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Search Results (281)

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Keywords = tissue—like P system

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13 pages, 732 KiB  
Article
A Preliminary Investigation of the Efficacy of Far-Infrared-Emitting Garments in Enhancing Objective and Subjective Recovery Following Resistance Exercise
by Jonathon R. Lever, Cara Ocobock, Valerie Smith-Hale, Casey J. Metoyer, Alan Huebner, John P. Wagle and Jonathan D. Hauenstein
J. Funct. Morphol. Kinesiol. 2025, 10(3), 280; https://doi.org/10.3390/jfmk10030280 - 18 Jul 2025
Viewed by 380
Abstract
Objective: This study aimed to investigate the efficacy of far-infrared (FIR) garments in enhancing recovery following resistance exercise in recreationally active individuals. Methods: Ten recreationally active adults (six females, four males; aged 20.7 ± 3.2 years) completed a resistance exercise protocol and were [...] Read more.
Objective: This study aimed to investigate the efficacy of far-infrared (FIR) garments in enhancing recovery following resistance exercise in recreationally active individuals. Methods: Ten recreationally active adults (six females, four males; aged 20.7 ± 3.2 years) completed a resistance exercise protocol and were randomly selected to wear either FIR (n = 5) or placebo (n = 5) tights post-exercise. The FIR garments incorporated Celliant-based fibers emitting wavelengths in the 2.5–20 µm range. The participants’ recovery was assessed using countermovement jump (CMJ) metrics, including their jump height, takeoff velocity, and modified reactive strength index (mRSI), along with their fatigue biomarkers and subjective recovery perceptions. The CMJ performance was tested immediately post-exercise and at 24 and 48 h. Results: The FIR garments led to significant improvements in neuromuscular recovery, with greater increases in the jump height, takeoff velocity, and mRSI observed at 48 h post-exercise (p < 0.05). Notably, the mRSI showed earlier improvements at 24 h. The fatigue biomarkers did not differ between the groups (p > 0.05), suggesting localized rather than systemic recovery effects. The participants in the FIR group reported faster subjective recovery, with a readiness to resume activity perceived within 48 h, compared to slower recovery in the placebo group. Conclusions: FIR garments may enhance neuromuscular recovery and subjective recovery perceptions following resistance exercise, likely by improving the peripheral blood flow, metabolic clearance, and tissue oxygenation. These findings suggest that FIR garments may be effective in enhancing both neuromuscular and perceived recovery following resistance exercise, supporting their potential use as a post-exercise recovery tool. Full article
(This article belongs to the Section Athletic Training and Human Performance)
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16 pages, 3453 KiB  
Article
Diagnostic Accuracy of Pre-Biopsy MRI and CT Features for Predicting Vertebral Biopsy Yield in Suspected Vertebral Discitis Osteomyelitis: A Retrospective Single-Center Study
by Amirmasoud Negarestani, Andrew Pasion, Caleb Bhatnagar, Zuhaib Khokhar, Ashima Kundu, Samantha Diulus, Jorge P. Parada and Emad Allam
Diagnostics 2025, 15(14), 1760; https://doi.org/10.3390/diagnostics15141760 - 11 Jul 2025
Viewed by 308
Abstract
Background/Objectives: Vertebral discitis osteomyelitis (VDO) is a serious infection involving the vertebral bodies and intervertebral discs, often requiring biopsy for pathogen identification. However, biopsy yields are variable, and guidance on patient selection remains limited. This study aimed to assess how biopsy culture [...] Read more.
Background/Objectives: Vertebral discitis osteomyelitis (VDO) is a serious infection involving the vertebral bodies and intervertebral discs, often requiring biopsy for pathogen identification. However, biopsy yields are variable, and guidance on patient selection remains limited. This study aimed to assess how biopsy culture results influence clinical management and to develop imaging-based scoring systems to predict biopsy outcomes. Methods: In this retrospective study, 70 patients who underwent image-guided vertebral biopsy for suspected VDO between 2013 and 2022 were reviewed. Pre-biopsy MRI and CT findings were scored using novel, simplified criteria. MRI was graded based on soft tissue involvement, while CT evaluated the presence or absence of a vacuum phenomenon. Culture results were correlated with imaging scores and subsequent changes in antibiotic management. Statistical analysis included logistic regression, ROC analysis, and interobserver agreement using Cohen’s Kappa. Results: Of the 70 patients, 27 (38.6%) had positive cultures, and 20 (28.5%) experienced changes in management. Among the 48 patients with both MRI and CT imaging, MRI scores indicating soft tissue involvement and absence of the vacuum sign on CT were independent predictors of positive culture (p = 0.022 and p = 0.047, respectively). The combined predictive model showed an AUC of 0.76. Interobserver agreement was excellent (κ = 0.90 for MRI, κ = 0.95 for CT). Conclusions: MRI and CT features can be used to predict biopsy yield and guide clinical decisions in suspected VDO. These scoring systems may help clinicians identify patients most likely to benefit from biopsy, potentially improving outcomes and minimizing unnecessary procedures. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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19 pages, 1277 KiB  
Review
What a Modern Physician Should Know About microRNAs in the Diagnosis and Treatment of Diabetic Kidney Disease
by Małgorzata Rodzoń-Norwicz, Patryk Kogut, Magdalena Sowa-Kućma and Agnieszka Gala-Błądzińska
Int. J. Mol. Sci. 2025, 26(14), 6662; https://doi.org/10.3390/ijms26146662 - 11 Jul 2025
Viewed by 338
Abstract
Diabetic kidney disease (DKD) remains the leading cause of end-stage kidney disease (ESKD) globally. Despite advances in our understanding of its pathophysiology, current therapies are often insufficient to stop its progression. In recent years, microRNAs (miRNAs)—small, non-coding RNA molecules involved in post-transcriptional gene [...] Read more.
Diabetic kidney disease (DKD) remains the leading cause of end-stage kidney disease (ESKD) globally. Despite advances in our understanding of its pathophysiology, current therapies are often insufficient to stop its progression. In recent years, microRNAs (miRNAs)—small, non-coding RNA molecules involved in post-transcriptional gene regulation—have emerged as critical modulators of key pathogenic mechanisms in DKD, including fibrosis, inflammation, oxidative stress, and apoptosis. Numerous studies have identified specific miRNAs that either exacerbate or mitigate renal injury in DKD. Among them, miR-21, miR-192, miR-155, and miR-34a are associated with disease progression, while miR-126-3p, miR-29, miR-146a, and miR-215 demonstrate protective effects. These molecules are also detectable in plasma, urine, and renal tissue, making them attractive candidates for diagnostic and prognostic biomarkers. Advances in therapeutic technologies such as antagomiRs, mimics, locked nucleic acids, and nanoparticle-based delivery systems have opened new possibilities for targeting miRNAs in DKD. Additionally, conventional drugs, including SGLT2 inhibitors, metformin, and GLP-1 receptor agonists, as well as dietary compounds like polyphenols and sulforaphane, may exert nephroprotective effects by modulating miRNA expression. Recent evidence also highlights the role of gut microbiota in regulating miRNA activity, linking metabolic and immune pathways relevant to DKD progression. Further research is needed to define stage-specific miRNA signatures, improve delivery systems, and develop personalized therapeutic approaches. Modulation of miRNA expression represents a promising strategy to slow DKD progression and improve patient outcomes. Full article
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19 pages, 1575 KiB  
Article
Looking for New P Fertilizers: Comparative Study of Mineral-, Organomineral- and Organic-Based Fertilizers for Lettuce (Lactuca sativa L.)
by Lucía Valverde-Vozmediano, Silvia Sánchez-Méndez, Luciano Orden, Miguel A. Mira-Urios, Francisco Javier Andreu, Jose A. Sáez, Encarnación Martínez-Sabater, María Ángeles Bustamante, Javier Martín-Pozuelo and Raúl Moral
Agronomy 2025, 15(7), 1661; https://doi.org/10.3390/agronomy15071661 - 9 Jul 2025
Viewed by 371
Abstract
In this study several phosphorus fertilizers were evaluated under controlled production conditions using Lactuca sativa var. baby leaf and a clay-loam soil of pH 6.5 as a plant–soil model system. Various inorganic (phosphate rock, monoammonium phosphate, struvite), organic (bone meal and bone meal [...] Read more.
In this study several phosphorus fertilizers were evaluated under controlled production conditions using Lactuca sativa var. baby leaf and a clay-loam soil of pH 6.5 as a plant–soil model system. Various inorganic (phosphate rock, monoammonium phosphate, struvite), organic (bone meal and bone meal pelletized with compost) and organomineral fertilizers (phosphate rock, monoammonium phosphate, struvite pelletized with compost) were compared. The soil properties, crop yield, morphological aspects and metabolomics of the plants were analyzed. After 45 days of the growing cycle, the organomineral fertilizers (OMFs) composed of compost and monoammonium phosphate (OMF2(MAP+C)) or struvite (OMF3(STR+C)) exhibited the best yield results: 101.37 g and 83.21 g, respectively. These treatments also exhibited the best phosphorus use efficiency (PUE) results: 7.40% and 8.33%, respectively. The yield of plants treated with MAP was 56.01 g, and its PUE was 5.33%. The yield of plants treated with STR was 62.10 g and the PUE was 4.67%. Accordingly, the development of OMFs with compost had a positive effect regarding MAP and STR fertilization. Lettuce fertilized with organic bone meal fertilizers had the lowest yield and nutrient use efficiency. The non-targeted metabolic study of green tissue revealed an overactivation of the TriCarboxylic Acids-TCA cycle and amino acid biosynthesis in plants fertilized with bone meal and phosphate rock treatments, likely as a plant stress response. The overall conclusion of this work is that the development of OMFs with compost is a good strategy to increase soil P availability and, accordingly, plant P uptake and %PUE. Full article
(This article belongs to the Section Soil and Plant Nutrition)
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10 pages, 205 KiB  
Article
The Effect of Intrauterine Device Use on the Quality of Sampling Material in Patients Undergoing Endometrial Biopsy
by Hüseyin Aksoy, Mehmet Çopuroğlu, Mehmet Genco, Merve Genco and Mürüvet Korkmaz Baştürk
Diagnostics 2025, 15(13), 1725; https://doi.org/10.3390/diagnostics15131725 - 7 Jul 2025
Viewed by 344
Abstract
Objective: This retrospective study aims to evaluate the effect of copper intrauterine device (Cu-IUD) use on the adequacy and diagnostic quality of endometrial biopsy specimens in women with abnormal uterine bleeding (AUB). Patients with levonorgestrel-releasing intrauterine systems (LNG-IUS, e.g., Mirena) were excluded from [...] Read more.
Objective: This retrospective study aims to evaluate the effect of copper intrauterine device (Cu-IUD) use on the adequacy and diagnostic quality of endometrial biopsy specimens in women with abnormal uterine bleeding (AUB). Patients with levonorgestrel-releasing intrauterine systems (LNG-IUS, e.g., Mirena) were excluded from the study. The study compares the histopathological adequacy of endometrial samples between Cu-IUD users and non-users, highlighting potential interpretation challenges in routine pathological assessment. Methods: The study was conducted on 409 women aged 25–55 who presented with abnormal uterine bleeding (AUB) to the Gynecology and Obstetrics Outpatient Clinic at Kayseri City Hospital between 1 April 2021 and 1 April 2023. The patients were divided into two groups: copper IUD (Cu-IUD) users (n = 215) and non-IUD users (n = 194). Patients using levonorgestrel-releasing intrauterine systems (LNG-IUS, e.g., Mirena) were excluded from the study. Endometrial biopsies were obtained using the Pipelle curette technique without anesthesia, preserved in 10% formalin, and assessed for pathological classification and diagnostic adequacy. Results: The proportion of unclassifiable pathological categories was significantly higher in copper IUD users (63.93%) compared to non-IUD users (36.05%) (p = 0.013). Additionally, a negative correlation was observed between pathological category and endometrial thickness (r = −0.3147, p < 0.001), suggesting that thinner endometrial lining may reflect atrophic or diagnostically ambiguous tissue patterns. However, no significant association was found between IUD use and endometrial thickness (p = 0.073). Conclusions: The findings indicate that copper IUD use may affect the diagnostic adequacy of endometrial biopsy specimens, likely due to inflammatory or structural changes in the endometrium. These results underline the importance of considering IUD-related alterations when interpreting biopsy findings. Further research is needed to refine diagnostic approaches and better understand the clinical implications of these effects. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
15 pages, 266 KiB  
Article
Adverse Drug Reactions in an Intensive Care Unit of a Secondary Care Lithuanian Hospital: A Prospective Observational Study
by Greta Masiliūnienė, Gintautas Gumbrevičius, Edgaras Stankevičius and Edmundas Kaduševičius
Healthcare 2025, 13(13), 1592; https://doi.org/10.3390/healthcare13131592 - 3 Jul 2025
Viewed by 318
Abstract
Background and Objectives: Previous studies have shown that a major part of adverse drug reactions (ADRs) are preventable, and they contribute to increased morbidity, mortality, and costs. To our knowledge, no study investigating preventable ADRs has been carried out in Lithuania. Therefore, [...] Read more.
Background and Objectives: Previous studies have shown that a major part of adverse drug reactions (ADRs) are preventable, and they contribute to increased morbidity, mortality, and costs. To our knowledge, no study investigating preventable ADRs has been carried out in Lithuania. Therefore, the aim of this study was to characterize ADRs in the intensive care unit (ICU) of a secondary care Lithuanian hospital as well as to identify drug classes and organ systems most commonly implicated in preventable and nonpreventable ADRs. Materials and Methods: This observational prospective study was conducted in an 18-bed ICU of Kaunas Hospital of the Lithuanian University of Health Sciences from 1 September 2021 to 31 August 2023. All ADRs were assessed for causality, severity, and preventability. The Anatomical Therapeutic and Chemical (ATC) system was used to classify drug classes implicated in ADRs. The organ systems affected were analyzed using the Medical Dictionary for Regulatory Activities (MedDRA). Results: A total of 154 patients with a median age of 78.8 years (range, 18–97) were enrolled into this study. There were 255 ADRs identified; preventable ADRs accounted for 87.5%. Among the preventable ADRs, the top three therapeutic subgroups were antithrombotic agents (26.5%), anti-inflammatory and antirheumatic products (22.0%), and blood substitutes and perfusion solutions (20.2%). Meanwhile, among nonpreventable ADRs, antibacterials for systemic use (62.5%) and antithrombotic agents (46.9%) were the two most common therapeutic subgroups. The gastrointestinal as well as the skin and subcutaneous tissues organ systems were more likely to be affected by nonpreventable ADRs (56.3% vs. 17.5%, p ˂ 0.05 and 12.5% vs. 0.4%, p ˂ 0.05, respectively), while the renal and urinary organ systems were more likely to be affected by preventable ADRs (38.1% vs. 6.3%, p ˂ 0.05). Conclusions: Our study showed a very high incidence of preventable ADRs (87.5%). Drugs affecting blood and blood-forming organs were most frequently implicated in these ADRs. This area deserves special attention and strategies need to be implemented to reduce the incidence of preventable ADRs and their impact on the healthcare system. Moreover, it emphasizes the need for future studies at a national level as, to our knowledge, this is the first study addressing the issues of avoidable harm at the ICU of one Lithuanian hospital. Full article
(This article belongs to the Section Critical Care)
29 pages, 4036 KiB  
Article
Lipopolysaccharide and Recombinant Prion Protein Induce Distinct Neurodegenerative Pathologies in FVB/N Mice
by Seyed Ali Goldansaz, Dagnachew Hailemariam, Elda Dervishi, Grzegorz Zwierzchowski, Roman Wójcik, David S. Wishart and Burim N. Ametaj
Int. J. Mol. Sci. 2025, 26(13), 6245; https://doi.org/10.3390/ijms26136245 - 28 Jun 2025
Viewed by 395
Abstract
Prion diseases are classically attributed to the accumulation of protease-resistant prion protein (PrPSc); however, recent evidence suggests that alternative misfolded prion conformers and systemic inflammatory factors may also contribute to neurodegeneration. This study investigated whether recombinant moPrPRes, generated by [...] Read more.
Prion diseases are classically attributed to the accumulation of protease-resistant prion protein (PrPSc); however, recent evidence suggests that alternative misfolded prion conformers and systemic inflammatory factors may also contribute to neurodegeneration. This study investigated whether recombinant moPrPRes, generated by incubating wild-type mouse PrPC with bacterial lipopolysaccharide (LPS), can induce prion-like disease in FVB/N female mice, whether LPS alone causes neurodegeneration, and how LPS modulates disease progression in mice inoculated with the Rocky Mountain Laboratory (RML) strain of prions. Wild-type female FVB/N mice were randomized into six subcutaneous treatment groups: saline, LPS, moPrPRes, moPrPRes + LPS, RML, and RML + LPS. Animals were monitored longitudinally for survival, body weight, and clinical signs. Brain tissues were analyzed histologically and immunohistochemically for vacuolar degeneration, PrPSc accumulation, reactive astrogliosis, and amyloid-β plaque deposition. Recombinant moPrPRes induced a progressive spongiform encephalopathy characterized by widespread vacuolation and astrogliosis, yet with no detectable PrPSc by Western blot or immunohistochemistry. LPS alone triggered a distinct neurodegenerative phenotype, including cerebellar amyloid-β plaque accumulation and terminal-stage spongiosis, with approximately 40% mortality by the end of the study. Co-administration of moPrPRes and LPS resulted in variable regional pathology and intermediate survival (50% at 750 days post-inoculation). Interestingly, RML + LPS co-treatment led to earlier clinical onset and mortality compared to RML alone; however, vacuolation levels were not significantly elevated and, in some brain regions, were reduced. These results demonstrate that chronic endotoxemia and non-infectious misfolded PrP conformers can independently or synergistically induce key neuropathological hallmarks of prion disease, even in the absence of classical PrPSc. Targeting inflammatory signaling and toxic prion intermediates may offer novel therapeutic strategies for prion and prion-like disorders. Full article
(This article belongs to the Special Issue Advanced Research on Immune Cells and Cytokines (2nd Edition))
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15 pages, 2609 KiB  
Review
Evaluation of the Circadian Rhythm Component Cipc (Clock-Interacting Pacemaker) in Leukemogenesis: A Literature Review and Bioinformatics Approach
by Leidivan Sousa da Cunha, Beatriz Maria Dias Nogueira, Flávia Melo Cunha de Pinho Pessoa, Caio Bezerra Machado, Deivide de Sousa Oliveira, Manoel Odorico de Moraes Filho, Maria Elisabete Amaral de Moraes, André Salim Khayat and Caroline Aquino Moreira-Nunes
Clocks & Sleep 2025, 7(3), 33; https://doi.org/10.3390/clockssleep7030033 - 25 Jun 2025
Viewed by 712
Abstract
Circadian rhythms (CRs) are a key biological system regulating physiological processes such as metabolism, cell growth, DNA repair, and immunity, adapting to environmental changes like the light/dark cycle. Governed by internal clocks, it modulates gene expression through feedback loops involving Clock Genes (CGs), [...] Read more.
Circadian rhythms (CRs) are a key biological system regulating physiological processes such as metabolism, cell growth, DNA repair, and immunity, adapting to environmental changes like the light/dark cycle. Governed by internal clocks, it modulates gene expression through feedback loops involving Clock Genes (CGs), with the cycle initiated by CLOCK–BMAL1 and NPAS2–BMAL1 heterodimers. Disruptions in circadian rhythms have been linked to diseases including metabolic disorders, neurodegeneration, and cancer. CIPC (CLOCK-interacting pacemaker) has been studied as a negative regulator of the CLOCK–BMAL1 complex, focusing on its role in cancer, particularly leukemias. Public datasets and bioinformatics tools were used to examine CIPC gene expression in healthy patients and acute myeloid leukemia (AML) samples. Our analysis revealed significant overexpression of CIPC in AML compared to healthy tissues (p < 0.0001 ****). Additionally, survival analysis indicated significant differences in overall survival based on CIPC expression, with a log-rank test p-value = 0.014, suggesting that CIPC expression may affect overall patient survival. Altered CIPC expression may contribute to leukemogenesis by inhibiting circadian genes, which are often disrupted in leukemia. Furthermore, CIPC interacts with oncogenic pathways, including the MAPK/ERK pathway, which is essential for cell proliferation. Additional studies are needed to validate these findings and explore the detailed role of CIPC in cancer development. Full article
(This article belongs to the Section Human Basic Research & Neuroimaging)
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23 pages, 6234 KiB  
Article
Characterizing Breast Tumor Heterogeneity Through IVIM-DWI Parameters and Signal Decay Analysis
by Si-Wa Chan, Chun-An Lin, Yen-Chieh Ouyang, Guan-Yuan Chen, Chein-I Chang, Chin-Yao Lin, Chih-Chiang Hung, Chih-Yean Lum, Kuo-Chung Wang and Ming-Cheng Liu
Diagnostics 2025, 15(12), 1499; https://doi.org/10.3390/diagnostics15121499 - 12 Jun 2025
Viewed by 1666
Abstract
Background/Objectives: This research presents a novel analytical method for breast tumor characterization and tissue classification by leveraging intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) combined with hyperspectral imaging techniques and deep learning. Traditionally, dynamic contrast-enhanced MRI (DCE-MRI) is employed for breast tumor diagnosis, but [...] Read more.
Background/Objectives: This research presents a novel analytical method for breast tumor characterization and tissue classification by leveraging intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) combined with hyperspectral imaging techniques and deep learning. Traditionally, dynamic contrast-enhanced MRI (DCE-MRI) is employed for breast tumor diagnosis, but it involves gadolinium-based contrast agents, which carry potential health risks. IVIM imaging extends conventional diffusion-weighted imaging (DWI) by explicitly separating the signal decay into components representing true molecular diffusion (D) and microcirculation of capillary blood (pseudo-diffusion or D*). This separation allows for a more comprehensive, non-invasive assessment of tissue characteristics without the need for contrast agents, thereby offering a safer alternative for breast cancer diagnosis. The primary purpose of this study was to evaluate different methods for breast tumor characterization using IVIM-DWI data treated as hyperspectral image stacks. Dice similarity coefficients and Jaccard indices were specifically used to evaluate the spatial segmentation accuracy of tumor boundaries, confirmed by experienced physicians on dynamic contrast-enhanced MRI (DCE-MRI), emphasizing detailed tumor characterization rather than binary diagnosis of cancer. Methods: The data source for this study consisted of breast MRI scans obtained from 22 patients diagnosed with mass-type breast cancer, resulting in 22 distinct mass tumor cases analyzed. MR images were acquired using a 3T MRI system (Discovery MR750 3.0 Tesla, GE Healthcare, Chicago, IL, USA) with axial IVIM sequences and a bipolar pulsed gradient spin echo sequence. Multiple b-values ranging from 0 to 2500 s/mm2 were utilized, specifically thirteen original b-values (0, 15, 30, 45, 60, 100, 200, 400, 600, 1000, 1500, 2000, and 2500 s/mm2), with the last four b-value images replicated once for a total of 17 bands used in the analysis. The methodology involved several steps: acquisition of multi-b-value IVIM-DWI images, image pre-processing, including correction for motion and intensity inhomogeneity, treating the multi-b-value data as hyperspectral image stacks, applying hyperspectral techniques like band expansion, and evaluating three tumor detection methods: kernel-based constrained energy minimization (KCEM), iterative KCEM (I-KCEM), and deep neural networks (DNNs). The comparisons were assessed by evaluating the similarity of the detection results from each method to ground truth tumor areas, which were manually drawn on DCE-MRI images and confirmed by experienced physicians. Similarity was quantitatively measured using the Dice similarity coefficient and the Jaccard index. Additionally, the performance of the detectors was evaluated using 3D-ROC analysis and its derived criteria (AUCOD, AUCTD, AUCBS, AUCTDBS, AUCODP, AUCSNPR). Results: The findings objectively demonstrated that the DNN method achieved superior performance in breast tumor detection compared to KCEM and I-KCEM. Specifically, the DNN yielded a Dice similarity coefficient of 86.56% and a Jaccard index of 76.30%, whereas KCEM achieved 78.49% (Dice) and 64.60% (Jaccard), and I-KCEM achieved 78.55% (Dice) and 61.37% (Jaccard). Evaluation using 3D-ROC analysis also indicated that the DNN was the best detector based on metrics like target detection rate and overall effectiveness. The DNN model further exhibited the capability to identify tumor heterogeneity, differentiating high- and low-cellularity regions. Quantitative parameters, including apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (PF), were calculated and analyzed, providing insights into the diffusion characteristics of different breast tissues. Analysis of signal intensity decay curves generated from these parameters further illustrated distinct diffusion patterns and confirmed that high cellularity tumor regions showed greater water molecule confinement compared to low cellularity regions. Conclusions: This study highlights the potential of combining IVIM-DWI, hyperspectral imaging techniques, and deep learning as a robust, safe, and effective non-invasive diagnostic tool for breast cancer, offering a valuable alternative to contrast-enhanced methods by providing detailed information about tissue microstructure and heterogeneity without the need for contrast agents. Full article
(This article belongs to the Special Issue Recent Advances in Breast Cancer Imaging)
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16 pages, 2228 KiB  
Article
Quantitative Fluorescence Imaging of Chemophototherapy Drug Pharmacokinetics Using Laparoscopic SFDI
by Rasel Ahmmed, Elias Kluiszo, Semra Aygun-Sunar, Matthew Willadsen, Hilliard L. Kutscher, Jonathan F. Lovell and Ulas Sunar
Int. J. Mol. Sci. 2025, 26(12), 5571; https://doi.org/10.3390/ijms26125571 - 11 Jun 2025
Viewed by 477
Abstract
Chemophototherapy (CPT) is an emerging cancer treatment that leverages the synergistic effects of photodynamic therapy (PDT) and chemotherapy. This approach utilizes photosensitizers like Porphyrin-Phospholipid (PoP) and combined with chemotherapeutic like Doxorubicin (Dox) to enable light-triggered drug release and targeted tumor destruction. Here, we [...] Read more.
Chemophototherapy (CPT) is an emerging cancer treatment that leverages the synergistic effects of photodynamic therapy (PDT) and chemotherapy. This approach utilizes photosensitizers like Porphyrin-Phospholipid (PoP) and combined with chemotherapeutic like Doxorubicin (Dox) to enable light-triggered drug release and targeted tumor destruction. Here, we present the validation of a wide-field laparoscopic spatial frequency domain imaging (SFDI) system in an ovarian cancer model. The system allows quantitative fluorescence imaging to obtain absolute drug concentrations in vivo to obtain the absolute concentrations of PoP and Dox fluorescence by correcting for tissue absorption and scattering effects. Fluorescence imaging revealed a significant reduction (~25%, p < 0.001) in PoP concentration in tumor regions post-illumination, demonstrating PDT-mediated photobleaching. Next, the Dox release experiment showed an increase of ~13 µg/mL Dox concentration at the local site. The ability to quantify both PoP and Dox fluorescence concentrations with a laparoscopic system underscores its potential for intraoperative monitoring of CPT efficacy. These findings indicate wide-field laparoscopic SFDI as a promising tool for guiding minimally invasive PDT and targeted drug delivery in preclinical and future clinical settings. Full article
(This article belongs to the Special Issue Photodynamic Therapy and Photodetection, 2nd Edition)
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27 pages, 6562 KiB  
Article
A Positive Feedback DNA-PK/MYT1L-CXCR1-ERK1/2 Proliferative Signaling Loop in Glioblastoma
by Bo Wang, Dongping Li, Yaroslav Ilnytskyy, Levon M. Khachigian, Nuanying Zhong, Rocio Rodriguez-Juarez, Igor Kovalchuk and Olga Kovalchuk
Int. J. Mol. Sci. 2025, 26(9), 4398; https://doi.org/10.3390/ijms26094398 - 6 May 2025
Viewed by 476
Abstract
Glioblastoma is the most common primary brain tumor in adults. Our previous studies revealed a functional interplay of myelin transcription factor 1-like (MYT1L) with the DNA-dependent protein kinase (DNA-PK) in the regulation of p21 transcription. However, the contributing role of this functional interplay [...] Read more.
Glioblastoma is the most common primary brain tumor in adults. Our previous studies revealed a functional interplay of myelin transcription factor 1-like (MYT1L) with the DNA-dependent protein kinase (DNA-PK) in the regulation of p21 transcription. However, the contributing role of this functional interplay in glioblastoma remains largely unknown. Here, we used cell lines with normal DNA-PK (HEK293 and M059K) or deficient DNA-PK (M059J) as a model system to demonstrate the importance of the DNA-PK-dependent activation of MYT1L in controlling the transcription of CXC chemokine receptor 1 (CXCR1) in a positive-feedback proliferative signaling loop in glioblastoma with numerous conventional techniques. In normal DNA-PK cells, MYT1L acted as an oncogene by promoting cell proliferation, inhibiting apoptosis, and shortening a cell cycle S phase. However, in DNA-PK-deficient cells, MYT1L functioned as a tumor suppressor by inhibiting cell proliferation and inducing a G1 arrest. The enforced expression of MYT1L promoted CXCR1 transcription in DNA-PK-normal cells but attenuated transcription in DNA-PK-deficient cells. Bioinformatics analysis predicted a MYT1L-binding sequence at the CXCR1 promoter. The functional dependence of MYT1L on DNA-PK in CXCR1 transcription was validated by luciferase assay. Although the expression of CXCR1 was lower in M059J cells as compared to M059K cells, it was higher than in normal brain tissue. The CXCR1 ligands interleukin 8 (IL-8) and GRO protein alpha (GROα) expressed in M059J and M059K cells may signal through the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway that can be blocked by CXCR1 siRNA. Our findings demonstrate the existence of a positive feedback DNA-PK/MYT1L-CXCR1-ERK1/2 proliferation loop in glioblastoma cells that may represent a pharmacological target loop for therapeutic intervention. Full article
(This article belongs to the Section Molecular Oncology)
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19 pages, 17036 KiB  
Article
The Uremic Toxins Inorganic Phosphate, Indoxylsulphate, p-Cresylsulphate, and TMAO Induce the Generation of Sulphated Glycosaminoglycans in Aortic Tissue and Vascular Cells via pAKT Signaling: A Missing Link in the “Gut–Matrix Axis”
by Christian Freise, Susanne Metzkow, Andreas Zappe, Monika Ebert, Nicola Stolzenburg, Julia Hahndorf, Jörg Schnorr, Kevin Pagel and Matthias Taupitz
Toxins 2025, 17(5), 217; https://doi.org/10.3390/toxins17050217 - 25 Apr 2025
Viewed by 733
Abstract
Gut-derived uremic toxins (UTs) contribute to cardiovascular disorders like atherosclerosis and cardiomyopathy in patients with chronic kidney disease (CKD), causing increased cardiovascular morbidity and mortality. The intermediate steps between higher concentrations of gut-derived UTs and organ damage caused by UTs are still insufficiently [...] Read more.
Gut-derived uremic toxins (UTs) contribute to cardiovascular disorders like atherosclerosis and cardiomyopathy in patients with chronic kidney disease (CKD), causing increased cardiovascular morbidity and mortality. The intermediate steps between higher concentrations of gut-derived UTs and organ damage caused by UTs are still insufficiently understood. Glycosaminoglycans (GAGs) as components of the extracellular matrix are known to interact with various ligands such as growth factors or receptors, thereby influencing (patho)physiological processes. We previously found that the UT inorganic phosphate (Pi) induces the synthesis and sulphation of the GAGs heparan sulphate and chondroitin sulphate in the rat vascular smooth muscle cell (VSMC) line A7r5 and in the human endothelial cell (EC) line EA.Hy926. The aim of this study was to investigate if other organic UTs modulate GAGs in vascular cells as well. We treated ex vivo cultures of rat aortic rings as well as primary rat VSMCs and human ECs with the UTs Pi, indoxylsulphate (IS), p-cresylsulphate (pCS), trimethylamine N-oxide (TMAO), and urea, and analyzed the samples by histological staining, qPCR, western blot, HPLC, and colorimetric assays. The UT treatment of aortic rings and cells increased contents of sulphated GAGs and hyaluronic acid. UT-treated cells contained higher amounts of 4S- and 6S-sulphated GAGs compared to controls. This was accompanied by altered expressions of genes and proteins relevant for GAG metabolism. Mechanistically, the effects of the UTs on GAGs involve the activation of the PI3K/Akt pathway and of the transcription factor NF-κB. In conclusion, the UT-induced remodeling of the cardiovascular matrix by upregulation of sulphated GAGs and hyaluronic acid in aortic tissue and vascular cells might be a missing link between gut-derived UT and pathophysiological alterations in the cardiovascular system in the sense of a gut–matrix axis. Full article
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13 pages, 808 KiB  
Communication
Toll-like Receptor Type 2 and 13 Gene Expression and Immune Cell Profiles in Diploid and Triploid Sterlets (Acipenser ruthenus): Insights into Immune Competence in Polyploid Fish
by Olga Jablonska, Sara Duda, Szczepan Gajowniczek, Anna Nitkiewicz and Dorota Fopp-Bayat
Int. J. Mol. Sci. 2025, 26(9), 3986; https://doi.org/10.3390/ijms26093986 - 23 Apr 2025
Viewed by 530
Abstract
Toll-like receptors (TLRs) are key components of the innate immune system in fish, responsible for recognizing pathogen-associated molecular patterns derived from bacteria, viruses, and fungi. The sterlet (Acipenser ruthenus), an endangered sturgeon species valued for its meat and caviar, is a [...] Read more.
Toll-like receptors (TLRs) are key components of the innate immune system in fish, responsible for recognizing pathogen-associated molecular patterns derived from bacteria, viruses, and fungi. The sterlet (Acipenser ruthenus), an endangered sturgeon species valued for its meat and caviar, is a promising model for studying the effects of polyploidy on immune gene regulation. This study examined the expression of Toll-like receptor type 2 (TLR2) and type 13 (TLR13) in the heart, liver, gills, spleen, and kidney of diploid and triploid healthy sterlets using real-time PCR. TLR2 and TLR13 were expressed in all tissues of both diploids and triploids. In diploids, TLR2 expression was the highest in the kidney and the lowest in the liver (p < 0.05). Similarly, TLR13 expression in diploids was highest in the kidney and gills, and lowest in the liver (p < 0.05). In triploids, no significant tissue-specific variation in TLR expression was observed (p > 0.05). Comparisons between diploid and triploid sterlets revealed higher TLR2 expression in the kidney and higher TLR13 expression in the heart and kidney of diploids (p < 0.05). These molecular findings were supported by leukocyte analysis, which showed a significantly lower percentage of lymphocytes and a higher proportion of neutrophils in triploids compared to diploids. Additionally, the proportion of thrombocytes was significantly elevated in triploids (p < 0.05). This study provides the first report of TLR expression in polyploid fish, offering new insights into immune modulation associated with polyploidy in sturgeons. Full article
(This article belongs to the Special Issue Fish Genomics and Developmental Biology, 2nd Edition)
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19 pages, 946 KiB  
Review
Nanotechnology-Based Delivery Systems for Enhanced Targeting of Tyrosine Kinase Inhibitors: Exploring Inorganic and Organic Nanoparticles as Targeted Carriers
by Yana Gvozdeva
Kinases Phosphatases 2025, 3(2), 9; https://doi.org/10.3390/kinasesphosphatases3020009 - 21 Apr 2025
Cited by 1 | Viewed by 997
Abstract
Kinase inhibitors are small molecules that block kinase activity and have significant applications in both therapy and diagnostics. Recent studies suggest that these inhibitors hold great potential as targets for treating a range of diseases, including autoimmune disorders, cardiovascular conditions, cancer, and inflammatory [...] Read more.
Kinase inhibitors are small molecules that block kinase activity and have significant applications in both therapy and diagnostics. Recent studies suggest that these inhibitors hold great potential as targets for treating a range of diseases, including autoimmune disorders, cardiovascular conditions, cancer, and inflammatory diseases like ulcerative colitis. Ongoing research focuses on developing effective carriers for tyrosine kinase inhibitors (TKIs) to enhance treatment outcomes while reducing side effects. The nano-scale drug carriers have demonstrated the ability to encapsulate a wide range of imaging and therapeutic agents, enhancing tumor diagnosis and treatment. Notably, the incorporation of drugs with poor pharmacokinetics into nanocarriers enhances their solubility and stability, offering a renewed opportunity to assess their full therapeutic potential. The entrapped agents can be released in a controlled manner to maintain a specific drug concentration within a treatment framework or triggered by specific stimuli such as time or pH to target particular tissues or cells. The multifunctionality of nanosystems offers a promising avenue for developing innovative tyrosine kinase inhibitor (TKI) delivery strategies that serve as alternative treatment options for cancer and other inflammatory diseases. This review aims to provide a comprehensive overview of innovative nano-scale delivery systems for TKIs, both as standalone treatments and in combination with other therapeutic agents or drug delivery approaches. We discuss their comparative advantages and limitations for future small-molecule TKIs research. Full article
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15 pages, 5464 KiB  
Article
Acanthopanax Senticosus Saponins Prevent Cognitive Decline in Rats with Alzheimer’s Disease
by Xue-Min Cui, Wang Wang, Lin Yang, Bao-Wen Nie, Qian Liu, Xiao-Hui Li and Dong-Xiao Duan
Int. J. Mol. Sci. 2025, 26(8), 3715; https://doi.org/10.3390/ijms26083715 - 14 Apr 2025
Viewed by 687
Abstract
Alzheimer’s disease (AD) is a progressive degenerative disease of the nervous system that affects older adults. Its main clinical manifestations include memory loss, cognitive dysfunction, abnormal behaviour, and social dysfunction. Neuroinflammation is typical in most neurodegenerative diseases, such as AD. Therefore, suppressing inflammation [...] Read more.
Alzheimer’s disease (AD) is a progressive degenerative disease of the nervous system that affects older adults. Its main clinical manifestations include memory loss, cognitive dysfunction, abnormal behaviour, and social dysfunction. Neuroinflammation is typical in most neurodegenerative diseases, such as AD. Therefore, suppressing inflammation may improve AD symptoms. This study investigated the neuroprotective effects of Acanthopanax senticosus saponins (ASS) in an AD model induced by streptozotocin (STZ). Here, we characterised a rat model of STZ-induced AD with the parallel deterioration of memory loss and neuroinflammation. Following the end of the treatment with ASS (50 mg/kg for 14 consecutive days), behavioural tests (Morris water maze test, Y-maze test) were performed on the rat, and the molecular parameters (DAPK1, Tau5, p-Tau, NF-κB, IL-1β, TNF-α, and NLRP3) of the rat hippocampus were also assessed. We demonstrated that ASS, which has potent anti-inflammatory effects, can reduce neuroinflammation and prevent cognitive impairment. In the water maze test, ASS-treated groups exhibited significantly increased average escape latency (p < 0.05), the percentage of stay in the target quadrant (p < 0.05), and the number of times each group of rats crossed the platform (p < 0.05) compared to the negative control. And ASS could reduce the phosphorylation of the Tau protein (p < 0.001) and death-associated protein kinase 1 (DAPK1, p < 0.001) in the hippocampal tissue, improving cognitive impairment in STZ-treated rats by suppressing the inflammatory response; the molecular analysis showed a significant reduction in pro-inflammatory markers like NLRP3, IL-1β, TNF-α, and NF-κB (p < 0.001). It was also discovered that the NF-κB inhibitor SN50 had the same effect. Therefore, the present study used ASS through its anti-inflammatory effects to prevent and treat AD. This study highlights the potential efficacy of ASS in alleviating cognitive dysfunction in AD. Full article
(This article belongs to the Special Issue Advances in the Molecular Biology of Proteins in Drug Research)
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