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12 pages, 645 KB  
Article
Urinary KIM-1 as a Marker of Renal Tubular Injury Associated with Urethral Obstruction in Non-Azotemic Cats
by Francisco Antônio Félix Xavier Júnior, Steffi Lima Araujo, Thyago Habner de Souza Pereira, Tiago Lima Sampaio, Alice Maria Costa Martins, Nina Bezerra de Morais, Ana Raquel Almeida Pinheiro, Isadora Oliveira de Carvalho, Hélio Noberto de Araújo Júnior, Isaac Neto Goes da Silva and Janaina Serra Azul Monteiro Evangelista
Animals 2026, 16(12), 1907; https://doi.org/10.3390/ani16121907 (registering DOI) - 19 Jun 2026
Abstract
Cats with urethral obstruction may develop tubular damage before conventional indicators of renal dysfunction become abnormal, making early recognition challenging when relying solely on conventional renal biomarkers. This study evaluated urinary kidney injury molecule-1 (KIM-1) concentrations in non-azotemic cats with urethral obstruction and [...] Read more.
Cats with urethral obstruction may develop tubular damage before conventional indicators of renal dysfunction become abnormal, making early recognition challenging when relying solely on conventional renal biomarkers. This study evaluated urinary kidney injury molecule-1 (KIM-1) concentrations in non-azotemic cats with urethral obstruction and compared its expression with conventional renal biomarkers. Twenty-four male cats were prospectively enrolled and allocated into a control group (n = 12) and a urethral obstruction group (n = 12), all presenting serum creatinine concentrations within the reference interval. Urinary KIM-1 concentrations were quantified by enzyme-linked immunosorbent assay (ELISA) and normalized to urinary creatinine concentrations. Serum creatinine and blood urea nitrogen (BUN) did not differ significantly between groups. In contrast, urinary KIM-1 concentrations were significantly higher in cats with urethral obstruction compared with healthy controls (p < 0.001). These findings suggest that increased urinary KIM-1 expression may be associated with renal tubular injury in non-azotemic cats with urethral obstruction, even in the absence of alterations in conventional renal biomarkers. Therefore, urinary KIM-1 may represent a useful non-invasive marker of renal tubular injury associated with obstructive urinary disease. Further prospective studies incorporating additional renal biomarkers, histopathological evaluation, and longitudinal follow-up are warranted to better define its clinical applicability. Full article
(This article belongs to the Special Issue Advances in Canine and Feline Nephrology and Urology)
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14 pages, 1041 KB  
Article
Serum Osteoprotegerin Is Associated Independently with Peripheral Arterial Stiffness in Chronic Kidney Disease
by Yahn-Bor Chern, Po-Yu Huang, Yu-Hsien Lai, Chih-Hsien Wang, Jen-Pi Tsai and Bang-Gee Hsu
Diagnostics 2026, 16(12), 1906; https://doi.org/10.3390/diagnostics16121906 (registering DOI) - 19 Jun 2026
Abstract
Background/Objectives: Patients with chronic kidney disease (CKD) often present with peripheral arterial stiffness (PAS), which is associated with an increased cardiovascular risk. This study assessed the association between circulating osteoprotegerin (OPG), a known mediator of vascular calcification, and PAS, measured as brachial–ankle [...] Read more.
Background/Objectives: Patients with chronic kidney disease (CKD) often present with peripheral arterial stiffness (PAS), which is associated with an increased cardiovascular risk. This study assessed the association between circulating osteoprotegerin (OPG), a known mediator of vascular calcification, and PAS, measured as brachial–ankle pulse wave velocity (baPWV), in patients with CKD. Methods: This cross-sectional investigation engaged 200 individuals with non-dialysis CKD. Serum OPG concentrations were measured using a commercial enzyme-linked immunosorbent assay. Participants were classified as having PAS when either left or right baPWV was greater than 18.0 m/s; those with baPWV values of 18.0 m/s or lower were assigned to the control group. Results: Eighty-six patients (43.0%) had PAS. In comparison to controls, PAS patients were older (p < 0.001) and had higher proportions of diabetes mellitus (p = 0.023) and hypertension (p = 0.010); systolic blood pressure was higher (p < 0.001), urine protein-to-creatinine ratio was elevated (p = 0.004), and serum OPG was markedly greater (p < 0.001), whereas estimated glomerular filtration rate was lower (p = 0.003). After full adjustment, OPG levels, in addition to older age and diabetes mellitus, demonstrated an independent association with PAS (odds ratio: 1.008; 95% confidence interval: 1.002–1.015; p = 0.010). The OPG level was positively associated with bilateral baPWV by Spearman’s correlation analysis (p < 0.001). Conclusions: Circulating OPG level showed an independent association with PAS and baPWV in CKD patients not yet on dialysis. Hence, OPG can be a potential marker of vascular risk in this patient population. Full article
(This article belongs to the Special Issue Laboratory Investigations in Nephrology)
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17 pages, 2661 KB  
Systematic Review
Health Effects of Plant-Based Diets in People with Overweight or Obesity: A Systematic Review and Meta-Analysis
by Ildikó Csölle, Viktória Cseh, Gábor Veres, László Czina, Daniela Kuellenberg de Gaudry, Dávid U. Nagy, Almut Georgi and Szimonetta Lohner
Nutrients 2026, 18(12), 1987; https://doi.org/10.3390/nu18121987 - 19 Jun 2026
Abstract
Background/Objectives: Nutrition plays a core role in chronic disease management, and there is growing interest in the health impact of plant-based diets (PBDs) in people with overweight or obesity. We conducted this systematic review and meta-analysis to summarize the evidence on the health [...] Read more.
Background/Objectives: Nutrition plays a core role in chronic disease management, and there is growing interest in the health impact of plant-based diets (PBDs) in people with overweight or obesity. We conducted this systematic review and meta-analysis to summarize the evidence on the health effect of PBDs compared to omnivorous diets in overweight or obese individuals. Methods: We searched the databases Cochrane Central Register of Controlled Trials, MEDLINE, Embase, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform from inception to 3 January 2024. Two review authors independently screened studies for eligibility, extracted data, evaluated the risk of bias, and rated the certainty of the evidence using GRADE. This study is registered with PROSPERO, CRD42021225525. We used random-effects meta-analysis to analyze data. Results: Of 2664 records identified, 10 randomized controlled trials (RCTs) and six ongoing studies met the inclusion criteria. The available evidence suggests little to no difference between plant-based and omnivorous diets for body weight, systolic blood pressure, diastolic blood pressure, serum glucose, serum insulin, insulin sensitivity, total cholesterol, triglyceride, HDL cholesterol and body fat mass. Plant-based diets may slightly reduce LDL cholesterol. They may also reduce BMI and HbA1c, although the certainty of the evidence is very low. Longer-duration dietary interventions (14 weeks or more) showed greater improvements in BMI, LDL cholesterol and HbA1c. Conclusions: Plant-based diets may represent a dietary option for people with overweight or obesity and may support modest improvements in selected cardiometabolic outcomes, although the available evidence is limited and uncertain. Most outcomes showed little or no difference between PBDs and comparison diets, while the observed effects on BMI and HbA1c were supported by very low certainty evidence. Full article
(This article belongs to the Section Nutrition and Obesity)
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16 pages, 874 KB  
Article
Effect of School-Based Physical Activity and Multi Micronutrient Supplementation on Micronutrient Concentrations Among Tanzanian Schoolchildren: Secondary Outcomes from the KaziAfya Cluster-Randomized Controlled Trial
by Elihaika G. Minja, Emmanuel C. Mrimi, Winfrida P. Mponzi, Johanna Beckmann, Marceline F. Finda, Fredros O. Okumu, Christin Lang, Markus Gerber, Jürg Utzinger and Kurt Z. Long
Nutrients 2026, 18(12), 1980; https://doi.org/10.3390/nu18121980 - 18 Jun 2026
Abstract
Background: Micronutrient deficiencies and physical inactivity can adversely affect child growth and development. This study assessed the effects of school-based physical activity and multi-micronutrient supplementation on micronutrient status among schoolchildren in Kilombero district, Tanzania. Methods: In a cluster-randomized trial, children aged 6–12 years [...] Read more.
Background: Micronutrient deficiencies and physical inactivity can adversely affect child growth and development. This study assessed the effects of school-based physical activity and multi-micronutrient supplementation on micronutrient status among schoolchildren in Kilombero district, Tanzania. Methods: In a cluster-randomized trial, children aged 6–12 years were allocated to physical activity, multi-micronutrient supplementation, combined physical activity plus supplementation, or placebo control. Anthropometric and biochemical assessments were conducted at baseline, 14 months, and 26 months. Dried blood spot samples were available for 923 children at baseline. Complete-case analyses used biomarker-specific subsamples with valid baseline and 26-month measurements. Results: The primary complete-case sample included 243 children with valid paired measurements for zinc and serum transferrin receptor; vitamin D analyses were restricted to 52 children because of missing or invalid samples. At baseline, iron and vitamin D deficiencies were common, affecting 42.8% and 39.9% of children, respectively, while zinc deficiency affected 11.9%. At 26 months, allocation to the physical activity intervention was associated with lower odds of zinc deficiency, both when delivered alone (OR = 0.16) and when combined with supplementation (OR = 0.57). Supplementation alone was not significantly associated with reduced zinc deficiency. Iron status did not differ between intervention groups. Vitamin D findings should be interpreted with caution because analyses were based on a very small biomarker-specific subsample. Conclusions: School-based physical activity, alone or combined with multi-micronutrient supplementation, was associated with lower odds of zinc deficiency among Tanzanian schoolchildren. Supplementation alone showed no clear benefit for zinc or iron status. Vitamin D findings remain inconclusive because of substantial biomarker-specific missingness. Future trials should strengthen adherence monitoring, biomarker follow-up, and repeated assessment of dietary and contextual factors. Full article
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25 pages, 464 KB  
Review
Biomarkers in Melanoma: Updates in Prognosis and Management
by Brett Crosby, Martin Guerra, Alyssa Crosby, Benjamin Linza, Kristel Lourdault and Richard Essner
Cancers 2026, 18(12), 1992; https://doi.org/10.3390/cancers18121992 - 18 Jun 2026
Abstract
Melanoma incidence rates have also been steadily increasing, emphasizing the need for improved prognostic and diagnostic tools with the goal of enhancing patients’ outcomes. Biomarkers in melanoma have emerged as an important component of melanoma management, offering insight into disease progression, tumor biology, [...] Read more.
Melanoma incidence rates have also been steadily increasing, emphasizing the need for improved prognostic and diagnostic tools with the goal of enhancing patients’ outcomes. Biomarkers in melanoma have emerged as an important component of melanoma management, offering insight into disease progression, tumor biology, and the potential for judging treatment responses. Traditionally, blood and immunohistochemical markers such as lactate dehydrogenase (LDH), S100 calcium-binding protein (S100B), human melanoma black-45 (HMB-45), and SRY-box transcription factor 10 (SOX10) have been widely used in melanoma diagnosis, staging, and monitoring. However, their clinical use has been limited because of their low specificity, especially in patients with early-stage disease. This has led to the development of molecular and genetic biomarkers, including BRAF, NRAS, and KIT mutations, which improved patients’ risk stratification and enabled targeted therapies, and gene expression signature assays such as DecisionDx (Castle Biosciences) and SkylineDx (Merlin) that are already used in clinics to help with surgical decisions and to assess patients’ prognosis. Other circulating biomarkers, including microRNAs, circulating tumor DNA and circulating tumor cells, have been developed to provide minimally invasive approaches to monitor tumor evolution and detect recurrence. However, none of these new approaches are used in clinics due to their low specificity and/or sensitivity. Additionally, nomograms or predictive models have been created using biomarkers and clinicopathologic data to assess patients’ outcomes and survival. While significant progress has been made, the integration of melanoma biomarkers into routine clinical practice remains limited. This review summarizes current advancements in melanoma biomarkers, including traditional serum and immunohistochemical markers, as well as developments in molecular, genetic, circulating, and predictive biomarker approaches. Full article
(This article belongs to the Special Issue The Latest Advancements in Cutaneous Melanoma)
2 pages, 176 KB  
Abstract
Pharmaceutical-Induced Disruption of Lipid Metabolism in Brown Trout: Hypolipidemic and Hyperlipidemic Responses
by Tiago Lourenço, Maria João Rocha, Eduardo Rocha and Tânia Vieira Madureira
Proceedings 2026, 146(1), 60; https://doi.org/10.3390/proceedings2026146060 - 18 Jun 2026
Abstract
Introduction: Fish and humans share evolutionarily conserved pathways regulating lipid metabolism. However, the effects of pharmaceuticals on lipid homeostasis in fish remain poorly understood, particularly regarding mechanistic lipid dysregulation and its implications for fish physiology and environmental toxicology. While hypolipidemic drugs such as [...] Read more.
Introduction: Fish and humans share evolutionarily conserved pathways regulating lipid metabolism. However, the effects of pharmaceuticals on lipid homeostasis in fish remain poorly understood, particularly regarding mechanistic lipid dysregulation and its implications for fish physiology and environmental toxicology. While hypolipidemic drugs such as statins have been shown to modulate lipid metabolism in teleosts, other lipid-lowering agents, including cholesterol absorption inhibitors, remain largely unexplored. Additionally, synthetic hormones have been shown to interfere with lipid regulation, although their effects—particularly those of progestins—remain poorly characterized. Objective: This study aimed to explore the mechanistic lipid disruptions induced by potential hypo- and hyperlipidemic modulating pharmaceuticals in brown trout juveniles exposed to subchronic pharmacological conditions. Methodology: Juvenile brown trout were exposed via intramuscular injection every 72 h for 28 days and allocated into six experimental groups (n = 12 per group): control (C; 0.7% NaCl), solvent control (SC; 0.7% NaCl, 0.9% ethanol, 0.1% dimethyl sulfoxide), atorvastatin (ATV; 0.3 µg·g−1), ezetimibe (EZB; 0.3 µg·g−1), 17α-ethinylestradiol (EE2; 2 µg·g−1), and levonorgestrel (LNG; 0.1 µg·g−1). All concentrations represented pharmacological doses. On day 28, the fish were euthanized and sampled. Endpoints included biometric measurements, blood lipid profiling, serum biochemistry, and hepatic lipid accumulation. Results: ATV fish displayed greater body length, whereas EE2 increased liver weight and hepatosomatic index. EE2 reduced high-density lipoproteins and increased low-density lipoproteins, while atorvastatin reduced low-density lipoproteins. EE2 exposure also increased albumin levels and decreased glucose concentrations. Furthermore, EE2 significantly enhanced hepatic lipid deposition. Conclusions: The hyperlipidemic effects of EE2 were the most pronounced, whereas ATV produced the strongest hypolipidemic responses, consistent with its known effects in humans, and also influenced biometry. These findings provide a robust foundation for understanding how pharmaceuticals influence lipid metabolism and related physiological processes such as growth in fish, with relevance for both fish physiology research and environmental toxicology. Full article
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 102
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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21 pages, 664 KB  
Review
Liquid Biopsy-Derived microRNAs in Pancreatic Ductal Adenocarcinoma: Matrix-Specific Evidence and Translational Challenges
by Maria Wołyniak, Edward Zheng, Mateusz Polak, Stanisław Trojanowski and Ewa Małecka-Wojciesko
Int. J. Mol. Sci. 2026, 27(12), 5468; https://doi.org/10.3390/ijms27125468 - 17 Jun 2026
Viewed by 175
Abstract
MicroRNAs are small noncoding RNA molecules that regulate gene expression at the post-transcriptional level and play a key role in cancer development, progression, and response to therapy. Their relative stability in biological fluids and disease-associated expression patterns have positioned microRNAs as promising candidates [...] Read more.
MicroRNAs are small noncoding RNA molecules that regulate gene expression at the post-transcriptional level and play a key role in cancer development, progression, and response to therapy. Their relative stability in biological fluids and disease-associated expression patterns have positioned microRNAs as promising candidates for non-invasive cancer biomarkers. Liquid biopsy enables the detection of circulating and fluid-derived microRNAs in a range of biological materials, including blood, urine, saliva, stool, pancreatic cyst fluid, and bile, offering a minimally invasive complement to tissue-based diagnostics. This approach is particularly relevant in pancreatic ductal adenocarcinoma, a malignancy with high mortality driven largely by late diagnosis, aggressive disease course, and limited opportunities for curative treatment. This review summarizes current evidence on microRNA-based liquid biopsy approaches in this cancer, with a focus on diagnostic, prognostic, and predictive relevance. Serum and plasma remain the most extensively studied sources, while urine-based microRNA profiling has shown relatively consistent diagnostic performance across available studies, including in early-stage disease. Pancreatic cyst fluid and bile offer more lesion-proximal molecular information but are limited to selected clinical scenarios because of invasive sampling requirements. In contrast, salivary microRNA signatures show greater variability and lower reproducibility across studies. Overall, liquid biopsy based on microRNA analysis shows promise as a complementary tool for pancreatic ductal adenocarcinoma detection and risk stratification. However, substantial methodological heterogeneity and limited cross-study reproducibility currently limit clinical translation, underscoring the need for standardized workflows and prospective validation of clinically relevant microRNA panels. Full article
(This article belongs to the Special Issue New Biomarkers in Pancreatic Diseases)
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13 pages, 263 KB  
Article
Effects of Replacing Oat Hay with Peanut Hull Depolymerization Product on Growth Performance, Serum Biochemical Parameters, and Rumen Fermentation in Holstein Dairy Bulls
by Zixin Qiao, Yihui Zhang, Yujie Feng, Yucong Wang, Shujing Tian, Meng Song, Yongjiu Huo, Dongyuan Zhang, Kexin Wang and Guoqi Zhao
Animals 2026, 16(12), 1864; https://doi.org/10.3390/ani16121864 - 17 Jun 2026
Viewed by 82
Abstract
Alternative roughage resources are increasingly important for sustainable ruminant production. This study evaluated the effects of replacing oat hay with a peanut hull depolymerization product (PHDP) on growth performance, apparent nutrient digestibility, serum biochemical variables, antioxidant status, and rumen fermentation characteristics in Holstein [...] Read more.
Alternative roughage resources are increasingly important for sustainable ruminant production. This study evaluated the effects of replacing oat hay with a peanut hull depolymerization product (PHDP) on growth performance, apparent nutrient digestibility, serum biochemical variables, antioxidant status, and rumen fermentation characteristics in Holstein dairy bulls. Thirty-six Holstein dairy bulls (18–22 months old) were randomly assigned to four dietary treatments in a completely randomized design (n = 9 per treatment): T0, a basal diet containing 24% oat hay; T1, T2, and T3, in which 25%, 50%, and 75% of the oat hay was replaced with PHDP, respectively. The trial comprised a 14 d adaptation period and a 60 d measurement period. Growth performance and rumen fermentation data were analyzed using one-way ANOVA with linear and quadratic contrasts, while serum biochemical and antioxidant variables were analyzed using ANCOVA with baseline values as covariates. PHDP substitution significantly affected average daily gain (ADG), dry matter intake (DMI), and feed conversion ratio (FCR). Compared with the control group, the 75% replacement group showed greater ADG and lower FCR, whereas DMI was lower in T1 than in the other groups. Ruminal pH was increased in the 75% replacement group, whereas ammonia nitrogen concentration, major volatile fatty acid (VFA) concentrations, total VFA concentration, and apparent nutrient digestibility were not significantly affected by treatment. Most hematological and serum biochemical variables were not markedly influenced by PHDP substitution. However, total antioxidant capacity at d 60 was higher in T2 and T3 than in T1, catalase activity at d 30 was higher in T3 than in T0, and serum insulin-like growth factor-1 concentration at d 60 was highest in T3. In conclusion, PHDP could partially replace oat hay in diets for Holstein dairy bulls without impairing rumen fermentation, apparent nutrient digestibility, or major blood biochemical indicators. The 75% replacement level showed the most favorable response by improving growth performance and feed efficiency while supporting antioxidant status and serum IGF-1 concentration. Full article
(This article belongs to the Section Animal Nutrition)
13 pages, 976 KB  
Article
Beyond Diagnostic Cut-Offs: Associations Between the sFlt-1/PlGF Ratio and Perinatal Outcomes in Low-Risk Term Pregnancies
by Karolina Bednarz, Maisa Manasar-Dyrbuś, Marcin Sadłocha, Magdalena Bednarek-Jędrzejek, Rafał Stojko and Jakub Staniczek
J. Clin. Med. 2026, 15(12), 4679; https://doi.org/10.3390/jcm15124679 - 16 Jun 2026
Viewed by 145
Abstract
Background/Objectives: The soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is an established biomarker in the diagnosis of preeclampsia; however, its significance outside overt hypertensive disorders of pregnancy remains unclear. Emerging evidence suggests that angiogenic imbalance may reflect subclinical [...] Read more.
Background/Objectives: The soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is an established biomarker in the diagnosis of preeclampsia; however, its significance outside overt hypertensive disorders of pregnancy remains unclear. Emerging evidence suggests that angiogenic imbalance may reflect subclinical placental dysfunction even in otherwise low-risk pregnancies. To investigate associations between the sFlt-1/PlGF ratio and maternal and neonatal outcomes in a low-risk term obstetric population, beyond established diagnostic cut-offs. Methods: This prospective cohort study included 87 women with singleton term pregnancies. Serum sFlt-1 and PlGF concentrations were measured at hospital admission before delivery, and the sFlt-1/PlGF ratio was calculated. The primary outcome was estimated blood loss at delivery. Secondary maternal outcomes included postpartum hemoglobin decline, uterine atony, and fibrinogen concentration. Neonatal outcomes included birthweight, umbilical artery pH, and bilirubin concentration. Multivariable regression models were used to evaluate associations between the ln-transformed sFlt-1/PlGF ratio and outcomes after adjustment for prespecified maternal and obstetric covariates. Results: Each doubling of the sFlt-1/PlGF ratio was associated with greater estimated peripartum blood loss (+78.0 mL, 95% CI 42.1–113.9; p < 0.001), a larger postpartum hemoglobin decline (+0.078 g/dL, 95% CI 0.008–0.148; p = 0.030), lower fibrinogen concentration (−20.7 mg/dL, 95% CI −30.5 to −10.9; p < 0.001), and lower neonatal birthweight (−64.6 g, 95% CI −102.0 to −27.2; p = 0.001). No significant associations were observed for uterine atony, premature rupture of membranes, or umbilical artery pulsatility index above the 75th centile. Conclusions: In low-risk term pregnancies, higher sFlt-1/PlGF ratios were associated with greater estimated peripartum blood loss, lower fibrinogen concentrations, and lower neonatal birthweight. These findings support the hypothesis that variation in angiogenic balance may reflect subclinical placental dysfunction even in apparently uncomplicated pregnancies. Further prospective studies are needed to validate these exploratory observations and determine their clinical relevance. Full article
(This article belongs to the Special Issue Challenges and Opportunities in Prenatal Diagnosis)
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20 pages, 37732 KB  
Article
Sophocarpine Alleviates Renal Ischemia–Reperfusion Injury by Mitigating Oxidative Stress and Mitochondrial Dysfunction via the SIRT1/PGC-1α Axis
by Zhan Chen, Qiangmin Qiu, Dalin He, Bo Yu, Nan Jiang, Yujie Zhou, Tianyu Wang, Jiefu Zhu, Tao Qiu and Jiangqiao Zhou
Biomedicines 2026, 14(6), 1357; https://doi.org/10.3390/biomedicines14061357 - 16 Jun 2026
Viewed by 102
Abstract
Background/Objectives: Renal ischemia–reperfusion injury (IRI) is a major cause of acute kidney injury and delayed graft function after kidney transplantation. Oxidative stress, mitochondrial dysfunction, and tubular epithelial cell apoptosis are central events in renal IRI. Sophocarpine (SOP), a quinolizidine alkaloid derived from [...] Read more.
Background/Objectives: Renal ischemia–reperfusion injury (IRI) is a major cause of acute kidney injury and delayed graft function after kidney transplantation. Oxidative stress, mitochondrial dysfunction, and tubular epithelial cell apoptosis are central events in renal IRI. Sophocarpine (SOP), a quinolizidine alkaloid derived from Sophora species, has reported antioxidant and anti-apoptotic activities, but its effects in renal IRI remain unclear. This study investigated the role and function of SOP in renal IRI. Methods: A bilateral renal IRI mouse model and a hypoxia/reoxygenation (H/R) model in HK-2 human proximal tubular epithelial cells were used. Renal function, histological injury, apoptosis, reactive oxygen species, malondialdehyde, superoxide dismutase activity, glutathione, mitochondrial morphology, mitochondrial membrane potential, and mitochondrial dynamics-related proteins were evaluated. SIRT1 dependency was examined using Sirt1 small interfering RNA in HK-2 cells and EX527-mediated SIRT1 inhibition in mice. Results: SOP pretreatment reduced serum creatinine and blood urea nitrogen levels, attenuated tubular injury and apoptosis, decreased oxidative stress, and preserved mitochondrial morphology and function after renal IRI. Similar protective effects were observed in HK-2 cells exposed to H/R. SOP increased SIRT1 and PGC-1α expression, whereas Sirt1 knockdown or pharmacological SIRT1 inhibition weakened the antioxidant and mitochondrial protective effects of SOP. Conclusions: SOP attenuates renal IRI-associated oxidative stress and mitochondrial dysfunction, at least in part through the SIRT1/PGC-1α axis. These findings support further investigation of SOP as a candidate renoprotective compound for ischemic kidney injury. Full article
(This article belongs to the Special Issue Innovations in Kidney Disease: From Pathogenesis to Therapy)
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19 pages, 2417 KB  
Article
Serum β-hCG Combined with Traditional Tumor Markers Improves Detection Efficacy and Prognostic Prediction in Cholangiocarcinoma
by Suppakrit Kongsintaweesuk, Thatsanapong Pongking, Keerapach Tunbenjasiri, Pakornkiat Tanasuka, Sittiruk Roytrakul, Sudarat Onsurathum, Chawalit Pairojkul, Kitti Intuyod, Vor Luvira, Somchai Pinlaor, David Blair and Porntip Pinlaor
Int. J. Mol. Sci. 2026, 27(12), 5438; https://doi.org/10.3390/ijms27125438 - 16 Jun 2026
Viewed by 105
Abstract
Cholangiocarcinoma (CCA) in Northeast Thailand is characterized by late diagnosis and poor prognosis, creating a critical need for effective early-detection biomarkers. This study utilized a multi-omics approach to identify novel diagnostic targets and improve CCA screening. Initial serum proteomic and transcriptomic analyses revealed [...] Read more.
Cholangiocarcinoma (CCA) in Northeast Thailand is characterized by late diagnosis and poor prognosis, creating a critical need for effective early-detection biomarkers. This study utilized a multi-omics approach to identify novel diagnostic targets and improve CCA screening. Initial serum proteomic and transcriptomic analyses revealed significant upregulation of the luteinizing hormone/choriogonadotropin receptor (LHCGR) in CCA patients, correlating with advanced disease stages. Interaction network analysis subsequently identified its circulating ligand, beta-human chorionic gonadotropin (β-hCG), as a highly translatable clinical target. The protein expression of β-hCG was assessed via immunohistochemistry (IHC) in 100 tissue samples, and serum levels of β-hCG, alongside routine markers (CA19-9, AFP, and CEA), were quantified in a cohort of 405 individuals, including 153 CCA patients. IHC confirmed significantly higher β-hCG expression in tumor tissues compared to adjacent areas (p < 0.0001). Serum β-hCG levels were significantly elevated in CCA patients and correlated with tumor volume and reduced overall survival. Diagnostically, a combined multiparameter panel (β-hCG, carbohydrate antigen 19-9, carcinoembryonic antigen, and alpha-fetoprotein) yielded excellent accuracy in distinguishing CCA from healthy controls (AUC: 0.962) and hepatocellular carcinoma cases (AUC: 0.890). However, discriminatory efficiency was notably lower when differentiating CCA from benign biliary diseases (AUC: 0.680) and liver metastases (AUC: 0.705). In conclusion, activation of the LHCGR signaling axis is a novel pathophysiological feature in CCA. When integrated into a multi-marker blood panel, circulating β-hCG serves as a valuable complementary risk-stratification and prognostic tool, though further optimization is required to overcome limited specificity in the presence of confounding liver pathologies before routine clinical implementation. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
15 pages, 2440 KB  
Article
Antihypertensive Peptide ENWAAL Derived from Coix Glutelin and Its Effect on the Expression of SHR Renin–Angiotensin System
by Wenjing Zhang, Jinjie Liang, Yiping Li, Yong Yang, Haiying Chen, Liansheng Qiao and Lingzhi Wang
Biomolecules 2026, 16(6), 888; https://doi.org/10.3390/biom16060888 - 16 Jun 2026
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Abstract
Hypertension is one major risk factor of cardiovascular diseases, and RAS plays vital role during the development of hypertension. To obtain a novel antihypertensive peptide, Coix glutelin was hydrolyzed by trypsin and further separated by Sephadex G10. Based on 751 identified sequences, pharmacophore [...] Read more.
Hypertension is one major risk factor of cardiovascular diseases, and RAS plays vital role during the development of hypertension. To obtain a novel antihypertensive peptide, Coix glutelin was hydrolyzed by trypsin and further separated by Sephadex G10. Based on 751 identified sequences, pharmacophore mapping, molecular docking, and in silico proteolysis were applied to screen and optimize the candidate sequence. Finally, a novel peptide, ENWAAL, was generated with IC50 of 210.57 μM, which acted with ACE in a competitively inhibitory pattern. The in vivo antihypertensive effect was evaluated in SHRs. Significant improvements were observed in hypertension-related characteristics, including blood pressure, cardiac structure and function, and serum angiotensin II (Ang II) level. In the brain, quantitative real-time PCR analysis revealed significant downregulation of angiotensin II type 1 receptor (AT1R) mRNA expression, concomitant with upregulation of angiotensin-converting enzyme 2 (ACE2) and MAS receptor. The protein expression of ACE and AT1R in the ENWAAL group also significantly decreased. This study can provide a candidate antihypertensive drug targeting RAS. Full article
(This article belongs to the Section Natural and Bio-derived Molecules)
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15 pages, 645 KB  
Article
Candidate Faecal microRNAs as Non-Invasive Biomarkers for Bovine Paratuberculosis in Marchigiana Beef Cattle
by Martina Torricelli, Laura Madeo, Anna Fratto, Andrea Felici, Linda Petrucci, Carla Sebastiani, Marco Ermini, Massimo Biagetti, Marcella Ciullo, Matteo Ricchi, Katia Cappelli and Piera Mazzone
Int. J. Mol. Sci. 2026, 27(12), 5412; https://doi.org/10.3390/ijms27125412 - 16 Jun 2026
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Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in the post-transcriptional regulation of gene expression. Since miRNAs modulate host immune responses, they represent promising molecular biomarkers of paratuberculosis (PTB), particularly during early or subclinical stages, when conventional diagnostic tests may [...] Read more.
MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in the post-transcriptional regulation of gene expression. Since miRNAs modulate host immune responses, they represent promising molecular biomarkers of paratuberculosis (PTB), particularly during early or subclinical stages, when conventional diagnostic tests may lack sensitivity. In this context, faecal miRNAs could provide valuable insights into intestinal immune responses and mucosal damage associated with Mycobacterium avium subsp. paratuberculosis (MAP) infection. Although miRNAs have been extensively investigated in serum, blood, and tissues, their detection and characterization in bovine faeces remain poorly explored. The aim of this study was to evaluate the expression profiles of selected candidate faecal miRNAs in Marchigiana beef cattle naturally exposed to MAP and to assess their association with different infection phenotypes. Thirty-four cows were classified into three phenotypic groups: healthy exposed, MAP-infected, and PTB-affected based on longitudinal diagnostic records including interferon-γ assay, serological testing (ELISA), and faecal qPCR. Five candidate miRNAs were selected from previous studies and quantified in faecal samples by RT-qPCR. Four of the five selected miRNAs were consistently detected across samples. Bta-miR-92a was significantly downregulated in both MAP-infected and PTB-affected animals compared with healthy cattle, suggesting early modulation during MAP infection. Bta-miR-223 was significantly upregulated in PTB-affected animals compared with both healthy and MAP-infected groups, consistent with its established role in the regulation of intestinal inflammation. The ortholog of hsa-miR-501-5p was significantly upregulated in MAP-infected cattle, potentially reflecting early host–pathogen interactions at the intestinal mucosal level, while bta-miR-24-3p showed no significant differences among groups. Overall, these findings support the feasibility of faecal miRNA analysis as a complementary non-invasive molecular approach to support traditional diagnostic tests for PTB, especially during the early and subclinical stages of MAP infection. Full article
(This article belongs to the Special Issue Molecular and Immune Mechanisms in Pathogenic Mycobacteria Infections)
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19 pages, 871 KB  
Article
Dietary Ewe’s Yogurt Intake Selectively Modulates HDL Subfractions Without Altering LDL Particle Size in Women: A Six-Week Intervention Study
by Martina Gažarová, Petra Lenártová, Jana Kopčeková, Marta Habánová, Lucia Civáňová, Mária Kijovská and Lucia Šubová
Nutrients 2026, 18(12), 1933; https://doi.org/10.3390/nu18121933 - 15 Jun 2026
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Abstract
Background/Objectives: The aim of the study was to assess the metabolic response of women to a six-week consumption of full-fat sheep milk yogurt, with a focus on cardiovascular risk markers, lipid profile, and subfractions of low-density (LDL) and high-density (HDL) lipoproteins of both [...] Read more.
Background/Objectives: The aim of the study was to assess the metabolic response of women to a six-week consumption of full-fat sheep milk yogurt, with a focus on cardiovascular risk markers, lipid profile, and subfractions of low-density (LDL) and high-density (HDL) lipoproteins of both atherogenic and non-atherogenic nature. Methods: A total of 55 women were enrolled in the nutritional intervention after the application of inclusion criteria. Blood samples were collected at baseline and after the six-week intervention period. Lipoprotein subfractions were determined in serum using the Lipoprint System LDL/HDL Subfractions Kit in combination with the Lipoprint® analyzer. Results: In the group of women over 40 years of age with overweight or obesity, without adjustment for total cholesterol, a significant increase was observed in selected HDL subfractions (intermediate HDL-6, HDL-7 and small HDL-8, HDL-9; p < 0.05), while the small/large HDL ratio, LDL subfractions, and mean LDL particle size remained unchanged (p > 0.05). A decrease in triglycerides, LDL/HDL ratio, TG/HDL ratio, and cardiovascular risk index was recorded, alongside a slight increase in LDL-C and HDL-C levels. After adjustment for total cholesterol (T-C), no significant deterioration in the lipid profile was observed in either the group with normal or elevated T-C levels; in the group with elevated T-C, only the intermediate HDL-7 subfraction increased significantly (p < 0.05). Despite the presence of risk-level values in some parameters already at baseline (VLDL, IDL-A, IDL-B, small HDL), no worsening was observed. Conclusions: Six-week consumption of full-fat sheep milk yogurt did not lead to deterioration of the lipid profile or lipoprotein subfractions. The results suggest a neutral to mildly beneficial effect on selected cardiovascular risk markers. Full article
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