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Search Results (459)

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15 pages, 993 KB  
Review
Antioxidants in Cardiovascular Health: Implications for Disease Modeling Using Cardiac Organoids
by Gracious R. Ross and Ivor J. Benjamin
Antioxidants 2025, 14(10), 1202; https://doi.org/10.3390/antiox14101202 - 3 Oct 2025
Abstract
Cardiovascular disease remains the leading cause of mortality worldwide, and at its molecular core lies a silent disruptor: oxidative stress. This imbalance between reactive oxygen species (ROS) and antioxidant defenses not only damages cellular components but also orchestrates a cascade of pathological events [...] Read more.
Cardiovascular disease remains the leading cause of mortality worldwide, and at its molecular core lies a silent disruptor: oxidative stress. This imbalance between reactive oxygen species (ROS) and antioxidant defenses not only damages cellular components but also orchestrates a cascade of pathological events across diverse cardiac cell types. In cardiomyocytes, ROS overload impairs contractility and survival, contributing to heart failure and infarction. Cardiac fibroblasts respond by promoting fibrosis through excessive collagen deposition. Macrophages intensify inflammatory responses, such as atherosclerosis, via ROS-mediated lipid oxidation—acting both as mediators of damage and targets for antioxidant intervention. This review examines how oxidative stress affects cardiac cell types and evaluates antioxidant-based therapeutic strategies. Therapeutic approaches include natural antioxidants (e.g., polyphenols and vitamins) and synthetic agents (e.g., enzyme modulators), which show promise in experimental models by improving myocardial remodeling. However, clinical trials reveal inconsistent outcomes, underscoring translational challenges (e.g., clinical biomarkers). Emerging strategies—such as targeted antioxidant delivery, activation of endogenous pathways, and disease modeling using 3D organoids—aim to enhance efficacy. In conclusion, we spotlight innovative technologies—like lab-grown heart tissue models—that help scientists better understand how oxidative stress affects heart health. These tools are bridging the gap between early-stage research and personalized medicine, opening new possibilities for diagnosing and treating heart disease more effectively. Full article
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16 pages, 1586 KB  
Article
Intranasal 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Administration Hampered Contractile Response of Dopamine in Isolated Rat Ileum
by Ana Silva, Sofia Viana, Inês Pita, Cristina Lemos, Filipe C. Matheus, Lina Carvalho, Carlos A. Fontes Ribeiro, Rui D. Prediger, Frederico C. Pereira and Sónia Silva
Biomedicines 2025, 13(10), 2400; https://doi.org/10.3390/biomedicines13102400 - 30 Sep 2025
Abstract
Background: Gastrointestinal (GI) disturbances occur frequently in the early premotor stage of Parkinson’s disease (PD). These GI impairments are associated, at least in part, with dopaminergic dysfunction in the myenteric plexus. However, the enteric nervous system (ENS) pathophysiology underlying GI dysfunction in [...] Read more.
Background: Gastrointestinal (GI) disturbances occur frequently in the early premotor stage of Parkinson’s disease (PD). These GI impairments are associated, at least in part, with dopaminergic dysfunction in the myenteric plexus. However, the enteric nervous system (ENS) pathophysiology underlying GI dysfunction in PD has been overlooked. Objectives: The aim of this study was to evaluate the premotor GI disturbances in rats submitted to intranasal (i.n.) MPTP, a valid experimental model of the premotor stage of PD. Methods: Ileum segments from male Wistar rats (21 weeks old) were collected 12 days following the i.n. MPTP administration for functional studies. Isometric contractile concentration–response (CR) curves (cumulative) for dopamine (DA) were performed in both the presence and absence of sulpiride, a selective dopamine D2-like receptor (D2R) antagonist. Results: Functional studies showed that DA induced a concentration-dependent contractile response in the ileum, which exhibited marked contraction at lower concentrations (0.01–0.9 µM) and relaxation at higher concentrations (3–90 µM). MPTP significantly attenuated both the contraction and the ensuing relaxation. Furthermore, sulpiride significantly reduced the contractile response to DA in the control group and blocked the relaxation in the MPTP group. The MPTP-induced dysmotility occurred with preserved DA homeostasis, as shown by normal DA, TH, and D2R ileal levels in the MPTP group. However, MPTP seemed to impose a decrease in S100β and GFAP (enteroglial markers) immunostaining in the ileal myenteric plexus. Conclusions: In summary, we provide pioneering functional, neurochemical, and morphological evidence showing that rats submitted to the i.n. MPTP model exhibited premotor DA-dependent ileum motile dysfunction accompanied by enteroglial disturbance within the myenteric plexus, but with preserved DA markers. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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16 pages, 823 KB  
Review
Diverse Biological Processes Contribute to Transforming Growth Factor β-Mediated Cancer Drug Resistance
by James P. Heiserman and Rosemary J. Akhurst
Cells 2025, 14(19), 1518; https://doi.org/10.3390/cells14191518 - 28 Sep 2025
Abstract
Therapy resistance is a major obstacle to cancer treatment, and transforming growth factor-beta (TGF-β) signaling has emerged as a major instigator across many cancer types and therapeutic regimens. Solid tumors overexpress TGF-β ligands, and canonical and non-canonical TGF-β signaling pathways drive molecular changes [...] Read more.
Therapy resistance is a major obstacle to cancer treatment, and transforming growth factor-beta (TGF-β) signaling has emerged as a major instigator across many cancer types and therapeutic regimens. Solid tumors overexpress TGF-β ligands, and canonical and non-canonical TGF-β signaling pathways drive molecular changes in most cell types within the tumor to hijack therapeutic responses. Cancer therapies further stimulate TGF-β release to potentiate this problem. Molecular mechanisms of TGF-β action supporting resistance include upregulation of drug efflux pumps, enhanced DNA Damage Repair, elaboration of stiffened extracellular matrix, and decreased neoantigen presentation. TGF-β also activates pro-survival pathways, such as epidermal growth factor receptor, B-cell lymphoma-2 expression, and AKT-mTOR signaling. TGF-β-induced epithelial-to-mesenchymal transformation leads to tumor heterogeneity and acquisition of stem-like states. In the tumor microenvironment, TGF-β induces extracellular matrix production, contractility, and secretion of immunosuppressive cytokines by cancer-associated fibroblasts that contribute to drug resistance. TGF-β also blunts cytotoxic T and NK cell activities and stimulates recruitment and differentiation of immunosuppressive cells, including T-regulatory cells, M2 macrophages, and myeloid-derived suppressor cells. The importance of TGF-β signaling in development of drug resistance cannot be understated and should be further explored mechanistically to identify novel molecular approaches and combinatorial drug dosing strategies to prevent drug-resistance. Full article
(This article belongs to the Section Cell Signaling)
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26 pages, 3132 KB  
Article
Revealing the Specific Contributions of Mitochondrial CB1 Receptors to the Overall Function of Skeletal Muscle in Mice
by Zoltán Singlár, Péter Szentesi, Nyamkhuu Ganbat, Barnabás Horváth, László Juhász, Mónika Gönczi, Anikó Keller-Pintér, Attila Oláh, Zoltán Máté, Ferenc Erdélyi, László Csernoch and Mónika Sztretye
Cells 2025, 14(19), 1517; https://doi.org/10.3390/cells14191517 - 28 Sep 2025
Abstract
Skeletal muscle, constituting 40–50% of total body mass, is vital for mobility, posture, and systemic homeostasis. Muscle contraction heavily relies on ATP, primarily generated by mitochondrial oxidative phosphorylation. Mitochondria play a key role in decoding intracellular calcium signals. The endocannabinoid system (ECS), including [...] Read more.
Skeletal muscle, constituting 40–50% of total body mass, is vital for mobility, posture, and systemic homeostasis. Muscle contraction heavily relies on ATP, primarily generated by mitochondrial oxidative phosphorylation. Mitochondria play a key role in decoding intracellular calcium signals. The endocannabinoid system (ECS), including CB1 receptors (CB1Rs), broadly influences physiological processes and, in muscles, regulates functions like energy metabolism, development, and repair. While plasma membrane CB1Rs (pCB1Rs) are well-established, a distinct mitochondrial CB1R (mtCB1R) population also exists in muscles, influencing mitochondrial oxidative activity and quality control. We investigated the role of mtCB1Rs in skeletal muscle physiology using a novel systemic mitochondrial CB1 deletion murine model. Our in vivo studies showed no changes in motor function, coordination, or grip strength in mtCB1 knockout mice. However, in vitro force measurements revealed significantly reduced specific force in both fast-twitch (EDL) and slow-twitch (SOL) muscles following mtCB1R ablation. Interestingly, knockout EDL muscles exhibited hypertrophy, suggesting a compensatory response to reduced force quality. Electron microscopy revealed significant mitochondrial morphological abnormalities, including enlargement and irregular shapes, correlating with these functional deficits. High-resolution respirometry further demonstrated impaired mitochondrial respiration, with reduced oxidative phosphorylation and electron transport system capacities in knockout mitochondria. Crucially, mitochondrial membrane potential dissipated faster in mtCB1 knockout muscle fibers, whilst mitochondrial calcium levels were higher at rest. These findings collectively establish that mtCB1Rs are critical for maintaining mitochondrial health and function, directly impacting muscle energy production and contractile performance. Our results provide new insights into ECS-mediated regulation of skeletal muscle function and open therapeutic opportunities for muscle disorders and aging. Full article
(This article belongs to the Special Issue Skeletal Muscle: Structure, Physiology and Diseases)
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16 pages, 3063 KB  
Article
A Newly Discovered Obolenskvirus Phage with Sustained Lytic Activity Against Multidrug-Resistant Acinetobacter baumannii
by Eduardo Vera-Jauregui, María Guadalupe Avila-Novoa, Berenice González-Torres, Pedro Javier Guerrero-Medina, Cristobal Chaidez, Irvin González-López, Jean Pierre González-Gómez and Melesio Gutiérrez-Lomelí
Antibiotics 2025, 14(10), 961; https://doi.org/10.3390/antibiotics14100961 - 24 Sep 2025
Viewed by 11
Abstract
Background: Acinetobacter baumannii is a highly concerning pathogen in hospital settings, responsible for severe infections such as ventilator-associated pneumonia, urinary tract infections, and meningitis. Its remarkable genetic plasticity facilitates the rapid acquisition of antibiotic resistance, significantly complicating treatment and increasing mortality rates. [...] Read more.
Background: Acinetobacter baumannii is a highly concerning pathogen in hospital settings, responsible for severe infections such as ventilator-associated pneumonia, urinary tract infections, and meningitis. Its remarkable genetic plasticity facilitates the rapid acquisition of antibiotic resistance, significantly complicating treatment and increasing mortality rates. As multidrug-resistant (MDR) infections continue to rise, phage therapy emerges as a viable alternative. Methods: This study reports the isolation and characterization of Acinetobacter phage vB_AbaM_A72 from stagnant water in Jalisco, Mexico. Results: Transmission electron microscopy revealed a myovirus-like morphology with an icosahedral head (91.32 ± 0.12 nm) and a contractile tail (123.77 ± 0.19 nm). The phage exhibited high environmental resilience, tolerating temperatures up to 60 °C and pH ranging from 5 to 11. Notably, A72 demonstrated a narrow host range but effectively inhibited the growth of an MDR A. baumannii strain for at least 12 h across different multiplicities of infection. Whole-genome sequencing confirmed the absence of virulence, antibiotic resistance, or lysogeny-associated genes. Comparative genomic analysis identified A72 as the first member of a newly described Obolenskvirus species, sharing only 76.4% similarity with its closest relatives. Conclusions: These findings underscore the importance of fully characterizing novel bacteriophages to expand therapeutic libraries and reinforce the feasibility of phage therapy as a promising approach against MDR A. baumannii infections. Full article
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35 pages, 1792 KB  
Review
Time to Reset: The Interplay Between Circadian Rhythms and Redox Homeostasis in Skeletal Muscle Ageing and Systemic Health
by Elizabeth Sutton and Vanja Pekovic-Vaughan
Antioxidants 2025, 14(9), 1132; https://doi.org/10.3390/antiox14091132 - 18 Sep 2025
Viewed by 621
Abstract
Skeletal muscle plays vital roles in locomotion, metabolic regulation and endocrine signalling. Critically, it undergoes structural and functional decline with age, leading to a progressive loss of muscle mass and strength (sarcopenia) and contributing to a systemic loss of tissue resilience to stressors [...] Read more.
Skeletal muscle plays vital roles in locomotion, metabolic regulation and endocrine signalling. Critically, it undergoes structural and functional decline with age, leading to a progressive loss of muscle mass and strength (sarcopenia) and contributing to a systemic loss of tissue resilience to stressors of multiple tissue systems (frailty). Emerging evidence implicates misalignments in both the circadian molecular clock and redox homeostasis as major drivers of age-related skeletal muscle deterioration. The circadian molecular clock, through core clock components such as BMAL1 and CLOCK, orchestrates rhythmic gene, protein and myokine expression impacting diurnal regulation of skeletal muscle structure and metabolism, mitochondrial function, antioxidant defence, extracellular matrix organisation and systemic inter-tissue communication. In parallel, the master redox regulator, NRF2, maintains cellular antioxidant defence, tissue stress resistance and mitochondrial health. Disruption of either system impairs skeletal muscle contractility, metabolism, and regenerative capacity as well as systemic homeostasis. Notably, NRF2-mediated redox signalling is clock-regulated and, in turn, affects circadian clock regulation. Both systems are responsive to external cues such as exercise and hormones, yet studies do not consistently include circadian timing or biological sex as key methodological variables. Given that circadian regulation shifts with age and differs between sexes, aligning exercise interventions with one’s own chronotype may enhance health benefits, reduce adverse side effects, and overcome anabolic resistance with ageing. This review highlights the essential interplay between circadian and redox systems in skeletal muscle homeostasis and systemic health and argues for incorporating personalised chrono-redox approaches and sex-specific considerations into future experimental research and clinical studies, aiming to improve functional outcomes in age-related sarcopenia and broader age-related metabolic and musculoskeletal conditions. Full article
(This article belongs to the Special Issue Antioxidant Response in Skeletal Muscle)
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24 pages, 2857 KB  
Article
Effects of 17β-Estradiol Treatment on Metabolic Function and Aortic Relaxation in Castrated Male Rats
by Rifat Ara Islam, Md Rahatullah Razan, Ankita Poojari, Mohammad Moshiur Rahman, Hao Wei, Hana S. Alhamadsheh, Melanie Felmlee, Atefeh Rabiee, Mitra Esfandiarei and Roshanak Rahimian
Int. J. Mol. Sci. 2025, 26(18), 8885; https://doi.org/10.3390/ijms26188885 - 12 Sep 2025
Viewed by 254
Abstract
Exogenous estrogen use in male-to-female individuals has been linked to increased cardiovascular disease risk, though the mechanisms remain unclear. This study examines the effects of 17β-estradiol (E2) on metabolic and aortic function in castrated (CAS) male Sprague Dawley rats. CAS rats [...] Read more.
Exogenous estrogen use in male-to-female individuals has been linked to increased cardiovascular disease risk, though the mechanisms remain unclear. This study examines the effects of 17β-estradiol (E2) on metabolic and aortic function in castrated (CAS) male Sprague Dawley rats. CAS rats received subcutaneous E2 (CAS + E2) or placebo (CAS + PL) pellets for ~35 days, with intact males serving as controls. Endothelium-dependent vasorelaxation (EDV) in response to acetylcholine and contractile responses to phenylephrine were measured in aorta before and after pharmacological inhibitors. Metabolic parameters and expression of proteins associated with vascular and insulin signaling were also determined in aorta and white adipose tissue (WAT). E2 treatment reduced body weight, improved HbA1c and enhanced glucose tolerance in CAS rats compared to the CAS + PL group. Improved glucose homeostasis was associated with upregulation of estrogen receptor alpha, phosphorylated Akt/Akt, and glucose transporter-4 expression in WAT. However, E2 increased plasma triglyceride and impaired EDV, indicating compromised vascular function. Our results suggest that impaired aortic relaxation in the CAS + E2 group may be partly attributable to increased contractility. Additionally, we observed reduced G protein-coupled estrogen receptor and elevated inducible nitric oxide synthase expression, warranting further investigation into whether these factors contribute to the effects of E2 on aortic relaxation. Full article
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13 pages, 2858 KB  
Article
A Single-Nucleus Transcriptomic Atlas of Human Supernumerary Tooth Pulp Reveals Lineage Diversity and Transcriptional Heterogeneity Using PCA-Based Analysis
by Eungyung Lee and In-Ryoung Kim
Appl. Sci. 2025, 15(18), 9900; https://doi.org/10.3390/app15189900 - 10 Sep 2025
Viewed by 270
Abstract
(1) Background: Supernumerary teeth are developmental anomalies, and their pulp tissue may harbor unique cellular and molecular features. However, the biology of this rare tissue remains poorly understood. This study aimed to characterize the cellular diversity and regenerative potential of supernumerary pulp at [...] Read more.
(1) Background: Supernumerary teeth are developmental anomalies, and their pulp tissue may harbor unique cellular and molecular features. However, the biology of this rare tissue remains poorly understood. This study aimed to characterize the cellular diversity and regenerative potential of supernumerary pulp at single-nucleus resolution. (2) Methods: Human supernumerary tooth pulp samples were analyzed using single-nucleus RNA sequencing. Gene expression profiles were processed and reduced to their main patterns of variation using principal component analysis (PCA), supported by clustering, pathway analysis, and lineage-specific scoring. (3) Results: The analysis suggested two dominant biological programs: a vascular–immune/stress axis and an extracellular matrix (ECM)/contractile remodeling axis. Vascular lineages were closely linked to immune and stress responses, while mesenchymal and perivascular populations were enriched in ECM-related pathways. Neural and glial contributions were relatively minor. (4) Conclusions: These findings suggest that supernumerary pulp appears to preserve key regenerative features similar to normal pulp, but with potential reinforcement of vascular–immune coupling and ECM remodeling. This work represents the first single-nucleus transcriptomic reference for supernumerary pulp, offering a foundation for future studies on dental pulp regeneration. Full article
(This article belongs to the Section Applied Dentistry and Oral Sciences)
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15 pages, 2796 KB  
Article
Liraglutide Increases Gastric Fundus Tonus and Reduces Food Intake in Type 2 Diabetic Rats
by Ana Catarina Carrêlo, Beatriz Martins, Raquel Seiça, Carlos Fontes-Ribeiro, Paulo Matafome and Sónia Silva
Diabetology 2025, 6(9), 96; https://doi.org/10.3390/diabetology6090096 - 5 Sep 2025
Viewed by 1281
Abstract
Background/Objectives: Incretin-based therapies have demonstrated benefits in glycemic control and the prevention of long-term complications of diabetes. In addition to glucose-dependent insulin secretion stimulation, glucagon-like peptide-1 (GLP-1) also inhibits gastric acid secretion, delays gastric emptying, inhibits gut motility and induces satiety. We aimed [...] Read more.
Background/Objectives: Incretin-based therapies have demonstrated benefits in glycemic control and the prevention of long-term complications of diabetes. In addition to glucose-dependent insulin secretion stimulation, glucagon-like peptide-1 (GLP-1) also inhibits gastric acid secretion, delays gastric emptying, inhibits gut motility and induces satiety. We aimed to understand the modulation of gastric fundus motility by GLP-1 receptor agonists (GLP-1RA). Methods: We have studied the relaxation to sodium nitroprusside (SNP) and noradrenaline (NA) of gastric fundus isolated from Wistar rats and Goto-Kakizaki (GK) rats, an animal model of spontaneous non-obese type 2 diabetes, after Liraglutide treatment (200 μg/kg s.c., b.i.d., 14 days). Results: Decreased relaxation induced by SNP and NA (0.01–889 μM) was observed in treated groups, with no significant changes in SNP maximum relaxation or in nNOS/p-nNOS levels between treated and non-treated rats of both animal models. Accordingly, in rat gastric fundus pre-contracted with 5 µM of carbachol, GLP-1RA (0.05–111.1 nM) induced contractile responses that were GLP-1R-dependent and -independent. Exenatide showed more intrinsic activity, while Liraglutide showed more potency than GLP-1 in Wistar rats. Moreover, GLP-1 showed more intrinsic activity in diabetic rats compared to control ones. Conclusions: Liraglutide-induced increased gastric muscle tone may contribute to the significant decrease in caloric intake and body weight in all treated rats, causing a reduction in gastric accommodation during food intake. Thus, the increased gastric fundus tone induced by GLP-1RA may constitute a peripheral mechanism by which they can reduce food intake and induce satiety. Full article
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24 pages, 3012 KB  
Review
Cellular and Molecular Mechanisms of VSMC Phenotypic Switching in Type 2 Diabetes
by Shreya Gupta, Gilbert Hernandez and Priya Raman
Cells 2025, 14(17), 1365; https://doi.org/10.3390/cells14171365 - 2 Sep 2025
Viewed by 862
Abstract
Vascular smooth muscle cells (VSMCs) are a major cell type in the arterial wall responsible for regulating vascular homeostasis. Under physiological conditions, VSMCs reside in the medial layer of the arteries, express elevated levels of contractile proteins, regulate vascular tone, and provide mechanical [...] Read more.
Vascular smooth muscle cells (VSMCs) are a major cell type in the arterial wall responsible for regulating vascular homeostasis. Under physiological conditions, VSMCs reside in the medial layer of the arteries, express elevated levels of contractile proteins, regulate vascular tone, and provide mechanical strength and elasticity to the blood vessel. In response to obesity, hyperglycemia, and insulin resistance, critical pathogenic hallmarks of Type 2 diabetes (T2D), VSMCs undergo a phenotypic transformation, adopting new phenotypes with increased proliferative (synthetic), inflammatory (macrophage-like), or bone-like (osteogenic) properties. While crucial for normal repair and vascular adaptation, VSMC phenotypic plasticity is a key driver for the development and progression of macrovascular complications associated with T2D. Despite advances in lineage tracing and multi-omics profiling that have uncovered key molecular regulators of VSMC phenotypic switching in vasculopathy, our understanding of the cellular and molecular mechanisms underlying VSMC transformation into diseased phenotypes in T2D remains incomplete. This review will provide a holistic summary of research from the past 15 years, with a focus on the signaling pathways and transcriptional regulators that govern VSMC phenotypic transition in response to obesity, hyperglycemia, and insulin resistance. We examine the integrated molecular mechanisms that orchestrate VSMC fate reprogramming in T2D and highlight the dynamic interplay among diverse signaling and transcriptional networks. Emphasis is placed on how these interconnected pathways collectively influence VSMC behavior and contribute to the pathogenesis of T2D-associated atherosclerosis. Full article
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14 pages, 3444 KB  
Article
Investigating the Pharmacological Impact of Atosiban, an Oxytocin Receptor Antagonist, on Bladder and Prostate Contractions Within OBESE and Non-Obese Rats
by Masroor Badshah, Jibriil Ibrahim, Nguok Su, Penny Whiley, Sarah M. Turpin-Nolan, Khaled A. Elnahriry, Ralf Middendorff, Michael Whittaker and Betty Exintaris
Biomedicines 2025, 13(9), 2097; https://doi.org/10.3390/biomedicines13092097 - 28 Aug 2025
Viewed by 641
Abstract
Background/Objectives: Lower urinary tract symptoms (LUTS), such as frequency, urgency, nocturia, and urge incontinence, are commonly linked to overactive bladder (OAB) and benign prostatic hyperplasia (BPH). Oxytocin receptor (OXTR) upregulation has been proposed to enhance bladder and prostate contractility, while obesity is a [...] Read more.
Background/Objectives: Lower urinary tract symptoms (LUTS), such as frequency, urgency, nocturia, and urge incontinence, are commonly linked to overactive bladder (OAB) and benign prostatic hyperplasia (BPH). Oxytocin receptor (OXTR) upregulation has been proposed to enhance bladder and prostate contractility, while obesity is a recognized risk factor for LUTS, OAB, and BPH. This study aimed to investigate whether the OXTR antagonist atosiban attenuates spontaneous and oxytocin-induced contractions in bladder and prostate tissues from obese and non-obese rats. Methods: Bladder and prostate tissues were obtained from obese and non-obese rats and studied in in vitro organ bath preparations. The effects of atosiban (1 µM and 10 µM) on spontaneous contractility and oxytocin-induced responses were examined. Immunohistochemistry was performed to evaluate OXTR expression in the bladder. Results: Atosiban significantly reduced spontaneous contractions in the bladder (p < 0.0001 in obese; p < 0.01 in non-obese) and prostate (p < 0.01 in obese; p < 0.0001 in non-obese). Oxytocin-induced bladder contractions were significantly increased in obese rats but were attenuated by atosiban at 10 µM (p < 0.05), an effect absent in non-obese rats. Immunohistochemical analysis confirmed elevated OXTR expression in both epithelial and stromal compartments of the bladder in obese rats (p < 0.05). Conclusions: These findings indicate that oxytocin contributes to bladder and prostate hypercontractility, particularly in obesity. Targeting OXTR with atosiban may represent a novel therapeutic strategy for the management of LUTS, OAB, and BPH. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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35 pages, 2589 KB  
Review
Sophisticated Interfaces Between Biosensors and Organoids: Advancing Towards Intelligent Multimodal Monitoring Physiological Parameters
by Yuqi Chen, Shuge Liu, Yating Chen, Miaomiao Wang, Yage Liu, Zhan Qu, Liping Du and Chunsheng Wu
Biosensors 2025, 15(9), 557; https://doi.org/10.3390/bios15090557 - 22 Aug 2025
Viewed by 1662
Abstract
The integration of organoids with biosensors serves as a miniaturized model of human physiology and diseases, significantly transforming the research frameworks surrounding drug development, toxicity testing, and personalized medicine. This review aims to provide a comprehensive framework for researchers to identify suitable technical [...] Read more.
The integration of organoids with biosensors serves as a miniaturized model of human physiology and diseases, significantly transforming the research frameworks surrounding drug development, toxicity testing, and personalized medicine. This review aims to provide a comprehensive framework for researchers to identify suitable technical approaches and to promote the advancement of organoid sensing towards enhanced biomimicry and intelligence. To this end, several primary methods for technology integration are systematically outlined and compared, which include microfluidic integrated systems, microelectrode array (MEA)-based electrophysiological recording systems, optical sensing systems, mechanical force sensing technologies, field-effect transistor (FET)-based sensing techniques, biohybrid systems based on synthetic biology tools, and label-free technologies, including impedance, surface plasmon resonance (SPR), and mass spectrometry imaging. Through multimodal collaboration such as the combination of MEA for recording electrical signals from cardiac organoids with micropillar arrays for monitoring contractile force, these technologies can overcome the limitations inherent in singular sensing modalities and enable a comprehensive analysis of the dynamic responses of organoids. Furthermore, this review discusses strategies for integrating strategies of multimodal sensing approaches (e.g., the combination of microfluidics with MEA and optical methods) and highlights future challenges related to sensor implantation in vascularized organoids, signal stability during long-term culture, and the standardization of clinical translation. Full article
(This article belongs to the Special Issue Feature Papers of Biosensors)
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10 pages, 260 KB  
Article
Video Urodynamic Predictors of Outcomes After Urethral Sphincter Botulinum Toxin A Injection in Spinal Cord-Injured Patients with Detrusor Sphincter Dyssynergia
by Cheng-Ling Lee and Hann-Chorng Kuo
Toxins 2025, 17(8), 412; https://doi.org/10.3390/toxins17080412 - 15 Aug 2025
Viewed by 864
Abstract
Purpose: Detrusor sphincter dyssynergia (DSD), a common lower urinary tract condition in patients with suprasacral spinal cord injury (SCI), can lead to urological complications and reduced quality of life. Urethral sphincter botulinum toxin A (BoNT-A) injection has been used to promote spontaneous voiding, [...] Read more.
Purpose: Detrusor sphincter dyssynergia (DSD), a common lower urinary tract condition in patients with suprasacral spinal cord injury (SCI), can lead to urological complications and reduced quality of life. Urethral sphincter botulinum toxin A (BoNT-A) injection has been used to promote spontaneous voiding, albeit with limited success. This study aimed to identify predictive factors for treatment success. Methods: This retrospective analysis included 207 patients (157 males and 50 females) with chronic SCI and varying DSD grades treated with urethral sphincter BoNT-A injection. Each received 100 U of onabotulinumtoxinA via transurethral sphincter injection. The primary outcome was voiding efficiency (VE) and symptom improvement, assessed via global response evaluation 3 months post-treatment. Baseline videourodynamic parameters were used to predict success. Results: Successful outcomes were observed in 33.8% of patients. These patients were older and had higher voiding pressure, maximum flow rate (Qmax), voided volume, bladder contractility index, and VE, as well as lower post-void residual (PVR) volume and bladder outlet obstruction index. Patients with SCI and DSD grade 1 had the highest success rate (65.7%) compared to those with DSD grade 2 (14.3%) or 3 (7.1%). Patients with DSD grade 3 had the highest failure rate (55.8%). Multivariate analysis showed that higher Qmax and lower PVR significantly predicted success, consistent with lower DSD grades. Conclusion: Grade 1 DSD, higher Qmax, and lower PVR were associated with higher success after urethral BoNT-A injection, whereas grade 3 DSD predicted failure. Thus, careful patient selection is essential for effective DSD treatment with urethral BoNT-A injection. Full article
18 pages, 2752 KB  
Article
Primary Dysmenorrhea Induced Using Diethylstilbestrol and Oxytocin Induces Impaired Uterine Reactivity in Virgin Female Wistar Rats
by Francisco Fernandes Lacerda-Júnior, Petruska Pessoa da Silva Souza, Paula Benvindo Ferreira, Anderson Fellyp Avelino Diniz, Bárbara Cavalcanti Barros, Maria da Conceição Correia Silva, Adriano Francisco Alves, Alexandre Sérgio Silva and Bagnólia Araújo da Silva
Pharmaceuticals 2025, 18(8), 1191; https://doi.org/10.3390/ph18081191 - 13 Aug 2025
Viewed by 624
Abstract
Background/Objectives: Primary dysmenorrhea (DysP) is a prevalent gynecological condition characterized by painful uterine contractions. However, the underlying mechanism of action of dysmenorrhea has not been fully elucidated. This study aimed to standardize an animal model of dysmenorrhea using diethylstilbestrol and oxytocin to mimic [...] Read more.
Background/Objectives: Primary dysmenorrhea (DysP) is a prevalent gynecological condition characterized by painful uterine contractions. However, the underlying mechanism of action of dysmenorrhea has not been fully elucidated. This study aimed to standardize an animal model of dysmenorrhea using diethylstilbestrol and oxytocin to mimic pathophysiological mechanisms in female Wistar rats. Methods: For the induction of dysmenorrhea, diethylstilbestrol (s.c.) and oxytocin (i.p.) were used. Results: The model effectively reproduced hypercontractility and impaired uterine relaxation. The in vivo evaluations demonstrated increased pain responses (DysP group = 119 ± 6.9; control group CG = 3.0 ± 1.0), which were partially attenuated by standard medications (scopolamine/dipyrone and ibuprofen). In vitro assays revealed greater contractile reactivity when compared to that in the control group, in the DysP group, using oxytocin (pEC50 = 3.6 ± 0.2 and Emax = 145.1 ± 8.7; CG (pEC50 = 3.1 ± 0.1 and Emax = 100%); KCl (DysP pEC50 = 2.2 ± 0.1 and Emax = 164 ± 8.0); CG (pEC50 = 1.8 ± 0.1) and PGF (DysP pEC50 = 7.4 ± 0.2 and Emax = 127.3 ± 15.6); CG (pEC50 = 6.2 ± 0.1)), while the relaxation responses to isoprenaline and nifedipine were decreased compared to those in the CG. The model promoted an imbalance in oxidative stress by increasing malondialdehyde (MDA) levels and reducing the total antioxidant capacity (TAC) in the uterine tissue. Conclusions: These findings suggest that the new virgin rat model is capable of replicating key aspects of the clinical features of DysP in humans and offers a valuable tool for studying its pathogenetic mechanisms and testing potential therapeutic agents. Full article
(This article belongs to the Special Issue Potential Therapeutic Targets for the Treatment of Pathological Pain)
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20 pages, 6154 KB  
Article
Age-Related Mitochondrial Alterations Contribute to Myocardial Responses During Sepsis
by Jiayue Du, Qing Yu, Olufisayo E. Anjorin and Meijing Wang
Cells 2025, 14(15), 1221; https://doi.org/10.3390/cells14151221 - 7 Aug 2025
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Abstract
Sepsis-induced myocardial injury is age-related and leads to increased mortality. Considering the importance of mitochondrial dysfunction in cardiac impairment, we aimed to investigate whether aging exacerbates the cardiac mitochondrial metabolic response to inflammation, thus leading to increased cardiac dysfunction in the elderly. Cecal [...] Read more.
Sepsis-induced myocardial injury is age-related and leads to increased mortality. Considering the importance of mitochondrial dysfunction in cardiac impairment, we aimed to investigate whether aging exacerbates the cardiac mitochondrial metabolic response to inflammation, thus leading to increased cardiac dysfunction in the elderly. Cecal ligation and puncture (CLP) was conducted in young adult (12–18 weeks) and aged (19–21 months) male C57BL/6 mice. Cardiac function was detected 20 h post-CLP. Additionally, cardiomyocytes isolated from young adult and aged male mice were used for assessments of mitochondrial respiratory function +/– TNFα or LPS. Protein levels of oxidative phosphorylation (OXPHOS), NADPH oxidase (NOX)2, NOX4, phosphor-STAT3 and STAT3 were determined in mouse hearts 24 h post-CLP and in cardiomyocytes following inflammatory stimuli. CLP significantly reduced cardiac contractility in both young and aged mice, with a higher incidence and greater severity of cardiac functional depression in the older group. Mitochondrial respiratory capacity was decreased in cardiomyocytes derived from aged mice, with increased susceptible to inflammatory toxic effects compared to those from young adult mice. The age-dependent changes were observed in myocardial OXPHOS complexes and NOX4. Importantly, CLP led to a significant increase in OXPHOS protein levels in the hearts of older mice, suggesting a possible compensatory response to decreased mitochondrial metabolic function and a greater potential for reactive oxygen species (ROS) generation. Our findings highlight that the response of aging-impaired mitochondria to inflammation may underlie the worsened cardiac functional depression in the aged group during sepsis. Full article
(This article belongs to the Section Cellular Aging)
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