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23 pages, 1099 KB  
Article
From Systemic Inflammation to Vascular Remodeling: Investigating Carotid IMT in COVID-19 Survivors
by Emilia Bielecka, Piotr Sielatycki, Paulina Pietraszko, Sara Anna Frankowska and Edyta Zbroch
Viruses 2025, 17(9), 1196; https://doi.org/10.3390/v17091196 (registering DOI) - 30 Aug 2025
Abstract
Background: Atherosclerosis is a chronic inflammatory condition that underlies both cardiovascular and cerebrovascular complications. Emerging evidence suggests that COVID-19 may play a role in its progression. Purpose: The aim of the study was to evaluate the potential impact of SARS-CoV-2 infection on the [...] Read more.
Background: Atherosclerosis is a chronic inflammatory condition that underlies both cardiovascular and cerebrovascular complications. Emerging evidence suggests that COVID-19 may play a role in its progression. Purpose: The aim of the study was to evaluate the potential impact of SARS-CoV-2 infection on the development of atherosclerosis. Patients and Methods: Common carotid artery (CCA) intima media thickness (IMT) was measured by ultrasonography twice, 12–18 months apart, in a cohort of 92 patients (47 with COVID-19 and 45 controls). Clinical data were collected from medical histories, physical examinations, and laboratory findings. Results: Baseline IMT values were comparable between the study groups (0.85 mm vs. 0.78 mm). However, the COVID-19 group exhibited a significantly greater increase in IMT over time, with a median change of 0.13 mm compared to 0.05 mm in the controls (p = 0.018). Furthermore, 69.2% of COVID-19 patients exceeded the median IMT progression threshold compared to 36% in the control group (p = 0.017). An elevated level of C-reactive protein (CRP) and a higher triglyceride (Tg)-to-High-Density Lipoprotein Cholesterol (HDL) ratio were significantly associated with increased IMT in the COVID-19 group. Age and heart rate were identified as significant predictors of IMT progression across both groups. Conclusion: COVID-19 may accelerate the progression of subclinical atherosclerosis. The strong associations of CRP and the TG/HDL ratio with IMT highlight the potential roles of chronic inflammation and metabolic dysregulation in driving these vascular changes. Further large-scale, multicenter studies are needed to elucidate the underlying mechanisms, confirm these observations, and guide targeted preventive and therapeutic strategies for individuals with an increased cardiovascular and cerebrovascular risk. Full article
(This article belongs to the Special Issue COVID-19 Complications and Co-infections)
18 pages, 1378 KB  
Article
Clinical Characteristics and Outcomes of Patients Presenting with Acute Coronary Syndromes and Suspected Plaque Erosion Based on Clinical and Laboratory Criteria
by Luca Di Vito, Giancarla Scalone, Federico Di Giusto, Filippo Bruscoli, Michele Alfieri, Domenico Delfino, Federico Panzella, Simona Silenzi, Ik-Kyung Jang and Pierfrancesco Grossi
J. Cardiovasc. Dev. Dis. 2025, 12(9), 335; https://doi.org/10.3390/jcdd12090335 (registering DOI) - 30 Aug 2025
Abstract
Background: Plaque erosion (PE) ranks as the second most prevalent pathology associated with acute coronary events, following plaque rupture. PE is characterized by endothelial denudation and the development of neutrophil extracellular traps. Specific clinical and laboratory predictors were shown to be associated with [...] Read more.
Background: Plaque erosion (PE) ranks as the second most prevalent pathology associated with acute coronary events, following plaque rupture. PE is characterized by endothelial denudation and the development of neutrophil extracellular traps. Specific clinical and laboratory predictors were shown to be associated with PE in patients with acute coronary syndrome. The aim of this study was to evaluate the clinical and laboratory results, as well as the outcomes of ACS patients with a high likelihood of PE. Methods: A total of 696 ACS patients were categorized into the suspected PE group and the less likely PE group based on the five validated predictors of PE. Baseline clinical characteristics and laboratory evaluations were analyzed between the two groups. Major adverse cardiovascular events were compared between the two groups at 20 months. Results: The group suspected of PE comprised 41% of patients, whereas the group with a lower likelihood of PE constituted 59%. The suspected PE group exhibited a greater incidence of current smokers and a higher BMI. Both CRP and fibrinogen levels were decreased; the incidence of one coronary vessel disease was elevated. The suspected PE group exhibited a markedly reduced incidence of MACEs at 20 months (7.4% compared to 28.8%, p = 0.0001). The recurrence of non-fatal coronary events tended to occur later in the suspected PE group (15 months (6–20) compared to 9 months (6–13), p = 0.062). A reduced coronary plaque burden and a low level of systemic inflammation characterized the distinctive features of the suspected PE cohort. Conclusions: The suspected PE group exhibited a more favorable prognosis at the 20-month follow-up, characterized by a considerably reduced mortality rate from all causes, whereas non-fatal coronary events tended to manifest at a later time. 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 (registering DOI) - 30 Aug 2025
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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15 pages, 14322 KB  
Article
Clinical Evaluation of Oxidative Stress Markers in Patients with Long COVID During the Omicron Phase in Japan
by Osamu Mese, Yuki Otsuka, Yasue Sakurada, Kazuki Tokumasu, Yoshiaki Soejima, Satoru Morita, Yasuhiro Nakano, Hiroyuki Honda, Akiko Eguchi, Sanae Fukuda, Junzo Nojima and Fumio Otsuka
Antioxidants 2025, 14(9), 1068; https://doi.org/10.3390/antiox14091068 (registering DOI) - 30 Aug 2025
Abstract
To characterize changes in markers of oxidative stress for the clinical evaluation of patients with long COVID, we assessed oxidative stress and antioxidant activity based on serum samples from patients who visited our clinic between May and November 2024. Seventy-seven patients with long [...] Read more.
To characterize changes in markers of oxidative stress for the clinical evaluation of patients with long COVID, we assessed oxidative stress and antioxidant activity based on serum samples from patients who visited our clinic between May and November 2024. Seventy-seven patients with long COVID (41 [53%] females and 36 [47%] males; median age, 44 years) were included. Median [interquartile range] serum levels of diacron-reactive oxygen metabolites (d-ROM; CARR Unit), biological antioxidant potential (BAP; μmol/L), and oxidative stress index (OSI) were 533.8 [454.9–627.6], 2385.8 [2169.2–2558.1] and 2.0 [1.7–2.5], respectively. Levels of d-ROMs (579.8 vs. 462.2) and OSI (2.3 vs. 1.8), but not BAP (2403.4 vs. 2352.6), were significantly higher in females than in males. OSI levels positively correlated with age and body mass index, whereas BAP levels negatively correlated with these parameters. d-ROM and OSI levels were significantly associated with inflammatory markers, including C-reactive protein (CRP) and fibrinogen, whereas BAP levels were inversely correlated with CRP and ferritin levels. Notably, serum free thyroxine levels were negatively correlated with d-ROMs and OSI, whereas cortisol levels were positively correlated with d-ROMs. Among long COVID symptoms, patients reporting brain fog exhibited significantly higher OSI levels (2.2 vs. 1.8), particularly among females (d-ROMs: 625.6 vs. 513.0; OSI: 2.4 vs. 2.0). The optimal OSI cut-off values were determined to be 1.32 for distinguishing long COVID from healthy controls and 1.92 for identifying brain fog among patients with long COVID. These findings suggest that oxidative stress markers may serve as indicators for the presence or prediction of psycho-neurological symptoms associated with long COVID in a gender-dependent manner. Full article
(This article belongs to the Special Issue Exploring Biomarkers of Oxidative Stress in Health and Disease)
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158 pages, 4392 KB  
Review
Molecular and Immunomodulatory Mechanisms of Statins in Inflammation and Cancer Therapeutics with Emphasis on the NF-κB, NLRP3 Inflammasome, and Cytokine Regulatory Axes
by Sara Khan, Bintul Huda, Farida Bhurka, Rajashree Patnaik and Yajnavalka Banerjee
Int. J. Mol. Sci. 2025, 26(17), 8429; https://doi.org/10.3390/ijms26178429 - 29 Aug 2025
Abstract
Statins, primarily prescribed for their lipid-lowering effects, have garnered significant attention for their potent anti-inflammatory effects. This review explores the underlying molecular pathways and clinical relevance of statins’ anti-inflammatory actions, extending beyond cardiovascular disease management to chronic inflammatory conditions and oncological applications. The [...] Read more.
Statins, primarily prescribed for their lipid-lowering effects, have garnered significant attention for their potent anti-inflammatory effects. This review explores the underlying molecular pathways and clinical relevance of statins’ anti-inflammatory actions, extending beyond cardiovascular disease management to chronic inflammatory conditions and oncological applications. The lipid-lowering effect of statins stems from their ability to suppress HMG-CoA reductase, a crucial enzyme in cholesterol synthesis; however, their pleiotropic effects include modulation of critical inflammatory pathways such as the inhibition of NF-κB signalling, a reduction in pro-inflammatory cytokine production, and enhancement of endothelial function. We delve into the molecular pathways influenced by statins, including their effects on inflammatory mediators like C-reactive protein (CRP), interleukins (IL-6, IL-1β), and tumour necrosis factor-alpha (TNF-α). Clinical evidence supporting the efficacy of statins in managing chronic inflammatory diseases, such as rheumatoid arthritis, chronic obstructive pulmonary disease, diabetes, and osteoarthritis, is critically reviewed. Additionally, we investigate the emerging role of statins in oncology, examining their impact on inflammation-driven carcinogenesis, tumour microenvironment modulation, and cancer progression. Despite their broad therapeutic potential, the safety profile of statins, particularly concerning adverse effects such as myopathy, hepatotoxicity, and potential diabetes risk, is discussed. Controversies surrounding the extent of their anti-inflammatory benefits and the variability in patient responses are also addressed. This review consolidates the current literature, elucidating the biochemical mechanisms underlying the anti-inflammatory properties of statins and evaluating their clinical applications and associated controversies. Future research directions are identified, including the development of novel statin analogues with enhanced anti-inflammatory effects and the investigation of new therapeutic indications in inflammatory diseases and cancer. By providing an in-depth analysis, this review underscores the expanding therapeutic scope of statins and advocates for their integration into broader clinical strategies for the management of inflammation and cancer. Full article
(This article belongs to the Topic Recent Advances in Anticancer Strategies, 2nd Edition)
16 pages, 984 KB  
Article
Resistance Exercise Training and Greek Yogurt Consumption Modulate Markers of Systemic Inflammation in Healthy Young Males—A Secondary Analysis of a Randomized Controlled Trial
by Emily C. Fraschetti, Ali A. Abdul-Sater, Christopher G. R. Perry and Andrea R. Josse
Nutrients 2025, 17(17), 2816; https://doi.org/10.3390/nu17172816 - 29 Aug 2025
Abstract
Background/Objectives: Chronic exercise training reduces markers of systemic inflammation; however, less is known about how to optimize this adaptation using nutrition. Dairy products, especially fermented ones, like Greek yogurt (GY), contain anti-inflammatory constituents. This secondary analysis aimed to examine the influence of post-exercise [...] Read more.
Background/Objectives: Chronic exercise training reduces markers of systemic inflammation; however, less is known about how to optimize this adaptation using nutrition. Dairy products, especially fermented ones, like Greek yogurt (GY), contain anti-inflammatory constituents. This secondary analysis aimed to examine the influence of post-exercise GY consumption vs. an isoenergetic carbohydrate pudding (CP; control) on markers of systemic inflammation during an exercise training intervention. Methods: Thirty healthy young males completed 12 weeks of resistance and plyometric exercise training and were randomized to consume GY (n = 15) or CP (n = 15). Rested/fasted blood samples were acquired at baseline, and weeks 1 and 12, and inflammatory biomarkers (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-6, IL-1 receptor antagonist [IL-1ra], IL-1Beta [IL-1β], IL-10, and C-reactive protein [CRP]) were measured. Linear mixed models were run on the absolute concentrations, and linear regressions were performed on the absolute change (baseline to week 12), allowing us to account for important covariates. Results: In both groups, CRP (pro) and IL-1ra (anti) increased at week 1 vs. baseline and week 12, while IL-1β (pro) decreased at week 12 vs. baseline (main time effects). We observed significant interactions for IL-6, TNF-α, and the TNF-α/IL-10 ratio, indicating that at week 12, IL-6 (pro) was lower in GY, whereas TNF-α and TNF-α/IL-10 (both pro-inflammatory) were higher in CP vs. week 1 and baseline, respectively. Additionally, within our linear regression models, higher baseline concentrations of IL-1ra (anti), IL-10 (anti) and CRP (pro) predicted greater change over the intervention. Conclusions: These results indicate that our intervention benefited circulating inflammatory markers, and GY supplementation may enhance these effects. Full article
(This article belongs to the Special Issue Effects of Nutrient Intake on Exercise Recovery and Adaptation)
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22 pages, 1862 KB  
Article
Effects of Dietary and Probiotic Interventions in Patients with Metabolic Syndrome and Obstructive Sleep Apnea
by Amina Venter, Amin-Florin El-kharoubi, Mousa El-kharoubi, Evelin Claudia Ghitea, Marc Cristian Ghitea, Timea Claudia Ghitea and Ciprian Florian Venter
Clin. Pract. 2025, 15(9), 159; https://doi.org/10.3390/clinpract15090159 - 29 Aug 2025
Abstract
Background: Metabolic syndrome (MS) and obstructive sleep apnea (OSA) frequently coexist, exacerbating systemic inflammation, oxidative stress, and metabolic dysregulation. This study evaluates the effects of dietary and probiotic interventions, compared to a non-intervention control group, on metabolic, hemodynamic, and neurochemical parameters, with a [...] Read more.
Background: Metabolic syndrome (MS) and obstructive sleep apnea (OSA) frequently coexist, exacerbating systemic inflammation, oxidative stress, and metabolic dysregulation. This study evaluates the effects of dietary and probiotic interventions, compared to a non-intervention control group, on metabolic, hemodynamic, and neurochemical parameters, with a specific focus on the neurotransmitters GABA and glutamate. Methods: In a prospective randomized study (2020–2023), 120 patients with coexisting MS and OSA were assigned to three groups: control (n = 36), diet therapy (n = 42), and diet therapy combined with probiotics (n = 42). Interventions lasted six months and included personalized dietary plans and probiotic supplementation. Outcome measures included BMI, visceral fat, HOMA index, lipid profile, oxygen saturation, and urinary GABA and glutamate levels. Unsupervised K-means clustering and principal component analysis (PCA) were applied to identify phenotypic response patterns based on delta values. Results: Diet therapy led to significant reductions in BMI (−15.7%, p = 0.001), visceral fat (−17.3%, p = 0.001), triglycerides (−14.6%, p = 0.003), uric acid (−9.5%, p = 0.011), and C-reactive protein (CRP) (−21.4%, p = 0.007). The combined intervention group exhibited further improvements in visceral fat (−22.8%, p = 0.001), glutamate (−18.2%, p = 0.002), and GABA levels (+19.5%, p = 0.001). Oxygen saturation improved across all groups, with the greatest increase in the probiotics group (+2.3%). Clustering analysis revealed three distinct response phenotypes—strong, moderate, and non-responders—highlighting inter-individual variability in treatment efficacy. Conclusions: Personalized dietary interventions, especially when paired with probiotics, effectively improve metabolic, inflammatory, and neurochemical profiles in patients with MS and OSA. Integrating clustering algorithms enables phenotype-specific stratification, offering a step toward precision lifestyle medicine. Future studies should explore long-term outcomes and refine microbiota-targeted approaches to optimize intervention efficacy. Full article
(This article belongs to the Special Issue The Effect of Dietary Compounds on Inflammation-Mediated Diseases)
20 pages, 382 KB  
Article
Association Between Redox and Inflammatory Biomarkers with the Presence and Severity of Obstructive Sleep Apnea
by Ana Ninić, Branislava Rajkov, Jelena Kotur-Stevuljević, Sanja Erceg, Miron Sopić, Jelena Munjas, Vesna Spasojević-Kalimanovska, Marija Mitrović, Lidija Memon, Vera Gardijan, Milica Brajković, Slobodan Klašnja and Marija Zdravković
Medicina 2025, 61(9), 1557; https://doi.org/10.3390/medicina61091557 - 29 Aug 2025
Abstract
Background and Objectives: Obstructive sleep apnea (OSA) represents an increasing public health concern, closely linked with cardiovascular, metabolic, and neurocognitive disorders, as well as impaired quality of life. The complex pathophysiology of OSA involves upper airway dysfunction, oxidative stress, and inflammation, with endothelial [...] Read more.
Background and Objectives: Obstructive sleep apnea (OSA) represents an increasing public health concern, closely linked with cardiovascular, metabolic, and neurocognitive disorders, as well as impaired quality of life. The complex pathophysiology of OSA involves upper airway dysfunction, oxidative stress, and inflammation, with endothelial dysfunction considered central to its associated comorbidities. Despite notable advances in OSA research, the biological mechanisms driving these complications remain insufficiently understood. The present study aimed to examine the associations between redox status, proinflammatory biomarkers, and the gene expression of full-length receptor for advanced glycation end products (flRAGE) and transforming growth factor beta 1 (TGF-β1) in relation to the presence and severity of OSA. Materials and Methods: The study cohort comprised 125 participants with diagnosed OSA and 42 controls without evidence of OSA. General and clinical characteristics were recorded for all participants. Laboratory analyses included the assessment of redox and inflammatory markers in serum and plasma, while flRAGE and TGF-β1 messenger ribonucleic acids (mRNA) were quantified in peripheral blood mononuclear cells. Results: Patients with OSA demonstrated elevated oxidative stress and inflammation, characterized by increased total antioxidant status (TAS) and C-reactive protein CRP levels, together with reduced concentrations of soluble RAGE (sRAGE). The severity of OSA, indicated by the apnea-hypopnea index, increases total oxidative status (TOS) and TGF-β1 mRNA, while sRAGE decreases. The sRAGE–ROS-related factor was negatively associated with OSA, whereas the redox status factor showed a positive association. TOS was independently and positively correlated with OSA severity. Conclusions: Individuals with OSA exhibit a state of enhanced oxidative stress and inflammation. Increasing severity of OSA was associated with rising TOS and TGF-β1 mRNA expression, accompanied by declining sRAGE concentrations. A combined redox–inflammatory biomarker profile was found to be associated with both the presence and severity of OSA. Full article
(This article belongs to the Section Pulmonology)
18 pages, 876 KB  
Article
Inflammation and Albumin-Based Biomarkers Are Not Independently Associated with Mortality in Critically Ill COPD Patients: A Retrospective Study
by Josef Yayan, Christian Biancosino, Marcus Krüger and Kurt Rasche
Life 2025, 15(9), 1371; https://doi.org/10.3390/life15091371 - 28 Aug 2025
Viewed by 216
Abstract
Background: Inflammation and nutritional status are known to affect outcomes in patients with chronic obstructive pulmonary disease (COPD). However, their prognostic relevance in critically ill COPD patients remains unclear. This study investigated whether C-reactive protein (CRP), serum albumin, and the CRP/albumin ratio (CAR) [...] Read more.
Background: Inflammation and nutritional status are known to affect outcomes in patients with chronic obstructive pulmonary disease (COPD). However, their prognostic relevance in critically ill COPD patients remains unclear. This study investigated whether C-reactive protein (CRP), serum albumin, and the CRP/albumin ratio (CAR) were associated with in-hospital mortality in ICU patients with COPD. Methods: We conducted a retrospective cohort study using data from the MIMIC-IV database. Adult ICU patients with a diagnosis of COPD were included. We analyzed CRP, albumin, CAR, glucose, lactate, and creatinine. The primary outcome was in-hospital mortality. Multivariable logistic regression was used to identify variables that were independently associated with in-hospital mortality. Subgroup analyses stratified by age and sex were performed. Results: We included 1000 ICU patients with COPD. In-hospital mortality was 19.6%. In univariate analyses, glucose, creatinine, and lactate levels were significantly higher in non-survivors. In multivariable models, only elevated creatinine (OR 1.60, 95% CI 1.01–2.53) remained independently associated with mortality, while glucose was no longer statistically significant. CRP, albumin, and CAR were not significantly associated with in-hospital mortality. Subgroup analyses showed consistent results across age and sex strata. Conclusion: In critically ill COPD patients, glucose and creatinine levels upon ICU admission were independently associated with in-hospital mortality, whereas inflammation- and nutrition-related markers, such as CRP, albumin, and CAR, were not. However, given that albumin is heavily influenced by systemic inflammation, it cannot serve as a standalone nutritional marker in the ICU setting. Composite nutritional scores such as the Nutritional Risk Screening (NRS-2002) or the Global Leadership Initiative on Malnutrition (GLIM), which were not available in the MIMIC-IV database, may provide more accurate assessments. These findings highlight the need for integrated risk models incorporating metabolic and renal parameters for early prognostication. Full article
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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 198
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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12 pages, 502 KB  
Article
Evaluation of C-Reactive Protein/Albumin Ratio in Diabetic Retinopathy Patients
by Şaban Kılıç, Emre Aydın and Çiğdem Deniz Genç
Diagnostics 2025, 15(17), 2178; https://doi.org/10.3390/diagnostics15172178 - 28 Aug 2025
Viewed by 170
Abstract
Purpose: This study aimed to investigate the relationship between the C-reactive protein/albumin (CRP/albumin) ratio and disease severity in diabetic retinopathy (DR) patients and to evaluate the potential of CRP/albumin as a clinical biomarker for inflammation and DR progression. Methods: This single-center, prospective, cross-sectional [...] Read more.
Purpose: This study aimed to investigate the relationship between the C-reactive protein/albumin (CRP/albumin) ratio and disease severity in diabetic retinopathy (DR) patients and to evaluate the potential of CRP/albumin as a clinical biomarker for inflammation and DR progression. Methods: This single-center, prospective, cross-sectional study included 158 DR patients and 150 healthy controls. Clinical, ophthalmologic, and laboratory evaluations were performed, including best-corrected visual acuity, optical coherence tomography, and measurements of inflammatory and glycemic markers. CRP/albumin ratios were calculated, and their relationships with DR severity were assessed. Receiver operating characteristic (ROC) analysis was performed to evaluate the predictive performance of CRP/albumin. Results: Before treatment, CRP/Alb ratios and other inflammatory markers, including NLR, MLR, PLR, and SII, were significantly elevated in DR patients compared to controls. Following treatment, CRP/albumin ratios decreased markedly from 0.14 ± 0.1 to 0.04 ± 0.04 (p < 0.001), aligning with improvements in retinal thickness (OCT: 269.2 ± 17.5 µm) and HbA1c levels (6.9 ± 1.2%). CRP levels decreased from 5.8 ± 3.2 mg/L to 1.5 ± 1.4 mg/L, while NLR dropped from 2.5 ± 1.1 to 1.29 ± 0.8 (p < 0.001). Significant reductions were also observed in PLR (169.6 ± 62.2 to 128.2 ± 54.3) and SII (743.0 ± 427 to 230.8 ± 187). ROC analysis revealed an AUC of 0.963 for CRP/albumin, indicating high predictive accuracy for DR severity with 95% sensitivity and 90% specificity at a cutoff of 0.052. Conclusions: The CRP/albumin ratio is a significant biomarker for inflammation and disease progression in DR. The observed reductions in inflammatory markers post-treatment highlight the importance of inflammation control in DR management. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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12 pages, 249 KB  
Article
Pilot Exploratory Analysis of Serum Gonadal Hormones, Inflammatory Proteins, and Intracerebral Hemorrhage Outcomes
by Yisi Ng, Wenjing Qi, Anna Covington, Bobby Boone, Cynthia Kuhn, Andrew B. Nixon, Nicolas Kon Kam King, Peter F. Kranz, Thomas Christianson, Roshni Thakkar, Daniel T. Laskowitz, Cina Sasannejad, Miran Bhima, Vijay Krishnamoorthy, Shreyansh Shah, Amy K. Wagner and Michael L. James
Int. J. Mol. Sci. 2025, 26(17), 8334; https://doi.org/10.3390/ijms26178334 - 28 Aug 2025
Viewed by 157
Abstract
Intracerebral hemorrhage (ICH) remains the least treatable form of stroke, with inflammation implicated as a major pathophysiological feature. Hence, this study sought to associate serum proteins and hormones associated with inflammation and ICH outcomes. Patients presenting to Duke University Hospital with computed tomography-verified [...] Read more.
Intracerebral hemorrhage (ICH) remains the least treatable form of stroke, with inflammation implicated as a major pathophysiological feature. Hence, this study sought to associate serum proteins and hormones associated with inflammation and ICH outcomes. Patients presenting to Duke University Hospital with computed tomography-verified spontaneous, supratentorial, non-traumatic ICH within 24 h of symptom onset were prospectively recruited. In this pilot study, equal numbers of men and women and Black and White individuals were included and matched by a 6-month modified Rankin Score (mRS). The primary analyses were the correlation of L-ratios (LR; Log2(Day 2/Day 1 concentrations)) of serum gonadal hormones and neuroinflammatory proteins with mRS > 3 at 6 months. A total of 40 participants were included in this pilot study. LRs were significantly higher for C-reactive protein (CRP; p = 0.013) and lower for interleukin-6 (IL-6; p = 0.026) and surfactant protein-D (p = 0.036) in participants with unfavorable outcomes at 6 months after ICH. Further, higher CRP (p = 0.02) and lower IL-6 (p = 0.035) and surfactant protein-D (p = 0.041) LRs were associated with mRS > 3 at 6 months after ICH in multiple logistic regression analyses, adjusted for race and sex. The relationship amongst gonadal hormones, neuroinflammatory proteins, and ICH outcome is complex. In this pilot study, unfavorable outcomes after ICH may have been associated with selected inflammatory biomarkers. A larger scale study is warranted to define interactions between hormones, proteins, and their effects on ICH outcomes. Full article
(This article belongs to the Special Issue Novel Mechanisms for the Prevention and Treatment of Stroke)
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 669
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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20 pages, 1484 KB  
Article
Novel Computed Tomography Perfusion and Laboratory Indices as Predictors of Long-Term Outcome and Survival in Acute Ischemic Stroke
by Eray Halil, Kostadin Kostadinov, Nikoleta Traykova, Neli Atanasova, Kiril Atliev, Elizabet Dzhambazova and Penka Atanassova
Neurol. Int. 2025, 17(9), 136; https://doi.org/10.3390/neurolint17090136 - 27 Aug 2025
Viewed by 784
Abstract
Background/Objectives: Acute ischemic stroke is a leading cause of mortality and long-term disability globally, with limited reliable early predictors of functional outcomes and survival. This study aimed to assess the prognostic value of two novel predictors: the hypoperfusion intensity ratio calculated from mean [...] Read more.
Background/Objectives: Acute ischemic stroke is a leading cause of mortality and long-term disability globally, with limited reliable early predictors of functional outcomes and survival. This study aimed to assess the prognostic value of two novel predictors: the hypoperfusion intensity ratio calculated from mean transit time and time-to-drain maps (HIR-MTT–TTD), derived from computed tomography perfusion (CTP) imaging parameters, and the Inflammation–Coagulation Index (ICI), which integrates systemic inflammatory (C-reactive protein and white blood cell count) and hemostatic (D-dimer) markers. Methods: This prospective, single-center observational study included 60 patients with acute ischemic stroke treated with intravenous thrombolysis and underwent pre-treatment CTP imaging. HIR-MTT–TTD evaluated collateral status and perfusion deficit severity, while ICI integrated C-reactive protein (CRP), white blood cell (WBC) count, and D-dimer levels. Functional outcomes were assessed using the National Institutes of Health Stroke Scale (NIHSS), Barthel Index, and modified Rankin Scale (mRS) at 24 h, 3 months, and 1 year. Results: Of 60 patients, 53.3% achieved functional independence (mRS 0–2) at 1 year. Unadjusted Cox models showed HIR-MTT–TTD (HR = 6.25, 95% CI: 1.48–26.30, p = 0.013) and ICI (HR = 1.08, 95% CI: 1.00–1.17, p = 0.052) were associated with higher 12-month mortality, worse mRS, and lower Barthel scores. After adjustment for age, BMI, smoking status, and sex, these associations became non-significant (HIR-MTT–TTD: HR = 2.83, 95% CI: 0.37–21.37, p = 0.314; ICI: HR = 1.07, 95% CI: 0.96–1.19, p = 0.211). Receiver operating characteristic (ROC) analysis indicated moderate predictive value, with ICI (AUC = 0.756, 95% CI: 0.600–0.867) outperforming HIR-MTT–TTD (AUC = 0.67, 95% CI: 0.48–0.83) for mortality prediction. Conclusions: The study introduces promising prognostic tools for functional outcomes. Elevated HIR-MTT–TTD and ICI values were independently associated with greater initial stroke severity, poorer functional recovery, and increased 1-year mortality. These findings underscore the prognostic significance of hypoperfusion intensity and systemic thrombo-inflammation in acute ischemic stroke. Combining the use of the presented indices may enhance early risk stratification and guide individualized treatment strategies. Full article
(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)
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14 pages, 1043 KB  
Systematic Review
C-Reactive Protein for Early Diagnosis and Severity Monitoring in Melioidosis: A Systematic Review and Meta-Analysis
by Atthaphong Phongphithakchai, Moragot Chatatikun, Jitabanjong Tangpong, Sa-ngob Laklaeng, Jason C. Huang, Pakpoom Wongyikul, Phichayut Phinyo, Jongkonnee Thanasai, Supphachoke Khemla, Chaimongkhon Chanthot, Anchalee Chittamma and Wiyada Kwanhian Klangbud
Life 2025, 15(9), 1360; https://doi.org/10.3390/life15091360 - 27 Aug 2025
Viewed by 214
Abstract
Background: Melioidosis, caused by Burkholderia pseudomallei, is a serious infectious disease in Southeast Asia and northern Australia. Methods: We systematically reviewed observational studies measuring C-reactive protein (CRP) in laboratory-confirmed melioidosis for diagnosis, severity assessment, or outcome evaluation. PubMed, Embase, and [...] Read more.
Background: Melioidosis, caused by Burkholderia pseudomallei, is a serious infectious disease in Southeast Asia and northern Australia. Methods: We systematically reviewed observational studies measuring C-reactive protein (CRP) in laboratory-confirmed melioidosis for diagnosis, severity assessment, or outcome evaluation. PubMed, Embase, and Scopus were searched up to May 2025. Data were pooled using a random-effects model; heterogeneity was quantified (I2). Results: Seven studies (n = 451) were included. The pooled mean CRP level in melioidosis was 74.37 mg/L (95% Confidence Interval [CI], 32.76–168.83; I2 = 99.1%), considerably higher than healthy reference values (<10 mg/L). Conclusions: CRP is consistently raised in melioidosis and may aid in early diagnosis and severity monitoring, although high heterogeneity limits the precision of pooled estimates. Integration of CRP into multimodal prediction tools, rather than use in isolation, is recommended. Further prospective studies should define optimal diagnostic thresholds. Full article
(This article belongs to the Section Proteins and Proteomics)
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