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20 pages, 24483 KB  
Article
Mogroside V Alleviates Renal Injury in Diabetic Mice via Regulation of the TLR4/NF-κB Pathway and Modulation of ECM Remodeling
by Xiangyu Guo, Hanzhe Shao, Jing Zhang, Xiangrong Xie, Dongcheng Peng and Qin Xu
Int. J. Mol. Sci. 2026, 27(14), 6271; https://doi.org/10.3390/ijms27146271 - 14 Jul 2026
Viewed by 266
Abstract
Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, yet effective therapeutic strategies targeting its underlying mechanisms remain limited. Mogroside V (MV), a natural saponin from Siraitia grosvenorii, exhibits anti-inflammatory and antioxidant properties, but its role in DKD is unclear. [...] Read more.
Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, yet effective therapeutic strategies targeting its underlying mechanisms remain limited. Mogroside V (MV), a natural saponin from Siraitia grosvenorii, exhibits anti-inflammatory and antioxidant properties, but its role in DKD is unclear. This study investigated the effects and mechanisms of MV on renal injury in DKD using db/db mice and high-glucose-induced human renal mesangial cells (HRMCs). MV (25–100 mg/kg/d) was orally administered to db/db mice for eight weeks; HRMCs were treated with 0.5–2 μM MV under high-glucose conditions. Renal function, pathological changes, the expression of TLR4/MyD88/NF-κB pathway components, inflammatory cytokines, apoptosis-related factors, and ECM markers were assessed. MV significantly reduced fasting blood glucose, proteinuria, serum creatinine, and urea nitrogen levels, and ameliorated renal pathological injury in db/db mice. Mechanistically, MV downregulated TLR4, MyD88, and p-NF-κBp65 expression, suppressed inflammatory cytokine release (TNF-α, IL-1β, IL-6, MCP-1, IL-18), attenuated apoptosis (increased Bcl-2/Bax ratio, decreased caspase-3), and reduced ECM accumulation (decreased MMP-9, Col IV) both in vivo and in vitro. These findings suggest that MV protects against diabetic kidney disease, potentially by regulating the TLR4/NF-κB signaling pathway and improving extracellular matrix remodeling. Full article
(This article belongs to the Section Molecular Biology)
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19 pages, 880 KB  
Article
Effects of Partial Replacement of Wheat Bran with Poplar Wood Composite Fiber on Growth Performance, Nutrient Apparent Digestibility, Immune Function, and Gut Microbiota in Growing Pigs
by Yuyang Fan, Ge Gao, Xinyue Jiang, Dongxu Ming, Yanpin Li, Wenjuan Sun, Xilong Li and Yu Pi
Vet. Sci. 2026, 13(6), 588; https://doi.org/10.3390/vetsci13060588 - 17 Jun 2026
Viewed by 408
Abstract
The objective of this study was to evaluate the effects of partially replacing wheat bran with poplar wood composite fiber (PWCF) on growth performance, immune status, apparent total tract digestibility (ATTD), and gut microbial composition in growing pigs. A total of 140 healthy [...] Read more.
The objective of this study was to evaluate the effects of partially replacing wheat bran with poplar wood composite fiber (PWCF) on growth performance, immune status, apparent total tract digestibility (ATTD), and gut microbial composition in growing pigs. A total of 140 healthy crossbred (Duroc × Landrace × Yorkshire) growing pigs with an initial body weight of 47.25 ± 0.49 kg were randomly assigned to two dietary treatments, with five replicates per treatment and fourteen pigs per replicate. The control (CT) group was fed a corn–soybean meal-based diet containing wheat bran and rice bran meal, whereas the experimental group received the same diet in which 2% wheat bran was replaced by PWCF. The experiment lasted for 60 days. Compared with the CT group, replacing wheat bran with PWCF did not affect body weight, average daily feed intake, feed conversion ratio, or average daily gain on days 30 or 60 (p > 0.05). In addition, no negative effects were observed on ATTD of nutrients and serum immunoglobulin A (IgA), IgG, and IgM levels at either time point, indicating that PWCF can serve as a suitable partial substitute for wheat bran in growing pig diets. However, it could regulate nitrogen metabolism by reducing blood urea nitrogen (BUN) concentration and the BUN/creatinine ratio, as well as decreasing total free amino acids in serum (p < 0.05). In addition, the antioxidant capacity can be transiently improved by increasing catalase activity. Gut microbiota analysis showed that the replacement significantly increased the relative abundances of Treponema, the Lachnospiraceae_XPB1014_group and Prevotellaceae_UCG-001 (p < 0.05). These changes suggest that PWCF modulates gut microbiota and enriches fiber-degrading bacterial populations. Overall, substituting wheat bran with PWCF did not impair growth performance, immunity, or digestibility, while altering microbial community composition. These findings support the potential application of PWCF as an alternative fiber source, contributing to greater diversity in feed formulation. Full article
(This article belongs to the Special Issue Nutritional Health of Monogastric Animals—2nd Edition)
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26 pages, 957 KB  
Article
Machine Learning-Based Prediction of Ultrasound-Detected Hepatic Steatosis Within the Metabolic Dysfunction-Associated Steatotic Liver Disease Spectrum Using Routine Clinical and Biochemical Parameters
by Canan Akkus, Gamze Sonmez, Ali Sahin, Yigit Yazarkan, Melis Gokgoz, Feride Caglar and Sanem Kayhan
Biomedicines 2026, 14(5), 1154; https://doi.org/10.3390/biomedicines14051154 - 20 May 2026
Viewed by 652
Abstract
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the leading cause of chronic liver disease globally, mirroring the increasing prevalence of obesity, insulin resistance, and type 2 diabetes. Early detection of hepatic steatosis is vital for cardiometabolic risk assessment; however, conventional imaging [...] Read more.
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the leading cause of chronic liver disease globally, mirroring the increasing prevalence of obesity, insulin resistance, and type 2 diabetes. Early detection of hepatic steatosis is vital for cardiometabolic risk assessment; however, conventional imaging is costly and impractical for population screening. This study aimed to develop interpretable machine-learning models to predict ultrasound-detected hepatic steatosis within the MASLD spectrum using routinely available clinical and biochemical data. Methods: We analyzed data from 644 adults, 50% of whom had ultrasound-detected hepatic steatosis. Preprocessing, imputation, and feature selection were implemented within a single scikit-learn pipeline to avoid information leakage. An Elastic Net-regularized logistic regression identified the top 20 predictors, which were subsequently used across nine supervised machine learning (ML) classifiers. Model performance was evaluated via repeated stratified 5-fold cross-validation (25 resamples) using accuracy, F1 score, sensitivity, specificity, Youden’s J, balanced accuracy, and Area Under the Receiver Operating Characteristic Curve (AUROC). Interpretability was assessed using SHapley Additive exPlanations (SHAP). Results: Participants with ultrasound-detected hepatic steatosis exhibited greater adiposity, insulin resistance, and dyslipidemia compared with controls [p < 0.05 for body mass index (BMI), waist circumference, glucose, glycated hemoglobin (HbA1c), triglycerides]. Elastic Net selection highlighted Weight, Ponderal Index, Fibrosis-4 Index (FIB-4), blood urea nitrogen (BUN)/Creatinine ratio, Aspartate Aminotransferase to Platelet Ratio Index (APRI), and Visceral Adiposity Index as the strongest predictors. Logistic Regression and Gradient Boosting achieved the best performance (accuracy = 0.65 ± 0.03; AUROC = 0.71 ± 0.04; balanced accuracy = 0.66 ± 0.06), outperforming rule-based indices such as Fatty Liver Index (FLI) and Hepatic Steatosis Index (HSI) reported in the literature. SHAP analysis confirmed clinically coherent feature effects, with higher anthropometric and hepatic injury indices increasing the predicted probability of ultrasound-detected hepatic steatosis. Conclusions: Routinely available clinical and biochemical parameters can predict hepatic steatosis with moderate accuracy using transparent, interpretable ML models. Logistic Regression and Gradient Boosting provided best discrimination and robust internal performance, offering a pragmatic, low-cost approach for early identification of ultrasound-detected hepatic steatosis within the MASLD spectrum in primary and metabolic care settings. Full article
(This article belongs to the Special Issue Emerging Trends in Liver Diseases and Cirrhosis Research)
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14 pages, 428 KB  
Article
Positive Correlates of Sclerostin and Association with Peripheral Arterial Stiffness in Patients with Type 2 Diabetes Mellitus
by Bang-Gee Hsu, Jer-Chuan Li, Du-An Wu and Ming-Chun Chen
Medicina 2026, 62(4), 643; https://doi.org/10.3390/medicina62040643 - 27 Mar 2026
Viewed by 719
Abstract
Background and Objectives: Sclerostin or dickkopf-1 (DKK1) inhibits the canonical Wnt/β-catenin signaling pathway, which regulates vascular calcification and may contribute to the development of arterial stiffness. The brachial–ankle pulse wave velocity (baPWV) measures peripheral arterial stiffness (PAS). This study aimed to investigate [...] Read more.
Background and Objectives: Sclerostin or dickkopf-1 (DKK1) inhibits the canonical Wnt/β-catenin signaling pathway, which regulates vascular calcification and may contribute to the development of arterial stiffness. The brachial–ankle pulse wave velocity (baPWV) measures peripheral arterial stiffness (PAS). This study aimed to investigate the correlation between sclerostin and DKK1 levels and PAS in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: Biochemical data and sclerostin and DKK1 levels were analyzed in the fasting blood samples of 125 patients with T2DM. baPWV measurements using the VaSera VS-1000 automatic pulse wave analyzer classified patients with values > 18.0 m/s on either side into the PAS group. Results: Among patients with T2DM, 47 (37.6%) were classified as having PAS. These patients exhibited higher hypertension prevalence (p = 0.002); greater age (p < 0.001); elevated systolic (p < 0.001) and diastolic blood (p = 0.012) pressures; and increased fasting glucose (p = 0.001), glycated hemoglobin (p = 0.008), triglyceride (p = 0.001), blood urea nitrogen (p < 0.001), and creatinine (p = 0.001) levels, urine albumin-to-creatinine ratio (p = 0.039), and C-reactive protein (p = 0.024) and serum sclerostin (p < 0.001) levels, but decreased estimated glomerular filtration rate (p < 0.001). Multivariate logistic regression analysis identified serum sclerostin level (odds ratio, 1.127; 95% confidence interval, 1.058–1.200; p < 0.001) as an independent PAS predictor in patients with T2DM. Serum log-transformed sclerostin levels were positively correlated with left (p = 0.005) and right (p = 0.001) baPWV via Spearman’s rank-order correlation coefficient analysis. Conclusions: Serum sclerostin levels, but not DKK1 levels, are positively correlated with PAS in patients with T2DM. Full article
(This article belongs to the Section Urology & Nephrology)
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16 pages, 3586 KB  
Article
miR-4516-Loaded Engineered Milk Extracellular Vesicles Attenuate Indoxyl Sulfate-Induced Mitochondrial Dysfunction and Improve Renal Function in a CKD Mouse Model
by Jeongkun Lee, Jun Young Yoon, Jae Young Lee and Sang Hun Lee
Int. J. Mol. Sci. 2026, 27(7), 2997; https://doi.org/10.3390/ijms27072997 - 25 Mar 2026
Viewed by 830
Abstract
Chronic kidney disease (CKD) involves uremic toxin-driven tubular injury and systemic vascular dysfunction, in which mitochondrial impairment and apoptotic cell loss contribute to progressive tissue deterioration. Accordingly, a targeted EV platform is required to enable efficient miRNA delivery to the toxin-stressed tubular–endothelial compartment. [...] Read more.
Chronic kidney disease (CKD) involves uremic toxin-driven tubular injury and systemic vascular dysfunction, in which mitochondrial impairment and apoptotic cell loss contribute to progressive tissue deterioration. Accordingly, a targeted EV platform is required to enable efficient miRNA delivery to the toxin-stressed tubular–endothelial compartment. Based on our previous study showing that melatonin restores miR-4516 levels under CKD-related stress, we directly loaded miR-4516 into engineered extracellular vesicles (EVs) to evaluate its effects on mitochondrial function and cell survival. Here, we engineered EVs with a G3-C12/RGD surface modification and established a miR-4516 loading strategy to enhance delivery to kidney proximal tubule cells and vascular endothelial cells. miR-4516 loading increased EV-associated miR-4516 levels without major changes in particle size distribution, and EV identity was supported by CD9 and CD81 expression. Confocal microscopy and flow cytometry demonstrated increased cellular uptake of miR-4516-loaded G3-C12/RGD-EVs compared with control EVs in TH1 proximal tubule cells and HUVECs. Under indoxyl sulfate stress, engineered EV treatment restored intracellular miR-4516 and improved mitochondrial function, as indicated by recovery of respiratory Complex I and Complex IV activities and improved Seahorse bioenergetic parameters (OCR/ECAR, basal and maximal respiration, ATP-linked respiration, and spare respiratory capacity). Annexin V staining further indicated reduced toxin-induced apoptosis. In an adenine diet-induced CKD mouse model, intravenous administration of miR-4516-loaded G3-C12/RGD-EVs improved urinary albumin-to-creatinine ratio (UACR), blood urea nitrogen (BUN), and serum creatinine. These findings indicate that miR-4516-loaded, targeting-engineered EVs may mitigate uremic toxin-associated mitochondrial dysfunction and renal impairment in CKD. Full article
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14 pages, 1164 KB  
Article
Albumin-Anchored Composite Ratios of Blood Urea Nitrogen, C-Reactive Protein, Lactate, and Creatinine for Predicting Mortality in Chronically Ill Intensive Care Unit Patients
by Nilgün Şahin, Semih Aydemir, Nazan Has Selmi, İbrahim Ertaş, Yavuz Kutay Gökçe, Cihan Döğer, Gökçen Terzi, Mesher Ensarioğlu and Recep Dokuyucu
J. Clin. Med. 2026, 15(7), 2470; https://doi.org/10.3390/jcm15072470 - 24 Mar 2026
Cited by 1 | Viewed by 673
Abstract
Background: This study aimed to evaluate the prognostic performance of four albumin-anchored ratios—blood urea nitrogen/albumin ratio (BAR), C-reactive protein/albumin ratio (CAR), lactate/albumin ratio (LAR), and albumin/creatinine ratio (ACR)—in predicting short-term mortality among intensive care unit (ICU) patients with pre-existing chronic comorbidities. Additionally, we [...] Read more.
Background: This study aimed to evaluate the prognostic performance of four albumin-anchored ratios—blood urea nitrogen/albumin ratio (BAR), C-reactive protein/albumin ratio (CAR), lactate/albumin ratio (LAR), and albumin/creatinine ratio (ACR)—in predicting short-term mortality among intensive care unit (ICU) patients with pre-existing chronic comorbidities. Additionally, we assessed their incremental prognostic value beyond established severity scores such as APACHE II and SOFA. Materials and Methods: This retrospective cohort study included 520 chronically ill adult ICU patients admitted between July 2022 and July 2025. Patients with missing laboratory data, ICU stay <24 h, or postoperative monitoring only were excluded. BAR, CAR, LAR, and ACR were calculated from admission laboratory values. The primary outcome was 28-day mortality. Receiver operating characteristic (ROC) analyses, multivariate logistic regression, and model improvement metrics (C-statistics, NRI, IDI) were used to assess predictive performance. Results: Non-survivors had significantly higher BAR (15.0 vs. 8.2), CAR (39.2 vs. 19.1), and LAR (0.86 vs. 0.44) values and lower ACR (2.0 vs. 3.4) (all p < 0.001). In multivariate analysis, all four ratios independently predicted 28-day mortality (p < 0.001 for each). CAR showed the highest AUC (0.80), followed by LAR (0.79), BAR (0.78), and ACR (0.76). Incorporating all four ratios improved model discrimination (C-statistic 0.872 vs. 0.823; Δ = +0.049, p < 0.001) and reclassification (NRI = 0.162; IDI = 0.052). Conclusions: BAR, CAR, LAR, and ACR are independent and complementary predictors of short-term mortality in ICU patients with chronic comorbidities. Among them, CAR exhibited the best discriminative power. The combined use of these ratios enhanced risk prediction beyond traditional severity scores, suggesting their utility as simple, cost-effective markers for early mortality assessment. Because these indices are calculated from routinely measured laboratory parameters, they may represent practical and widely accessible tools for mortality risk stratification in routine ICU practice. Full article
(This article belongs to the Special Issue Clinical Management for Anesthesia Critical Care)
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27 pages, 8038 KB  
Article
Effects of Repeated Intravenous Injections of Autologous Adipose-Derived Mesenchymal Stromal Cells Expressing an Allogeneic MHC Protein in a Mouse Model of Diabetic Nephropathy
by Fuxuan Li, Liangyu Zhao, Shengkun Wang, Ruixue Chen, Meiqi Meng, Yan Fu, Lin Wei, Wei Liu, Huixian Cui, Jun Ma, Matthew D. Griffin and Cuiqing Ma
Cells 2026, 15(2), 196; https://doi.org/10.3390/cells15020196 - 20 Jan 2026
Cited by 2 | Viewed by 1052
Abstract
Diabetic nephropathy (DN) is the most common cause of kidney failure worldwide. Mesenchymal stromal cells (MSCs) have demonstrated promise for treating DN by promoting kidney repair and regulating inflammation. Allogeneic (Allo)-MSCs may have similar or superior anti-inflammatory effects to autologous (Auto)-MSCs but also [...] Read more.
Diabetic nephropathy (DN) is the most common cause of kidney failure worldwide. Mesenchymal stromal cells (MSCs) have demonstrated promise for treating DN by promoting kidney repair and regulating inflammation. Allogeneic (Allo)-MSCs may have similar or superior anti-inflammatory effects to autologous (Auto)-MSCs but also have potential to elicit adverse immune responses due to major histocompatibility complex (MHC) mismatches. To better understand how MSC-delivered allo-antigens influence therapeutic effects of Allo-MSCs compared to Auto-MSCs in DN, lentiviral transduction was used to generate adipose-derived MSCs (ADSCs) from DBA/2J (H-2d) mice which expressed an allogeneic class I MHC protein (H-2Kb). H-2Kb-ADSCs were injected intravenously into male DBA/2J mice at 11 and 13 weeks after initiation of diabetes, and their effects on renal functional and structural indices were compared at week 15 with those of diabetic DBA/2J recipients of vehicle alone or of empty vector-transduced DBA/2J ADSCs (EV-ADSCs). Both EV-ADSCs and H-2Kb-ADSCs resulted in reduced kidney/total body weight ratio, blood urea nitrogen (BUN), urine albumin creatinine ratio (uACR), mesangial matrix expansion (MME) and renal fibrosis compared to vehicle alone, without influencing glycemia or survival. However, H-2Kb-ADSCs recipients had greater reductions in BUN and uACR, reduced intra-renal myeloid cell infiltration, increased splenic regulatory T cell (Treg) proportions and increased intra-renal Treg infiltration and FOXP3 and IL-10 mRNA. Nonetheless, recipients of H-2Kb-ADSCs also had decreased splenic CD4/CD8 T cell ratios, increased circulating anti-H-2Kb IgG antibodies and histological and biochemical evidence of inflammatory liver injury. These novel findings demonstrated that ADSCs expressing an MHC-I allo-antigen had superior beneficial effects on DN than fully autologous ADSCs. Improved DN severity was associated with immune modulation, including Treg enhancement, but also had potentially detrimental immunological effects in mice with established diabetes. The results highlight the need for further investigation of the immune modulatory effects of Allo-MSCs in diabetes and its organ-specific complications. Full article
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13 pages, 256 KB  
Article
A Cross-Sectional Study of Sex-Specific Associations of Renin and Electrolytes on the Development of Hypertension
by Seong Beom Cho
J. Clin. Med. 2026, 15(2), 643; https://doi.org/10.3390/jcm15020643 - 13 Jan 2026
Viewed by 548
Abstract
Background/Objectives: Blood renin and electrolyte levels are associated with blood pressure and hypertension. While sex-specific effects of such factors have been investigated, exact comparisons of the factors between the sexes have been scarce. Methods: Using cohort data from the Korean Genome [...] Read more.
Background/Objectives: Blood renin and electrolyte levels are associated with blood pressure and hypertension. While sex-specific effects of such factors have been investigated, exact comparisons of the factors between the sexes have been scarce. Methods: Using cohort data from the Korean Genome and Environmental Study (KoGES), the study population that did not receive any interventions for blood pressure was determined. Blood levels of renin and electrolytes, including sodium, potassium, chloride, and calcium, were used to test their relationship with hypertension and blood pressure. Confounding variables, including age, body mass index (BMI), waist-to-hip ratio, family history of hypertension, alcohol consumption, smoking, blood urea nitrogen, creatinine, protein, and albumin levels, were used for adjustment in the multiple regression analysis. Results: In the single-variable analysis, sodium levels were significantly higher in the female population, and showed strong associations in the multiple regression analysis. Blood potassium levels showed no significant sex-specific differences. Among these factors, renin showed the greatest significance in both the total population and sex-specific groups. Moreover, in the development of hypertension, the effect size of renin was significantly different between sexes. Additionally, BMI tended to show stronger associations in females. Conclusions: This study identified sex-specific differential effects of renin and other electrolytes that are important in the pathophysiology of blood pressure. These findings provide clues for the more precise management of hypertension. Full article
(This article belongs to the Section Cardiovascular Medicine)
13 pages, 1105 KB  
Article
Metabolic and Muscular Determinants of Weaning Failure: The Role of BUN/Creatinine Ratio and Rectus Femoris Thickness
by Erdem Yalçınkaya, Muhammet Topçu, Umut Sabri Kasapoğlu, Hüseyin Arıkan, Hasan Basri Yapıcı, Semiha Emel Eryüksel and Sait Karakurt
J. Clin. Med. 2026, 15(1), 314; https://doi.org/10.3390/jcm15010314 - 1 Jan 2026
Cited by 1 | Viewed by 1035
Abstract
Background: Weaning failure remains a major challenge in intensive care practice, often reflecting the interplay between systemic catabolism and skeletal muscle wasting. The blood urea nitrogen-to-creatinine (BUN/Cr) ratio is a routinely available biochemical index influenced by renal handling, hemodynamic status, protein metabolism, [...] Read more.
Background: Weaning failure remains a major challenge in intensive care practice, often reflecting the interplay between systemic catabolism and skeletal muscle wasting. The blood urea nitrogen-to-creatinine (BUN/Cr) ratio is a routinely available biochemical index influenced by renal handling, hemodynamic status, protein metabolism, and muscle mass, and has been associated with adverse outcomes in critical illness. This study aimed to evaluate the association between BUN/Cr ratio, weaning outcomes, and ultrasound-based rectus femoris thickness. Methods: This retrospective observational study included 42 mechanically ventilated adults admitted to the medical ICU of Marmara University between December 2024 and September 2025. Rectus femoris thickness was measured via bedside ultrasonography at the time of the spontaneous breathing trial (SBT). Weaning success was defined as extubation without reintubation, death, or need for NIV/HFNO due to respiratory distress within 7 days. Laboratory and clinical variables—including BUN/Cr ratio, SOFA, APACHE II, mNUTRIC, and albumin—were recorded. Multivariable logistic regression and receiver operating characteristic (ROC) analyses were performed. Results: Weaning failure occurred in 13 patients (31.0%). These patients had higher BUN/Cr ratios (58.7 [44.6–76.9] vs. 39.7 [23.8–49.2], p = 0.007) and lower rectus femoris thickness (6.2 [5.4–7.0] vs. 7.8 [6.9–8.6] mm, p = 0.021). The BUN/Cr ratio independently predicted weaning failure (OR 1.07; 95% CI 1.01–1.14; p = 0.024). ROC analysis identified a BUN/Cr cut-off of 44.6 (AUC = 0.76) for weaning failure. An exploratory composite metabolic–muscle indicator (MMI), combining BUN/Cr ratio and rectus femoris thickness, demonstrated higher discriminative performance in this cohort (AUC = 0.81). Conclusions: An elevated BUN/Cr ratio was independently associated with weaning failure and lower rectus femoris thickness in this cohort. Given the observational design and potential confounding, these findings should be interpreted as hypothesis-generating. Combined biochemical and ultrasound-based assessment highlights the potential value of integrating metabolic and morphologic information when characterizing patients at risk for weaning failure. However, whether incorporation of such markers into clinical decision-making improves weaning outcomes requires prospective validation. Full article
(This article belongs to the Section Intensive Care)
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14 pages, 807 KB  
Article
Beyond the GRACE Score: A Multi-Biomarker Model for Improved Risk Stratification in Acute Coronary Syndromes
by Gamze Yeter Arslan and Erkan Baysal
Diagnostics 2026, 16(1), 12; https://doi.org/10.3390/diagnostics16010012 - 19 Dec 2025
Viewed by 1151
Abstract
Background: The GRACE score is widely used to estimate early mortality in acute coronary syndromes (ACS), yet its ability to capture the complex interaction between inflammation, hepatic dysfunction, renal impairment, and myocardial injury remains limited. Integrating biomarkers that reflect these complementary physiological pathways [...] Read more.
Background: The GRACE score is widely used to estimate early mortality in acute coronary syndromes (ACS), yet its ability to capture the complex interaction between inflammation, hepatic dysfunction, renal impairment, and myocardial injury remains limited. Integrating biomarkers that reflect these complementary physiological pathways may enhance risk prediction and allow earlier identification of high-risk patients. This study evaluated whether a multi-biomarker model incorporating the C-reactive protein/albumin ratio (CAR), the albumin–bilirubin (ALBI) score, and the blood urea nitrogen/creatinine (BUN/Cr) ratio provides incremental prognostic value beyond the GRACE score and traditional cardiac markers. Methods: This retrospective study included patients hospitalized with ACS. Baseline laboratory results were used to calculate CAR, ALBI, and BUN/Cr ratios. Troponin and hemoglobin values were recorded as standard cardiac and hematologic indicators. The primary outcome was in-hospital mortality. Logistic regression models, receiver operating characteristic (ROC) curve analysis, and comparisons of area under the curve (AUC) were performed to determine whether the multi-biomarker model improved risk stratification beyond the GRACE score alone. Results: Higher CAR, ALBI, and BUN/Cr values were each associated with increased in-hospital mortality. When combined with the GRACE score, the multi-biomarker model significantly improved predictive accuracy. The integrated model demonstrated a higher AUC compared with GRACE alone, indicating incremental prognostic value across inflammatory, hepatic, and renal pathways. Conclusions: A multi-biomarker strategy combining CAR, ALBI, and BUN/Cr ratios enhances early mortality prediction beyond the GRACE score in patients with ACS. Incorporating these readily available laboratory indices may help clinicians identify high-risk patients more precisely at the time of hospital admission. Full article
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15 pages, 3247 KB  
Article
Comprehensive Clinical Profile of Amanita exitialis Poisoning: Integrating Toxin Detection and Autopsy Pathology
by Chong-Gui Chen, Ping Xu, Ji-Pin Li, Xiao-Li Bi, Qun-Mei Yao, Cheng-Min Yu, Yan Tang, Cheng-Ye Sun, Zhi-Jun Wu, Jia-Ju Zhong and Hai-Ying Wu
Toxins 2025, 17(12), 576; https://doi.org/10.3390/toxins17120576 - 29 Nov 2025
Cited by 2 | Viewed by 1499
Abstract
Amanita exitialis is a lethal mushroom species found in southern China. Its amatoxins can cause acute liver injury with a high case-fatality rate. However, reports combining toxin detection in clinical specimens with autopsy pathology remain limited. We conducted a retrospective analysis of A. [...] Read more.
Amanita exitialis is a lethal mushroom species found in southern China. Its amatoxins can cause acute liver injury with a high case-fatality rate. However, reports combining toxin detection in clinical specimens with autopsy pathology remain limited. We conducted a retrospective analysis of A. exitialis poisoning events treated at Chuxiong Yi Autonomous Prefecture People’s Hospital from 2019 to 2024. Toxins were measured in collected mushrooms, patient blood, and urine. Clinical data included demographics, complications, laboratory parameters, and autopsy findings. Associations between a time-weighted urinary amatoxin exposure metric and laboratory indices were assessed. Ten poisoning incidents involving 27 individuals were identified, including five deaths. We collected 10 mushroom samples, 120 urine samples, and 108 blood samples. α-amanitin, β-amanitin, phallacidin, and phallisacin were detected in mushrooms and urine. The detection rates of α-AMA, β-AMA, PCD, and PSC in urine samples were 31.67%, 5.00%, 38.33%, and 49.17%, respectively. Only three blood samples tested positive for α-AMA. The time-weighted urinary amatoxin exposure metric was positively correlated with total bilirubin (TBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine (Cr), creatine kinase (CK), creatine kinase isoenzymes (CK-MB), prothrombin time (PT), activated partial thromboplastin time (APTT), and international normalized ratio (INR). Early symptoms included nausea, vomiting, diarrhea, abdominal pain, and distention; later findings involved injury to the liver, kidneys, intestines, heart, and lungs. On the fourth day following ingestion, there was a marked increase in bilirubin levels and a concurrent decrease in liver enzymes, indicating severe damage to the hepatocytes. Platelet count, white blood cell count, hemoglobin, and red blood cell count decreased over time. Autopsies demonstrated hepatic, renal, and myocardial injury, gastrointestinal mucosal exfoliation, and multiorgan hemorrhage. In summary, A. exitialis poisoning is primarily characterized by liver damage, accompanied by injuries to the kidneys, myocardium, and intestines, as well as multiorgan hemorrhaging, which may lead to blood toxicity. The detection rate of toxins in urine samples is relatively high, and early urine toxin testing can help clarify the diagnosis and guide treatment. Full article
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14 pages, 889 KB  
Article
Association Between the Blood Urea Nitrogen-to-Creatinine Ratio Trajectories and Clinical Outcomes in Critically Ill Hemorrhagic Stroke Patients: Insights from MIMIC-IV Database
by Xinyuejia Huang, Huixuan Luo, Hao Deng, Yang Wu, Mengqi Wang, Linglong Xiao, Xiaoman Shi, Wei Pan, Yuan Gao and Wei Wang
J. Clin. Med. 2025, 14(22), 8141; https://doi.org/10.3390/jcm14228141 - 17 Nov 2025
Cited by 2 | Viewed by 1588
Abstract
Background: Hemorrhagic stroke (HS) accounts for approximately 30% of all stroke cases and has high mortality in the intensive care unit (ICU). The blood urea nitrogen-to-creatinine ratio (BUNCR) is a potential biomarker of catabolic stress in critically ill patients. Meanwhile, its dynamic prognostic [...] Read more.
Background: Hemorrhagic stroke (HS) accounts for approximately 30% of all stroke cases and has high mortality in the intensive care unit (ICU). The blood urea nitrogen-to-creatinine ratio (BUNCR) is a potential biomarker of catabolic stress in critically ill patients. Meanwhile, its dynamic prognostic value in ICU-admitted HS patients remains unclear. This study utilized Group-based Trajectory Modeling (GBTM) to investigate associations between early BUNCR patterns and mortality. Methods: This study was conducted using data from the MIMIC-IV (v2.2) database. HS cases were identified via ICD-9/10. BUNCR trajectories were assessed by applying GBTM during the first 7 days. Outcomes were all-cause mortality (ACM) on day 28, on day 90, and at 1 year, with ICU and in-hospital mortality also evaluated. Kaplan–Meier survival curves and log-rank test compared survival across groups. Multivariable Cox proportional models adjusted for confounders and subgroup analysis assessed robustness. Results: Among 2559 patients (52.48% male), mortality was 10.16% (ICU), 14.07% (in-hospital), 17.00% (28-day), 22.43% (90-day), and 36.97% (1-year). Three BUNCR trajectories were identified: Group 1 (upward–downward, n = 655), Group 2 (stable upward, n = 1270), and Group 3 (downward–upward, n = 634). Group 2 had the highest ACM risk at 28-day, 90-day, and 1-year (p < 0.01), and was identified as a significant risk factor in multivariate Cox regression. Subgroup revealed significant interactions of BUNCR trajectories with age and sepsis. Conclusions: Distinct BUNCR trajectories were significantly associated with ACM in critically ill HS patients. Persistently increasing BUNCR predicted the poorest outcomes, underscoring its potential as a dynamic biomarker for timely risk stratification and informed ICU decisions. Full article
(This article belongs to the Special Issue Clinical Management and Long-Term Prognosis in Intensive Care)
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13 pages, 696 KB  
Article
Blood Urea/Creatinine Ratio and Mortality in Ambulatory Patients with Heart Failure with Reduced Ejection Fraction
by Andrew S. Oswald, Muhammad S. Hussain, Mohsin H. K. Roshan, Filippo Pigazzani, Anna-Maria Choy, Faisel Khan, Ify R. Mordi and Chim C. Lang
Diseases 2025, 13(11), 362; https://doi.org/10.3390/diseases13110362 - 7 Nov 2025
Cited by 2 | Viewed by 1624
Abstract
Background: Chronic heart failure with reduced ejection fraction (HFrEF) is associated with high mortality, and renal dysfunction is common in these patients. Blood urea/creatinine ratio (UCR) has been identified as a potential prognostic marker, reflecting both renal function and neurohormonal activity. We assessed [...] Read more.
Background: Chronic heart failure with reduced ejection fraction (HFrEF) is associated with high mortality, and renal dysfunction is common in these patients. Blood urea/creatinine ratio (UCR) has been identified as a potential prognostic marker, reflecting both renal function and neurohormonal activity. We assessed whether a UCR ≥ 95 at discharge from an outpatient service was associated with increased mortality. Methods: This retrospective study reviewed 337 patients (age 72.7 ± 14.3 years; 64.7% Male; Mean LVEF 33.2 ± 8.9%) with HFrEF referred to the Heart Failure Nurse Service at NHS Tayside for optimisation of heart failure medication. Cox proportional hazards models were used to assess the association between UCR and all-cause mortality. Results: Receiver operating characteristic (ROC) analysis identified a UCR threshold of 95 (area under the curve [AUC] 0.701) as predictive of mortality. Results demonstrated that a UCR ≥ 95 was independently associated with increased mortality (HR 1.85, 95% CI 1.09–3.14, p = 0.022). A high UCR was associated with increased mortality even in patients with preserved eGFR, a group typically considered at lower risk (HR 4.03, 95% CI 1.50–10.9, p = 0.006). Conclusions: These findings suggest that UCR could be a useful addition for identifying high-risk patients who may benefit from closer monitoring and more aggressive intervention following optimisation of heart failure medication. Full article
(This article belongs to the Special Issue Insights into the Management of Cardiovascular Disease Risk Factors)
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16 pages, 435 KB  
Article
Longitudinal Changes of BMI and Renal Function Biomarkers During the Final 3 Years of Life Among Hospitalized Patients with Schizophrenia in Japan: A Preliminary Study
by Yoshihiro Mifune, Hirokazu Ito, Krishan Soriano, Leah Anne Bollos, Toshiya Akiyama, Kyoko Osaka, Hidehiro Umehara, Itsuro Endo, Rick Yiu Cho Kwan, Anson Chui Yan Tang, Kazushi Mifune and Tetsuya Tanioka
Psychiatry Int. 2025, 6(4), 140; https://doi.org/10.3390/psychiatryint6040140 - 5 Nov 2025
Viewed by 1403
Abstract
Patients with schizophrenia face high mortality from physical comorbidities; nonetheless, the gradual physiological decline preceding death is not well characterized. This retrospective study investigated temporal changes in key biomarkers among 64 inpatients with schizophrenia who died between 2014 and 2022. We analyzed data [...] Read more.
Patients with schizophrenia face high mortality from physical comorbidities; nonetheless, the gradual physiological decline preceding death is not well characterized. This retrospective study investigated temporal changes in key biomarkers among 64 inpatients with schizophrenia who died between 2014 and 2022. We analyzed data on body mass index (BMI), serum albumin (ALB), blood urea nitrogen/creatinine ratio (BCR), blood urea nitrogen/ALB ratio (BAR), and estimated glomerular filtration rate (eGFR) collected at five time points: 3, 2, and 1 year, 6 months before death, and prior to death. We hypothesized that these markers would exhibit significant changes during the last 3 years of life. BMI and ALB significantly decreased, while BCR and BAR increased (all p < 0.001). This pattern was also noted in the pneumonia subgroup, the leading cause of death (47%). A high BCR concomitant with low eGFR was attributable to chronic kidney failure in only 6% of patients, suggesting the elevated ratio was mostly driven by non-renal factors such as dehydration or sarcopenia. Therefore, the concurrent decline in BMI and ALB and rise in BCR and BAR represent a pattern of terminal physiological decline among patients with schizophrenia, supporting the need for timely risk assessment. Full article
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18 pages, 3019 KB  
Article
Sulfur-Rich Garlic Extract (DNR) as a Promising Natural Therapeutic for Diabetic Nephropathy: Evidence from a db/db Mouse Model
by Ju Hee Park, Byung Sik Cho, Xue Bi Zhou, Richard Kyung and Myong Jo Kim
Int. J. Mol. Sci. 2025, 26(20), 10184; https://doi.org/10.3390/ijms262010184 - 20 Oct 2025
Viewed by 1998
Abstract
Diabetic nephropathy (DNR) remains a major complication of type 2 diabetes with limited options to halt progression. We evaluated whether DNR (a sulfur-rich extract from Hongsan garlic) confers renoprotection in a db/db mouse model. Seventy male C57BLKS/J mice were randomized into [...] Read more.
Diabetic nephropathy (DNR) remains a major complication of type 2 diabetes with limited options to halt progression. We evaluated whether DNR (a sulfur-rich extract from Hongsan garlic) confers renoprotection in a db/db mouse model. Seventy male C57BLKS/J mice were randomized into seven groups (db/m control, db/db control, metformin 250 mg/kg, DNR 100/300/900 mg/kg, and metformin 250 mg/kg + DNR 300 mg/kg) and treated orally for eight weeks. Physiological, biochemical, urinary, histological, and immunohistochemical(IHC) endpoints were assessed, including serum creatinine, blood urea nitrogen(BUN), lipids, glucose, urinary microalbumin/albumin-to-creatinine ratio(ACR), glomerular area, mesangial expansion, and renal KIM-1 and TGF-β1 expression. Chemical profiling of the DNR extract by HPLC and LC–MS/MS identified allicin as a principal sulfur-containing constituent, exhibiting a distinct retention peak at 2.90 min and a protonated molecular ion at m/z 162.1 [M]+ with diagnostic fragment ions at m/z 145.1, 120.1, and 99.0. Allicin was qualitatively confirmed as a characteristic component of DNR, serving as a representative chemical marker for compositional characterization. DNR produced dose-dependent improvements: reductions in serum creatinine and BUN, improved lipid and glycemic profiles, decreased urinary microalbumin and ACR, and amelioration of glomerular hypertrophy and mesangial matrix expansion. IHC showed lower KIM-1 and TGF-β1 staining in treated groups. Effects at higher DNR doses were comparable to or additive with metformin for several endpoints. These findings indicate that DNR has promising renoprotective effects in this preclinical model. Full article
(This article belongs to the Section Molecular Biology)
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