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Search Results (282)

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19 pages, 1691 KB  
Article
Repercussions of Symbiotic Bacteria Associated with Entomopathogenic Nematodes and Their Biogenic Silver Nanoparticles on Immune Responses at Root-Knot Nematode Suppression
by Rehab Y. Ghareeb, Shawky M. Eid, Hanan Alfy and Mohamed H. Elsheikh
Microorganisms 2026, 14(1), 92; https://doi.org/10.3390/microorganisms14010092 - 31 Dec 2025
Viewed by 204
Abstract
Root-knot nematodes (RKNs) of the Meloidogyne genus impact various plants, including crops, fruits, and vegetables. Few chemical control options exist globally, and many nematicides are banned due to health and environmental risks. This study tested a new nematicidal agent, the symbiotic bacterium Xenorhabdus [...] Read more.
Root-knot nematodes (RKNs) of the Meloidogyne genus impact various plants, including crops, fruits, and vegetables. Few chemical control options exist globally, and many nematicides are banned due to health and environmental risks. This study tested a new nematicidal agent, the symbiotic bacterium Xenorhabdus indica, which was molecularly identified (PV845100). Cell-free culture supernatants of Xenorhabdus spp. and their biogenic Ag-NPs were used in nematicidal assays. Meloidogyne incognita showed high mortality rates of 95.3%, 74.6%, and 72.6% after 72 h of treatment with the X. indica filtrate at three concentrations. At the same concentrations, biogenic Ag-NPs resulted in 82.0%, 90.0%, and 85.3% mortality rates, respectively. After 72 h, hatchability decreased by 53%, 74.6%, and 72.6% for the X. indica filtrate and 82.0%, 90.0%, and 85.3% for Ag-NPs. Quantitative real-time PCR (Q-PCR) revealed that Mi-Ache1 expression was lower in M. incognita second-stage juveniles (J2s) treated with the filtrate and Ag-NPs after 72 h compared to controls. Mi-Ache2 expression was also decreased, but only slightly. Furthermore, both the X. indica filtrate and biogenic Ag-NPs were safe in human lung (WI-38) and skin (HFB4) cell lines. These findings suggest that bacterial filtrates and their biogenic Ag-NPs could serve as cost-effective, environmentally friendly alternatives to commercial nematicides. Full article
(This article belongs to the Special Issue Silver Nanoparticles as Antimicrobial Agents)
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23 pages, 2718 KB  
Systematic Review
Bridging Imaging and Pathohistology in Pancreatic Hamartoma: A Systematic Review of the Literature with an Integrated Case Report
by Dunja Stankic, Nina Rajovic, Nikola Grubor, Jelena Rakocevic, Aleksandar Ninic, Marjan Micev, Jelena Vladicic Masic, Luka Joksimovic, Natasa Milic, Kristina Davidovic and Nikica Grubor
J. Clin. Med. 2026, 15(1), 136; https://doi.org/10.3390/jcm15010136 - 24 Dec 2025
Viewed by 207
Abstract
Background: Pancreatic hamartoma (PH) is an exceptionally rare, benign, mass-forming lesion accounting for less than 1% of all pancreatic tumors. Its rarity and non-neoplastic nature contribute to significant diagnostic challenges, often leading to misclassification as malignant disease. This study presents a case of [...] Read more.
Background: Pancreatic hamartoma (PH) is an exceptionally rare, benign, mass-forming lesion accounting for less than 1% of all pancreatic tumors. Its rarity and non-neoplastic nature contribute to significant diagnostic challenges, often leading to misclassification as malignant disease. This study presents a case of PH and a systematic review of all reported cases, with emphasis on histopathological and imaging characteristics. Methods: A comprehensive electronic search of PubMed, Scopus, and Web of Science was conducted up to 1 April 2025, to identify eligible case reports and series. Results: We describe a 37-year-old woman with a cystic lesion of the pancreatic tail, ultimately confirmed histologically as a cystic pancreatic hamartoma following distal pancreatectomy with splenectomy, with an uneventful postoperative course. Of 687 screened studies, 51 met the inclusion criteria, comprising 77 cases (68 adults, 9 pediatric). PHs occurred most frequently in males (52.9%), with a mean age of 59.5 ± 12.9 years, and were often asymptomatic (57.4%). The pancreatic head was the most common site (52.9%). On MRI, PHs typically exhibited low T1-weighted and high T2-weighted signal intensity, with no FDG uptake (82%) and moderate or no restriction on DWI, distinguishing them from neuroendocrine tumors (NETs). Histologically, most lesions were solid (64.7%) or solid–cystic (35.3%), with low spindle cell cellularity and absent Langerhans islets. Conclusions: Low T1WI signal and moderate DWI signal are the key features distinguishing PHs from NETs. Incorporating these findings with EUS-FNA and immunohistochemistry can support a provisional diagnosis and help avoid unnecessary radical surgery. Full article
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16 pages, 2732 KB  
Article
Biocompatibility and Drug Release Properties of Carboxymethyl Cellulose Hydrogel for Carboplatin Delivery
by Hiroyuki Kono, Shion Kinjyo, Ryou Uyama, Sayaka Fujita, Yuko Murayama and Shinya Ikematsu
Gels 2026, 12(1), 5; https://doi.org/10.3390/gels12010005 - 20 Dec 2025
Viewed by 315
Abstract
Carboxymethylcellulose (CMC) is a biocompatible and biodegradable polysaccharide suitable for biomedical applications. Herein, an epichlorohydrin (ECH)-crosslinked CMC hydrogel (CMCG) was developed as a carrier for sustained drug release. Ether-type crosslinking between the hydroxyl groups of CMC and ECH yielded a transparent, highly water-absorbent [...] Read more.
Carboxymethylcellulose (CMC) is a biocompatible and biodegradable polysaccharide suitable for biomedical applications. Herein, an epichlorohydrin (ECH)-crosslinked CMC hydrogel (CMCG) was developed as a carrier for sustained drug release. Ether-type crosslinking between the hydroxyl groups of CMC and ECH yielded a transparent, highly water-absorbent gel. Structural analyses employing Fourier-transform infrared and solid-state 13C nuclear magnetic resonance spectroscopies confirmed successful crosslinking, and the hydrogel exhibited pH-dependent swelling. Carboplatin (CBP), a platinum-based anticancer drug, was incorporated into CMCG to prepare CBP-CMCG. In phosphate-buffered saline (pH 7.4), approximately 70% of CBP was released within 12 h, followed by a plateau phase, indicating diffusion-controlled release. Cytocompatibility assays using WI-38 normal human fibroblasts demonstrated that CMCG was non-cytotoxic, whereas free CBP induced significant cell death. In colorectal cancer HT-29 cells, CBP-CMCG exhibited gradual cytotoxicity, resulting in >80% nonviable cells after 24 h, indicating a sustained antitumor effect compared with free CBP. These results demonstrate that the newly developed ECH-crosslinked CMC hydrogel is a safe and effective platform for controlled drug delivery, enabling sustained release and prolonged therapeutic activity of CBP. Full article
(This article belongs to the Special Issue Design and Optimization of Pharmaceutical Gels (2nd Edition))
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16 pages, 3281 KB  
Article
Assessment of Android Network Positioning as an Alternate Source for Robust PNT
by Joohan Chun, Jacob Spagnolli, Tanner Holmes and Dennis Akos
Sensors 2025, 25(23), 7324; https://doi.org/10.3390/s25237324 - 2 Dec 2025
Viewed by 499
Abstract
Android devices employ several methods to calculate their position. This paper’s focus is the Network Location Provider (NLP), which leverages Wi-Fi and cell tower signals via the fingerprinting/database approach. Unlike GNSS-based positioning, the NLP should be able to compute positions even when the [...] Read more.
Android devices employ several methods to calculate their position. This paper’s focus is the Network Location Provider (NLP), which leverages Wi-Fi and cell tower signals via the fingerprinting/database approach. Unlike GNSS-based positioning, the NLP should be able to compute positions even when the device is indoors or experiencing GNSS radio frequency interference (RFI), making it an enticing candidate for ensuring robust PNT solutions. However, the inner workings of NLP are largely undisclosed, remaining as a ‘black-box’ system. Using the Samsung S24 and Xiaomi Redmi K80 Ultra, we explored the NLP’s response to GNSS spoofing and offline operation (no network connection), as well as attempting NLP spoofing. The GNSS spoofing test confirmed that when satellite signals are spoofed, the NLP solution is maintained at the truth location. This reinforces the robustness of the NLP in RFI environments. In offline mode, NLP continued to operate without a Google server connection, indicating that it can compute positions locally using internally stored cache data. This behavior deviates from the conventional understanding of NLP and offers valuable insights into the latest NLP mechanism. These findings build upon previous work to uncover the inner workings of the NLP and ultimately contribute to robust smartphone PNT. Full article
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31 pages, 1965 KB  
Review
Reciprocal Paracrine Signaling and Dynamic Coordination of Transitional States in the Alveolar Epithelial Type 2 Cells and Associated Alveolar Lipofibroblasts During Homeostasis, Injury and Repair
by Georgios-Dimitrios Panagiotidis, Mengqing Chen, Xiuyue Yang, Manuela Marega, Stefano Rivetti, Xuran Chu and Saverio Bellusci
Cells 2025, 14(23), 1869; https://doi.org/10.3390/cells14231869 - 26 Nov 2025
Viewed by 773
Abstract
Single-cell RNA-sequencing has transformed our understanding of alveolar epithelial type 2 (AT2) cells and alveolar lipofibroblasts (LIFs) during lung injury and repair. Both cell types undergo dynamic transitions through intermediate states that determine whether the lung proceeds toward regeneration or fibrosis. Emerging evidence [...] Read more.
Single-cell RNA-sequencing has transformed our understanding of alveolar epithelial type 2 (AT2) cells and alveolar lipofibroblasts (LIFs) during lung injury and repair. Both cell types undergo dynamic transitions through intermediate states that determine whether the lung proceeds toward regeneration or fibrosis. Emerging evidence highlights reciprocal paracrine signaling between AT2/AT1 transitional cells and LIF-derived myofibroblasts (aMYFs) as a key regulatory axis. Among these, amphiregulin (AREG)–EGFR signaling functions as a central profibrotic pathway whose inhibition can restore alveolar differentiation and repair. The human WI-38 fibroblast model provides a practical platform to study the reversible LIF–MYF switch and screen antifibrotic and pro-regenerative compounds. Candidate therapeutics including metformin, haloperidol and FGF10 show promise in reprogramming fibroblast and epithelial states through metabolic and signaling modulation. Integrating WI-38-based assays, alveolosphere co-cultures, and multi-omics profiling offers a translational framework for identifying interventions that halt fibrosis and actively induce lung regeneration. This review highlights a unifying framework in which epithelial and mesenchymal plasticity converge to define repair outcomes and identifies actionable targets for promoting alveolar regeneration in chronic lung disease. Full article
(This article belongs to the Special Issue Mechanisms of Lung Growth and Regeneration)
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35 pages, 16280 KB  
Article
Engineering Mesoporous Silica Hosts for Ultrasmall ZnO Nanoparticles: A Dendritic Polymer-Assisted Strategy Towards Sustainable, Safe, and Effective Antibacterial Systems
by Aggeliki Papavasiliou, Kyriaki Marina Lyra, Elias Sakellis, Albany Milena Lozano Násner, Jose Gallego, Fotios K. Katsaros and Zili Sideratou
Nanomaterials 2025, 15(22), 1697; https://doi.org/10.3390/nano15221697 - 9 Nov 2025
Viewed by 836
Abstract
In response to the urgent need for sustainable antibacterial solutions against antibiotic-resistant pathogens, this study presents a facile dendritic polymer-assisted approach for synthesizing highly active ZnO/mesoporous silica nanocomposites (SBA-15, SBA-16, KIT-6, MSU-X). Two hyperbranched polymers—polyethyleneimine (PEI) and carboxy-methylated polyethyleneimine (Trilon-P, TrP)—were employed as [...] Read more.
In response to the urgent need for sustainable antibacterial solutions against antibiotic-resistant pathogens, this study presents a facile dendritic polymer-assisted approach for synthesizing highly active ZnO/mesoporous silica nanocomposites (SBA-15, SBA-16, KIT-6, MSU-X). Two hyperbranched polymers—polyethyleneimine (PEI) and carboxy-methylated polyethyleneimine (Trilon-P, TrP)—were employed as templating and metal-trapping agents. The influence of pore geometry, polymer functionality, and polymer-loading method (wet or dry impregnation) on ZnO nanoparticle (NP) formation was systematically examined. All nanocomposites exhibited high structural homogeneity, incorporating ultrasmall or amorphous ZnO NPs (1–10 nm) even at 8 wt.% Zn loading. Zn uptake was strongly dependent on polymer end groups, while the spatial distribution of ZnO NPs was dictated by the silica host structure. Antibacterial assays against Staphylococcus aureus revealed remarkable activity, particularly for ZnO/SBA-15_PEI, ZnO/SBA-16_PEI, and ZnO/MSU-X_TrP nanocomposites, with minimum inhibitory concentrations of 1–2.5 μg mL−1 Zn and over 90% mammalian cell viability. Life Cycle Assessment identified energy use as the main environmental factor, with ZnO/SBA-15_PEI_WI displaying the lowest impact. Overall, the interplay between silica pore architecture, polymer type, and impregnation method governs ZnO accessibility and bioactivity, establishing a versatile strategy for designing next-generation ZnO/SiO2 nanocomposites with tunable antibacterial efficacy and minimal cytotoxic and environmental footprint. Full article
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1392 KB  
Proceeding Paper
Design and Implementation of a Wi-Fi-Enabled BMS for Real-Time LiFePO4 Cell Monitoring
by Ioannis Christakis, Vasilios A. Orfanos, Chariton Christoforidis and Dimitrios Rimpas
Eng. Proc. 2025, 118(1), 13; https://doi.org/10.3390/ECSA-12-26613 - 7 Nov 2025
Viewed by 164
Abstract
This paper presents the design and implementation of a custom-built LiFePO4 battery monitoring system that offers real-time visibility into the status of individual battery cells. The system is based on a Battery Management System (BMS) architecture and is implemented by measuring the [...] Read more.
This paper presents the design and implementation of a custom-built LiFePO4 battery monitoring system that offers real-time visibility into the status of individual battery cells. The system is based on a Battery Management System (BMS) architecture and is implemented by measuring the voltage, current, and temperature of each cell in a multi-cell pack. These key parameters are essential for ensuring safe operation, prolonging battery life, and optimizing energy usage in off-grid or mobile power systems. The system architecture is based on an ESP32 microcontroller that interfaces with INA219 and DS18B20 sensors to continuously measure individual cell voltage, current, and temperature. Data are transmitted wirelessly via Wi-Fi to a remote time-series database for centralized storage, analysis, and visualization. Experimental validation, conducted over a 15-day period, demonstrated stable system performance and reliable data transmission. Analytically, the findings indicate that utilizing an advanced smart charger for precise cell balancing and improving the physical layout for cooling led to superior thermal performance. Even when load current nearly tripled to 110 mA, the system maintained a stable cell operating temperature range of 29.8 °C to 30.3 °C. This result confirms significantly reduced cell stress compared to previous iterations, which is critical for enhancing battery health and lifespan. The application of this project aimed to demonstrate how a combination of open hardware components and lightweight network protocols can be used to create a robust, cost-effective battery monitoring solution suitable for integration into smart energy systems or remote IoT infrastructures. Full article
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20 pages, 3573 KB  
Article
Lactic Acid Bacteria-Mediated Synthesis of Selenium Nanoparticles: A Smart Strategy Against Multidrug-Resistant Pathogens
by Nahla Fadel, Mohammed Abu-Elghait, Hassan Gebreel, Takeshi Zendo and HebatAllah Youssef
Appl. Microbiol. 2025, 5(4), 121; https://doi.org/10.3390/applmicrobiol5040121 - 29 Oct 2025
Cited by 1 | Viewed by 1013
Abstract
This study reports the biosynthesis of selenium nanoparticles (Se-NPs) using four newly isolated strains of lactic acid bacteria, molecularly identified as Lactiplantibacillus pentosus, Lactiplantibacillus plantarum, Lactiplantibacillus plantarum, and Lactobacillus acidophilus. The synthesized Se-NPs were characterized using Transmission Electron Microscopy [...] Read more.
This study reports the biosynthesis of selenium nanoparticles (Se-NPs) using four newly isolated strains of lactic acid bacteria, molecularly identified as Lactiplantibacillus pentosus, Lactiplantibacillus plantarum, Lactiplantibacillus plantarum, and Lactobacillus acidophilus. The synthesized Se-NPs were characterized using Transmission Electron Microscopy (TEM), Energy Dispersive X-ray Spectroscopy (EDX), Fourier Transform Infrared Spectroscopy (FTIR), and UV-Vis Spectroscopy, and zeta potential analysis. The result revealed that their size ranged from 16 nm to 90 nm with favorable stability and purity. The Se-NPs exhibited significant antimicrobial and antibiofilm activities against certain Gram-positive, Gram-negative bacteria, and Candida albicans, particularly those produced by isolate S4, which showed the lowest MIC values and highest biofilm inhibition. Furthermore, MTT assays revealed selective cytotoxicity against the A549 cancerous lung cell line, with minimal toxicity toward normal Wi38 cells. These findings suggest that biosynthesized Se-NPs are a promising, biocompatible candidate for combating antibiotic-resistant pathogens and biofilm-associated infections. Full article
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13 pages, 1211 KB  
Article
Establishment of a VSV-Based Pseudovirus Platform for In Vitro and In Vivo Evaluation of Nipah Vaccine-Induced Neutralizing Responses
by Seong Eun Bae, Minhyuk Yoon, Younghye Moon, Min Jung Kim, Jeong-In Kim, Kee-Jong Hong and Jae-Ouk Kim
Viruses 2025, 17(11), 1429; https://doi.org/10.3390/v17111429 - 28 Oct 2025
Viewed by 966
Abstract
The Nipah virus (NiV) is a zoonotic pathogen characterized by high fatality rates and pandemic potential, whereby there is an urgent need for developing safe and effective vaccines. However, the evaluation of NiV vaccine-induced immunity is hindered by the requirement of Biosafety Level-4 [...] Read more.
The Nipah virus (NiV) is a zoonotic pathogen characterized by high fatality rates and pandemic potential, whereby there is an urgent need for developing safe and effective vaccines. However, the evaluation of NiV vaccine-induced immunity is hindered by the requirement of Biosafety Level-4 (BSL-4) containment. In this study, we developed a recombinant vesicular stomatitis virus (rVSV)-based pseudovirus-expressing NiV fusion (F) and attachment (G) glycoproteins using a luciferase reporter gene for bioluminescence detection. This pseudovirus was optimized for production in BHK-21 (WI-2) cells, and simultaneous incorporation of NiV-F and NiV-G onto the surface of the pseudotyped virus was confirmed via immunoprecipitation and Western blotting. We evaluated our pseudovirus-based neutralization assay using NiV-F-immunized mouse sera and a commercial anti-NiV-G antibody, confirming robust neutralization by the latter. To establish a BSL-2-compatible model for evaluating in vivo protective efficacy, we performed in vivo imaging, which revealed a marked reduction in the luminescence signal in NiV-G-immunized mice compared to naïve controls, indicating vaccine-induced protection. Our study established an integrated in vitro and in vivo pseudovirus platform using rVSV that enables safe, quantitative, and BSL-2-compatible evaluation of NiV vaccine candidates. This model offers a valuable tool for preclinical screening of vaccine-induced neutralizing antibody responses and protective efficacy. Full article
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16 pages, 1920 KB  
Article
Multi-Kinase Inhibition by New Quinazoline–Isatin Hybrids: Design, Synthesis, Biological Evaluation and Mechanistic Studies
by Mohammed M. Alanazi and Reem I. Al-Wabli
Pharmaceuticals 2025, 18(10), 1546; https://doi.org/10.3390/ph18101546 - 14 Oct 2025
Cited by 1 | Viewed by 726
Abstract
Background/Objectives: Cancer is a worldwide health concern and is the second leading cause of death, responsible for nearly one in six deaths. Discovery of new anticancer agents is still a challenge for medicinal chemists and further research will improve patients’ chances of survival. [...] Read more.
Background/Objectives: Cancer is a worldwide health concern and is the second leading cause of death, responsible for nearly one in six deaths. Discovery of new anticancer agents is still a challenge for medicinal chemists and further research will improve patients’ chances of survival. Protein kinases are among the most popular and successful biological targets for developing anticancer drugs. In this context, protein kinases were selected as targets, and a series of isatin–quinazoline hybrids were synthesized. Methods: Their antiproliferative activity was evaluated against four cancer cell lines (HepG2, MCF-7, MDA-MB-231, and HeLa) and one normal fibroblast cell line (WI38) using MTT assays. Results: The tested compounds showed variable cytotoxic effects on the four cancer cell lines. Compound 6c exhibited the most potent anticancer activity against all cancer cells. In addition, this compound was tested for the effect on the expression of anti-apoptotic Bcl-2 protein and pro-apoptotic proteins Bax, caspase-3, and caspase-9, which revealed induction of apoptosis similar to staurosporine. Furthermore, an annexin V-FITC/PI dual staining assay confirmed that compound 6c induced cell death by apoptosis. Flow cytometric analysis revealed that compound 6c induced cell cycle arrest at the sub-G1 and S phases in the HepG2 cell line. Moreover, compound 6c was found to be a multi-kinase inhibitor with potent inhibitory activity on CDK2, EGFR, VEGFR-2, and HER2, with IC50 values of 0.183 ± 0.01, 0.083 ± 0.005, 0.076 ± 0.004, and 0.138 ± 0.07 μM, respectively. Finally, a molecular docking simulation was conducted to predict possible binding interactions with the active site of CDK2. Conclusions: These findings suggest that compound 6c is a promising multi-kinase inhibitor with potent anticancer activity, warranting further investigation as a potential therapeutic agent. Full article
(This article belongs to the Section Medicinal Chemistry)
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39 pages, 16563 KB  
Article
Innovative Amino-Functionalization of Pyrido[2,3-d]pyrimidine Scaffolds for Broad Therapeutic Applications Supported by Computational Analyses
by Hagar S. El-Hema, Haitham E. Shehata, Mohamed A. Hawata, Eman S. Nossier, Ahmed F. El-Sayed, Najla A. Altwaijry, Asmaa Saleh, Modather F. Hussein, Amr Sabry and Adel A.-H. Abdel-Rahman
Pharmaceuticals 2025, 18(10), 1472; https://doi.org/10.3390/ph18101472 - 30 Sep 2025
Cited by 2 | Viewed by 1608
Abstract
Background: Derivatives of Pyrido[2,3-d]pyrimidine-6-carboxylate are promising multi-target scaffolds. This study focused on synthesizing 16 amino-functionalized derivatives and evaluating their dual anticancer and antibacterial activities, supported by mechanistic and computational analyses. Objectives: Design and synthesize derivatives, evaluate cytotoxicity against HeLa, HepG-2, and [...] Read more.
Background: Derivatives of Pyrido[2,3-d]pyrimidine-6-carboxylate are promising multi-target scaffolds. This study focused on synthesizing 16 amino-functionalized derivatives and evaluating their dual anticancer and antibacterial activities, supported by mechanistic and computational analyses. Objectives: Design and synthesize derivatives, evaluate cytotoxicity against HeLa, HepG-2, and MCF-7 (selectivity against WI-38), investigate EGFRWT and EGFRT790M inhibition, assess cell cycle, apoptosis, and migration effects, antibacterial efficacy against E. coli and P. aeruginosa, and perform in silico ADMET, docking, molecular dynamics, DFT, and antiviral predictions. Methods: Synthesized 16 derivatives; tested for cytotoxicity, EGFR inhibition, cell cycle, apoptosis, migration; assessed antibacterial activity; performed ADMET profiling, molecular docking, molecular dynamics, and DFT calculations. Results: Derivatives 1, 2, and 7 showed highest cytotoxicity (IC50 = 3.98–17.52 μM; WI-38 IC50 = 64.07–81.65 μM). Compound 1 potently inhibited EGFRWT (IC50 = 0.093 μM) and EGFRT790M (IC50 = 0.174 μM), induced G0/G1 arrest (74.86%) and apoptosis (26.37%), and reduced MCF-7 migration (69.63%). Moderate antibacterial activity observed (MIC = 50 μg/mL). ADMET indicated favorable pharmacokinetics, low CYP inhibition, negative mutagenicity, and oral toxicity class III. Molecular dynamics confirmed stable binding (EGFRWT RMSD 3 Å; EGFRT790M 3.5–4.6 Å) with persistent hydrogen bonds. In silico antiviral evaluation suggested strong binding to HCV NS5A (–9.36 kcal/mol), SARS-CoV-2 Mpro (–9.82 kcal/mol), and E.coli DNA gyrase (–10.25 kcal/mol). Conclusions: Compound 1 exhibits dual anticancer and antibacterial activity, supported by mechanistic and computational analyses, highlighting pyrido[2,3-d]pyrimidines as promising multi-target therapeutic scaffolds. Full article
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14 pages, 1881 KB  
Article
MRI Radiomics for Predicting the Diffuse Type of Tenosynovial Giant Cell Tumor: An Exploratory Study
by Seul Ki Lee, Min Wook Joo, Jee-Young Kim and Mingeon Kim
Diagnostics 2025, 15(18), 2399; https://doi.org/10.3390/diagnostics15182399 - 20 Sep 2025
Viewed by 794
Abstract
Objective: To develop and validate a radiomics-based MRI model for prediction of diffuse-type tenosynovial giant cell tumor (D-TGCT), which has higher postoperative recurrence and more aggressive behavior than localized-type (L-TGCT). The study was conducted under the hypothesis that MRI-based radiomics models can predict [...] Read more.
Objective: To develop and validate a radiomics-based MRI model for prediction of diffuse-type tenosynovial giant cell tumor (D-TGCT), which has higher postoperative recurrence and more aggressive behavior than localized-type (L-TGCT). The study was conducted under the hypothesis that MRI-based radiomics models can predict D-TGCT with diagnostic performance significantly greater than chance level, as measured by the area under the receiver operating characteristic (ROC) curve (AUC) (null hypothesis: AUC ≤ 0.5; alternative hypothesis: AUC > 0.5). Materials and Methods: This retrospective study included 84 patients with histologically confirmed TGCT (54 L-TGCT, 30 D-TGCT) who underwent preoperative MRI between January 2005 and December 2024. Tumor segmentation was manually performed on T2-weighted (T2WI) and contrast-enhanced T1-weighted images. After standardized preprocessing, 1691 radiomic features were extracted, and feature selection was performed using minimum redundancy maximum relevance. Multivariate logistic regression (MLR) and random forest (RF) classifiers were developed using a training cohort (n = 52) and tested in an independent test cohort (n = 32). Model performance was assessed AUC, sensitivity, specificity, and accuracy. Results: In the training set, D-TGCT prevalence was 32.6%; in the test set, it was 40.6%. The MLR model used three T2WI features: wavelet-LHL_glszm_GrayLevelNonUniformity, wavelet-HLL_gldm_LowGrayLevelEmphasis, and square_firstorder_Median. Training performance was high (AUC 0.94; sensitivity 75.0%; specificity 90.9%; accuracy 85.7%) but dropped in testing (AUC 0.60; sensitivity 62.5%; specificity 60.6%; accuracy 61.2%). The RF classifier demonstrated more stable performance [(training) AUC 0.85; sensitivity 43.8%; specificity 87.9%; accuracy 73.5% and (test) AUC 0.73; sensitivity 56.2%; specificity 72.7%; accuracy 67.3%]. Conclusions: Radiomics-based MRI models may help predict D-TGCT. While the MLR model overfitted, the RF classifier demonstrated relatively greater robustness and generalizability, suggesting that it may support clinical decision-making for D-TGCT in the future. Full article
(This article belongs to the Special Issue Innovative Diagnostic Imaging Technology in Musculoskeletal Tumors)
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24 pages, 5298 KB  
Article
Therapeutic Potential of Ozonated Ocimum basilicum L. from Saudi Arabia: Phytochemical Characterization and Enhanced Bioactivities
by Husam Qanash, Sulaiman A. Alsalamah, Abdulrahman S. Bazaid, Mohammed Ibrahim Alghonaim, Amro Duhduh and Ibtisam Hudani
Pharmaceuticals 2025, 18(8), 1223; https://doi.org/10.3390/ph18081223 - 19 Aug 2025
Cited by 1 | Viewed by 1211
Abstract
Background/Objectives: Medicinal plants are an abundant source of bioactive molecules, particularly in arid environments, such as Saudi Arabia, where Ocimum basilicum L. (Saudi basil) has long been used for its therapeutic properties. This study aimed to examine the phytochemical profile and bioactivities [...] Read more.
Background/Objectives: Medicinal plants are an abundant source of bioactive molecules, particularly in arid environments, such as Saudi Arabia, where Ocimum basilicum L. (Saudi basil) has long been used for its therapeutic properties. This study aimed to examine the phytochemical profile and bioactivities of non-ozonated (untreated) and ozonated methanolic extracts of O. basilicum and to determine whether ozonation enhances their biological effects, with a focus on antidiabetic, anti-Alzheimer, anti-inflammatory, antimicrobial, and cytotoxic properties. Methods: Fresh leaves of O. basilicum were extracted with methanol, subjected to ozonation, and analyzed by HPLC. In vitro assays were conducted to evaluate α-amylase, α-glucosidase, and BChE inhibition, RBC membrane stabilization, antibacterial activity against Helicobacter pylori and cytotoxicity using normal lung fibroblasts (WI-38) and human colorectal adenocarcinoma cell line (Caco-2). Results: Ozonation modified the phytochemical profile, enriching chlorogenic and rosmarinic acids. Ozonated extracts exhibited stronger inhibition of α-amylase with an IC50 of 5.09 µg/mL compared to 13.6 µg/mL of untreated Saudi basil and α-glucosidase (IC50 6.15 µg/mL vs. 9.42 µg/mL). They also showed enhanced BChE inhibition with an IC50 of 13.4 µg/mL compared to 31.8 µg/mL of non-ozonated extract. In addition, ozonated extracts produced significant anti-inflammatory effects by stabilizing RBCs, with an IC50 of 8.04 µg/mL compared to 8.44 µg/mL for untreated extracts and 4.41 µg/mL for indomethacin. Ozonated extracts produced larger H. pylori inhibition zones (26.7 mm) and an MBC/MIC ratio of 1. Cytotoxicity testing revealed that ozonated extracts were less toxic to WI-38 cells, with IC50 values of 437.89 µg/mL versus 191.06 µg/mL, and 149.14 µg/mL compared to 103.7 µg/mL of untreated Saudi basil in Caco-2 cells. Conclusions: Ozonation enriches the phytochemical composition of O. basilicum, enhancing antidiabetic, neuroprotective, anti-inflammatory, and antibacterial activities while reducing cytotoxicity on normal cells. These findings support the potential of ozonated O. basilicum as a safe and promising natural therapeutic candidate for metabolic, neurodegenerative, and infectious diseases. Full article
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23 pages, 8591 KB  
Article
Targeting Cellular Senescence with Liposome-Encapsulated Fisetin: Evidence of Senomorphic Effect
by Agata Henschke, Bartosz Grześkowiak, Olena Ivashchenko, María Celina Sánchez-Cerviño, Emerson Coy and Sergio Moya
Int. J. Mol. Sci. 2025, 26(15), 7489; https://doi.org/10.3390/ijms26157489 - 2 Aug 2025
Cited by 1 | Viewed by 3030
Abstract
Cellular senescence is closely connected with cancer progression, recurrence, and metastasis. Senotherapy aims to soothe the harmful effects of senescent cells either by inducing their apoptosis (senolytic) or by suppressing the senescence-associated secretory phenotype (SASP) (senomorphic). Fisetin, a well-studied senotherapeutic drug, was selected [...] Read more.
Cellular senescence is closely connected with cancer progression, recurrence, and metastasis. Senotherapy aims to soothe the harmful effects of senescent cells either by inducing their apoptosis (senolytic) or by suppressing the senescence-associated secretory phenotype (SASP) (senomorphic). Fisetin, a well-studied senotherapeutic drug, was selected for this study to evaluate its efficiency when delivered in a liposomal formulation. The experiment evaluated the impact of liposome-encapsulated fisetin on senescent cells induced by doxorubicin (DOX) from two cell lines: WI-38 (normal lung fibroblasts) and A549 (lung carcinoma). Senescence was characterized by SA-β-galactosidase (SA-β-gal) activity, proliferation, morphology, and secretion of pro-inflammatory interleukin 6 (IL-6) and interleukin 8 (IL-8). Due to fisetin’s hydrophobic nature, it was encapsulated in liposomes to enhance cellular delivery. Cellular uptake studies confirmed that the liposomes were effectively internalized by both senescent cell types. Treatment with fisetin-loaded liposomes revealed a lack of senolytic effects but showed senomorphic activity, as evidenced by a significant reduction in IL-6 and IL-8 secretion in senescent cells. The liposomal formulation enhanced fisetin’s therapeutic efficacy, showing comparable results even at the lowest tested concentration. Full article
(This article belongs to the Section Molecular Pharmacology)
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22 pages, 2732 KB  
Article
Anticancer Activity of Roburic Acid: In Vitro and In Silico Investigation
by Adrianna Gielecińska, Mateusz Kciuk, Somdutt Mujwar, Johannes A. Schmid and Renata Kontek
Int. J. Mol. Sci. 2025, 26(13), 6420; https://doi.org/10.3390/ijms26136420 - 3 Jul 2025
Cited by 1 | Viewed by 1356
Abstract
Natural compounds remain a valuable source of anticancer agents due to their structural diversity and multi-targeted mechanisms of action. Roburic acid (RA), a tetracyclic triterpenoid, has been identified as a substance capable of inhibiting key NF-κB and MAPK signaling pathways through direct interaction [...] Read more.
Natural compounds remain a valuable source of anticancer agents due to their structural diversity and multi-targeted mechanisms of action. Roburic acid (RA), a tetracyclic triterpenoid, has been identified as a substance capable of inhibiting key NF-κB and MAPK signaling pathways through direct interaction with TNF-α, as well as preventing the production of inflammatory mediators and cancer progression. In this study, we evaluated the biological activity of RA against a panel of human cancer cell lines—DLD-1, HT-29, and HCT-116 (colorectal), PC-3 (prostate), and BxPC-3 (pancreatic)—as well as two non-malignant lines: WI-38 (fibroblasts) and CCD-841 CoN (colon epithelium). RA exhibited a concentration-dependent inhibitory effect on cancer cell metabolic activity, with colorectal cancer cells showing relatively higher sensitivity, particularly at shorter incubation times. To distinguish between cytotoxic and cytostatic effects, we performed trypan blue exclusion combined with a cell density assessment, clonogenic assay, and BrdU incorporation assay. The results from these complementary assays confirmed that RA acts primarily through an antiproliferative mechanism rather than by inducing cytotoxicity. In addition, NF-κB reporter assays demonstrated that RA attenuates TNF-α-induced transcriptional activation at higher concentrations, supporting its proposed anti-inflammatory properties and potential to modulate pro-tumorigenic signaling. Finally, our in silico studies predicted that RA may interact with proteins such as CAII, CES1, EGFR, and PLA2G2A, implicating it in the modulation of pathways related to proliferation and cell survival. Collectively, these findings suggest that RA may serve as a promising scaffold for the development of future anticancer agents, particularly in the context of colorectal cancer. Full article
(This article belongs to the Section Molecular Pharmacology)
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