulgaria. Fifty-five patients elected to purchase and use home-based CPAP (intervention group), while 87 declined CPAP—either because of cost or personal preference—and continued standard medical care without CPAP (control group). All participants underwent thorough outpatient evaluations at baseline (month 0) and at six months, including measurement of HbA1c, hsCRP, BMI, fasting lipid profile (LDL), and patient-reported QoL, via the SF-36 Health Survey. Survival was tracked throughout follow-up. Results. After six months, the CPAP group experienced a significant reduction in HbA1c from a median of 8.2% (IQR 7.5–9.5%) to 7.7% (6.7–8.7%), p < 0.001, whereas the control group’s HbA1c decreased modestly from a median of 8.6% (IQR 7.9–9.4%) to 8.3% (7.6–9.1%); p < 0.001), with a significant between-group difference at follow-up (p = 0.005). High-sensitivity CRP in the CPAP arm fell from a median of 2.34 mg/L (IQR 1.81–3.41) to 1.45 mg/L (IQR 1.25–2.20), p < 0.001, while remaining unchanged in controls (p = 0.847). BMI in the CPAP group declined significantly from 28.6 kg/m2, IQR 26.6–30.6 to 28 kg/m2, IQR 25.6–29.2 (p < 0.001), compared to no significant change in controls (median 28.9 kg/m2), p = 0.599. LDL decreased in the CPAP group from a median of 3.60 mmol/L (IQR 3.03–3.89) to 3.22 mmol/L (IQR 2.68–3.48), p < 0.001, with no significant reduction in controls (p = 0.843). Within the CPAP arm, both SF-36 PCS and SF-36 MCS scores improved significantly from baseline (p < 0.001 for each), although between-group differences at six months did not reach statistical significance (PCS: 48 ± 10 vs. 46 ± 9, p = 0.098; MCS: 46, IQR 40–54 vs. 46, IQR 39–53, p = 0.291). All-cause mortality during follow-up included 2 events in the CPAP group and 11 events in the control group (log-rank p = 0.071). Conclusions. In Bulgarian outpatients with T2D and moderate-to-severe OSA, six months of CPAP therapy significantly improved glycemic control, reduced systemic inflammation, lowered BMI and LDL, and enhanced QoL, with a non-significant trend toward reduced mortality. These findings underscore the importance of integrating CPAP into multidisciplinary management despite financial barriers. Full article
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15 pages, 919 KB  
Article
Modulating Effect of Carbohydrate Antigen 125 on the Prognostic Value of High-Sensitivity C-Reactive Protein in Heart Failure
by Enrique Santas, Arancha Martí-Martínez, Elena Revuelta-López, Sandra Villar, Rafael de la Espriella, Patricia Palau, Pau Llàcer, Gema Miñana, Enrique Rodriguez-Borja, Arturo Carratalá, Arantxa Gonzalez, Antoni Bayés-Genís, Juan Sanchis and Julio Núñez
Biomolecules 2025, 15(9), 1260; https://doi.org/10.3390/biom15091260 - 30 Aug 2025
Viewed by 234
Abstract
Inflammation and congestion are key pathophysiological processes in heart failure (HF). Our aim was to evaluate the potential modulatory effect of carbohydrate antigen 125 (CA125) on inflammation, assessed by high-sensitivity C-reactive protein (hs-CRP). We analyzed a cohort of 4043 consecutive patients in whom [...] Read more.
Inflammation and congestion are key pathophysiological processes in heart failure (HF). Our aim was to evaluate the potential modulatory effect of carbohydrate antigen 125 (CA125) on inflammation, assessed by high-sensitivity C-reactive protein (hs-CRP). We analyzed a cohort of 4043 consecutive patients in whom hs-CRP and CA125 levels were measured during a hospitalization for acute HF. Multivariate Cox regression models were applied to assess the association between the biomarkers and all-cause mortality and death/HF rehospitalization at 6 months. In multivariable analysis, a significant interaction between hs-CRP and CA125 was observed for both outcomes (p-value for interaction = 0.036 and <0.001, respectively). hs-CRP was significantly associated with an increased risk of death (HR = 1.27; 95% CI 1.16–1.41; p < 0.001) and death/HF rehospitalization (HR = 1.18; 95% CI 1.09–1.28; p < 0.001) if CA125 > 35 U/mL. In contrast, hs-CRP was not predictive of events when CA125 ≤ 35 U/mL. In conclusion, in patients with acute HF, the association between hs-CRP and clinical outcomes was modulated by CA125 levels. hs-CRP was associated with a higher risk of events only in patients with elevated CA125. These findings support a potential modulatory and amplifying role for CA125 in the inflammatory response in HF. Full article
(This article belongs to the Special Issue Biomolecules in Myocarditis and Inflammatory Heart Disease)
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22 pages, 6284 KB  
Article
Integrative Evidence on Mulberry Extract for Modulating Metabolic Risk Factors Associated with Vascular Dementia
by Jui-Ting Yu, Chen-Pi Li, Yao Hsiao, Kuan-Po Cheng and Ru-Yin Tsai
Int. J. Mol. Sci. 2025, 26(17), 8380; https://doi.org/10.3390/ijms26178380 - 28 Aug 2025
Viewed by 370
Abstract
Metabolic syndrome refers to a group of conditions that commonly occur together, including abdominal obesity, high blood pressure, elevated blood sugar, high triglyceride levels, and low high-density lipoprotein cholesterol (HDL). These factors collectively increase the risk of cardiovascular disease, diabetes, and cognitive impairment. [...] Read more.
Metabolic syndrome refers to a group of conditions that commonly occur together, including abdominal obesity, high blood pressure, elevated blood sugar, high triglyceride levels, and low high-density lipoprotein cholesterol (HDL). These factors collectively increase the risk of cardiovascular disease, diabetes, and cognitive impairment. Recent research has identified a connection between metabolic syndrome and cognitive disorders such as mild cognitive impairment and vascular dementia (VaD). Mulberry (Morus alba L.) is a natural source of bioactive compounds with antioxidant, anti-inflammatory, and lipid-regulating properties. This meta-analysis assessed the potential of mulberry extract as an adjunctive treatment for metabolic risk factors linked to vascular dementia. We systematically reviewed randomized controlled trials (RCTs) published up to May 2025 that compared mulberry extract to placebo or standard care in adults with metabolic disorders. Fifteen trials including 1202 participants met the inclusion criteria. The primary outcomes were fasting glucose, fasting insulin, liver enzyme levels, lipid profiles, and inflammatory markers such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP). The pooled results indicated that mulberry supplementation improved blood sugar control and lowered total cholesterol, low-density lipoprotein cholesterol (LDL), triglycerides, fasting blood glucose, glycosylated hemoglobin (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), and inflammatory markers. Aspartate aminotransferase (AST) improved, whereas alanine aminotransferase (ALT) showed no significant change. Subgroup analyses revealed that greater benefits were associated with shorter treatment durations and doses below 500 milligrams per day. Furthermore, extracts from different parts of the mulberry plant showed varying effects on lipid and glucose metabolism. None of the included trials directly measured cognitive or neurovascular outcomes, so any potential neurovascular protection is inferred from changes in metabolic and inflammatory markers rather than demonstrated. In summary, these findings suggest that mulberry extract may be a promising complementary approach for managing metabolic risk factors in people at risk for VaD. However, further large-scale and rigorously designed studies are required to confirm its clinical benefits and to identify the most effective preparations. Full article
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15 pages, 1388 KB  
Article
The Impact of Basal Inflammatory Status on Post-CABG Atrial and Ventricular Ectopy and Remodeling Pathways
by Dan-Alexandru Cozac, Cristina Somkereki, Adina Huțanu, Tunde Renata Nicoara and Alina Scridon
Medicina 2025, 61(9), 1545; https://doi.org/10.3390/medicina61091545 - 27 Aug 2025
Viewed by 761
Abstract
Background and Objectives: Premature atrial contractions (PACs) and premature ventricular contractions (PVCs) commonly occur after coronary artery bypass grafting (CABG) surgery, with frequent ectopics linked to atrial fibrillation risk and reduced heart function. While CABG-induced inflammation causes arrhythmogenic changes, the connection between preoperative [...] Read more.
Background and Objectives: Premature atrial contractions (PACs) and premature ventricular contractions (PVCs) commonly occur after coronary artery bypass grafting (CABG) surgery, with frequent ectopics linked to atrial fibrillation risk and reduced heart function. While CABG-induced inflammation causes arrhythmogenic changes, the connection between preoperative inflammatory markers and postoperative ectopic burden has not been studied. Therefore, the aim of the present study is to evaluate the association between preoperative inflammatory biomarkers and postoperative atrial and ventricular ectopic burden, and to determine their influence on clinical outcomes following elective CABG procedures. Materials and methods: This study assessed preoperative plasma levels of highly sensitive C-reactive protein (hs-CRP), von Willebrand factor (vWF), transforming growth factor-β (TGF-β), interleukin (IL)-2, IL-1β, IL-6, IL-8, and vascular endothelial growth factor (VEGF) using the Multiplex technique in patients undergoing elective CABG. A continuous 24-h ECG Holter monitoring was performed one day before CABG, as well as on days 2, 3, and 4 post-CABG. The PACs and PVCs burdens were quantified, and correlations with clinical parameters were analyzed. Results: Preoperative plasma concentrations of vWF, TGF-β, and IL-8 exhibited significant positive correlations with postoperative PACs (p < 0.001, p = 0.03, and p < 0.001, respectively). Preprocedural hs-CRP, TGF-β, IL-6, and IL-8 levels showed significant positive associations with PVCs (p < 0.0001, p < 0.0001, p = 0.02, and p < 0.0001, respectively). However, none of the tested biomarkers could predict other postoperative outcomes, such as acute kidney injury, acute liver failure, duration of inotropic support, and days of hospitalization. Conclusions: Preoperative inflammatory biomarkers may serve as predictive tools for postoperative ectopic activity following CABG. Early identification of high-risk patients could enable prophylactic strategies and improve post-CABG outcomes. Full article
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16 pages, 2017 KB  
Article
Assessment of Serum Endocan Levels and Their Associations with Arterial Stiffness Parameters in Young Patients with Systemic Lupus Erythematosus
by Ágnes Diószegi, Hajnalka Lőrincz, Eszter Kaáli, Sára Csiha, Judit Kaluha, Éva Varga, Dénes Páll, Tünde Tarr and Mariann Harangi
J. Clin. Med. 2025, 14(17), 5955; https://doi.org/10.3390/jcm14175955 - 23 Aug 2025
Viewed by 396
Abstract
Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with premature atherosclerosis and vascular impairment. However, the role of endocan, a biomarker of glycocalyx injury, is not completely clarified in the detection of vascular damage. Therefore, our aim was to investigate [...] Read more.
Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with premature atherosclerosis and vascular impairment. However, the role of endocan, a biomarker of glycocalyx injury, is not completely clarified in the detection of vascular damage. Therefore, our aim was to investigate serum endocan in comparison with conventional inflammatory markers, arterial stiffness parameters, and carotid ultrasound findings in a cohort of young patients with SLE. Methods: We enrolled 47 clinically active young SLE patients (40 females and 7 males) in the study. Arterial stiffness indicated by augmentation index and pulse wave velocity (PWV) was measured by arteriography. Brachial artery flow-mediated dilatation and common carotid intima-media thickness were detected by ultrasonography. The serum concentrations of endocan, IL-6, MPO, MCP-1, MMP-3, -7, and -9, as well as TNFα, were measured by an enzyme-linked immunosorbent assay (ELISA). Results: We found significant negative correlations between serum endocan and both CH50 and C3. Serum endocan was higher in active SLE patients compared to inactive patients, however, the difference was not statistically significant (241.4 (183–295) vs. 200.3 (167–278) pg/mL; p = 0.313). Serum TNFα and hsCRP significantly correlated with PWV. However, we did not detect significant correlations between vascular diagnostic tests and serum endocan levels. Conclusions: Based on our results, serum endocan is associated with disease activity; however, further studies are needed to clarify the value of serum endocan in the cardiovascular risk estimation of SLE patients. Measurement of serum endocan, as well as the routine assessment of arterial stiffness parameters, should be integrated into the comprehensive management plans of young patients with SLE. Full article
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18 pages, 8983 KB  
Article
Weizmannia coagulans BC179 Alleviates Post-Alcohol Discomfort May via Taurine-Related Metabolism and Antioxidant Regulation: A Randomized, Double-Blind, Placebo-Controlled Trial
by Mengyao Duan, Ying Wu, Jie Zhang, Saman Azeem, Yao Dong, Zhonghui Gai, Jianguo Zhu, Shuguang Fang and Shaobin Gu
Antioxidants 2025, 14(9), 1038; https://doi.org/10.3390/antiox14091038 - 23 Aug 2025
Viewed by 479
Abstract
Excessive alcohol consumption is associated with various health complications, including liver damage and systemic inflammation. Probiotic interventions have emerged as promising strategies to mitigate alcohol-induced harm, yet their mechanisms of action remain incompletely understood. This randomized, double-blind, placebo-controlled clinical trial aimed to evaluate [...] Read more.
Excessive alcohol consumption is associated with various health complications, including liver damage and systemic inflammation. Probiotic interventions have emerged as promising strategies to mitigate alcohol-induced harm, yet their mechanisms of action remain incompletely understood. This randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the protective effects of Weizmannia coagulans BC179 in chronic alcohol consumers. Seventy participants with a history of long-term alcohol intake were randomly assigned to receive either BC179 (3 g/day, 1 × 1010 CFU) or a placebo for a 30-day intervention period. Following alcohol ingestion, dynamic monitoring of blood alcohol concentration (BAC), inflammatory and oxidative stress biomarkers, and serum metabolomic profiles was conducted. BC179 supplementation significantly reduced BAC and enhanced the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), while decreasing levels of alkaline phosphatase (ALP), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Conversely, the anti-inflammatory cytokine interleukin-10 (IL-10), superoxide dismutase (SOD), and glutathione (GSH) were significantly upregulated. Levels of cytochrome P4502E1 (CYP2E1) and malondialdehyde (MDA) were also markedly reduced. Metabolomic analysis revealed significant modulation of taurine and hypotaurine metabolism, as well as downregulation of caffeine-related pathways. Collectively, these findings indicate that W. coagulans BC179 alleviates alcohol-induced discomfort by enhancing alcohol metabolism, attenuating inflammation, reducing oxidative stress, and modulating key metabolic pathways. This probiotic strain may represent a promising adjunctive strategy for managing alcohol-related health issues. Full article
(This article belongs to the Special Issue Oxidative Stress in Human Diseases—4th Edition)
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12 pages, 454 KB  
Article
Copeptin, Routine Laboratory Parameters, and Ischemic Etiology of Heart Failure Predict Outcomes in Elderly Patients with Decompensated Heart Failure
by Paulina Nadziakiewicz, Wioletta Szczurek-Wasilewicz, Michał Jurkiewicz, Michał Skrzypek, Agnieszka Gorzkowska, Mariusz Gąsior and Bożena Szyguła-Jurkiewicz
Biomedicines 2025, 13(9), 2048; https://doi.org/10.3390/biomedicines13092048 - 22 Aug 2025
Viewed by 368
Abstract
Background: Diagnosing and predicting outcomes in elderly patients with heart failure (HF) is challenging due to atypical symptoms and the limited value of natriuretic peptides, highlighting the need to search for new risk stratification biomarkers in this population. Aim: We aimed [...] Read more.
Background: Diagnosing and predicting outcomes in elderly patients with heart failure (HF) is challenging due to atypical symptoms and the limited value of natriuretic peptides, highlighting the need to search for new risk stratification biomarkers in this population. Aim: We aimed to analyze factors associated with the composite endpoint (all-cause mortality or decompensated HF-related hospitalization) within six months of follow-up in elderly patients with left ventricular systolic dysfunction and decompensated HF, with particular emphasis on copeptin concentration. Methods: This is a retrospective observational study based on prospectively collected data of 279 consecutive elderly patients hospitalized between 2018 and 2023 due to decompensated HF. Inclusion criteria were age > 65 years, history of HF diagnosed at least two years before the index hospitalization, and left ventricular ejection fraction < 40% on admission echocardiography. Serum copeptin levels were measured using an Enzyme-Linked Immunosorbent Assay (ELISA) (Human Copeptin ELISA kit, Sunred Biological Technology Co, Shanghai, China). The primary endpoint was all-cause mortality or decompensated HF-related hospitalization during the six-month follow-up. Results: The median age of the study population was 77 years (IQR: 69–79), and 221 (79.2%) were male. The composite endpoint occurred in 110 patients (38.1%). Multivariable analysis showed that serum concentrations of copeptin [hazard ratio (HR) 1.053 (1.042–1.064), p < 0.0001], bilirubin [HR 1.085 (1.057–1.114), p < 0.0001], uric acid [HR 1.005 (1.003–1.006), p < 0.0001], high-sensitivity C-reactive protein (hs-CRP) [HR 1.208 (1.088–1.342), p < 0.0001], and sodium [HR 1.111 (1.025–1.203), p = 0.01], as well as ischemic etiology of HF [HR 3.969 (2.396–6.575), p < 0.0001], were independently associated with worse outcomes. Conclusions: Our study demonstrated that higher concentrations of copeptin, bilirubin, hs-CRP, and uric acid, as well as lower sodium levels and ischemic etiology of HF, were independently associated with all-cause mortality or HF-related hospitalization during a six-month follow-up in elderly patients with decompensated HF. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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16 pages, 1167 KB  
Article
Association of TCF7L2 rs7903146 (C/T) Polymorphism with Type 2 Diabetes Mellitus in a Chinese Population: Clinical Characteristics and Ethnic Context
by Yung-Chuan Lu, Teng-Hung Yu, Chin-Feng Hsuan, Chia-Chang Hsu, Wei-Chin Hung, Chao-Ping Wang, Wei-Hua Tang, Min-Chih Cheng, Fu-Mei Chung, Yau-Jiunn Lee and Thung-Lip Lee
Diagnostics 2025, 15(16), 2110; https://doi.org/10.3390/diagnostics15162110 - 21 Aug 2025
Viewed by 489
Abstract
Background/Objectives: The transcription factor 7-like 2 (TCF7L2) rs7903146 polymorphism has been strongly associated with type 2 diabetes mellitus (T2DM) in various populations; however, its impact on different ethnic groups is not fully understood. Given the distinct minor allele frequency in [...] Read more.
Background/Objectives: The transcription factor 7-like 2 (TCF7L2) rs7903146 polymorphism has been strongly associated with type 2 diabetes mellitus (T2DM) in various populations; however, its impact on different ethnic groups is not fully understood. Given the distinct minor allele frequency in Chinese populations, this study aimed to analyze the association of rs7903146 with the risk of T2DM in a Han Chinese cohort and its relationship with relevant clinical parameters. Methods: We conducted a case–control study including 600 patients with type 2 diabetes mellitus (T2DM) and 511 sex-matched non-diabetic controls of Han Chinese descent. The TCF7L2 rs7903146 (C/T) polymorphism was genotyped using a TaqMan™ SNP assay. Clinical parameters, including body mass index (BMI), fasting plasma glucose, hemoglobin A1c, lipid profile, and high-sensitivity C-reactive protein (hs-CRP), were compared between genotypes. Logistic regression analyses were performed under a dominant genetic model (CT/TT vs. CC), adjusting for age, sex, systolic and diastolic blood pressure, BMI, and smoking status. Subgroup analyses were conducted by sex, BMI category, age at diagnosis, and family history of T2DM. Given the exploratory nature of this study and the low frequency of the TT genotype, no formal correction for multiple testing was applied. Results: Frequencies of the CT and TT genotypes were higher in the diabetic group (p = 0.045) and were significantly associated with an increased risk of T2DM under a dominant genetic model (adjusted OR = 2.24, p = 0.025). Individuals with CT/TT genotypes had elevated fasting glucose and hs-CRP levels; these genotypes were also linked to higher BMI in the female T2DM patients. The T allele frequency varied across ethnic groups, being lowest in East Asians and highest in Latin (Brazilian/mixed ancestry) populations. Mechanistically, the T allele may contribute to T2DM via altered TCF7L2 expression, impaired insulin secretion, inflammation, and metabolic dysregulation. Conclusions: The TCF7L2 rs7903146 T allele was associated with an increased risk of T2DM and higher fasting glucose and hs-CRP levels in this Han Chinese cohort. The CT/TT genotypes were also associated with higher BMI in the female T2DM patients. While the findings are consistent with the known effects of this variant in other populations, mechanistic hypotheses such as the involvement of inflammatory or metabolic pathways remain hypothetical and warrant further functional validation. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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19 pages, 1485 KB  
Review
The Influence of Insulin Resistance and Type 2 Diabetes on Cognitive Decline and Dementia in Parkinson’s Disease: A Systematic Review
by Osama Zeidan, Noor Jaragh, Maya Tama, Maryam Alkhalifa, Maryam Alqayem and Alexandra E. Butler
Int. J. Mol. Sci. 2025, 26(16), 8078; https://doi.org/10.3390/ijms26168078 - 21 Aug 2025
Viewed by 630
Abstract
Parkinson’s disease (PD) is a common neurodegenerative disorder caused by progressive loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies. While PD is most recognized by its motor symptoms (resting tremor, rigidity, bradykinesia, and postural instability), cognitive decline [...] Read more.
Parkinson’s disease (PD) is a common neurodegenerative disorder caused by progressive loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies. While PD is most recognized by its motor symptoms (resting tremor, rigidity, bradykinesia, and postural instability), cognitive decline (CD) may become apparent as PD progresses, leading to Parkinson’s disease dementia (PDD). Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) are risk factors for dementia, especially Alzheimer’s disease; however, their influence on dementia in PD is underexplored. Therefore, we sought to determine the effect of T2DM and IR on dementia in PD. A systematic search of articles from 2005 to March 2025 was undertaken using Embase, PubMed, Scopus, Web of Science, and citation searching. Case–control, cross-sectional, longitudinal, and non-human population studies assessing cognitive outcomes in individuals with PD, with and without T2DM and IR, were included (PROSPERO registration number CRD420251013367). In total, 27 studies met the inclusion criteria, with clinical sample sizes ranging from 23 to 544,162 participants. Among the 23 clinical studies, 15 identified T2DM as a contributor to cognitive decline (CD) in PD, and 4 specifically examined insulin resistance (IR). Elevated HbA1c was consistently associated with poorer cognitive performance and increased risk of Parkinson’s disease dementia (PDD); HbA1c ≥ 7% independently predicted cognitive impairment (OR = 4.25, 95% CI: 1.59–11.34). Vascular and inflammatory markers, including elevated LDL-C, fibrinogen, and hs-CRP, further exacerbated CD. MoCA and MMSE scores were the most common cognitive measures, consistently showing worse outcomes in PD patients with T2DM. Preclinical studies supported these associations, showing that high-fat-diet-induced T2DM and IR aggravated dopaminergic neuronal loss by 38–45%, increased α-synuclein by 35%, and heightened microglial activation, providing mechanistic evidence for the observed clinical associations. This systematic review, the first to examine the impact of T2DM and IRs on the occurrence and advancement of CD in PD patients, demonstrates a possible association between the two. However, these results demonstrate the need for larger sample sizes and the inclusion of additional clinical variables, such as HbA1c levels and pharmacological interventions, providing further information about the link between metabolic dysfunction and CD in PD. To further strengthen this link, longitudinal studies with systematic follow-ups are essential to establish causal links and avoid misdiagnosis in clinical practice. Full article
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13 pages, 253 KB  
Article
Association Between Serum High Sensitivity C-Reactive Protein Levels and Low Muscle Strength Among Korean Adults
by Bo-Hyun Choi and Sunhye Shin
Nutrients 2025, 17(16), 2698; https://doi.org/10.3390/nu17162698 - 20 Aug 2025
Viewed by 641
Abstract
Purpose: Chronic low-grade inflammation is increasingly recognized as a contributor to age-related muscle loss and functional decline, yet its association with muscle strength in Asian populations remains underexplored. Therefore, this study aimed to investigate the relationship between high-sensitivity C-reactive protein (hsCRP) and low [...] Read more.
Purpose: Chronic low-grade inflammation is increasingly recognized as a contributor to age-related muscle loss and functional decline, yet its association with muscle strength in Asian populations remains underexplored. Therefore, this study aimed to investigate the relationship between high-sensitivity C-reactive protein (hsCRP) and low muscle strength in Korean adults. Materials and Methods: Data were obtained from 14,354 participants aged ≥ 19 years in the 7th Korea National Health and Nutrition Examination Survey (KNHANES VII, 2016–2018). Low muscle strength was defined as handgrip strength < 28 kg for men and <18 kg for women, and serum hsCRP levels were categorized as normal (<1.0 mg/L), elevated (1.0–3.0 mg/L), and high (≥3.0 mg/L). Multivariable logistic regression was used to assess the association between serum hsCRP level and low muscle strength with adjustment for possible confounders. Results: Among Korean adults, 27.7% had elevated or high hsCRP level, and low muscle strength was prevalent in older adults ≥ 65 years (men 22.7%, women 34.1%). Elevated hsCRP was associated with increased odds of low muscle strength in middle-aged women 40–64 years (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.04−2.09) and in older women ≥ 65 years (OR, 1.34; 95% CI, 1.04−1.74). High hsCRP was associated with higher risk in older men (OR, 1.71; 95% CI, 1.06–2.75) and older women (OR, 1.66; 95% CI, 1.14–2.42). Conclusions: Higher hsCRP levels were independently associated with low muscle strength in middle-aged women and older adults. Downregulating inflammation through nutritional strategies could help prevent muscle decline with aging. Full article
14 pages, 1534 KB  
Article
Are Dietary and Serum Advanced Glycation End Products (AGEs) Potential Contributors to Inflammation in Women with Polycystic Ovary Syndrome?
by Merve Yurt and Hülya Gökmen-Özel
J. Clin. Med. 2025, 14(16), 5803; https://doi.org/10.3390/jcm14165803 - 16 Aug 2025
Viewed by 471
Abstract
Background/Objectives: Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by metabolic and hormonal imbalances in women of reproductive age. Various studies have emphasized that a diet high in advanced glycation end products (AGEs) and high serum AGE levels may be associated [...] Read more.
Background/Objectives: Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by metabolic and hormonal imbalances in women of reproductive age. Various studies have emphasized that a diet high in advanced glycation end products (AGEs) and high serum AGE levels may be associated with reproductive and metabolic dysfunction in PCOS. Recently, the role played by dietary and serum AGE levels in the pathogenesis of PCOS was emphasized. Methods: In this study, we investigated the relationships between dietary AGE intake and serum AGE levels, some metabolic parameters, and anthropometric measurements in individuals with PCOS and a control group of women without PCOS. A total of 87 women with PCOS (n = 43) and without PCOS (n = 44) of a similar age and with a similar body mass index were included in this study. We analyzed dietary AGE intake, serum AGE (CML, sRAGE, and MGO) levels, and markers of inflammation (TNF-α and hs-CRP). Results: The daily dietary AGE intake in the PCOS group (13,191.05 ± 3360.12 kU/day) was higher than that in the control group (11,740.28 ± 2940.61 kU/day) (p = 0.035). The serum CML/sRAGE ratio was found to be higher in the PCOS group (413.94 ± 1114.79) than in the control group (143.24 ± 124.71) (p = 0.002). The cut-off points for dietary AGE intake, serum CML, and the CML/sRAGE ratio levels, which may be associated with the risk of PCOS development, were determined to be 11,359.06 kU/day, 417.50 ng/mL, and 140.91 ng/mL, respectively. Conclusions: Regular monitoring of serum AGE levels may reduce the health risks associated with PCOS. Moreover, to reduce dietary AGE intake in patients with PCOS, we recommend using steaming, boiling, poaching, or simmering with minimal water instead of dry-heat cooking methods. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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18 pages, 1248 KB  
Article
Low Levels of Adropin Predicted New Incidents of Atrial Fibrillation in Patients with Heart Failure with Preserved Ejection Fraction
by Tetiana A. Berezina, Oleksandr O. Berezin, Evgen V. Novikov and Alexander E. Berezin
Biomolecules 2025, 15(8), 1171; https://doi.org/10.3390/biom15081171 - 15 Aug 2025
Viewed by 369
Abstract
Background: Atrial fibrillation (AF) is common complication of heart failure with preserved ejection fraction (HFpEF) that sufficiently intervenes in the prognosis. The aim of the study is a) to investigate the possible discriminative value of adropin for newly onset AF in patients with [...] Read more.
Background: Atrial fibrillation (AF) is common complication of heart failure with preserved ejection fraction (HFpEF) that sufficiently intervenes in the prognosis. The aim of the study is a) to investigate the possible discriminative value of adropin for newly onset AF in patients with HFpEF without a previous history of AF and who are being treated in accordance with conventional guideline and b) to compare it with predictive potencies of conventionally used predictors. Methods: A total of 953 patients with HFpEF who had sinus rhythm on ECG were enrolled in the study. The course of the observation was 3 years. Echocardiography and assessment of conventional hematological, biochemical parameters and biomarker assay including N-terminal brain natriuretic pro-peptide (NT-proBNP), high-sensitivity cardiac troponin T, tumor necrosis factor-alpha, high-sensitivity C-reactive protein (hs-CRP), galectin-3, interleukin-6, soluble suppressor tumorigenisity-2 (sST2) and adropin, were performed at baseline. Results: Incident atrial fibrillation was found in 172 patients with HFpEF, whereas 781 had sinus rhythm. In unadjusted rough Cox regression model, age ≥ 75 years, type 2 diabetes mellitus, chronic kidney disease (CKD) stages 1–3, left atrial volume index (LAVI) ≥ 40 mL/m2, NT-proBNP ≥ 1440 pmol/mL, hs-CRP ≥ 5.40 mg/L, adropin ≤ 2.95 ng/mL, sST2 ≥ 15.5 ng/mL were identified as the predictors for new onset AF in HFpEF patients. After adjusting for age ≥ 75 years, a presence of type 2 diabetes mellitus and CKD stages 1–3, the levels of NT-proBNP ≥ 1440 pmol/mL and adropin ≤ 2.95 ng/mL were independent predictors of new onset AF in patients HFpEF. We also found that discriminative value of adropin was superior to NT-proBNP, while adding adropin to NT-proBNP did not improve predictive information of adropin alone. Conclusions: adropin ≤ 2.95 ng/mL presented more predictive information than NT-proBNP ≥ 1440 pmol/mL alone for new cases of AF in symptomatic patients with HFpEF, whereas the combination of both biomarkers did not improve the predictive ability of adropin alone. Full article
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21 pages, 7534 KB  
Article
Investigation of Pharmacological Mechanisms and Active Ingredients of Cichorium intybus L. in Alleviating Renal Urate Deposition via lncRNA H19/miR-21-3p Regulation to Enhance ABCG2 Expression
by Xiaoye An, Yi Xu, Qiuyue Mao, Chengjin Lu, Xiaoyang Yin, Siying Chen, Bing Zhang, Zhijian Lin and Yu Wang
Int. J. Mol. Sci. 2025, 26(16), 7892; https://doi.org/10.3390/ijms26167892 - 15 Aug 2025
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Abstract
Renal urate deposition is a pathological inflammatory condition characterized by the accumulation of urate crystals in the kidneys, resulting from uric acid supersaturation. Cichorium intybus L. (chicory) is a traditional medicinal herb recognized for its efficacy in treating hyperuricemia and gout; however, its [...] Read more.
Renal urate deposition is a pathological inflammatory condition characterized by the accumulation of urate crystals in the kidneys, resulting from uric acid supersaturation. Cichorium intybus L. (chicory) is a traditional medicinal herb recognized for its efficacy in treating hyperuricemia and gout; however, its effectiveness and underlying mechanisms in mitigating renal urate deposition remain inadequately understood. This study investigates the role of the ATP-binding cassette sub-family G member 2 (ABCG2) transporter and the lncRNA H19/miR-21-3p in renal urate deposition, while also validating the therapeutic effects and mechanisms of chicory extract. Renal urate deposition was induced in rats through the administration of potassium oxonate, adenine, yeast extract, and lipopolysaccharide. The levels of serum uric acid (SUA), urate deposition, inflammation, renal function, and histological changes were analyzed. Dual-luciferase assays, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry were utilized to elucidate the relationship among ABCG2, lncRNA H19, and miR-21-3p. The chemical composition and active ingredients of chicory were analyzed using UPLC-LTQ-Orbitrap-MS, along with molecular docking and cell experiments. In rats with renal urate deposition, serum UA levels were elevated, renal UA excretion was reduced, and levels of low inflammatory factors, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and hypersensitivity C-reactive protein (hs-CRP), were increased. Additionally, significant renal tissue damage accompanied the urate deposition. Notably, these abnormalities were substantially reversed following treatment with chicory extract. A dual-luciferase reporter assay confirmed the regulatory relationships among miR-21-3p, lncRNA H19, and ABCG2. Immunohistochemical analysis and RT-qPCR demonstrated a significant upregulation of miR-21-3p expression, alongside a downregulation of lncRNA H19, ABCG2 mRNA, and ABCG2 expression in the kidney tissue of rats with renal urate deposition. Chicory extract may exert its inhibitory effect on renal urate deposition by regulating the lncRNA H19/miR-21-3p axis to enhance ABCG2 expression. Furthermore, UPLC-LTQ-Orbitrap-MS identified 69 components in the chicory extract, including scopoletin, quercetin-3-O-β-D-glucuronide, 11β,13-dihydrolactucopicrin, and kaempferol-3-O-β-D-glucuronide, which were absorbed into the blood of both normal rats and those with renal urate deposition. Molecular docking and cell experiment further validated the effective regulation of 11β,13-dihydrolactucopicrin in ABCG2 and the lncRNA H19/miR-21-3p axis. The downregulation of ABCG2, mediated by the lncRNA H19/miR-21-3p axis, may represent a critical pathogenic mechanism in renal urate deposition. Chicory alleviates this deposition by modulating the lncRNA H19/miR-21-3p axis to enhance ABCG2 expression, potentially through its component, 11β,13-dihydrolactucopicrin, thereby revealing novel therapeutic insights for renal urate deposition. Full article
(This article belongs to the Section Molecular Pharmacology)
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15 pages, 727 KB  
Article
The Influence of Maternal Inflammatory Status on Fetal Telomere Length at Birth
by Mircea Diaconu, Flavius Olaru, Ahmed Abu-Awwad, Simona-Alina Abu-Awwad, Tiberiu Dragomir, Geanina Sacarin, Nicolae Ciprian Pilut, Bogdan Sorop, Melisa Bicu and Razvan Nitu
Biomedicines 2025, 13(8), 1974; https://doi.org/10.3390/biomedicines13081974 - 14 Aug 2025
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Abstract
Background/Objectives: Fetal telomere length (FTL) at birth is considered a key marker of early biological aging and future disease risk. While chronic inflammation is known to accelerate telomere attrition in adults, limited evidence exists on how maternal inflammation during pregnancy impacts FTL. [...] Read more.
Background/Objectives: Fetal telomere length (FTL) at birth is considered a key marker of early biological aging and future disease risk. While chronic inflammation is known to accelerate telomere attrition in adults, limited evidence exists on how maternal inflammation during pregnancy impacts FTL. This study aimed to investigate the association between maternal systemic inflammatory status in late pregnancy and FTL at birth. Methods: We conducted a prospective cohort study including 150 clinically healthy pregnant women recruited in the third trimester. Participants were stratified post hoc into an inflammation group (n = 67) and a control group (n = 83) based on circulating inflammatory markers: high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), TNF-α, and IL-10. Umbilical cord blood was collected at birth, and telomere length was quantified using real-time PCR. Correlation and multivariable linear regression analyses were performed to evaluate associations between maternal inflammation and FTL. Results: Mothers in the inflammation group had significantly elevated hsCRP, IL-6, and TNF-α levels, and lower IL-10 concentrations. FTL was significantly shorter in this group compared to the controls. Unlike previous investigations that relied on single pro-inflammatory markers, our study tests a composite immune-balance index (IL-6/IL-10 ratio) together with hsCRP in a prospectively followed cohort of clinically healthy pregnancies. Using its correlation coefficient, the IL-6/IL-10 ratio alone explained approximately 28% of the total variance in fetal telomere length—almost double the variance captured by IL-6 assessed in isolation. IL-6 and hsCRP emerged as independent negative predictors of FTL in multivariable models (β = −0.37 and −0.29, respectively). The IL-6/IL-10 ratio showed the strongest inverse correlation with FTL (r = −0.53, p < 0.001). Conclusions: Subclinical systemic inflammation in late pregnancy is independently associated with shorter fetal telomere length at birth, highlighting maternal immune imbalance (especially IL-6/IL-10 ratio) as a modifiable determinant of early biological aging. These findings underscore the need to consider maternal inflammatory profiling in pregnancy as a potential target for early-life preventive strategies. Full article
(This article belongs to the Section Cell Biology and Pathology)
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17 pages, 2121 KB  
Article
Blood Pressure Variability and Low-Grade Inflammation in Pediatric Patients with Primary Hypertension
by Katarzyna Dziedzic-Jankowska, Michał Szyszka, Adam Bujanowicz, Anna Stelmaszczyk-Emmel and Piotr Skrzypczyk
J. Clin. Med. 2025, 14(16), 5737; https://doi.org/10.3390/jcm14165737 - 13 Aug 2025
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Abstract
Background/Objectives: Increased blood pressure variability (BPV) was found in adults with primary (essential) hypertension (PH) and is associated with increased cardiovascular risk. Our study aimed to analyze the relation between BPV and low-grade inflammation in children with primary hypertension. Methods: In [...] Read more.
Background/Objectives: Increased blood pressure variability (BPV) was found in adults with primary (essential) hypertension (PH) and is associated with increased cardiovascular risk. Our study aimed to analyze the relation between BPV and low-grade inflammation in children with primary hypertension. Methods: In 56 treatment-naive pediatric patients with PH (15.1 ± 2.1 years) and 30 healthy children (14.9 ± 1.4 years), we evaluated BPV: BP dipping, standard deviation (SD) of ambulatory blood pressure measurements (ABPMs), pulse pressure (PP)/systolic blood pressure ratio (24 h PP/SBP), rate–pressure index (24 h RPI), 24-h weighted BPV (24 h WSBPV, 24 h WDBV, 24 h WMAPV), coefficient of variation (24 h CoVSBP, 24 h CoVDBP, 24 h CoVMAP), ambulatory arterial stiffness index (AASI), and morning BP surge. We also analyzed indices of subclinical inflammation (markers derived from complete blood count, high-sensitivity C-reactive protein (CRP), interleukin 18), and office and ambulatory BP. Results: Patients with PH had significantly higher hsCRP, neutrophils, monocytes, and platelets, neutrophil-to-lymphocyte (NLR), platelet-to-mean platelet volume (PMPVR), and lower monocyte-to-neutrophil (MNR) ratios, and higher BPV: 24 h ABPM SBP SD, 24 h ABPM MAP SD, 24 h RPI, 24 h WSBPV, 24 h WDBV, 24 h WMAPV, and 24 h CoVSBP. Low-grade inflammation markers correlated with BPV indices in both groups. In multivariate analysis, MNR predicted 24 h ABPM MAP SD (beta = 0.290, 95CI: 0.029–0.551), 24 h RPI (beta = −0.348, 95CI: −0.587–−0.108), and 24 h WDBPV (beta = 0.286, 95CI: 0.032–0.540); monocyte count—24 h RPI (beta = 0.281, 95CI: 0.041–0.521), and hsCRP—24 h WDBV (beta = 0.310, 95CI: 0.055–0.564). ROC analysis revealed a good diagnostic profile for lymphocyte count as a positive determinant of non-dipping status in PH children (cut-off point 2.59 [×103/µL]). Conclusions: BPV is higher in children with PH compared to healthy peers and is associated with low-grade inflammation. MNR may be the most helpful indicator of BPV, whereas high lymphocyte count predicts the best non-dipping status in these patients. Full article
(This article belongs to the Special Issue Pathophysiology of Hypertension and Related Diseases: 2nd Edition)
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