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16 pages, 2545 KiB  
Article
Combined Pharmacological Conditioning of Endothelial Cells for Improved Vascular Graft Endothelialization
by Zhiyao Lu, Xuqian Zhou, Xiaowen Liu, Chunyan Liu, Junfeng Zhang and Lei Dong
Int. J. Mol. Sci. 2025, 26(15), 7183; https://doi.org/10.3390/ijms26157183 - 25 Jul 2025
Viewed by 90
Abstract
The development of functional endothelial monolayers on synthetic vascular grafts remains challenging, particularly for small-diameter vessels (<6 mm) prone to thrombosis. Here, we present a pharmacological strategy combining 8-(4-chlorophenylthio) adenosine 3′,5′-cyclic monophosphate sodium salt (pCPT-cAMP, a tight junction promoter) with nitric oxide/cGMP pathway [...] Read more.
The development of functional endothelial monolayers on synthetic vascular grafts remains challenging, particularly for small-diameter vessels (<6 mm) prone to thrombosis. Here, we present a pharmacological strategy combining 8-(4-chlorophenylthio) adenosine 3′,5′-cyclic monophosphate sodium salt (pCPT-cAMP, a tight junction promoter) with nitric oxide/cGMP pathway agonists 3-morpholinosydnonimine (SIN-1), captopril, and sildenafil) to enhance endothelialization. In human umbilical vein endothelial cells (HUVECs), this four-agent cocktail induced a flat, extended phenotype with a 3-fold increased cell area and 57.5% fewer cells required for surface coverage compared to controls. Immunofluorescence analysis revealed enhanced ZO-1 expression and continuous tight junction formation, while sustained nitric oxide (NO) production (3.9-fold increase) and restored prostacyclin (PGI2) secretion demonstrated preserved endothelial functionality. Anticoagulation assays confirmed a significant reduction in thrombus formation (p < 0.01) via dual inhibition of platelet activation and thrombin binding. These findings establish a synergistic drug combination that promotes rapid endothelialization while maintaining antithrombogenic activity, offering a promising solution for small-diameter vascular grafts. Further studies should validate long-term stability and translational potential in preclinical models. Full article
(This article belongs to the Section Molecular Pharmacology)
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15 pages, 4132 KiB  
Article
Crotoxin-Loaded Silica Nanoparticles: A Nanovenom Approach
by Florencia Silvina Conti, Exequiel Giorgi, Laura Montaldo, Juan Pablo Rodríguez, Mauricio Cesar De Marzi and Federico Gastón Baudou
Pharmaceutics 2025, 17(7), 879; https://doi.org/10.3390/pharmaceutics17070879 - 4 Jul 2025
Viewed by 359
Abstract
Background: Ophidism is a globally neglected health problem. In Argentina, Crotalus durissus terrificus (C.d.t., South American rattlesnake) is one of the species of greatest medical importance since its venom contains mainly crotoxin (CTX), a potent enzyme–toxin with PLA2 activity, [...] Read more.
Background: Ophidism is a globally neglected health problem. In Argentina, Crotalus durissus terrificus (C.d.t., South American rattlesnake) is one of the species of greatest medical importance since its venom contains mainly crotoxin (CTX), a potent enzyme–toxin with PLA2 activity, which is responsible for its high lethality. Objective: In this work, we aimed to generate nanovenoms (NVs), complexes formed by CTX adsorbed onto 150 nm silica nanoparticles (SiNPs), and to study their physicochemical, biological, and immunomodulatory activities for potential use as adjuvants (ADJs) in antivenom (AV) production. Methods: CTX was isolated and corroborated by SDS-PAGE. Then, CTX was adsorbed on the synthetized Stöber SiNPs’ surfaces, forming a monolayer and retaining its biological activity (as observed by the MTT cell proliferation assay using the THP-1 cell line). Results: Immunomodulatory activity revealed a high pro-inflammatory (IL-1β) response induced by SiNPs followed by NVs. In the case of the anti-inflammatory response, NVs presented significant differences for TGF-β only after cell activation with LPS. No significant differences were observed in IL-10 levels. Conclusions: Thus, these results suggest that NVs together with SiNPs could increase immunogenicity and enhance immune response, turning them into potential tools for the generation of new antivenoms. Full article
(This article belongs to the Special Issue Delivery System for Biomacromolecule Drugs: Design and Application)
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20 pages, 994 KiB  
Article
Impact of Different Thermal Processing Techniques on the Phytochemical Composition, Antioxidant Capacity, and DNA-Protective Properties of Broccoli
by Karlo Miškec, Marta Frlin and Ivana Šola
Appl. Sci. 2025, 15(13), 7469; https://doi.org/10.3390/app15137469 - 3 Jul 2025
Viewed by 389
Abstract
Vegetables are usually thermally processed before consumption to improve their flavor and safety. In this work, the effect of boiling (BO), blanching (BL), steaming (ST), air-frying (AF), and pan-frying (PF)on the nutritional value and bioactivity of broccoli (Brassica oleracea var. italica) [...] Read more.
Vegetables are usually thermally processed before consumption to improve their flavor and safety. In this work, the effect of boiling (BO), blanching (BL), steaming (ST), air-frying (AF), and pan-frying (PF)on the nutritional value and bioactivity of broccoli (Brassica oleracea var. italica) heads was investigated, including a comparative analysis of the tissue and the cooking water remaining after the treatments. Using spectrophotometric methods, AF broccoli was found to have the highest levels (p ≤ 0.05) of hydroxycinnamic acids (1.58 ± 0.71 mg CAE/g fw), total glucosinolates (3.76 ± 2.09 mg SinE/g fw), carotenoids (6.73 ± 2.89 mg/kg fw), and lycopene (0.91 ± 0.19 mg/kg fw). Steamed and AF broccoli had the highest total phenolics (0.72 ± 0.12 mg GAE/g fw and 0.65 ± 0.15 mg GAE/g fw, respectively; p ≤ 0.05). ST broccoli also had the highest levels of soluble sugars (11.04 ± 2.45 mg SucE/g fw) and total tannins (0.46 ± 0.19 mg GAE/g fw). The water remaining after cooking broccoli (BOW) had the highest total flavonoids (2.72 ± 0.59 mg QE/g fw) and antioxidant capacity (ABTS and FRAP, 57.57 ± 18.22% and 79.34 ± 3.28%, respectively; p ≤ 0.05). The DPPH assay showed that AF (36.12 ± 15.71%) and ST (35.48 ± 2.28%) had the strongest antioxidant potential. DNA nicking assay showed that BOW and BLW were the most effective in preserving plasmid DNA supercoiled form (99.51% and 94.81%, respectively; p ≤ 0.05). These results demonstrate that thermal processing significantly affects the phytochemical composition and functional properties of broccoli, with steaming and air-frying generally preserving the highest nutritional quality. Additionally, cooking water, often discarded, retains high levels of bioactive compounds and exhibits strong antioxidant and DNA-protective effects. To the best of our knowledge, this is the first study to investigate how different thermal processing techniques of vegetables influence their ability to protect plasmid DNA structure. Furthermore, this is the first study to compare the DNA-protective effects of broccoli tissue extracts and the water remaining after cooking broccoli. Full article
(This article belongs to the Special Issue New Trends in the Structure Characterization of Food)
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25 pages, 3946 KiB  
Review
Application Possibilities of Sustainable Nanostructured Silica-Based Materials in Cosmetics
by Veronica Latini, Agnieszka Feliczak-Guzik and Agata Wawrzyńczak
Cosmetics 2025, 12(4), 134; https://doi.org/10.3390/cosmetics12040134 - 25 Jun 2025
Viewed by 707
Abstract
Nanostructured silica-based materials, including mesoporous silica nanoparticles (SiNPs), show a wide range of applications in various areas, such as food, pharmaceutical, and cosmetic industries. This is mainly due to their unique properties, namely biocompatibility, stability, adjustable pore size, a highly developed specific surface [...] Read more.
Nanostructured silica-based materials, including mesoporous silica nanoparticles (SiNPs), show a wide range of applications in various areas, such as food, pharmaceutical, and cosmetic industries. This is mainly due to their unique properties, namely biocompatibility, stability, adjustable pore size, a highly developed specific surface area, and simplicity in surface modification. Currently, special emphasis is placed on obtaining nanostructured silica-based materials using so-called green methods, which not only reduce toxic by-products, but also enable the use of raw materials from plants, agricultural and industrial waste, as well as bacteria or fungi. This trend is particularly evident in the cosmetic industry, which is striving to reduce the adverse environmental and social impacts of cosmetic production. Therefore, this article presents a review of the literature from the last ten years, which describes issues related to the possibilities of replacing synthetic silica-based ingredients in cosmetic products with their more environmentally friendly counterparts. Special emphasis has been placed on the application possibilities of sustainable nanostructured silica-based materials and their potential toxicity in topical formulations. The possibilities of obtaining nanostructured silica-based materials through green synthesis and using natural silica precursors have been briefly presented, as well as the options for modifying the surface of these materials. Full article
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16 pages, 1185 KiB  
Article
Iliotibial Band Behavior Assessed Through Tensor Fasciae Latae Electromyographic Activity with Different Foot Orthoses in Recreational Runners According to Foot Type: A Cross-Sectional Study
by Ruben Sanchez-Gomez, Álvaro Gómez Carrión, Ismael Ortuño Soriano, Paola Sanz Wozniak, Ignacio Zaragoza García, Fatma Ben Waer, Cristina Iona Alexe and Dan Iulian Alexe
J. Funct. Morphol. Kinesiol. 2025, 10(3), 237; https://doi.org/10.3390/jfmk10030237 - 23 Jun 2025
Viewed by 401
Abstract
Background: Iliotibial band syndrome (ITBS) through the tensor fascia latae (TFL) is a well-known pathology among runners whose etiology is not completely clear, nor is the effectiveness of plantar insoles for different types of feet known well enough for them to be considered [...] Read more.
Background: Iliotibial band syndrome (ITBS) through the tensor fascia latae (TFL) is a well-known pathology among runners whose etiology is not completely clear, nor is the effectiveness of plantar insoles for different types of feet known well enough for them to be considered a possible approach for this issue. Objective: to understand how foot type and foot orthotics may influence the electromyographic (EMG) activity of the TFL. Methods: A total of 41 healthy recreational runners (mean age 32.66 ± 3.51) were recruited for the present cross-sectional study, categorizing them as neutral (NEUg = 15), supinators (SUPg = 15), and pronators (PROg = 11) according to the foot postural index, over a period of 11 months. The EMG of the TFL was measured using a surface electromyograph device while they ran on a treadmill at a constant speed of 9 km/h for 3 min, randomly using supinating (SUP), pronating (PRO), or heel lift (TAL) insoles of 5 mm each one, compared to the baseline condition (SIN). The intraclass correlation coefficient (ICC) was performed to check the reproducibility of the tests, pairwise comparisons with Bonferroni adjustment were made, and to test the differences between measurements, the Friedman test was performed. Results: The Shapiro–Wilk test indicated a normal distribution of the sample (p > 0.05). Almost all obtained results showed a “perfect reproducibility” close to one; a significant statistical increase was observed in the mean EMG values from NEUg (87.58 ± 4.81 mV) to SUPg (97.17 ± 4.3 mV) (p < 0.05) during SIN+ basal condition. Additionally, there was a statistical reduction from SIN (87.58 ± 4.81 mV) vs. PRO (74.69 ± 3.77 mV) (p < 0.001) in NEUg and from SIN (97.17 ± 4.3 mV) vs. PRO (90.96 ± 4 mV) (p < 0.001) in SUPg. Conclusions: The SUPg exhibited increased activation of TFL fibers compared to the NEUg, likely due to the biomechanical demands associated with a supinated foot type. In contrast, the use of PRO appeared to promote relaxation of the TFL fibers by inducing internal rotation of the lower limb. Based on these preliminary results from a cross-sectional study in a healthy population, it is recommended to assess foot type when addressing ITBS and to consider the use of PRO as a complementary therapeutic strategy alongside conventional treatments. Full article
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19 pages, 24617 KiB  
Article
Research on Sinomenine Inhibiting the cGAS-STING Signaling Pathway to Alleviate Renal Inflammatory Injury in db/db Mice
by Xiaofei Jin, Tongtong He, Tianci Zhang, Xiaorong Wang, Xiangmei Chen, Bin Cong and Weijuan Gao
Pharmaceuticals 2025, 18(7), 934; https://doi.org/10.3390/ph18070934 - 20 Jun 2025
Viewed by 374
Abstract
Objectives: This study aims to elucidate the potential molecular mechanism of Sinomenine (SIN) in treating renal injury in Diabetic Nephropathy (DN) through network pharmacology, molecular docking, and in vivo validation. Materials and Methods: db/db mice were used as a DN model to [...] Read more.
Objectives: This study aims to elucidate the potential molecular mechanism of Sinomenine (SIN) in treating renal injury in Diabetic Nephropathy (DN) through network pharmacology, molecular docking, and in vivo validation. Materials and Methods: db/db mice were used as a DN model to evaluate the therapeutic effects of SIN on body weight, blood glucose levels, renal function, and histopathology. Network pharmacology and molecular docking were integrated to predict the potential molecular mechanisms of SIN in DN treatment. Subsequently, in vivo validation was performed on db/db mice using ELISA, Western blotting, RT-qPCR, immunofluorescence, and immunohistochemistry. Results: Firstly, we found that SIN (62.4 mg/kg) improved general conditions and renal function in db/db mice, alleviating renal pathological damage. Network pharmacology analysis identified IL-1β, IL-6, and TNF-α as key targets of SIN in DN. SIN reduced IL-1β, IL-6, and TNF-α levels by inhibiting the cGAS/STING signaling pathway and its downstream p-TBK1, p-IRF3, and NF-κB expression. Conclusions: SIN alleviates inflammatory injury in DN, potentially through the cGAS/STING pathway. Full article
(This article belongs to the Section Natural Products)
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15 pages, 1742 KiB  
Article
Silicon Reduce Structural Carbon Components and Its Potential to Regulate the Physiological Traits of Plants
by Baiying Huang, Danghui Xu, Wenhong Zhou, Yuqi Wu and Wei Mou
Plants 2025, 14(12), 1779; https://doi.org/10.3390/plants14121779 - 11 Jun 2025
Viewed by 376
Abstract
Phosphorus (P) and silicon (Si) could profoundly affect the net primary productivity (ANPP) of grassland ecosystems. However, how ecosystem biomass will respond to different Si addition, especially under a concurrent increase in P fertilization, remains limited. With persistent demand for grassland utilization, there [...] Read more.
Phosphorus (P) and silicon (Si) could profoundly affect the net primary productivity (ANPP) of grassland ecosystems. However, how ecosystem biomass will respond to different Si addition, especially under a concurrent increase in P fertilization, remains limited. With persistent demand for grassland utilization, there is a need to enhance and sustain the productivity of grasslands on the Qinghai–Tibet Plateau. Three P addition rates (0, 400, 800, and 1200 kg Ca(H2PO4)2 ha−1 yr−1) without Si and with Si (14.36 kg H4SiO4 ha−1 yr−1) were applied to alpine grassland on the Qinghai–Tibet Plateau to evaluate the responses of aboveground biomass and the underlying mechanisms linking to structural carbon composition and physiological traits of grasses and forbs. Our results show that the application of Si significantly reduced the lignin, cellulose, hemicellulose, and total phenol contents of both grasses and forbs. Additionally, the addition of P, Si, and phosphorus and silicon (PSi) co-application significantly increased the net photosynthetic rate (Pn) and light use efficiency (LUE) of grasses and forbs. Moreover, Si promoted the absorption of N and P by plants, resulting in significant changes in the Si:C, Si:P, and Si:N ratios and increasing the aboveground biomass. Our findings suggest that Si can replace structural carbohydrates and regulate the absorption and utilization of N and P to optimize the photosynthetic process of leaves, thereby achieving greater biomass. In summary, Si supplementation improves ecosystem stability in alpine meadows by optimizing plant functions and increasing biomass accumulation. Full article
(This article belongs to the Special Issue Silicon and Its Physiological Role in Plant Growth and Development)
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37 pages, 1769 KiB  
Review
Economic and Social Aspects of the Space Sector Development Based on the Modified Structure–Conduct–Performance Framework
by Michał Pietrzak
World 2025, 6(2), 79; https://doi.org/10.3390/world6020079 - 1 Jun 2025
Viewed by 2440
Abstract
Background: The global space economy has grown remarkably, witnessing a 10-fold increase in active satellites during the last 15 years. This growth was accompanied by both the increase in geopolitical tensions feeding huge investments (the New Space Race), on the one hand, and [...] Read more.
Background: The global space economy has grown remarkably, witnessing a 10-fold increase in active satellites during the last 15 years. This growth was accompanied by both the increase in geopolitical tensions feeding huge investments (the New Space Race), on the one hand, and the transformation, shifting from a domain historically dominated by government-led programs to one partially energized by commercial players and innovative business models (“New Space”), on the other hand. Objective: To assess the space economy’s current state and future prospects by considering its economic and social dimensions. Methods: Over 120 scholarly articles and “grey” literature positions (e.g., industry reports) were reviewed. The review was structured by a modified Structure–Conduct–Performance framework originally developed by industrial organization (IO) scholars. Findings: Outer space creates extremely harsh conditions for placing and operating objects in orbits, which results in high launching costs, steep reliability standards, capital intensity, and risks that are unmatched in most terrestrial industries. One of the main motivations to venture into this harsh domain was, and still is, the desire to dominate or the fear of being subjugated by others. This “original sin”, born of geopolitical rivalries, continues to cast a shadow over the space economy, channeling the majority of public space budgets into military-related programs. Moreover, many space technologies have a dual-use feature. Not surprisingly, governments are still the major source of demand, dominating midstream in the space value chain. This triad—harsh physics, great power rivalry, and a state-centric midstream—produces a specificity of the sector. In the recent two decades, new entrants (called “New Space”) have begun altering market structure, resulting in new conduct patterns focused on pursuits towards serial production, reusability, and lowering costs. Performance outcomes are mixed. While some efficiency gains are unprecedented, some doubts about market power and negative externalities arise. The assessment of the space economy’s performance is a challenge, as such, due to the blurred boundary between political objectives (supplying public goods, mitigating negative externalities) and economic optimization. Such trade-offs are becoming even more complicated considering the potential conflict between national and global perspectives. The paper offers a preliminary, descriptive study of the space economy through the lens of the modified S-C-P framework, laying basic foundations for the future, possibly more rigorous research of the increasingly important space economy. Full article
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17 pages, 836 KiB  
Review
Silicon Nanoparticles and Apoplastic Protein Interaction: A Hypothesized Mechanism for Modulating Plant Growth and Immunity
by Guopeng Miao, Juan Han and Taotao Han
Plants 2025, 14(11), 1630; https://doi.org/10.3390/plants14111630 - 27 May 2025
Viewed by 622
Abstract
Silicon nanoparticles (SiNPs) have emerged as multifunctional tools in sustainable agriculture, demonstrating significant efficacy in promoting crop growth and enhancing plant resilience against diverse biotic and abiotic stresses. Although their ability to strengthen antioxidant defense systems and activate systemic immune responses is well [...] Read more.
Silicon nanoparticles (SiNPs) have emerged as multifunctional tools in sustainable agriculture, demonstrating significant efficacy in promoting crop growth and enhancing plant resilience against diverse biotic and abiotic stresses. Although their ability to strengthen antioxidant defense systems and activate systemic immune responses is well documented, the fundamental mechanisms driving these benefits remain unclear. This review synthesizes emerging evidence to propose an innovative paradigm: SiNPs remodel plant redox signaling networks and stress adaptation mechanisms by forming protein coronas through apoplastic protein adsorption. We hypothesize that extracellular SiNPs may elevate apoplastic reactive oxygen species (ROS) levels by adsorbing and inhibiting antioxidant enzymes, thereby enhancing intracellular redox buffering capacity and activating salicylic acid (SA)-dependent defense pathways. Conversely, smaller SiNPs infiltrating symplastic compartments risk oxidative damage due to direct suppression of cytoplasmic antioxidant systems. Additionally, SiNPs may indirectly influence heavy metal transporter activity through redox state regulation and broadly modulate plant physiological functions via transcription factor regulatory networks. Critical knowledge gaps persist regarding the dynamic composition of protein coronas under varying environmental conditions and their transgenerational impacts. By integrating existing mechanisms of SiNPs, this review provides insights and potential strategies for developing novel agrochemicals and stress-resistant crops. Full article
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20 pages, 4632 KiB  
Article
Endosomal H2O2 Molecules Act as Signaling Mediators in Akt/PKB Activation
by Sujin Park, Chaewon Kim, Sukyeong Heo and Dongmin Kang
Antioxidants 2025, 14(5), 594; https://doi.org/10.3390/antiox14050594 - 16 May 2025
Viewed by 557
Abstract
Receptor-mediated endocytosis (RME) is a commonly recognized receptor internalization process of receptor degradation or recycling. However, recent studies have supported that RME is closely related to signal propagation and amplification from the plasma membrane to the cytosol. Few studies have elucidated the role [...] Read more.
Receptor-mediated endocytosis (RME) is a commonly recognized receptor internalization process of receptor degradation or recycling. However, recent studies have supported that RME is closely related to signal propagation and amplification from the plasma membrane to the cytosol. Few studies have elucidated the role of H2O2, a mild oxidant among reactive oxygen species (ROS) in RME and second messenger of signal propagation. In the present study, we investigated the regulatory function of H2O2 in early endosomes during signaling throughout receptor-mediated endocytosis. In mammalian cells with a physiological amount of H2O2 generated during epidermal growth factor (EGF) activation, fluorescence imaging showed that the levels of two activating phosphorylations on Ser473 and Thr308 of Akt were transiently increased in the plasma membrane, but the predominant p-Akt on Ser473 appeared in early endosomes. To examine the role of endosomal H2O2 molecules as signaling mediators of Akt activation in endosomes, we modulated endosomal H2O2 through the ectopic expression of an endosomal-targeting catalase (Cat-Endo). The forced removal of endosomal H2O2 inhibited the Akt phosphorylation on Ser473 but not on Thr308. The levels of mSIN and rictor, two components of mTORC2 that work as a kinase in Akt phosphorylation on Ser473, were also selectively diminished in the early endosomes of Cat-Endo-expressing cells. We also observed a decrease in the endosomal level of the adaptor protein containing the PH domain, the PTB domain, and the Leucine zipper motif 1 (APPL1) protein, which is an effector of Rab5 and key player in the assembly of signaling complexes regulating the Akt pathway in Cat-Endo-expressing cells compared with those in normal cells. Therefore, the H2O2-dependent recruitment of the APPL1 adaptor protein into endosomes was required for full Akt activation. We proposed that endosomal H2O2 is a promoter of Akt signaling. Full article
(This article belongs to the Special Issue Metabolic Dysfunction and Oxidative Stress)
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10 pages, 1544 KiB  
Article
Role of Denosumab in Patients with Intermediate Spinal Instability Neoplastic Score (SINS)
by JunYeop Lee, Bong-Soon Chang, Hyoungmin Kim, Sung Taeck Kim, Seonpyo Jang and Sam Yeol Chang
Cancers 2025, 17(9), 1539; https://doi.org/10.3390/cancers17091539 - 1 May 2025
Viewed by 403
Abstract
Objectives: The current study aimed to evaluate the effect of denosumab on patients with impending instability due to spinal metastasis, including whether it can improve spinal instability neoplastic score (SINS) and reduce the need for surgical treatment. Methods: This study retrospectively reviewed patients [...] Read more.
Objectives: The current study aimed to evaluate the effect of denosumab on patients with impending instability due to spinal metastasis, including whether it can improve spinal instability neoplastic score (SINS) and reduce the need for surgical treatment. Methods: This study retrospectively reviewed patients initially treated non-operatively for metastatic spinal lesions with intermediate SINS (7–12 points) between January 2017 and December 2023 in a single tertiary cancer hospital. Patients were divided into two groups based on the use of denosumab for the intermediate SINS lesion: D-group and N-group. Propensity score matching (PSM) was conducted with a caliper width of 0.025 for the covariates (age, sex, and primary cancer). The study outcomes were (1) the rate of conversion to surgery, (2) the change in SINS, and (3) the change in HU (Hounsfield unit) during the follow-up period. Results: A total of 286 patients (male 151, female 135) with a mean age of 68.0 ± 12.6 years and a mean follow-up period of 37.1 ± 26.5 months were included. Forty-one (14.3%) patients received denosumab (D-group), whereas 245 (85.7%) did not receive denosumab (N-group). Before PSM, 9.8% (4/41) in the D-group and 18.8% (46/245) in the N-group underwent surgical treatment. The rate of conversion to surgery was similar after PSM: the D-group, 8.3% (3/36) vs. the N-group, 16.6% (6/36). Survival analysis using Kaplan–Meier curves also showed that the D-group had a significantly lower probability of conversion to surgery before and after PSM (p = 0.015 and p = 0.023, respectively). In addition, the D-group showed significant improvements in the SINS (total score, pain, and bone lesion scores) and HU after denosumab treatment. Conclusions: In this study, denosumab lowered the rate of conversion to surgery in patients with impending instability (intermediate SINS) due to spinal metastasis. Patients who received denosumab treatment showed significant improvements in the SINS and HU for their metastatic spinal lesions. Full article
(This article belongs to the Special Issue Advances in Spine Oncology: Research and Clinical Studies)
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9 pages, 204 KiB  
Article
The Early Detection of Malignant Transformation of Potentially Malignant Disorders: Oral Lichen Planus
by Camilla Lüdecke, Heinrich Neumann and Torsten W. Remmerbach
Cancers 2025, 17(9), 1489; https://doi.org/10.3390/cancers17091489 - 28 Apr 2025
Viewed by 650
Abstract
Background: The aim of this study was to evaluate the usefulness of close clinical surveillance intervals combined with oral brush biopsies to enable the early detection of malignant transformations in patients with oral lichen planus (OLP) performed in our oral medicine clinic. Methods: [...] Read more.
Background: The aim of this study was to evaluate the usefulness of close clinical surveillance intervals combined with oral brush biopsies to enable the early detection of malignant transformations in patients with oral lichen planus (OLP) performed in our oral medicine clinic. Methods: This retrospective study was carried out on 414 patients suffering from OLP, based on pre-established clinical and histopathological criteria, who received long-term follow-up between 1993–2022 (ranging from 6 months to 22.2 years). Results: A total of 297 patients were included in this study. Four people developed an oral squamous cell carcinoma (OSCC) during the observation period. Patients with close follow-up intervals were detected at early stages (two cases showed histologically SIN III and one patient was classified as having a pT1N0M0 tumour). One case was dropped in the consultation hour during the COVID19 pandemic and appeared again two years later, staged as a pT3N1M0 tumour based on an OLP. Three of the cases were clinically doubtful, which led to brush biopsies. Afterwards, additional DNA-image cytometry was performed, in which all the specimens of brush biopsies showed aneuploidy as a marker for malignancy, regarding both stem line and single cell aneuploidy. Conclusions: A careful surveillance programme consisting of check-ups every 3–4 months, oral brush biopsies, and static DNA image cytometry in cytologically diagnosed doubtful or suspicious cases assures the early detection of malignant transformation in the cancer’s early intraepithelial and microinvasive stages. Full article
(This article belongs to the Special Issue Oral Potentially Malignant Disorders and Oral Cavity Cancer)
10 pages, 2336 KiB  
Article
Effect of the Occurrence State of Dodecylamine on the Adsorption Behavior of Calcium Sulfate Dihydrate and Silica
by Xu Li, Renjie Chen and Lan Xiang
Minerals 2025, 15(4), 413; https://doi.org/10.3390/min15040413 - 14 Apr 2025
Viewed by 448
Abstract
In this work, the effects of dodecylamine storage state on the adsorption behavior of calcium sulfate dihydrate and silica were systematically investigated by using Raman detection, solution equilibrium calculation, and calculation based on density functional theory. The results show that the selective adsorption [...] Read more.
In this work, the effects of dodecylamine storage state on the adsorption behavior of calcium sulfate dihydrate and silica were systematically investigated by using Raman detection, solution equilibrium calculation, and calculation based on density functional theory. The results show that the selective adsorption behavior of dodecylamine with calcium sulfate dihydrate and silica is closely related to its occurrence state. The adsorption of dodecylamine in the ionic state with calcium sulfate dihydrate and silica is dominated by the strong electrostatic adsorption between the H-O atoms under acidic conditions, while that of dodecylamine in the molecular state is dominated by the weak electrostatic adsorption between the Ca-N or Si-N atoms under alkaline conditions. Finally, by comparing the distribution coefficients and adsorption energies of the ionic/molecular states of dodecylamine with the change in pH, the reason why dodecylamine adsorbs calcium sulfate dihydrate more readily under acidic conditions was explained at the atomic level. Full article
(This article belongs to the Section Mineral Processing and Extractive Metallurgy)
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15 pages, 1521 KiB  
Article
Safety Profile, Toxicokinetic, and Intestinal Absorption Differences of a Naturally-Derived Anti-Rheumatic Drug, Sinomenine Hydrochloride, in Normal and Arthritic Rats
by Yini He, Hong Huang, Gejing Li, Ye Zhang, Junjie He, Ye Lin, Feichi Wu, Jianye Yan, Xiong Cai and Liang Liu
Pharmaceutics 2025, 17(4), 484; https://doi.org/10.3390/pharmaceutics17040484 - 7 Apr 2025
Viewed by 485
Abstract
Background/Objective: Sinomenine hydrochloride (SH), a natural anti–rheumatic drug derived from the Chinese medicinal plant Sinomenium acutum, demonstrates disease–modifying properties but lacks comprehensive safety and toxicokinetic (TK) comparisons between physiological and pathological states. This study evaluated SH’s safety profile, TK parameters, and [...] Read more.
Background/Objective: Sinomenine hydrochloride (SH), a natural anti–rheumatic drug derived from the Chinese medicinal plant Sinomenium acutum, demonstrates disease–modifying properties but lacks comprehensive safety and toxicokinetic (TK) comparisons between physiological and pathological states. This study evaluated SH’s safety profile, TK parameters, and intestinal absorption differences in adjuvant–induced arthritis (AIA) and normal rats. Methods: Safety assessments determined median lethal doses (LD50) in female Sprague Dawley rats. TK parameters were analyzed via a validated ultrahigh performance liquid chromatography-tandem mass spectrometry approach after single oral administration of 600 mg/kg SH. Plasma protein binding (PPB) were measured using equilibrium dialysis. Intestinal absorption was evaluated through everted gut sac experiments, with P–glycoprotein (P–gp) inhibition tested via verapamil co–administration. Results: LD50 values revealed AIA rats tolerated SH better than normal rats (1179 vs. 805 mg/kg). TK analysis showed that Cmax, AUC(0-t), and AUC(0-∞) of SIN in normal rats were 2.01, 1.94, and 2.14 times higher than in AIA rats, respectively, while CL/F and V/F in AIA rats were 2.24 times greater. In addition, the PPB of SIN in normal rats was 2 times greater than that in AIA rats. AIA rats exhibited significantly lower SH absorption in the jejunum and ileum compared to normal rats. Notably, verapamil co–administration markedly increased SH absorption across most intestinal segments. Conclusions: Pathological states significantly alter SH’s safety and TK profiles. Enhanced tolerance in AIA rats correlates with reduced intestinal absorption via altered P–gp activity and decreased PPB. These findings emphasize the necessity of disease–specific evaluations for optimizing SH’s therapeutic safety in pathological contexts. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
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15 pages, 1536 KiB  
Article
Screening of Piglets for Signs of Inflammation and Necrosis as Early Life Indicators of Animal Health and Welfare Hazards
by Karien Koenders-van Gog, Thomas Wijnands, Mirjam Lechner, Gerald Reiner and Johanna Fink-Gremmels
Animals 2025, 15(3), 378; https://doi.org/10.3390/ani15030378 - 28 Jan 2025
Cited by 1 | Viewed by 1661
Abstract
Ensuring animal health and well-being requires animal-based measures for early and direct intervention at the point of care. Insight into the pathophysiology of Swine Inflammation and Necrosis Syndrome (SINS) has led to a non-invasive, clinical scoring system that can be used in daily [...] Read more.
Ensuring animal health and well-being requires animal-based measures for early and direct intervention at the point of care. Insight into the pathophysiology of Swine Inflammation and Necrosis Syndrome (SINS) has led to a non-invasive, clinical scoring system that can be used in daily practice. This provides information on the cause of observed lesions for direct intervention in affected herds. The aim of the current study was to re-evaluate the practicality of the SINS scoring system under field conditions. In addition, this is the first study to provide insight into the prevalence of SINS on Dutch farms. This study involved the scoring of 5958 piglets from 20 visits on 13 farms randomly selected by a veterinary practice in the Netherlands. The results showed that up to 64.1% of the piglets had visible inflammatory alterations in different body parts within the first seven days of life. Sow rectal temperature, signs of coprostasis and water intake during pregnancy were significantly (p ≤ 0.05) correlated with the prevalence of SINS in piglets. In conclusion, the SINS scoring system is an easy-to-use, non-invasive diagnostic tool that summarises animal-based observations at the point of care, providing a valuable communication tool between farmers, nutritionists and veterinarians in their efforts to improve animal health and welfare. Full article
(This article belongs to the Section Animal Welfare)
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