Biomedicines

18 pages, 1685 KB

Open AccessArticle

Precision Proteomic Profiling of Systemic Lupus Erythematosus—Correlating Disease Activity and Complement Levels with Clinical Phenotypes

by Jacob Skallerup, Christopher Aboo, Dorte B. Bekker-Jensen, Katherine Tran, Jie Ren, Malene Møller Jørgensen, Jonathan M. Blackburn, Anne Troldborg and Allan Stensballe

Biomedicines 2026, 14(6), 1408; https://doi.org/10.3390/biomedicines14061408 - 22 Jun 2026

Viewed by 682

Abstract

Background/Objectives: Systemic lupus erythematosus (SLE) is characterized by diverse clinical presentations and complex immunological mechanisms. This study aimed to characterize patient serology associated with disease activity scored using the systemic lupus erythematosus disease activity index (SLEDAI) and investigate the molecular signature of complement [...] Read more.

Background/Objectives: Systemic lupus erythematosus (SLE) is characterized by diverse clinical presentations and complex immunological mechanisms. This study aimed to characterize patient serology associated with disease activity scored using the systemic lupus erythematosus disease activity index (SLEDAI) and investigate the molecular signature of complement activation (measured through C3dg, a complement breakdown product) in SLE patients utilizing high-throughput mass spectrometry and autoantibody profiling. Methods: Plasma samples from 39 SLE patients in four mutually exclusive groups based on either disease activity scores (high/low SLEDAI) or complement activation levels (high/low C3dg) were analyzed using rapid LC-MS/MS, followed by unsupervised and supervised protein expression analysis. Complement activation was evaluated by measuring C3dg levels, and disease activity was scored using SLEDAI. Autoantibody reactivities were profiled using global autoantibody protein microarrays. Data are available via ProteomeXchange with identifier PXD066214. Results: Differential proteomic analyses revealed 25 proteins associated with SLE disease activity (high vs. low SLEDAI scores) and 25 proteins linked to complement activation levels (high vs. low C3dg). Enriched pathways indicated that adaptive immune response, classical complement activation, and immunoglobulin production correlated with disease activity, while complement activation and coagulation cascades were primarily associated with complement activation levels. Autoantibody profiling highlighted distinct reactivity patterns between subgroups, suggesting varying degrees of immune-mediated tissue damage. Conclusions: In this study, disease activity and complement activation markers were associated with overlapping yet non-identical plasma proteomic patterns in SLE. These findings support the feasibility of rapid mass spectrometry-based proteomics and autoantibody profiling for generating candidate molecular signatures in SLE. These findings serve as exploratory signatures that require validation in larger independent cohorts before they can be considered for clinical stratification and decision-making. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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19 pages, 2865 KB

Open AccessReview

The Role of Salivary Microbiota in Pancreatic Cancer: From Screening to Tumor Progression and Treatment Response

by Marco Donatello Delcuratolo, Giovanna Cocomazzi, Viria Beccia, Concetta Panebianco, Elena Binda, Valerio Pazienza and Tiziana Pia Latiano

Biomedicines 2026, 14(6), 1407; https://doi.org/10.3390/biomedicines14061407 - 22 Jun 2026

Viewed by 458

Abstract

Pancreatic cancer (PC) remains one of the malignancies with the most unfavorable prognosis and limited treatment options. The lack of biomarkers for early diagnosis and the asymptomatic nature of the disease contribute to delays in diagnosis and high mortality rates. In recent years, [...] Read more.

Pancreatic cancer (PC) remains one of the malignancies with the most unfavorable prognosis and limited treatment options. The lack of biomarkers for early diagnosis and the asymptomatic nature of the disease contribute to delays in diagnosis and high mortality rates. In recent years, the role of the human microbiota in cancer biology has become increasingly significant, and the oral microbiota in particular has been found to be involved in the pathogenesis and prognosis of several neoplasms. This review summarizes the current evidence relating the salivary microbiota to PC in three key areas: screening and diagnostic potential, pathophysiology and tumor progression, as well as presenting prognostic implications and potential influence on therapy. With regard to early diagnosis, it has been reported that patients with PC have reduced levels of Neisseria elongata (N. elongata) and Streptococcus mitis (S. mitis) and elevated levels of Granulicatella adiacens. Several studies have shown that bacteria present in the saliva can migrate from the oral cavity to pancreatic tissue via hematogenous or enteric routes, where they may actively contribute to tumor development and progression. In particular, it has been shown that Porphyromonas gingivalis (P. gingivalis) and Veillonella atypica (V. atypica) translocate from the mouth to pancreatic tumors, promoting carcinogenesis by inducing a pro-inflammatory tumor microenvironment. Furthermore, some studies have identified certain species associated with prognosis and response to PC treatment. Despite the encouraging results, differences in study methodology, the lack of standardized methods and the scarcity of longitudinal data currently hinder clinical application. Large-scale, multi-omics prospective studies are needed to clarify causality and validate their clinical utility. Overall, the salivary microbiota represents a promising and non-invasive tool for improving early diagnosis, understanding prognosis and enhancing the management of PC. Full article

(This article belongs to the Special Issue Advances of Microbiome in Human Cancers)

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30 pages, 1090 KB

Open AccessReview

Diagnostic Utility of Surface Electromyography for Identifying Muscles Affected by Myofascial Trigger Points: A Scoping Review

by Jakub Matuska, Ryszard Śliwiński, Jędrzej Pepliński, Wiktoria Frącz, Clara Leśniak, Elżbieta Skorupska and Manel M. Santafé

Biomedicines 2026, 14(6), 1406; https://doi.org/10.3390/biomedicines14061406 - 22 Jun 2026

Cited by 1 | Viewed by 521

Abstract

Background: The diagnostic value of surface electromyography (sEMG) for identifying muscles affected by myofascial trigger points (TrPs) remains controversial. However, advances in pain neurophysiology and discussions regarding TrPs within the International Classification of Diseases (ICD-11) have renewed interest in objective diagnostic approaches. [...] Read more.

Background: The diagnostic value of surface electromyography (sEMG) for identifying muscles affected by myofascial trigger points (TrPs) remains controversial. However, advances in pain neurophysiology and discussions regarding TrPs within the International Classification of Diseases (ICD-11) have renewed interest in objective diagnostic approaches. Objective: To synthesize current evidence on the diagnostic utility of sEMG for detecting TrP-related muscle alterations across different electromyographic signal analysis domains. Methods: A scoping review was conducted following JBI guidance and PRISMA-ScR guidelines. PubMed, Scopus, Web of Science, CINAHL and Cochrane were searched for studies involving adults with symptomatic or asymptomatic TrPs, myofascial pain syndrome, or TrP-related referred pain. Fifteen studies met the inclusion criteria. Analyses included amplitude-, frequency-, time–frequency-, and spatial-domain sEMG parameters. Results: Muscles affected by TrPs showed increased resting electromyographic activity and reduced activation during maximal voluntary contraction in several studies. Frequency domain analyses indicated changes in median frequency and muscle fatigue index, whereas time–frequency analyses suggested redistribution of sEMG signal energy toward lower-frequency components or altered spectral power during experimentally provoked referred pain. Spatial analyses revealed altered activation patterns, although these findings did not consistently correspond with TrP anatomical locations. Overall, the limited number of studies assessing diagnostic sensitivity and specificity prevents firm conclusions. Conclusions: sEMG may be useful as a non-invasive complementary tool for functional assessment and monitoring of TrP-related muscle dysfunction. However, current evidence does not support its use as a standalone diagnostic method. Time–frequency, machine learning-supported and spatial analyses appear promising for future clinical research, but standardized protocols and external validation are required before clinical diagnostic criteria can be proposed. Full article

(This article belongs to the Special Issue Mechanisms and Management of Chronic Pain: Nociceptive, Neuropathic, and Nociplastic Perspectives)

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17 pages, 1565 KB

Open AccessArticle

Performance Assessment of a Locally Semi-Automated NGS-Based Workflow for Homologous Recombination Deficiency Testing in High-Grade Serous Ovarian Carcinoma

by Maria Colomar-Roig, Lara Navarro, Javier Megías, Martín Núñez-Abad, Esther Roselló-Sastre, Nuria Santonja-López and Teresa San-Miguel

Biomedicines 2026, 14(6), 1405; https://doi.org/10.3390/biomedicines14061405 - 22 Jun 2026

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Abstract

Background/Objectives: Homologous recombination deficiency (HRD) is a predictive biomarker in high-grade serous ovarian carcinoma for platinum-based chemotherapy and PARP inhibitors. The implementation of HRD testing in routine diagnostics has generated multiple commercial assays that differ in genomic targets, bioinformatic analysis, and HRD [...] Read more.

Background/Objectives: Homologous recombination deficiency (HRD) is a predictive biomarker in high-grade serous ovarian carcinoma for platinum-based chemotherapy and PARP inhibitors. The implementation of HRD testing in routine diagnostics has generated multiple commercial assays that differ in genomic targets, bioinformatic analysis, and HRD scoring strategies. We aimed to assess the analytical performance and feasibility of a locally semi-automated workflow based on the Agilent SureSelect CD HRR17 panel with SeqOne/SomaHRD analysis, and to compare it with established commercial HRD assays currently used in routine clinical practice: Myriad MyChoice CDx and SOPHiA DDM Dx HRD Solution. Methods: Thirty high-grade serous ovarian carcinoma cases diagnosed between 2019 and 2023 were retrospectively analyzed. HRD status was assessed with the Agilent-SeqOne workflow and compared with Myriad (n = 12) and SOPHiA (n = 18). Concordance and correlation between genomic instability metrics were evaluated. Results: The Agilent/SeqOne workflow showed high concordance with both comparison workflows. Genomic instability metrics strongly correlated across assays (R² up to 0.96). A lower proportion of inconclusive classifications was observed with the Agilent/SeqOne workflow. Discordances were mainly observed in borderline cases near classification thresholds. Variant detection was highly concordant within shared genomic regions. Conclusions: The locally semi-automated HRD workflow demonstrated high analytical concordance with established commercial assays in evaluable cases. Operational advantages related to workflow flexibility and local reanalysis support its potential implementation in routine molecular diagnostics. Full article

(This article belongs to the Special Issue New Advances in Ovarian Cancer)

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15 pages, 458 KB

Open AccessArticle

Coupling and Uncoupling Pleiotropy Between Hypertension and Type 2 Diabetes Contribute to Exploring Potential Heterogeneity in Cardiovascular Risk in East Asian Population

by Huan Yu, Liuyan Zheng, Jingxian Wu, Ruotong Yang, Kun Wang, Huairong Wang, Shuting Xie, Yalin Chen, Teng Li, Xueying Qin, Yonghua Hu and Yiqun Wu

Biomedicines 2026, 14(6), 1404; https://doi.org/10.3390/biomedicines14061404 - 22 Jun 2026

Viewed by 404

Abstract

Background/Objectives: This study aims to systematically deconstruct the shared genetic architecture underlying the comorbidity of hypertension (HTN) and type 2 diabetes (T2D) and evaluate how these divergent genetic architectures are associated with differential cardiovascular risk in East Asian population. Methods: This [...] Read more.

Background/Objectives: This study aims to systematically deconstruct the shared genetic architecture underlying the comorbidity of hypertension (HTN) and type 2 diabetes (T2D) and evaluate how these divergent genetic architectures are associated with differential cardiovascular risk in East Asian population. Methods: This two-stage study first leveraged the largest genetic dataset from >300,000 East Asian individuals to identify pleiotropic loci between hypertension and type 2 diabetes using conjunctional false discovery rates, classifying them into coupling and uncoupling types based on effect directions. Corresponding polygenic risk scores (PRSs) were then constructed and validated in an independent family-based cohort. A logistic regression model was used to examine the associations between different genetic architectures and cardiovascular risk, including comorbidity onset and cardiovascular outcomes. Results: A total of 463 pleiotropic loci were identified, including 439 coupling loci and 24 uncoupling loci. The coupling PRS showed a significant association with single T2D (OR = 1.53; 95% CI: 1.08–2.18; p = 0.017), whereas the other associations were not significant, although the effect estimates were directionally consistent with our hypothesis. Crucially, coupling and uncoupling PRSs showed divergent cardiovascular risk profiles and exhibited distinct gene–environment interactions. Conclusions: Our findings suggest that coupling and uncoupling pleiotropy between hypertension and type 2 diabetes may contribute to the heterogeneity of cardiovascular risk in East Asians. Deconstructing genetic pleiotropy offers a potential framework for precision prevention strategies, although these findings are exploratory and warrant further validation in larger cohorts. Full article

(This article belongs to the Section Endocrinology and Metabolism Research)

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12 pages, 246 KB

Open AccessArticle

Maternal Response to Therapeutic Plasma Exchange in Early Gestation: A Case Series of Thrombotic Microangiopathies and Neurological Disorders

by Onur Karaaslan, Gürcan Türkyılmaz, Latif Hacıoğlu, Çağrı Ateş, Ersin Onat, Erbil Karaman, Hanım Güler Şahin and Ali Doğan

Biomedicines 2026, 14(6), 1403; https://doi.org/10.3390/biomedicines14061403 - 22 Jun 2026

Viewed by 551

Abstract

Background/Objectives: Therapeutic plasma exchange (TPE) is an extracorporeal treatment used in thrombotic microangiopathies (TMAs) and various autoimmune and neurological disorders. However, data regarding its use during early pregnancy remain limited. This study aimed to evaluate maternal laboratory response and perinatal outcomes in pregnant [...] Read more.

Background/Objectives: Therapeutic plasma exchange (TPE) is an extracorporeal treatment used in thrombotic microangiopathies (TMAs) and various autoimmune and neurological disorders. However, data regarding its use during early pregnancy remain limited. This study aimed to evaluate maternal laboratory response and perinatal outcomes in pregnant women who underwent TPE before 26 weeks of gestation. Methods: This retrospective case series included 10 pregnant women diagnosed before 26 weeks of gestation who underwent TPE between 2010 and 2023. Clinical and laboratory parameters before and after TPE were compared. Results: Indications for TPE included HELLP syndrome (n = 4), thrombotic thrombocytopenic purpura (n = 3), presumed atypical haemolytic uremic syndrome (n = 1), neuromyelitis optica (n = 1), and Guillain–Barré syndrome (n = 1). The mean gestational age at diagnosis was 22.1 ± 3.1 weeks, and the mean gestational age at delivery was 27.1 ± 6.9 weeks. Five fetuses (50%) died and five (50%) survived to discharge. In patients with TMAs, TPE was associated with significant decreases in LDH, INR, APTT, ALT, AST, and total bilirubin levels, along with a significant increase in platelet count and ADAMTS13 activity (p < 0.01). No maternal complications occurred in neurological cases, all of which resulted in term deliveries with healthy neonates. Conclusions: In this uncontrolled case series, TPE was associated with rapid maternal clinical and laboratory improvement in selected pregnant women with TMAs, although a causal effect cannot be established from these data. However, perinatal outcomes were primarily determined by gestational age at delivery: all fetal losses occurred before 26 weeks, whereas all infants survived when delivery occurred after 26 weeks. Larger studies are needed to confirm these findings. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics and Therapeutics in Obsterics and Gynaecology (2nd Edition))

17 pages, 1642 KB

Open AccessArticle

Metabolic Chaos After Aneurysmal Subarachnoid Haemorrhage: Longitudinal Glucose–Potassium Ratio Dynamics and Clinical Outcomes

by Adrianna Lebiedzińska, Jarosław Kędziora, Jowita Woźniak, Waldemar Goździk and Małgorzata Burzyńska

Biomedicines 2026, 14(6), 1402; https://doi.org/10.3390/biomedicines14061402 - 22 Jun 2026

Viewed by 426

Abstract

Background: Hyperglycemia after aneurysmal subarachnoid hemorrhage (aSAH) is associated with poor outcome, but admission glucose may not reflect dynamic metabolic stress during neurocritical care. Unlike previous studies focused primarily on admission measurements, we evaluated longitudinal glycemic trajectories and repeated glucose–potassium ratio (GPR) assessment [...] Read more.

Background: Hyperglycemia after aneurysmal subarachnoid hemorrhage (aSAH) is associated with poor outcome, but admission glucose may not reflect dynamic metabolic stress during neurocritical care. Unlike previous studies focused primarily on admission measurements, we evaluated longitudinal glycemic trajectories and repeated glucose–potassium ratio (GPR) assessment across multiple observation windows in relation to clinical outcomes after aSAH. Methods: This retrospective single-center cohort study included 199 consecutive adults with aSAH treated between 2014 and 2025. Serial glucose and potassium measurements obtained during intensive care unit (ICU) stay were used to calculate admission values, longitudinal means across predefined observation windows, glycemic variability, hyperglycemia burden, and GPR. Primary outcomes were 30-day mortality and poor functional outcome at discharge (modified Rankin Scale ≥ 3). Secondary outcomes included delayed cerebral ischemia (DCI), delayed neurological deterioration (DND), transcranial Doppler (TCD) vasospasm, neurological deficit at ICU discharge, and length of stay. Results: Thirty-day mortality occurred in 35 patients (17.6%). Longitudinal metabolic markers demonstrated stronger associations with outcomes than admission values. Mean 30-day GPR was independently associated with mortality (OR 2.56, 95% CI 1.66–4.16; p < 0.001) and poor functional outcome (OR 2.90, 95% CI 1.80–5.03; p < 0.001). Hyperglycemia burden was associated with mortality (OR 1.10 per additional hyperglycemic day, 95% CI 1.02–1.20; p = 0.020) and poor functional outcome (OR 1.39, 95% CI 1.19–1.71; p < 0.001). Early GPR during the early brain injury period was associated with DCI (OR 1.40, 95% CI 1.01–1.93; p = 0.043), whereas 30-day GPR was associated with DND (OR 1.47, 95% CI 1.08–2.07; p = 0.019). ICU-specific GPR was associated with neurological deficit at ICU discharge (OR 2.06, 95% CI 1.29–3.50; p = 0.004), but not with TCD-defined vasospasm. Addition of GPR improved mortality prediction compared with the clinical model alone (AUC 0.86 vs. 0.77; p = 0.002). Conclusions: Longitudinal metabolic dysregulation after aSAH is strongly associated with mortality and neurological outcomes. Persistent hyperglycemia and repeated GPR assessment provide prognostic information beyond admission glucose, with early abnormalities associated with DCI and sustained disturbances linked to mortality and disability. Full article

(This article belongs to the Section Neurobiology and Clinical Neuroscience)

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17 pages, 6379 KB

Open AccessArticle

A Hydrogel Delivery System Based on Selenium Nanoparticles and bFGF for Promoting the Repair of Skin Wounds

by Yue Wang, Ruoyang Chen, Chaoqun Wang, Pei Zheng, Min Chen and Huihui Lu

Biomedicines 2026, 14(6), 1401; https://doi.org/10.3390/biomedicines14061401 - 22 Jun 2026

Viewed by 507

Abstract

Objectives: Skin wound repair has long remained a crucial clinical challenge, in response to which, in this study, we propose a novel injectable hydrogel delivery system. In particular, we focus on the efficient delivery of bioactive factors and modulation of the local wound [...] Read more.

Objectives: Skin wound repair has long remained a crucial clinical challenge, in response to which, in this study, we propose a novel injectable hydrogel delivery system. In particular, we focus on the efficient delivery of bioactive factors and modulation of the local wound microenvironment. Methods: The hydrogel integrates selenium nanoparticles (SeNPs) and basic fibroblast growth factor (bFGF), which serve as key therapeutic components in the proposed system, and are additionally co-integrated with oxidized hyaluronic acid (OHA) and heparin-grafted carboxymethyl chitosan (CMCS-g-Hep) to construct a multifunctional SeNPs/bFGF-loaded CMCS-g-Hep/OHA hydrogel network. Accordingly, this proposed hydrogel was systematically evaluated using chemical synthesis, physicochemical characterization, in vitro cellular assays, and C57BL6J mice studies, which we used to jointly assess the biocompatibility and wound-healing efficacy of the proposed system. Results: The results demonstrated that the hydrogel enabled sustained bFGF release and was capable of significantly enhancing fibroblast proliferation, migration, and collagen deposition. In a mouse skin defect model, treatment with the loaded hydrogel markedly accelerated wound closure. Additionally, we conducted mechanistic investigations to further illustrate that the hydrogel can modulate the wound microenvironment by regulating inflammatory and chemotactic signaling pathways. Conclusions: These findings suggest a promising therapeutic pathway for chronic wound repair. Full article

(This article belongs to the Special Issue Biomaterials and Nanotechnology for Advanced Wound Dressings)

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18 pages, 3316 KB

Open AccessArticle

Hippuric Acid Suppresses Triple-Negative Breast Cancer via the EGFL8-Notch Signaling Axis

by Tianhan Xu, Saijun Wang, Shuai Chen, Yan Zhou and Dongmei Wang

Biomedicines 2026, 14(6), 1400; https://doi.org/10.3390/biomedicines14061400 - 21 Jun 2026

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Abstract

Background/Objectives: Triple-negative breast cancer (TNBC) remains a highly aggressive malignancy with limited therapeutic options due to the absence of well-defined molecular targets. Diet-induced obesity (DIO) promotes TNBC progression by reshaping systemic metabolism and inflammatory responses; however, the key circulating metabolites involved and their [...] Read more.

Background/Objectives: Triple-negative breast cancer (TNBC) remains a highly aggressive malignancy with limited therapeutic options due to the absence of well-defined molecular targets. Diet-induced obesity (DIO) promotes TNBC progression by reshaping systemic metabolism and inflammatory responses; however, the key circulating metabolites involved and their mechanisms remain largely unclear. This study aimed to identify key metabolites associated with TNBC progression and further investigate their biological functions and molecular mechanisms. Methods: Targeted metabolomics profiling was performed on serum samples from MMTV-PyMT spontaneous breast cancer mice to identify differential metabolites associated with DIO. Functional assays were conducted to evaluate the effects of hippuric acid on TNBC cell proliferation, migration, and invasion. RNA sequencing was conducted to explore downstream regulatory pathways, followed by validation of candidate targets using gain- and loss-of-function approaches as well as rescue experiments. Results: Hippuric acid was identified as a significantly altered metabolite in DIO conditions. Functional studies demonstrated that hippuric acid markedly inhibited the proliferation, migration, and invasion of TNBC cells, with minimal effects on non-TNBC cells. Transcriptomic analysis identified EGFL8 as a potential downstream target, which was further confirmed by qPCR and functional assays. Overexpression of EGFL8 suppressed malignant phenotypes, whereas its knockdown promoted tumor progression. Rescue experiments showed that EGFL8 partially mitigated the inhibitory effects of hippuric acid on TNBC, suggesting that it functions as an important mediator in this process. Mechanistically, hippuric acid exerted its anti-tumor effects at least in part through modulation of the EGFL8-Notch signaling axis. Conclusions: Hippuric acid suppresses TNBC progression via the EGFL8-Notch signaling pathway. These findings highlight a previously unrecognized role of a gut microbiota-derived metabolite in TNBC and suggest its potential as a therapeutic candidate, providing new prospective targets and a theoretical basis for metabolic intervention for TNBC. Full article

(This article belongs to the Section Cancer Biology and Oncology)

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32 pages, 27048 KB

Open AccessArticle

Gallic Acid Enhances Carboplatin-Induced Antitumoral Responses in Cervical Cancer Cells Through Oxidative Stress-Associated Mitochondrial and Apoptotic Mechanisms

by Mehmet Emin Ayağ, Mehmet Cudi Tuncer and İlhan Özdemir

Biomedicines 2026, 14(6), 1399; https://doi.org/10.3390/biomedicines14061399 - 21 Jun 2026

Viewed by 441

Abstract

Background/Objectives: Gallic acid (GA) is a naturally occurring polyphenol with reported antioxidant and anticancer properties. This study investigated whether GA enhances carboplatin (CARB)-associated anticancer activity in HeLa cervical cancer cells through mechanisms related to oxidative stress, mitochondrial dysfunction, apoptosis, and cell cycle dysregulation, [...] Read more.

Background/Objectives: Gallic acid (GA) is a naturally occurring polyphenol with reported antioxidant and anticancer properties. This study investigated whether GA enhances carboplatin (CARB)-associated anticancer activity in HeLa cervical cancer cells through mechanisms related to oxidative stress, mitochondrial dysfunction, apoptosis, and cell cycle dysregulation, while comparatively evaluating cytotoxicity in HaCaT cells. Methods: The effects of GA and CARB, individually and in combination, were evaluated using cell viability assays, apoptosis and cell cycle analyses, intracellular reactive oxygen species (ROS) measurements, N-acetylcysteine (NAC)-mediated rescue experiments, mitochondrial membrane potential assessment, reverse transcription–quantitative polymerase chain reaction (RT-qPCR), immunocytochemistry, and three-dimensional (3D) tumor spheroid models. Bioinformatic analyses were performed to explore pathways associated with the observed molecular responses. Results: The GA + CARB combination demonstrated enhanced cytotoxicity and apoptotic activity in HeLa cells compared with either monotherapy, while exhibiting comparatively lower toxicity in HaCaT cells. Combination treatment increased intracellular ROS levels, whereas NAC pretreatment partially reversed ROS accumulation and cytotoxicity, supporting a contributory role of oxidative stress in treatment-associated responses. The combination also induced mitochondrial membrane depolarization, increased G2/M arrest and SubG1 accumulation, and modulated apoptosis- and cell cycle-related gene expression. In 3D spheroid models, GA + CARB reduced spheroid growth and viability and disrupted spheroid integrity more effectively than single-agent treatments. Bioinformatic analyses identified interconnected pathways associated with oxidative stress, apoptosis, and cell cycle regulation. Conclusions: GA may enhance CARB-associated anticancer activity through mechanisms linked to oxidative stress, mitochondrial dysfunction, apoptosis, and cell cycle dysregulation. The incorporation of ROS/NAC rescue experiments and 3D spheroid validation further supports the biological relevance of the observed effects. Nevertheless, these findings remain preliminary and require confirmation in advanced in vivo and translational cervical cancer models. Full article

(This article belongs to the Special Issue Gynecological Cancers: Progress and Challenges)

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23 pages, 3974 KB

Open AccessArticle

Clinical Application of Heparin-Conjugated Fibrin Hydrogel in the Treatment of Osteochondral Defects of the Talus: Preliminary Results

by Dina Saginova, Meruyert Makhmetova, Yerik Raimagambetov, Bagdat Balbossynov, Vyacheslav Ogay and Ulunay Kanatli

Biomedicines 2026, 14(6), 1398; https://doi.org/10.3390/biomedicines14061398 - 21 Jun 2026

Viewed by 438

Abstract

Background: Osteochondral lesions of the talus (OLT) remain a challenging condition due to the limited regenerative potential of articular cartilage. Conventional bone marrow stimulation (BMS) techniques often result in fibrocartilage formation with inferior biomechanical properties. This study aimed to evaluate the safety [...] Read more.

Background: Osteochondral lesions of the talus (OLT) remain a challenging condition due to the limited regenerative potential of articular cartilage. Conventional bone marrow stimulation (BMS) techniques often result in fibrocartilage formation with inferior biomechanical properties. This study aimed to evaluate the safety and preliminary clinical efficacy of an arthroscopically assisted, single-stage injection of a heparin-conjugated fibrin hydrogel (HCFH) for OLT treatment. Methods: Twelve patients with symptomatic OLT underwent arthroscopic debridement, microfracturing, and HCFH injection containing autologous mesenchymal stromal cells (MSCs) and growth factors. Safety was assessed through systematic monitoring of adverse events (graded according to Common Terminology Criteria for Adverse Events criteria), wound healing, and serial laboratory inflammatory markers (leukocytes, erythrocyte sedimentation rate, C-reactive protein) during early and late follow-up. Clinical outcomes were evaluated using the Visual Analog Scale (VAS) and American Orthopedic Foot and Ankle Society score (AOFAS) preoperatively and at 6 and 12 months. Morphological assessment was performed using magnetic resonance imaging (MRI) with the modified Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring system, evaluated independently by two blinded musculoskeletal radiologists. Results: No serious adverse events (Grade III–IV) were observed during the 12-month follow-up. All adverse events were mild (Grade I) and self-limited. A transient postoperative elevation in inflammatory markers was observed, returning to clinically acceptable levels by day 14. Significant improvements were noted in pain (VAS decreased from 6.0 to 2.0) and ankle function (AOFAS increased from 70.0 to 90.6) (p < 0.001). MRI demonstrated progressive morphological improvement, with the MOCART score increasing from 34.16 ± 17.1 at 6 months to 75 ± 5.43 at 12 months (p < 0.001). This increase corresponded with imaging features consistent with tissue maturation over time. The favorable MOCART outcomes observed in this study may be explained by the regenerative properties of heparin-conjugated fibrin hydrogels; however, larger randomized controlled trials with longer follow-up are needed to confirm the durability of the regenerated tissue. Interobserver agreement was substantial to almost perfect for MOCART scoring (κ = 0.68–0.84), with perfect agreement observed for surface assessment, bony defect/overgrowth, and cysts. Conclusions: Within the limitations of this study, single-stage HCFH injection demonstrated an acceptable safety profile and favorable preliminary clinical and radiological outcomes at 12 months. These findings suggest potential regenerative capability; however, controlled studies with larger cohorts and longer follow-up are required to determine comparative efficacy and long-term durability. Full article

(This article belongs to the Section Biomedical Engineering and Materials)

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15 pages, 308 KB

Open AccessReview

Intravascular Imaging Versus Physiology Assessment for Intermediate Lesions During PCI

by Marios Sagris, Athanasios Makris, Svetlana Aghayan, Stergios Soulaidopoulos, Alexios Giannakodimos, Konstantinos Platanias, Andreas Tzoumas, Nikolaos Ktenopoulos, Konstantinos Pamporis, Nikolaos Stalikas, Gerasimos Gavrielatos, Efstratios Karagiannidis, Nikolaos Patsourakos, Dimitris Tousoulis and Konstantinos Tsioufis

Biomedicines 2026, 14(6), 1397; https://doi.org/10.3390/biomedicines14061397 - 21 Jun 2026

Viewed by 437

Abstract

Coronary artery disease (CAD) is the leading cause of mortality, with percutaneous coronary intervention (PCI) constituting the gold standard treatment. However, in an important proportion of the cases, lesion severity is debatable since conventional angiography provides only a two-dimensional representation of the vessel [...] Read more.

Coronary artery disease (CAD) is the leading cause of mortality, with percutaneous coronary intervention (PCI) constituting the gold standard treatment. However, in an important proportion of the cases, lesion severity is debatable since conventional angiography provides only a two-dimensional representation of the vessel lumen and fails to quantify ischemic significance or plaque morphology. In these cases, several adjunctive tools considering physiology and imaging guidance may assist in quantifying the severity of the disease. Imaging modalities such as intravascular ultrasonography (IVUS) and optical coherence tomography (OCT), as well as physiology such as fractional flow reserve (FFR) and instantaneous wave-free (iFR), revolutionized revascularization strategy by linking anatomical stenosis to its functional consequence on myocardial perfusion. The present review summarizes and contrasts the available evidence for physiology and imaging guidance, considering the assessment of intermediate lesions during PCI and providing insights for their use in specific lesion subsets. Full article

(This article belongs to the Section Biomedical Engineering and Materials)

17 pages, 9183 KB

Open AccessReview

Reframing Telomere Biology in Exercise Science: From Descriptive Metrics to Redox–Metabolic Mechanisms for Precision Healthy Aging (2000–2025)

by Kun-Ho Lee, Kwon-Jae Song and Yun-A Shin

Biomedicines 2026, 14(6), 1396; https://doi.org/10.3390/biomedicines14061396 - 21 Jun 2026

Viewed by 633

Abstract

Background/Objectives: Telomeres are critical biomarkers of biological aging, with shortened leukocyte telomere length strongly linked to all-cause mortality and age-related disease risk. Although exercise modulates telomere dynamics, the field’s evolution from descriptive measurements to mechanistic inquiries involving redox biology and epigenetics remains [...] Read more.

Background/Objectives: Telomeres are critical biomarkers of biological aging, with shortened leukocyte telomere length strongly linked to all-cause mortality and age-related disease risk. Although exercise modulates telomere dynamics, the field’s evolution from descriptive measurements to mechanistic inquiries involving redox biology and epigenetics remains incompletely mapped. This study systematically characterized the global research landscape of telomere–exercise science over 25 years to establish a strategic evidence base for precision exercise prescription. Methods: A bibliometric analysis was conducted on 858 publications from the Web of Science Core Collection (2000–2025). CiteSpace and VOSviewer were used for keyword co-occurrence analysis, strategic thematic mapping, and citation burst detection to visualize global research trends and identify emerging frontiers. Results: Annual publication volume grew from 2 (2000) to 71 (2025), with a compound annual growth rate of 15.4%. China emerged as one of the leading global contributors. Thematic analysis revealed a paradigm shift from descriptive leukocyte telomere length studies toward mechanistic investigations of oxidative stress, mitochondrial homeostasis, and epigenetic clocks. Keyword network analysis confirmed oxidative stress and inflammation as central hubs, mediating telomere protection via redox regulation and non-canonical telomerase functions. Conclusions: Exercise preserves telomere integrity primarily through redox–mitochondrial homeostasis, hormesis-driven antioxidant upregulation, and non-canonical telomerase activation. For aging populations and individuals at metabolic risk, aerobic training and high-intensity interval training (HIIT) are recommended as first-line non-pharmacological interventions for healthspan extension. Leukocyte telomere length and telomerase activity should be integrated as biomarkers in preventive medicine practice. Future large-scale randomized controlled trials incorporating multi-omics approaches and sex-stratified analyses are warranted to establish individualized dose–response guidelines for precision exercise prescription. Full article

(This article belongs to the Special Issue Impacts of Exercise, Nutrition, Obesity, Metabolism and Ageing on Regenerative Medicine and Their Applications in Tissue Engineering and Therapeutics)

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15 pages, 1075 KB

Open AccessArticle

Multisite Atherosclerosis and SCORE2-Based Risk Stratification in Psoriatic Arthritis: A Phenotype-Dependent Role of Vascular Territories

by Lilyan C. Charca, Ignacio Braña, Marta Loredo, Paula Alvarez, Estefanía Pardo, Stefanie Burger and Rubén Queiro

Biomedicines 2026, 14(6), 1395; https://doi.org/10.3390/biomedicines14061395 - 20 Jun 2026

Viewed by 419

Abstract

Background: Cardiovascular (CV) risk is increased in psoriatic arthritis (PsA), yet vascular assessment has largely focused on carotid arteries, potentially underestimating systemic atherosclerosis. Objective: The objective of this study was to characterize the distribution and concordance of atherosclerotic plaques across carotid, femoral, and [...] Read more.

Background: Cardiovascular (CV) risk is increased in psoriatic arthritis (PsA), yet vascular assessment has largely focused on carotid arteries, potentially underestimating systemic atherosclerosis. Objective: The objective of this study was to characterize the distribution and concordance of atherosclerotic plaques across carotid, femoral, and aortic territories in PsA and evaluate their incremental value over SCORE2. Methods: In this cross-sectional study, 250 unselected patients with PsA underwent carotid and femoral ultrasound and abdominal X-ray. Plaque prevalence and multiterritorial involvement (≥2 vascular beds) were assessed. Agreement between territories was evaluated using Cohen’s κ. In patients aged 50–69 years, the incremental value of vascular territories over SCORE2 was evaluated using ROC curves, bootstrap-corrected decision curve analysis (DCA), and reclassification metrics (IDI and continuous NRI). Results: Plaques were detected in carotid (36.0%), femoral (62.8%), and aortic (31.6%) territories, with multiterritorial involvement in 43.2%. Agreement between vascular beds was moderate (κ ≈ 0.35). Notably, 48.1% of patients without carotid plaques had femoral involvement. SCORE2 categories showed a strong gradient with plaque prevalence (p < 0.0001). In patients aged 50–69 years, adding vascular imaging improved discrimination for multiterritorial disease (AUC 0.73 vs. 0.86–0.90). Reclassification analyses demonstrated that carotid plaque substantially improved the identification of multiterritorial atherosclerosis (IDI 0.32, 95% CI 0.18–0.50; continuous NRI 1.33, 95% CI 1.08–1.60), with similar results observed for aortic plaque (IDI 0.33, 95% CI 0.20–0.50; continuous NRI 1.24, 95% CI 0.99–1.48). Femoral plaque provided a more modest improvement (IDI 0.26, 95% CI 0.16–0.37; continuous NRI 1.11, 95% CI 0.80–1.33). Conversely, when the outcome was defined as the presence of any plaque, femoral plaque provided the greatest incremental value over SCORE2 (AUC 0.96, 95% CI 0.93–0.99). Bootstrap-corrected DCA confirmed improved net benefit. Conclusions: The incremental value of vascular imaging over SCORE2 appears to be phenotype-dependent. Femoral plaque provided the greatest improvement for detecting the presence of subclinical atherosclerosis, whereas carotid and aortic plaques offered greater incremental value for identifying multiterritorial vascular involvement. These findings support a tailored, multiterritorial approach to cardiovascular risk assessment in patients with PsA. Full article

(This article belongs to the Topic Cardiovascular Disease in Special Populations: From Basic Science to Clinical Practice)

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24 pages, 2557 KB

Open AccessReview

Role of α-Synuclein in the Prefrontal Cortex: From Physiological Synaptic Modulation to Synaptic Failure in Parkinson’s Disease

by Uxia Argibay, María Sancho-Alonso, Claudia Yanes-Castilla, Judith Jericó-Escolar, Verónica Paz, Esther Ruiz-Bronchal, Lluis Miquel-Rio and Analia Bortolozzi

Biomedicines 2026, 14(6), 1394; https://doi.org/10.3390/biomedicines14061394 - 20 Jun 2026

Viewed by 816

Abstract

α-Synuclein (α-Syn) is a key presynaptic protein, primarily known for its role in the pathogenesis of Parkinson’s disease (PD) and other synucleinopathies, including dementia with Lewy bodies (DLB). Although much of the research has focused on the nigrostriatal dopamine (DA) pathway, there is [...] Read more.

α-Synuclein (α-Syn) is a key presynaptic protein, primarily known for its role in the pathogenesis of Parkinson’s disease (PD) and other synucleinopathies, including dementia with Lewy bodies (DLB). Although much of the research has focused on the nigrostriatal dopamine (DA) pathway, there is growing recognition that the accumulation of misfolded α-Syn in the prefrontal cortex (PFC) is a critical driver of non-motor symptoms and cognitive deficits in PD and DLB. This review examines the dual role of α-Syn in the PFC circuitry, initially exploring its regulation of synaptic vesicle (SV) dynamics and recycling to maintain stable neurotransmission. We highlight its contribution to the modulation of glutamatergic (Glu) and GABAergic (γ-aminobutyric acid, GABA) synapses, which ensures the functional excitatory/inhibitory (E/I) balance of prefrontal circuits. Conversely, in PD and DLB, the transition of functional α-Syn monomers to pathological oligomers triggers a cascade of synaptic failures. We analyze how α-Syn aggregation causes pathology in dendritic spines, leads to a progressive reduction in the density of synaptic markers, and impairs cortical plasticity. Synthesizing evidence from neuroimaging studies, post-mortem human cortical samples, and animal models, this review emphasizes the PFC as a vulnerable brain region where α-Syn-mediated synaptic dysfunction translates into cognitive and emotional deficits. Deciphering these early synaptic alterations is essential for developing neuroprotective strategies that preserve cortical function in PD and DLB. Full article

(This article belongs to the Special Issue Synaptic Function and Modulation in Health and Disease)

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27 pages, 2821 KB

Open AccessReview

Surgical Rodent Models for the Study of Peripheral Arterial Disease

by Lauren Carmon, Kristopher Maier and Vivian Gahtan

Biomedicines 2026, 14(6), 1393; https://doi.org/10.3390/biomedicines14061393 - 20 Jun 2026

Viewed by 503

Abstract

Cardiovascular disease remains the leading cause of morbidity and mortality worldwide, with atherosclerosis and maladaptive vascular remodeling serving as central drivers of clinical events. Mechanistic investigation of arterial disease processes relies heavily on experimental animal models that permit precise control of vascular injury, [...] Read more.

Cardiovascular disease remains the leading cause of morbidity and mortality worldwide, with atherosclerosis and maladaptive vascular remodeling serving as central drivers of clinical events. Mechanistic investigation of arterial disease processes relies heavily on experimental animal models that permit precise control of vascular injury, hemodynamic forces, and ischemic stress. Over the past several decades, murine and rat models have become indispensable tools for studying endothelial dysfunction, intimal hyperplasia, flow-mediated remodeling, and ischemia–reperfusion injury. Each model reproduces distinct aspects of human vascular pathology while offering unique technical and biological advantages. This review summarizes commonly used murine and rat models of arterial disease, emphasizing the biological mechanisms they study, the surgical techniques used, pathophysiology, experimental endpoints, advantages, and limitations. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Physiology—Second Edition)

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11 pages, 495 KB

Open AccessArticle

Influence of PPM1D Mutations on Response and Survival Outcomes Following Bispecific Antibody Therapy in Relapsed and Refractory Multiple Myeloma Patients

by Elena Fiori, Martina Bertschinger, Ulrike Bacher, Michele Hoffmann, Henning Nilius, Katja Seipel and Thomas Pabst

Biomedicines 2026, 14(6), 1392; https://doi.org/10.3390/biomedicines14061392 - 20 Jun 2026

Viewed by 591

Abstract

Background/Objectives: Therapeutic options for patients with relapsed and refractory multiple myeloma (RRMM) have advanced substantially in recent years. In particular, T-cell-engaging therapies, including chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies (bsAbs), have emerged as highly effective treatment modalities. However, data on [...] Read more.

Background/Objectives: Therapeutic options for patients with relapsed and refractory multiple myeloma (RRMM) have advanced substantially in recent years. In particular, T-cell-engaging therapies, including chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies (bsAbs), have emerged as highly effective treatment modalities. However, data on predictive biomarkers for response to these therapies remain limited. Patients currently receiving T-cell-engaging therapies are typically heavily pretreated and frequently exhibit clonal hematopoiesis. Clonal hematopoiesis, especially involving PPM1D mutations, may adversely affect the efficacy of T-cell-engaging therapies. Methods: We conducted a retrospective, single-center study including 27 patients with RRMM who were treated with bsAbs (teclistamab, elranatamab, or talquetamab) between June 2022 and September 2025 and for whom genetic material was available before bsAB treatment. We evaluated the impact of PPM1D mutations on treatment response, progression-free survival (PFS), and overall survival (OS). Results: The prevalence of PPM1D mutations in our cohort was 27%. Compared with patients without PPM1D mutations, mutation carriers showed a trend toward less deep remissions and demonstrated significantly inferior 6-month PFS (43% vs. 85%, p = 0.0272) and 6-month OS (57% vs. 90%, p = 0.0473). Conclusions: These findings suggest that PPM1D mutations may represent a promising biomarker in patients with RRMM treated with bsAbs. Larger, prospective studies are warranted to validate and further elucidate these observations. Full article

(This article belongs to the Section Cancer Biology and Oncology)

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22 pages, 958 KB

Open AccessReview

Strategic Adhesion and Dental Tissue Conservation: Contemporary Perspectives on Interfacial Bond Longevity and Minimally Invasive Restorative Designs

by Cristiana Cuzic, Mihai Rominu, Horatiu Urechescu, Alisia Pricop, Ovidiu Stefan Cuzic, Raul Rotar, Marius Octavian Pricop and Anca Jivanescu

Biomedicines 2026, 14(6), 1391; https://doi.org/10.3390/biomedicines14061391 - 19 Jun 2026

Viewed by 694

Abstract

Modern prosthetic dentistry has been significantly reshaped by adhesive dentistry, CAD/CAM technologies, and advanced ceramic materials, leading to the development of minimally invasive all-ceramic restorative approaches. However, the longevity of the adhesive interface is fundamental to the long-term effectiveness of these restorations. With [...] Read more.

Modern prosthetic dentistry has been significantly reshaped by adhesive dentistry, CAD/CAM technologies, and advanced ceramic materials, leading to the development of minimally invasive all-ceramic restorative approaches. However, the longevity of the adhesive interface is fundamental to the long-term effectiveness of these restorations. With a focus on bond durability and clinical performance, this narrative review aims to evaluate modern adhesive strategies, tooth preparation requirements, and cementation techniques in all-ceramic minimally invasive restorations. Methods: A narrative review of the literature was performed using Google Scholar, Web of Science, and PubMed/MEDLINE databases. Publications from 2000 to 2026 were analysed. In vitro research, narrative reviews, and systematic reviews related to adhesive systems, resin cements, CAD/CAM materials, and minimally invasive prosthodontic principles were the core subjects of the research. Results: The findings indicate that material selection, surface conditioning techniques, and cementation methods have a significant impact on the clinical effectiveness of all-ceramic restorations. Retention and marginal sealing are greatly enhanced by resin-based adhesive systems. Nevertheless, hydrolytic degradation, procedure sensitivity, and substrate-related factors remain a challenge to the adhesive interface. Advances in CAD/CAM and ultra-conservative designs, like occlusal veneers and partial-coverage restorations, have increased treatment alternatives while ensuring acceptable functional and aesthetic results. Conclusions: Minimally invasive all-ceramic restorations represent a conservative and clinically effective treatment approach in modern prosthodontics. Their long-term performance is primarily dependent on adhesive interface stability and adherence to evidence-based clinical protocols. Continued developments in adhesive materials and ceramic systems are expected to improve bond durability and broaden clinical indications. Full article

(This article belongs to the Special Issue Biomedicine in Dental and Oral Rehabilitation)

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19 pages, 906 KB

Open AccessArticle

Association of Circulating C-C Motif Chemokine Ligand 4 to Disease Severity and Clinical Outcomes in Sepsis: A Prospective Observational Study

by Hilal Sipahioglu, Koca Caliskan, Berkan Akcakaya, Sibel Kuzuguden, Hatice Kubra Zenger Ilik and Hatice Aslan Sirakaya

Biomedicines 2026, 14(6), 1390; https://doi.org/10.3390/biomedicines14061390 - 19 Jun 2026

Viewed by 377

Abstract

Background: Sepsis is a life-threatening syndrome characterized by a dysregulated host response and organ dysfunction and remains a major cause of mortality in intensive care units (ICUs). Early risk stratification is essential for clinical management. C-C motif chemokine ligand 4 (CCL4), a [...] Read more.

Background: Sepsis is a life-threatening syndrome characterized by a dysregulated host response and organ dysfunction and remains a major cause of mortality in intensive care units (ICUs). Early risk stratification is essential for clinical management. C-C motif chemokine ligand 4 (CCL4), a pro-inflammatory chemokine involved in immune cell recruitment, may reflect the severity of systemic inflammation; however, its prognostic value in adult patients with sepsis has not been fully elucidated. Methods: In this prospective, single-center observational study, 75 adult patients with sepsis admitted to the ICU were enrolled. Plasma CCL4 levels were measured at admission using an enzyme-linked immunosorbent assay (ELISA). Logistic regression, receiver operating characteristic (ROC) curve analysis, DeLong testing, and reclassification analyses using net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were performed. Results: CCL4 levels were significantly higher in non-survivors than survivors (1784 ± 752 vs. 1397 ± 528 pg/mL, p = 0.011). In multivariable analysis, the CCL4 (odds ratio [OR] 1.001, p = 0.023) and Pitt bacteremia score (OR 1.523, p = 0.003) were independently associated with ICU mortality. CCL4 alone showed modest discriminative performance (AUC 0.645, 95% confidence interval [CI] 0.508–0.782). However, the addition of CCL4 to clinical severity scores significantly improved discrimination, with the highest observed in the combined model (AUC 0.885). Reclassification analyses further supported the incremental prognostic value of CCL4. Conclusions: CCL4 is independently associated with ICU mortality in sepsis, and its integration with clinical severity scores may improve prognostic accuracy for risk stratification. Full article

(This article belongs to the Section Cell Biology and Pathology)

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22 pages, 2402 KB

Open AccessArticle

Clinical Outcomes of Plasma-Assisted Saline Irrigation in Nonsurgical Root Canal Treatment: A Preliminary Retrospective Cohort Study

by Young-Hee Kim, Jeong-Hyo Lyu, Hyun-Sook Chung, Sang-Yoon Park, Sang-Min Yi, Soo-Hwan Byun, Sung-Woon On, Jae-Seo Lee, Dong-Jun Kim and Byoung-Eun Yang

Biomedicines 2026, 14(6), 1389; https://doi.org/10.3390/biomedicines14061389 - 19 Jun 2026

Viewed by 776

Abstract

Background: Effective root canal disinfection is essential for successful nonsurgical root canal treatment (RCT). Although sodium hypochlorite (NaOCl) remains the standard irrigant, it carries a risk of chemical tissue injury if extruded beyond the root canal system and may have limited penetration into [...] Read more.

Background: Effective root canal disinfection is essential for successful nonsurgical root canal treatment (RCT). Although sodium hypochlorite (NaOCl) remains the standard irrigant, it carries a risk of chemical tissue injury if extruded beyond the root canal system and may have limited penetration into anatomically complex regions. Underwater discharge plasma (UDP) generates reactive oxygen and nitrogen species (RONS) through high-frequency, high-voltage electrical discharge in aqueous media, and preclinical and in vitro studies have reported broad-spectrum antimicrobial activity. This study evaluated the clinical and radiographic outcomes of nonsurgical RCT performed using physiological saline-based UDP irrigation without NaOCl in a heterogeneous real-world clinical cohort. Methods: This single-center retrospective cohort study included 186 teeth from 134 patients treated with the PLAZEN RCT^® UDP device and physiological saline irrigation, without NaOCl. The median follow-up period was 16 months. Radiographic outcomes were assessed using the Periapical Index (PAI) system, and treatment success was evaluated according to prespecified Strict and Loose criteria incorporating both radiographic and clinical findings. Stratified analysis was performed according to preoperative PAI score: Group A (PAI 1–2) and Group B (PAI 3–5). UDP-related adverse events, defined as thermal tissue injury caused by discharge heat, were ascertained through retrospective review of clinical records, operative notes, and serial periapical radiographs. Results: Among the 186 treated teeth, radiographic outcomes were classified as Healed (85.5%), Healing (3.8%), and Unhealed (10.8%). Overall Strict and Loose success rates were 79.6% and 82.3%, respectively. Initial treatment showed numerically higher success rates than retreatment. In the stratified analysis, Group A showed an 84.1% success rate with 100% tooth survival, whereas Group B demonstrated Strict and Loose success rates of 68.5% and 83.3%, respectively. Exploratory multivariable analysis showed that periodontal pocket depth > 3 mm was the most consistent factor associated with lower odds of treatment success, whereas associations involving canal obliteration and higher preoperative PAI score were less stable across sensitivity analyses and should be interpreted with caution. No UDP-related adverse events were recorded during follow-up. Attrition sensitivity analyses were performed, and the outcome estimates should be interpreted with caution, given the retrospective design and substantial loss to follow-up. Conclusions: In this preliminary observational cohort, physiological saline-based UDP irrigation without NaOCl was associated with favorable observed periapical healing outcomes and no recorded UDP-related adverse events over a median follow-up of 16 months. However, loss to follow-up was substantial; when all 116 teeth lost to follow-up were classified as treatment failures, the worst-case Strict success rate decreased to 49.0%. Therefore, these findings should be interpreted as preliminary descriptive evidence of clinical feasibility rather than as evidence of comparative efficacy or definitive clinical safety. Adequately powered randomized controlled trials with concurrent NaOCl control arms and long-term follow-up are warranted to evaluate the comparative effectiveness, safety, and reproducibility of physiological saline-based UDP irrigation protocols. Full article

(This article belongs to the Special Issue Biomedicine in Dental and Oral Rehabilitation)

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18 pages, 1368 KB

Open AccessArticle

Predictors of In-Hospital Mortality in Traumatic Acute Subdural Hematoma: The Role of Admission International Normalized Ratio, Imaging Parameters and Neurological Severity

by Serban Iancu Papacocea, Miruna Ioana Lazăr, Romica Cergan, Ioana Anca Badarau and Toma Marius Papacocea

Biomedicines 2026, 14(6), 1388; https://doi.org/10.3390/biomedicines14061388 - 19 Jun 2026

Cited by 1 | Viewed by 521

Abstract

Background/Objectives: Acute subdural hematomas (aSDH) represent a frequent and potentially life-threatening form of traumatic intracranial hemorrhage. This study aims to assess prognostic factors associated with mortality and clinical outcome, with particular emphasis on coagulation-related parameters, especially international normalized ratio (INR). Methods: [...] Read more.

Background/Objectives: Acute subdural hematomas (aSDH) represent a frequent and potentially life-threatening form of traumatic intracranial hemorrhage. This study aims to assess prognostic factors associated with mortality and clinical outcome, with particular emphasis on coagulation-related parameters, especially international normalized ratio (INR). Methods: A single-center retrospective cohort study was performed. We included 151 patients with traumatic aSDH, admitted between January 2020 and June 2025 to the Department of Neurosurgery of the Clinical Emergency Hospital “Saint Pantelimon”. Demographic, clinical, laboratory, and imaging parameters obtained at admission were analyzed. Univariate and multivariable regression analyses were performed to identify predictors of in-hospital mortality. Internal validation included bootstrap resampling, calibration analysis, penalized regression and spline modeling. Results: The cohort had a mean age of 67.4 years and was predominantly male (72.8%). Overall, in-hospital mortality was 36.4%, while 58.3% of patients underwent surgical intervention. Admission Glasgow Coma Scale (GCS) score represented the strongest predictor of mortality. Hematoma thickness was significantly associated with midline shift, mortality, and surgical intervention. Elevated INR was significantly associated with increased hematoma thickness, greater midline shift, lower GCS, and increased mortality. In multivariable analysis, INR ≥ 1.4 remained independently associated with mortality (OR 4.08, 95% CI 1.56–11.29, p = 0.005), together with lower GCS. The final model demonstrated very good discrimination (AUC 0.887) and good calibration. Conclusions: Outcome in traumatic aSDH appears to be influenced by neurological severity, hematoma burden, and coagulation status. Admission GCS remained the strongest predictor of mortality, while elevated INR independently predicted poor outcome. Full article

(This article belongs to the Special Issue Traumatic CNS Injury: From Bench to Bedside (2nd Edition))

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14 pages, 1965 KB

Open AccessArticle

Smaller Optic Discs Show Higher Macular Flow Density: An Optical Coherence Tomography Angiography Study

by Charlotte Egbring, Sarah Kleemann, Moritz Fabian Danzer, Nicole Eter and Jens Julian Storp

Biomedicines 2026, 14(6), 1387; https://doi.org/10.3390/biomedicines14061387 - 19 Jun 2026

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Abstract

Background/Objectives: This study aimed to investigate the correlation between macular flow density (FD) as well as foveal avascular zone (FAZ) characteristics and optic disc size, quantified by Bruch’s membrane opening area (BMOA). In addition, potential differences in FD and FAZ parameters among [...] Read more.

Background/Objectives: This study aimed to investigate the correlation between macular flow density (FD) as well as foveal avascular zone (FAZ) characteristics and optic disc size, quantified by Bruch’s membrane opening area (BMOA). In addition, potential differences in FD and FAZ parameters among optic disc size cohorts were evaluated. Methods: In this retrospective, single-centre study, 151 eyes from 151 healthy participants examined at the University Hospital Münster, Germany, were included. Each subject underwent macular and optic disc optical coherence tomography angiography (OCT-A). Rank correlation coefficients for clustered data were computed to assess associations between FD values and BMOA. Further analyses compared FD and FAZ parameters among three optic disc size groups based on their quantiles. Results: Statistical analysis revealed a significant negative correlation between FD in several macular subsectors and BMOA. When stratified by optic disc size, FD in the superficial capillary plexus (SCP) was significantly higher in eyes with the smallest discs compared with intermediate ones, and FD in the deep capillary plexus (DCP) was significantly higher in intermediate discs compared with the largest group. Additionally, both SCP and DCP showed higher absolute FD values in eyes with the smallest optic discs compared with those with the largest. No significant group differences were detected for foveal FD, FAZ area, or FAZ perimeter. Conclusions: This study contributes to normative OCT-A data by incorporating optic disc size as a variable. While FAZ parameters appeared independent of BMOA, eyes with smaller optic discs demonstrated higher FD values in both SCP and DCP. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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23 pages, 1569 KB

Open AccessReview

Specificity vs. Synergy Between Single-Strain and Multi-Strain Probiotics for Ulcerative Colitis Treatment: A Review of the Literature

by Muhammad Ikhmal Rosali, Dinesh Prasad V. Thanga Velu, Mohd Helmy Mokhtar, Raja Affendi Raja Ali, Norfilza Mohd Mokhtar and Adila A. Hamid

Biomedicines 2026, 14(6), 1386; https://doi.org/10.3390/biomedicines14061386 - 19 Jun 2026

Cited by 1 | Viewed by 1530

Abstract

Ulcerative colitis (UC) is a chronic disease marked by mucosal inflammation of the colon, and its prevalence has progressively increased worldwide. Gut dysbiosis is recognized as a key contributor to its pathogenesis. Although conventional treatments are effective in managing symptoms, they often fail [...] Read more.

Ulcerative colitis (UC) is a chronic disease marked by mucosal inflammation of the colon, and its prevalence has progressively increased worldwide. Gut dysbiosis is recognized as a key contributor to its pathogenesis. Although conventional treatments are effective in managing symptoms, they often fail to address the underlying gut microbial imbalance, prompting growing interest in microbiota-based therapies. Probiotic supplementation has demonstrated potential to modulate the disease. However, its clinical application is limited by variability in formulations and strain composition. Debate persists regarding the relative benefits of single-strain probiotics (SSPs), which depend on strain specificity, versus multi-strain probiotics (MSPs), which may provide synergistic effects. The literature remains inconclusive, with some studies indicating that MSPs outperform SSPs, while others emphasize the importance of strain specificity. This review describes the mechanistic basis of both approaches and descriptively synthesizes their clinical efficacy in UC management based on the clinical studies published between 2018 and 2025. Several studies report that both SSPs and MSPs are associated with clinical improvements, including reduced disease activity, symptom alleviation, and enhanced endoscopic outcomes. Given the methodological heterogeneity across included studies, comparative findings should be interpreted with appropriate caution. A direct head-to-head trial could provide a better understanding to determine the optimal approach. Advancing toward personalized probiotic therapy may further enhance the clinical application of probiotics for disease management. Full article

(This article belongs to the Special Issue Crohn's Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (4th Edition))

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24 pages, 21365 KB

Open AccessArticle

Ellagic Acid Attenuates Gentamicin Nephrotoxicity by Integrated Modulation of ER Stress-Associated Apoptosis-Autophagy Crosstalk and Attenuation of Nrf2/HO-1 Signaling

by Azad Salimi, Mohammad Javad Khoshnoud, Forouzan Khodaei Halani, Shekoofeh Jokar, Samaneh Bina, Seyyed Sajad Daneshi, Marziyeh Haghshenas and Marzieh Rashedinia

Biomedicines 2026, 14(6), 1385; https://doi.org/10.3390/biomedicines14061385 - 19 Jun 2026

Viewed by 574

Abstract

Background: Gentamicin-induced nephrotoxicity limits clinical pharmacotherapy and involves multiple converging stress-response pathways. Ellagic acid (EA) has renoprotective potential, yet its role in coordinating endoplasmic reticulum (ER) stress-mediated apoptosis, autophagy, and inflammation remains unclear. We hypothesized that EA co-treatment would protect the kidney by [...] Read more.

Background: Gentamicin-induced nephrotoxicity limits clinical pharmacotherapy and involves multiple converging stress-response pathways. Ellagic acid (EA) has renoprotective potential, yet its role in coordinating endoplasmic reticulum (ER) stress-mediated apoptosis, autophagy, and inflammation remains unclear. We hypothesized that EA co-treatment would protect the kidney by modulating ER stress-dependent pathways and associated inflammatory and adaptive signaling. Methods: For an integrated mechanistic analysis in a rat model of gentamicin nephrotoxicity, 40 male Sprague-Dawley rats were assigned to control, gentamicin (100 mg/kg), EA (100 mg/kg), and gentamicin + EA groups for 14 days. Renal function, oxidative stress, inflammatory mediators, ER stress markers, apoptosis, autophagy, tubular injury markers, and histopathological changes were assessed. Results: Gentamicin induced renal dysfunction, tubular injury, and ER stress across all unfolded protein response (UPR) branches (IRE1α, PERK, ATF6), C/EBP homologous protein (CHOP)-associated apoptosis, dysregulated autophagy, and upregulated kidney injury molecule-1 (KIM-1). A selective inflammatory signature was observed, with increased cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6), whereas tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) remained unchanged. Co-administration of ellagic acid with gentamicin significantly improved renal function markers compared to the gentamicin group. In contrast, ellagic acid alone did not show significant differences compared to the control group. Notably, gentamicin induced compensatory upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) expression, while ellagic acid co-treatment attenuated this compensatory upregulation, likely secondary to reduced oxidative stress burden. Conclusions: This study provides integrated evidence that ER stress is closely associated with gentamicin nephrotoxicity. The key novel findings include selective suppression of IL-6, modulation of the apoptosis-autophagy balance, and attenuation of Nrf2/HO-1 signaling without direct reactive oxygen species (ROS) scavenging, demonstrating a multi-target framework for EA’s renoprotective effects. These findings suggest that ellagic acid mitigates renal injury in a context-dependent manner rather than confirming a direct causal mechanism. Full article

(This article belongs to the Section Cell Biology and Pathology)

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17 pages, 3122 KB

Open AccessArticle

The Relationship of Vaginal Symptoms and Cervical Inflammation Severity with Cytological Abnormalities and HPV Positivity: A Prospective Observational Study

by Alihan Tigli, Rulin Deniz, Toros Taskin, Guzide Ece Akinci, Sultan Deniz Altindag, Nazli Sener, Yasemin Ercan Degirmenci, Sefer Ustebay, Muhammet Bora Uzuner, Erdem Gurkan, Oguzhan Karakoc and Yakup Baykus

Biomedicines 2026, 14(6), 1384; https://doi.org/10.3390/biomedicines14061384 - 19 Jun 2026

Viewed by 528

Abstract

Background/Objectives: This study aimed to evaluate the association between the clinical parameters of vaginal infection—specifically the presence, type, number of concurrent symptoms, and recurrence frequency—and cervical cytology findings, including inflammation severity, Candida, bacterial vaginosis, cellular abnormalities, and Human Papillomavirus (HPV) positivity. Methods [...] Read more.

Background/Objectives: This study aimed to evaluate the association between the clinical parameters of vaginal infection—specifically the presence, type, number of concurrent symptoms, and recurrence frequency—and cervical cytology findings, including inflammation severity, Candida, bacterial vaginosis, cellular abnormalities, and Human Papillomavirus (HPV) positivity. Methods: This prospective, cross-sectional, observational study included 458 women attending our gynecology outpatient clinic for Pap smear screening. Vaginal symptoms were documented through face-to-face interviews using a structured data collection form. Cervical samples were evaluated via liquid-based cytology by a single, experienced cytopathologist, who was blinded to the clinical data; cellular abnormalities, the degree of inflammation and cytomorphological findings indicative of infection were reported. HPV analysis was performed on the 218 women for whom results were available. Chi-square and trend chi-square tests were used in the statistical analysis. Results: No significant association was found between the clinical parameters of vaginal symptoms—specifically presence, concurrency, and recurrence frequency—and cytological abnormalities, HPV positivity and bacterial vaginosis (p > 0.05). In contrast, the prevalence of moderate-to-severe inflammation was significantly higher in women with vaginal discharge and a greater symptom burden (p < 0.05). Pruritus, dysuria, and vaginal burning were significantly associated with Candida positivity (p < 0.05). However, no significant association was found between the severity of cervical inflammation and abnormal cytology or HPV positivity (p > 0.05). In multivariable logistic regression analyses, neither symptom burden nor cervical inflammation severity was independently associated with abnormal cytology or HPV positivity. Conclusions: Our findings indicate that vaginal symptoms and the severity of cervical inflammation may not serve as definitive or independent discriminatory markers for cellular abnormalities or HPV positivity in this context. Nevertheless, specific symptom patterns may assist clinicians in evaluating localized infectious processes. Consequently, while standard cytological and molecular protocols remain essential for oncogenic screening, evaluating the overall symptom burden provides clinicians with a valuable framework for identifying benign dysbiotic and inflammatory processes. These findings remained consistent after adjustment for major clinical confounders. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics and Therapeutics in Obsterics and Gynaecology (2nd Edition))

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12 pages, 839 KB

Open AccessArticle

Inflammation-Based C-Reactive Protein-to-Albumin Ratio for No-Reflow Prediction in STEMI

by Xhevdet Krasniqi, Altinë Spanca, Gresa Gojani, Josip Vincelj, Blerim Berisha and Aurora Bakalli

Biomedicines 2026, 14(6), 1383; https://doi.org/10.3390/biomedicines14061383 - 18 Jun 2026

Viewed by 500

Abstract

Background: The C-reactive protein/albumin ratio (CAR) has increasingly attracted attention as a reliable predictive marker in patients with acute myocardial infarction (AMI). Purpose: This study aimed to evaluate the predictive value of the CAR for no-reflow development. Methods: A total of 201 patients [...] Read more.

Background: The C-reactive protein/albumin ratio (CAR) has increasingly attracted attention as a reliable predictive marker in patients with acute myocardial infarction (AMI). Purpose: This study aimed to evaluate the predictive value of the CAR for no-reflow development. Methods: A total of 201 patients with STEMI who underwent PCI were included in the study. Admission laboratory tests included CRP, albumin, CK, CK-MB, troponin T, and other biochemical parameters. The CAR was calculated as CRP divided by albumin ×100, while the CUAR was calculated as the base-10 logarithm of CRP × UA divided by albumin. Patients were then divided into two groups based on CAR levels. Results: A total of 201 STEMI patients were included: 106 (52.7%) in the low-CAR group (≤48.4) and 95 (47.3%) in the high-CAR group (>48.4). Significant differences between groups were observed for smoking, albumin, cholesterol, CRP, CUAR, and TIMI flow grade ≤ 2. Logistic regression analysis identified albumin, cholesterol, CRP, BUN, uric acid, CK-MB, CAR, and CUAR as significant predictors of TIMI flow grade. A receiver operating characteristic (ROC) curve of CRP, albumin, CAR, and CUAR was used to plot the true positive rate against the false positive rate across various cut-off points; the area under the curve (AUC) was 0.87 (95% CI, 0.81–0.94, p < 0.0001) for CRP, 0.73 (95% CI, 0.65–0.81, p < 0.0001) for albumin, 0.9 (95% CI, 0.84–0.95, p < 0.0001) for the CAR, and 0.94 (95%, 0.89–0.99, p < 0.0001) for the CUAR. The cut-off values were 2.11 for the CUAR, 48.4 for the CAR, 18 for CRP, and 38 for albumin. Conclusions: The ratio of C-reactive protein to albumin (CAR) may serve as a reliable and clinically accessible marker associated with the no-reflow phenomenon in STEMI patients undergoing PCI. A defined CAR cut-off has been proposed to help stratify patients at increased risk of no-reflow. Full article

(This article belongs to the Special Issue Acute and Chronic Heart Failure: Pathophysiology and New Therapeutic Developments, 3rd Edition)

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18 pages, 18415 KB

Open AccessArticle

Wnt/Chemerin Signaling Involved in Exercise Training Preventing Diaphragm Dysfunction Induced by Cigarette Smoke

by Peijun Li, Jian Li, Yingqi Wang, Xiaoyu Han, Yuanyuan Cao, Meiling Jiang, Yidie Bao, Weibing Wu and Xiaodan Liu

Biomedicines 2026, 14(6), 1382; https://doi.org/10.3390/biomedicines14061382 - 18 Jun 2026

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Abstract

Objectives: The current study examined whether exercise training alleviates cigarette smoke (CS)-induced diaphragm dysfunction by modulating inflammation through the Wnt and Chemerin signaling pathways. Methods: Mechanical stretching was applied for 3 consecutive days to explore the effects on cell proliferation and [...] Read more.

Objectives: The current study examined whether exercise training alleviates cigarette smoke (CS)-induced diaphragm dysfunction by modulating inflammation through the Wnt and Chemerin signaling pathways. Methods: Mechanical stretching was applied for 3 consecutive days to explore the effects on cell proliferation and chemerin/chemokine-like receptor 1 (CMKLR1) expression in C2C12 cells pretreated with lipopolysaccharide. Male wild-type (WT) and CMKLR1 knockout (KO) mice (6–8 weeks old) were exposed to CS for 6 months (1–2 h a day, 6 days a week) to determine the role of chemerin/CMKLR1 in the progression of diaphragm dysfunction. Given that Wnt/β-catenin is a potential modulator of chemerin/CMKLR1, its expression was detected in CS-exposed mice and mice subjected to treadmill exercise training after CS exposure. Wnt/β-catenin agonist lithium chloride (LiCl) and antagonist XAV939 were then intraperitoneally injected into the CS-exposed mice during exercise training to further investigate their potential synergistic effects with exercise training on improving CS-induced diaphragm dysfunction. Isolated diaphragm contraction strength and fiber cross-sectional area were measured to determine the diaphragm dysfunction. Results: Mechanical stretching improved the proliferation level of myoblasts and decreased inflammation and CMKLR1 protein expression (p < 0.05). The KO mice showed diminished diaphragm dysfunction compared with the WT mice after long-term CS exposure. Combined LiCl and exercise training further enhanced the improvement of diaphragmatic isolated strength in mice exposed to CS (p < 0.01), activated the protein degradation and synthesis pathways, and decreased IL-1β level (p < 0.05). Combined XAV939 and exercise training significantly decreased chemerin protein level (p < 0.01). Conclusions: Exercise training can downregulate inflammation levels and improve diaphragm dysfunction in CS-exposed mice, partially by enhancing Wnt expression and reducing abnormally activated chemerin. Full article

(This article belongs to the Special Issue Navigating the Complex Landscape of Non-Communicable Respiratory Diseases: Emerging Challenges and Opportunities)

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11 pages, 864 KB

Open AccessArticle

Pneumococcal Detection and Bacterial Co-Detection in Children After COVID-19: A Two-Year Multiplex PCR Study

by Loredana Stavăr-Matei, Lavinia Țocu, Aurel Nechita, Luiza Camelia Nechita, Oana Mariana Mihailov, Florentin Dimofte and George Țocu

Biomedicines 2026, 14(6), 1381; https://doi.org/10.3390/biomedicines14061381 - 18 Jun 2026

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Abstract

Background: Non-pharmaceutical interventions during the COVID-19 pandemic altered respiratory pathogen circulation, and a bacterial rebound followed once restrictions were lifted. We describe pediatric pneumococcal respiratory infections and their bacterial co-detections in the immediate post-pandemic period. Methods: We retrospectively analyzed respiratory specimens [...] Read more.

Background: Non-pharmaceutical interventions during the COVID-19 pandemic altered respiratory pathogen circulation, and a bacterial rebound followed once restrictions were lifted. We describe pediatric pneumococcal respiratory infections and their bacterial co-detections in the immediate post-pandemic period. Methods: We retrospectively analyzed respiratory specimens from children aged 0–18 years tested with a multiplex real-time PCR panel (Allplex Respiratory Panel, Seegene, Seoul, South Korea; seven bacterial pathogens) restricted to this predefined bacterial spectrum at a tertiary pediatric hospital in Galați, Romania, during 2022 and 2023. A total of 2546 panels were performed in 2022 and 3250 in 2023, allowing pneumococcal positivity rates to be calculated. Proportions are reported with Wilson 95% confidence intervals; associations were tested with Pearson chi-square and Fisher exact tests in SPSS v.23. Results: Children with detected Streptococcus pneumoniae rose from 100 to 415, corresponding to a rise in pneumococcal positivity from 3.9% (100/2546) to 12.8% (415/3250). Among the positive children, pneumococcus–Haemophilus influenzae co-detection increased from 33.0% to 45.1% (odds ratio 1.63, 95% CI 1.02–2.61; p = 0.029), while pneumococcus alone fell from 60.0% to 50.1%. Boys, urban residence, and early childhood predominated, and community-acquired pneumonia diagnoses rose from 61 to 214. No profile–demographic association reached significance (panel–residence 2023, p = 0.063). Conclusions: A post-pandemic rise in pediatric pneumococcal detections and increasing H. influenzae co-detection were observed, supporting syndromic multiplex PCR in rapid pediatric diagnostics and antimicrobial stewardship. Full article

(This article belongs to the Section Microbiology in Human Health and Disease)

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16 pages, 6497 KB

Open AccessArticle

Impact of Vascular Access Type and Obesity on Long-Term Thrombosis and Access Failure in Hemodialysis: A Real-World Cohort Study from the TriNetX Global Collaborative Network

by Hung-Jin Huang, Pao-Ting Wu, Li-Chin Sung, Cai-Mei Zheng and Hui-Wen Chiu

Biomedicines 2026, 14(6), 1380; https://doi.org/10.3390/biomedicines14061380 - 18 Jun 2026

Viewed by 466

Abstract

Background/Objectives: Optimal vascular access remains a critical determinant of outcomes in patients undergoing maintenance hemodialysis. While an arteriovenous fistula (AVF) is generally preferred over an arteriovenous graft (AVG), the impact of obesity and antithrombotic therapy on access-related complications remains incompletely defined. This [...] Read more.

Background/Objectives: Optimal vascular access remains a critical determinant of outcomes in patients undergoing maintenance hemodialysis. While an arteriovenous fistula (AVF) is generally preferred over an arteriovenous graft (AVG), the impact of obesity and antithrombotic therapy on access-related complications remains incompletely defined. This study evaluated the association between vascular access type, obesity status, and adverse outcomes in a large real-world cohort. Methods: We conducted a retrospective cohort study using de-identified electronic health record data from the TriNetX Global Collaborative Network. Adult patients (≥18 years) receiving maintenance hemodialysis were stratified by vascular access type (AVF vs. AVG), body mass index (normal: 18.5–24.9 kg/m², obese: ≥30 kg/m²), and antithrombotic medication exposure. Propensity score matching (1:1) was performed within BMI strata. Primary outcomes included vascular access thrombosis, AVG failure, and AVF failure. Time-to-event analyses used Kaplan–Meier and Cox proportional hazards models. Results: AVG was associated with significantly higher rates of thrombosis and access failure compared with AVF in both obese and normal-weight cohorts (all p < 0.0001). In patients with obesity, thrombosis rates increased from 10.47% (AVF) to 17.54% (AVG) at 3 months to 34.32% versus 42.24% at 5 years. Kaplan–Meier analysis demonstrated early and persistent separation of thrombosis-free survival curves, with AVG associated with increased risk (HR 1.23; 95% CI, 1.07–1.41; log-rank p = 0.0001). Antithrombotic therapy reduced absolute risks but did not eliminate the relative disadvantage of AVG. Conclusions: In this large real-world cohort, AVG was consistently associated with higher risks of thrombosis and access failure compared with AVF, regardless of obesity status or medication exposure. These findings support preferential use of AVF and highlight the need for individualized vascular access strategies in patients undergoing hemodialysis. Full article

(This article belongs to the Special Issue Nephrotic Syndrome: Pathomechanism, Diagnostics and Novel Treatment Options—2nd Edition)

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34 pages, 1837 KB

Open AccessReview

Non-ST-Elevation Myocardial Infarction: A Heterogeneous Syndrome with Evolving Management—A Narrative Review

by Silviu Raul Muste, Elena Emilia Babes, Cristiana Bustea, Luciana Dobjanschi, Francesca Andreea Muste and Dana Carmen Zaha

Biomedicines 2026, 14(6), 1379; https://doi.org/10.3390/biomedicines14061379 - 18 Jun 2026

Cited by 1 | Viewed by 827

Abstract

Non-ST-segment elevation myocardial infarction (NSTEMI) has become the predominant form of acute coronary syndrome (ACS) and is frequently associated with multivessel coronary artery disease (MVD). Patients presenting with NSTEMI and MVD represent a particularly high-risk population characterized by advanced age, comorbidities, and an [...] Read more.

Non-ST-segment elevation myocardial infarction (NSTEMI) has become the predominant form of acute coronary syndrome (ACS) and is frequently associated with multivessel coronary artery disease (MVD). Patients presenting with NSTEMI and MVD represent a particularly high-risk population characterized by advanced age, comorbidities, and an increased atherosclerotic burden. Although advances in pharmacological therapy and early invasive management have improved prognosis, the optimal revascularization strategy in this setting remains uncertain. In contrast to ST-segment elevation myocardial infarction (STEMI), where randomized controlled trials consistently support complete revascularization, evidence in NSTEMI with MVD is limited and is largely derived from observational studies and registry data. This has generated ongoing debate regarding whether complete revascularization offers superior outcomes compared with culprit-only percutaneous coronary intervention (PCI), and whether non-culprit lesions should be treated during the index procedure (immediate strategy) or in a staged manner. Current data suggest that complete PCI is generally associated with reduced recurrent ischemia, reinfarction, and repeat revascularization, with potential long-term survival benefits. However, patient comorbidities, lesion complexity, and procedural risk continue to influence outcomes, highlighting the importance of individualized decision-making. This narrative review synthesizes contemporary evidence on PCI-based revascularization strategies in NSTEMI with MVD, focusing on two central aspects: the extent of revascularization (complete versus incomplete) and the timing of intervention (single-stage versus staged). By integrating findings from registries, randomized trials and guideline recommendations, the review identifies areas of consensus, persisting uncertainties, and key evidence gaps. Ultimately, it underscores the need for large, dedicated trials to guide practice and optimize outcomes for NSTEMI patients with multivessel coronary disease. Full article

(This article belongs to the Special Issue Feature Reviews on Cardiovascular and Metabolic Diseases)

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Biomedicines, Volume 14, Issue 6 (June 2026) – 232 articles

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