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Search Results (7,143)

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Keywords = plasma proteins

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9 pages, 309 KiB  
Article
Pharmacokinetic Characteristics of Tolfenamic Acid in Freshwater Crocodiles (Crocodylus siamensis)
by Seavchou Laut, Saranya Poapolathep, Kraisiri Khidkhan, Narumol Klangkaew, Napasorn Phaochoosak, Tara Wongwaipairoj, Mario Giorgi, Elisa Escudero, Pedro Marin and Amnart Poapolathep
Animals 2025, 15(5), 684; https://doi.org/10.3390/ani15050684 - 26 Feb 2025
Abstract
The present study was undertaken to characterize the plasma kinetic disposition of tolfenamic acid (TA) in freshwater crocodiles. In total, 15 freshwater crocodiles were used in the experiment and randomly divided into three groups, with TA administered at 2 mg/kg body weight (b.w.) [...] Read more.
The present study was undertaken to characterize the plasma kinetic disposition of tolfenamic acid (TA) in freshwater crocodiles. In total, 15 freshwater crocodiles were used in the experiment and randomly divided into three groups, with TA administered at 2 mg/kg body weight (b.w.) intravenously (IV) or at 2 or 4 mg/kg b.w. intramuscularly (IM). Blood samples were collected at predetermined times up to 168 h after IV or IM drug administration. Plasma concentrations of TA were determined using validated high-performance liquid chromatography with a UV detector and then analyzed based on the non-compartmental method. The maximum concentration values of TA were 3.03 µg/mL and 6.83 µg/mL following IM administration at a dose of 2 mg/kg b.w. or 4 mg/kg b.w., respectively. The elimination half-lives were 21.89 h (2 mg/kg; IV), 17.74 h (2 mg/kg; IM), and 13.57 h (4 mg/kg; IM). Following IV administration, the volume of distribution and clearance were 1.58 L/kg and 50.04 mL/h/kg, respectively. The absolute IM bioavailability was 71.0% at a dose of 2 mg/kg b.w. and 92.63% at a dose of 4 mg/kg b.w. The average ± SD of plasma protein binding of TA was 26.15 ± 4.93%. Good bioavailability levels and favorable plasma concentrations of TA were obtained in freshwater crocodiles after IM administrations, considering that this is the preferred route of drug administration in freshwater crocodiles. Multi-dose and pharmacodynamic studies are needed to better establish the safety and efficacy of using TA in this crocodilian species. Full article
(This article belongs to the Special Issue Pharmacokinetics and Pharmacodynamics in Animal Anesthesiology)
15 pages, 4072 KiB  
Article
Postbiotic Sodium Butyrate Mitigates Hypertension and Kidney Dysfunction in Juvenile Rats Exposed to Microplastics
by You-Lin Tain, Ying-Jui Lin, Chih-Yao Hou, Guo-Ping Chang-Chien, Shu-Fen Lin and Chien-Ning Hsu
Antioxidants 2025, 14(3), 276; https://doi.org/10.3390/antiox14030276 - 26 Feb 2025
Abstract
Background: Plastic production has led to widespread microplastic (MP) pollution, with children more vulnerable to MPs than adults. However, the mechanisms linking MP exposure to hypertension and kidney disease in children remain unclear. This study explored whether sodium butyrate, a short-chain fatty acid [...] Read more.
Background: Plastic production has led to widespread microplastic (MP) pollution, with children more vulnerable to MPs than adults. However, the mechanisms linking MP exposure to hypertension and kidney disease in children remain unclear. This study explored whether sodium butyrate, a short-chain fatty acid (SCFA) with antioxidant and anti-inflammatory properties, could mitigate MP-induced hypertension and kidney damage in juvenile rats. Methods: Male Sprague-Dawley rats (3 weeks old) were randomly assigned to four groups (n = 8/group): control, low-dose MP (1 mg/L), high-dose MP (10 mg/L), and high-dose MP with sodium butyrate (400 mg/kg/day). Rats were euthanized at 12 weeks. Results: High-dose MP exposure impaired kidney function and increased blood pressure, which were alleviated by sodium butyrate through reduced oxidative stress, modulation of gut microbiota, increased plasma butyric acid levels, and enhanced renal SCFA-sensing G protein-coupled receptor 43 expression. Conclusions: Sodium butyrate holds potential for mitigating MP-induced hypertension by reducing oxidative stress, modulating the gut microbiota, and elevating butyric acid levels. Full article
(This article belongs to the Special Issue Environmental Pollution and Oxidative Stress)
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21 pages, 3470 KiB  
Article
Systematic Identification of Phosphate Transporter Family 1 (PHT1) Genes and Their Expression Profiling in Response to Low Phosphorus and Related Hormones in Fagopyrum tataricum (L.) Gaertn.
by Yanyu Zhou, Jianjiang Fan, Qingtao Wu, Haihua Wang, Xiaoyan Huang, Limei Liao, Huan Xie and Xixu Peng
Agronomy 2025, 15(3), 576; https://doi.org/10.3390/agronomy15030576 - 26 Feb 2025
Viewed by 26
Abstract
Accumulating evidence suggests that the plasma membrane-localized phosphate transporter 1 (PHT1) family plays a fundamental role in the absorption, translocation, and re-mobilization of phosphorus in plants. Buckwheat (Fagopyrum spp.) exhibits high efficiency in phosphate uptake and wide adaptability to grow in under-fertilized [...] Read more.
Accumulating evidence suggests that the plasma membrane-localized phosphate transporter 1 (PHT1) family plays a fundamental role in the absorption, translocation, and re-mobilization of phosphorus in plants. Buckwheat (Fagopyrum spp.) exhibits high efficiency in phosphate uptake and wide adaptability to grow in under-fertilized soils. Despite their physiological importance, a systematic analysis of PHT1 genes in buckwheat has not been conducted yet. In this study, we performed a genome-wide identification and expression profile of the PHT1 gene family in Tartary buckwheat (Fagopyrum tataricum Gaertn). A total of eleven putative PHT1 genes (FtPHT1;1 to 1;11) were identified with an uneven distribution on all the F. tataricum chromosomes except for chromosomes 2, 3, and 5. All the FtPHT1s share the conserved domain GGDYPLSATIxSE, a typical signature of PHT1 transporters. A phylogenetic analysis indicated that FtPHT1 proteins could be clustered into four distinct subgroups, well supported by the exon–intron structure, consensus motifs, and the domain architecture. A gene duplication analysis suggested that tandem duplication may largely contribute to the expansion of the FtPHT1 gene family members. In silico predictions of cis-acting elements revealed that low-phosphate-responsive elements, such as W-box, P1BS, and MBS, were enriched in the promoter regions of FtPHT1 genes. Quantitative real-time PCR assays showed differential but partially overlapping expression patterns of some FtPHT1 genes in various organs under limited Pi supply and hormone stimuli, implying that these FtPHT1 transporters may be essential for Pi uptake, translocation, and re-mobilization, possibly through signaling cross-talk between the low phosphate and hormones. These observations provide molecular insights into the FtPHT1 gene family, which paves the way to a functional analysis of FtPHT1 members in the future. Full article
(This article belongs to the Special Issue Crop Genomics and Omics for Future Food Security)
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26 pages, 2630 KiB  
Review
NINJ1 in Cell Death and Ferroptosis: Implications for Tumor Invasion and Metastasis
by Ssu-Yu Chen, Ing-Luen Shyu and Jen-Tsan Chi
Cancers 2025, 17(5), 800; https://doi.org/10.3390/cancers17050800 - 26 Feb 2025
Viewed by 83
Abstract
NINJ1 was initially recognized for its role in nerve regeneration and cellular adhesion. Subsequent studies have uncovered its participation in cancer progression, where NINJ1 regulates critical steps in tumor metastasis, such as cell migration and invasion. More recently, NINJ1 has emerged as a [...] Read more.
NINJ1 was initially recognized for its role in nerve regeneration and cellular adhesion. Subsequent studies have uncovered its participation in cancer progression, where NINJ1 regulates critical steps in tumor metastasis, such as cell migration and invasion. More recently, NINJ1 has emerged as a multifunctional protein mediating plasma membrane rupture (PMR) in several lytic cell death processes, including apoptosis, necroptosis, and pyroptosis. However, its role in ferroptosis—an iron-dependent form of lytic cell death characterized by lipid peroxidation—remained unclear until 2024. Ferroptosis is a tumor suppression mechanism that may be particularly relevant to detached and metastatic cancer cells. This review explores the role of NINJ1 in tumor invasion and metastasis, focusing on its regulation of ferroptosis via a non-canonical mechanism distinct from other cell deaths. We discuss the process of ferroptosis and its implications for cancer invasion and metastasis. Furthermore, we review recent studies highlighting the diverse roles of NINJ1 in ferroptosis regulation, including its canonical function in PMR and its non-canonical function of modulating intracellular levels of glutathione (GSH) and coenzyme A (CoA) via interaction with xCT anti-porter. Given that ferroptosis has been associated with tumor suppression, metastasis, the elimination of treatment-resistant cancer cells, and tumor dormancy, NINJ1′s modulation of ferroptosis presents a promising therapeutic target for inhibiting metastasis. Understanding the dual role of NINJ1 in promoting or restraining ferroptosis depending on cellular context could open avenues for novel anti-cancer strategies to enhance ferroptotic vulnerability in metastatic tumors. Full article
(This article belongs to the Special Issue Cell Biology of Cancer Invasion)
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14 pages, 13271 KiB  
Article
SERPINA3: A Novel Therapeutic Target for Diabetes-Related Cognitive Impairment Identified Through Integrated Machine Learning and Molecular Docking Analysis
by Yu An, Zhaoming Cao, Yage Du, Guangyi Xu, Jingya Wang, Yinchao Ma, Ziyuan Wang, Jie Zheng and Yanhui Lu
Int. J. Mol. Sci. 2025, 26(5), 1947; https://doi.org/10.3390/ijms26051947 - 24 Feb 2025
Viewed by 67
Abstract
Diabetes-related cognitive impairment (DCI) is a severe complication of type 2 diabetes mellitus (T2DM), with limited understanding of its molecular mechanisms hindering effective therapeutic development. This study identified SERPINA3 as a potential therapeutic target for DCI through integrated machine learning and molecular docking [...] Read more.
Diabetes-related cognitive impairment (DCI) is a severe complication of type 2 diabetes mellitus (T2DM), with limited understanding of its molecular mechanisms hindering effective therapeutic development. This study identified SERPINA3 as a potential therapeutic target for DCI through integrated machine learning and molecular docking analyses. Transcriptomic data from cortical neuronal samples of T2DM patients were analysed using support vector machine recursive feature elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO) regression, revealing SERPINA3 as a significantly upregulated gene in DCI. Experimental validation via Western blot confirmed elevated SERPINA3 protein levels in DCI patient plasma. Molecular docking demonstrated the stable binding of sulfonylurea hypoglycaemic agents, such as gliclazide and glimepiride, to SERPINA3, with binding energies of −6.8 and −6.6 kcal/mol, respectively. These findings suggest that SERPINA3 plays a pivotal role in DCI pathogenesis and that sulfonylurea drugs may exert neuroprotective effects through SERPINA3-mediated pathways. This study provides novel insights into the molecular mechanisms of DCI and highlights the potential of SERPINA3-targeted therapies for early intervention and treatment. Further research is warranted to validate these findings in larger cohorts and explore their clinical applicability. Full article
(This article belongs to the Special Issue Neurological Diseases: From Molecular Basis to Therapy)
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16 pages, 2776 KiB  
Article
Agomelatine Mitigates Kidney Damage in Obese Insulin-Resistant Rats by Inhibiting Inflammation and Necroptosis via the TNF-α/NF-ĸB/p-RIPK3 Pathway
by Sasivimon Promsan, Nattavadee Pengrattanachot, Nichakorn Phengpol, Prempree Sutthasupha, La-ongdao Thongnak, Krit Jaikumkao and Anusorn Lungkaphin
Int. J. Mol. Sci. 2025, 26(5), 1940; https://doi.org/10.3390/ijms26051940 - 24 Feb 2025
Viewed by 119
Abstract
Obesity is a risk factor for chronic kidney disease. The expansion of adipose tissues in obesity induces insulin resistance and low-grade systemic inflammation, promoting kidney damage. Our previous studies have demonstrated that agomelatine (AGOM) exerts renoprotective effects in experimental models of obesity and [...] Read more.
Obesity is a risk factor for chronic kidney disease. The expansion of adipose tissues in obesity induces insulin resistance and low-grade systemic inflammation, promoting kidney damage. Our previous studies have demonstrated that agomelatine (AGOM) exerts renoprotective effects in experimental models of obesity and insulin resistance through various mechanisms, including the attenuation of ER stress and oxidative stress. This study aimed to further explore the effects of agomelatine on renal inflammation, insulin signaling, and necroptosis in obese, insulin-resistant rats. Obesity was induced in rats with a high-fat diet for 16 weeks, followed by 4 weeks of treatment with 20 mg kg−1 day−1 of AGOM or 10 mg kg−1 day−1 of pioglitazone (PIO). The results showed that insulin resistance was improved after treatment with AGOM and PIO, as demonstrated by the reduction in fasting plasma glucose, insulin, and HOMA-IR. Both treatments restored the levels of renal insulin signaling proteins. Moreover, AGOM inhibited TNFα, TNFR1, NF-ĸB, COX2, and IL1β, which attenuated the necroptosis-related proteins RIPK3 and MLKL. AGOM also prevented kidney DNA fragmentation, as detected by the TUNEL assay. In an obese condition, the level of the tight junction protein claudin-1 (CLDN1) was enhanced after being treated with AGOM. In conclusion, the novel mechanisms associated with AGOM and involved in limiting kidney injury were the inhibition of the TNFα/NF-ĸB/p-RIPK3 pathway and a reduction in inflammation and necroptosis. This suggested that AGOM could be an effective treatment for inhibiting kidney dysfunction in cases of obesity and insulin resistance. These findings open new avenues for the management of renal dysfunction, with implications for personalized medicine. Full article
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14 pages, 5555 KiB  
Article
Evaluation of Metal Accumulation in Escherichia coli Expressing SPL2 by Single-Cell Inductively Coupled Plasma Mass Spectrometry
by Yasunori Fukumoto, Enhui Li, Yu-ki Tanaka, Noriyuki Suzuki and Yasumitsu Ogra
Int. J. Mol. Sci. 2025, 26(5), 1905; https://doi.org/10.3390/ijms26051905 - 22 Feb 2025
Viewed by 276
Abstract
Rare earth elements, comprising 17 elements including 15 lanthanides, are essential components in numerous high-tech applications. While physicochemical methods are commonly employed to remove toxic heavy metals (e.g., cadmium and mercury) from industrial wastewater, biological approaches offer increasingly attractive alternatives. Biomining, which utilizes [...] Read more.
Rare earth elements, comprising 17 elements including 15 lanthanides, are essential components in numerous high-tech applications. While physicochemical methods are commonly employed to remove toxic heavy metals (e.g., cadmium and mercury) from industrial wastewater, biological approaches offer increasingly attractive alternatives. Biomining, which utilizes microorganisms to extract valuable metals from ores and industrial wastes, and bioremediation, which leverages microorganisms to adsorb and transport metal ions into cells via active transport, provide eco-friendly solutions for resource recovery and environmental remediation. In this study, we investigated the potential of three recently identified lanthanide-binding proteins—SPL2, lanpepsy, and lanmodulin—for applications in these areas using single-cell inductively coupled plasma mass spectrometry (scICP-MS). Our results demonstrate that SPL2 exhibits superior characteristics for lanthanide and cadmium bioremediation. Heterologous expression of a cytosolic fragment of SPL2 in bacteria resulted in high expression levels and solubility. Single-cell ICP-MS analysis revealed that these recombinant bacteria accumulated lanthanum, cobalt, nickel, and cadmium, effectively sequestering lanthanum and cadmium from the culture media. Furthermore, SPL2 expression conferred enhanced bacterial tolerance to cadmium exposure. These findings establish SPL2 as a promising candidate for developing recombinant bacterial systems for heavy metal bioremediation and rare earth element biomining. Full article
(This article belongs to the Special Issue Mechanisms of Heavy Metal Toxicity: 3rd Edition)
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18 pages, 2155 KiB  
Article
Towards Rapid and Low-Cost Stroke Detection Using SERS and Machine Learning
by Cristina Freitas, João Eleutério, Gabriela Soares, Maria Enea, Daniela Nunes, Elvira Fortunato, Rodrigo Martins, Hugo Águas, Eulália Pereira, Helena L. A. Vieira, Lúcio Studer Ferreira and Ricardo Franco
Biosensors 2025, 15(3), 136; https://doi.org/10.3390/bios15030136 - 22 Feb 2025
Viewed by 264
Abstract
Stroke affects approximately 12 million individuals annually, necessitating swift diagnosis to avert fatal outcomes. Current hospital imaging protocols often delay treatment, underscoring the need for portable diagnostic solutions. We have investigated silver nanostars (AgNS) incubated with human plasma, deposited on a simple aluminum [...] Read more.
Stroke affects approximately 12 million individuals annually, necessitating swift diagnosis to avert fatal outcomes. Current hospital imaging protocols often delay treatment, underscoring the need for portable diagnostic solutions. We have investigated silver nanostars (AgNS) incubated with human plasma, deposited on a simple aluminum foil substrate, and utilizing Surface-Enhanced Raman Spectroscopy (SERS) combined with machine learning (ML) to provide a proof-of-concept for rapid differentiation of stroke types. These are the seminal steps for the development of low-cost pre-hospital diagnostics at point-of-care, with potential for improving patient outcomes. The proposed SERS assay aims to classify plasma from stroke patients, differentiating hemorrhagic from ischemic stroke. Silver nanostars were incubated with plasma and spiked with glial fibrillary acidic protein (GFAP), a biomarker elevated in hemorrhagic stroke. SERS spectra were analyzed using ML to distinguish between hemorrhagic and ischemic stroke, mimicked by different concentrations of GFAP. Key innovations include optimized AgNS–plasma incubates formation, controlled plasma-to-AgNS ratios, and a low-cost aluminum foil substrate, enabling results within 15 min. Differential analysis revealed stroke-specific protein profiles, while ML improved classification accuracy through ensemble modeling and feature engineering. The integrated ML model achieved rapid and precise stroke predictions within seconds, demonstrating the assay’s potential for immediate clinical decision-making. Full article
(This article belongs to the Special Issue Surface-Enhanced Raman Scattering in Biosensing Applications)
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12 pages, 1374 KiB  
Article
Application of Biomimetic Chromatography and QSRR Approach for Characterizing Organophosphate Pesticides
by Katarzyna Ewa Greber, Karol Topka Kłończyński, Julia Nicman, Beata Judzińska, Kamila Jarzyńska, Yash Raj Singh, Wiesław Sawicki, Tomasz Puzyn, Karolina Jagiello and Krzesimir Ciura
Int. J. Mol. Sci. 2025, 26(5), 1855; https://doi.org/10.3390/ijms26051855 - 21 Feb 2025
Viewed by 124
Abstract
Biomimetic chromatography is a powerful tool used in the pharmaceutical industry to characterize the physicochemical properties of molecules during early drug discovery. Some studies have indicated that biomimetic chromatography may also be useful for the evaluation of toxicologically relevant molecules. In this study, [...] Read more.
Biomimetic chromatography is a powerful tool used in the pharmaceutical industry to characterize the physicochemical properties of molecules during early drug discovery. Some studies have indicated that biomimetic chromatography may also be useful for the evaluation of toxicologically relevant molecules. In this study, we evaluated the usefulness of the biomimetic chromatography approach for determining the lipophilicity, affinity to phospholipids, and bind to plasma proteins of selected organophosphate pesticides. Quantitative structure–retention relationship (QSRR) models were proposed to understand the structural features that influence the experimentally determined properties. ACD/labs, Chemicalize, and alvaDesc software were used to calculate theoretical descriptors. Multilinear regression was used as the regression type, and feature selection was supported by a genetic algorithm. The obtained QSRR models were validated internally and externally, and they demonstrated satisfactory performance with key statistical parameters ranged from 0.844 to 0.914 for R2 and 0.696–0.898 for R2ext, respectively, indicating good predictive ability. Full article
(This article belongs to the Special Issue Molecular Toxicology on the Environmental Impact of Pharmaceuticals)
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15 pages, 1559 KiB  
Article
Novel Approach to Rule-Out Unnecessary Urine Bence Jones Protein Testing: A Serum Free Light Chain Algorithm
by Vanessa García Moreira, Javier Cepeda Piorno, Jùlia Sanders Vegara, Ana Eyo González, Cristina Alberdi García del Castillo, Claudia González García, Nana Vaktangova, Sandra García Castañón, Daniel Al Kassam Martínez, Paula Chávez Collazos and Esther González García
Diagnostics 2025, 15(5), 525; https://doi.org/10.3390/diagnostics15050525 - 21 Feb 2025
Viewed by 179
Abstract
Background/Objectives: Bence Jones proteins (BJPs) are monoclonal immunoglobulin free light chains (FLCs) that appear in the urine of patients with plasma cell disorders, including multiple myeloma (MM), Waldenström’s macroglobulinemia (WM), or light chain amyloidosis (AL). Their presence can provide valuable information about disease [...] Read more.
Background/Objectives: Bence Jones proteins (BJPs) are monoclonal immunoglobulin free light chains (FLCs) that appear in the urine of patients with plasma cell disorders, including multiple myeloma (MM), Waldenström’s macroglobulinemia (WM), or light chain amyloidosis (AL). Their presence can provide valuable information about disease progression and treatment efficacy. These proteins are typically detected through a 24-h urine collection, as recommended by clinical guidelines. However, this method can be inconvenient for both patients and laboratory personnel due to its time-consuming nature and the potential for collection errors. We propose an algorithm based on serum FLC (sFLC) to rule out the presence of BJPs and diminish the need for urine testing. Methods: A retrospective data analysis of 268 serum and urine samples from 44 patients with MM was performed, and cutoffs were established to predict BJP absence: total urine protein (0.115 g/L), sFLC κ/λ ratio (>0.82 λ monoclonality and <1.99 κ monoclonality), and difference of involved–uninvolved FLC (dFLC; <11.93 mg/L). A subsequent algorithm validation was performed in 716 samples from patients who underwent the same testing in routine 2023 other laboratory activity. Results: The validation of these cutoffs to rule out the presence of BJP showed that, if the protocol based on the sFLC κ/λ ratio and dFLC had been applied, 42% of the urine studies would have been avoided, achieving a sensitivity of 93.9% and a false negative rate of 6.11%. Conclusions: We propose a laboratory work protocol that would allow for the avoidance of almost half of the 24-h urine studies based on sFLC measurement, a faster and more objective alternative to urine analysis for screening out the presence of BJP, with a good sensitivity and a low false negative rate. Full article
(This article belongs to the Special Issue Diagnosis, Prognosis and Management of Hematologic Malignancies)
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17 pages, 3774 KiB  
Article
Design, Synthesis, and Biological Evaluation of a Novel [18F]AlF-H3RESCA-FAPI Radiotracer Targeting Fibroblast Activation Protein
by Qingyu Zhang, Zhoumi Hu, Haitao Zhao, Fuqiang Du, Chun Lv, Tukang Peng, Yukai Zhang, Bowu Zhang, Jianjun Liu and Cheng Wang
Pharmaceuticals 2025, 18(2), 277; https://doi.org/10.3390/ph18020277 - 19 Feb 2025
Viewed by 261
Abstract
Background: Cancer-associated fibroblasts (CAFs) are key contributors to the tumorigenic process, with fibroblast activation protein (FAP) overexpressed on CAFs in numerous epithelial carcinomas. FAP represents a promising target for tumor imaging and therapy. We aimed to develop a novel [18F]AlF-H3 [...] Read more.
Background: Cancer-associated fibroblasts (CAFs) are key contributors to the tumorigenic process, with fibroblast activation protein (FAP) overexpressed on CAFs in numerous epithelial carcinomas. FAP represents a promising target for tumor imaging and therapy. We aimed to develop a novel [18F]AlF-H3RESCA-FAPI radiotracer with a high labeling yield at room temperature for positron emission tomography (PET) imaging of FAP-expressing tumors. Methods: The H3RESCA-FAPI chelator was synthesized and radiolabeled with [18F]AlF. Its radiotracer binding affinity to FAP was assessed using surface plasmon resonance (SPR). Its in vitro stability, plasma clearance, and biodistribution were evaluated. PET imaging was performed in U87MG tumor-bearing mice, with a blocking study to assess tracer specificity. Results: The [18F]AlF-H3RESCA-FAPI radiotracer demonstrated a high binding affinity to FAP (KD < 10.09 pM) and favorable radiochemical yields (92.4 ± 2.4%) with >95% radiochemical purity. In vitro and in vivo studies showed good stability and rapid clearance from non-target tissues. PET imaging revealed specific tumor uptake, which was significantly reduced by co-injection with unlabeled DOTA-FAPI-04. Conclusions: [18F]AlF-H3RESCA-FAPI is a promising radiotracer for PET imaging of FAP-expressing tumors. Further optimization of its pharmacokinetics could make it a potential candidate for clinical translation. Full article
(This article belongs to the Section Radiopharmaceutical Sciences)
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19 pages, 1621 KiB  
Review
Non-Melanoma Skin Cancer: Assessing the Systemic Burden of the Disease
by Emmanouil Karampinis, Dimitra Koumaki, Dimitrios Sgouros, Paraskevi-Maria Nechalioti, Olga Toli, Georgia Pappa, Marios Papadakis, Konstantina-Eirini Georgopoulou, Angeliki-Victoria Schulze-Roussaki and Demetrios Kouretas
Cancers 2025, 17(4), 703; https://doi.org/10.3390/cancers17040703 - 19 Feb 2025
Viewed by 333
Abstract
The emergence of systemic therapies and photoprotection against non-melanoma skin cancer (NMSC) raises questions on the broader systematic impact of the disease. Personalized medicine involves a holistic patient approach, through which the evaluation of systemic biomarkers can reveal the interconnected aspects of patient [...] Read more.
The emergence of systemic therapies and photoprotection against non-melanoma skin cancer (NMSC) raises questions on the broader systematic impact of the disease. Personalized medicine involves a holistic patient approach, through which the evaluation of systemic biomarkers can reveal the interconnected aspects of patient health and tailored therapies. Cumulative UV exposure disrupts redox equilibrium and triggers inflammation and cutaneous immunosuppression, processes that contribute independently or via their interplay to cutaneous carcinogenesis. This systemic impact can be further reinforced by biomolecules derived from the NMSC microenvironment, fueling a continuous cycle of oxidative stress and inflammation in the organism. Regarding investigation of the systemic burden of NMSC, we conducted a narrative review focusing on parameters related to redox status, inflammation, and immune suppression observed in the blood components (serum, plasma, and erythrocytes) of NMSC patients. Our findings revealed an association of NMSC patients with perturbations of redox homeostasis, as evidenced by the decreased antioxidant activity, lower levels of non-enzymatic antioxidants, and increased byproducts of lipid, protein, and DNA oxidative damage. Additionally, NMSC patients presented augmented levels of pro-inflammatory interleukins, reduced anti-tumor biomolecule levels, and enhanced immune response markers, as well as elevated vitamin D levels. These systemic changes may lead to the association of NMSC with a higher risk of secondary malignancies in other organs. Overall, the findings of the present study suggest that NMSC affects systemic health beyond the skin, underscoring the need for a comprehensive and individualized approach to the management and monitoring of the patient. Full article
(This article belongs to the Special Issue Skin Cancer: Epidemiology, Management and New Therapies)
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25 pages, 363 KiB  
Review
Exploring the Potential of Non-Cellular Orthobiologic Products in Regenerative Therapies for Stifle Joint Diseases in Companion Animals
by Maria Guerra-Gomes, Carla Ferreira-Baptista, Joana Barros, Sofia Alves-Pimenta, Pedro Gomes and Bruno Colaço
Animals 2025, 15(4), 589; https://doi.org/10.3390/ani15040589 - 18 Feb 2025
Viewed by 241
Abstract
Stifle joint diseases present a significant challenge in companion animals that often lead to hind limb lameness, with osteoarthritis being a prevalent degenerative condition causing pain and reduced mobility. Regenerative medicine offers a promising avenue for improving treatment outcomes, with a range of [...] Read more.
Stifle joint diseases present a significant challenge in companion animals that often lead to hind limb lameness, with osteoarthritis being a prevalent degenerative condition causing pain and reduced mobility. Regenerative medicine offers a promising avenue for improving treatment outcomes, with a range of emerging therapies showing potential to alleviate symptoms and promote joint health. Among these, hyaluronic acid and platelet-rich plasma have been widely used as intra-articular treatments to enhance joint lubrication, reduce inflammation, and provide symptomatic relief. Interleukin-1 receptor antagonist protein, autologous conditioned serum, and autologous protein solution represent the next generation of regenerative therapies, offering more disease-modifying effects by inhibiting key mediators of joint inflammation. More recently, the MSC-derived secretome has emerged as an innovative, cell-free approach that leverages the diverse bioactive factors secreted by MSCs to support tissue repair and modulate inflammation. This review highlights the evidence base behind these non-cellular orthobiologic treatments for stifle joint disease, aiming to inform veterinary practitioners and owners about available options and their efficacy in supporting conventional treatments. Full article
(This article belongs to the Section Companion Animals)
14 pages, 2915 KiB  
Article
Effects of Daratumumab (Anti-CD38) Monoclonal Antibody Therapy on Flow Cytometry Analysis in Multiple Myeloma
by Sharon Koorse Germans, Christine Wamsley Kahlow, Weina Chen and Franklin Fuda
Therapeutics 2025, 2(1), 2; https://doi.org/10.3390/therapeutics2010002 - 18 Feb 2025
Viewed by 235
Abstract
Background: Plasma cell myeloma is an incurable malignancy of clonal plasma cells. Recent success in immunotherapeutic strategies has altered the landscape of myeloma treatment. Daratumumab is an anti-CD38 IgG kappa monoclonal antibody that has shown great efficacy in the treatment of myeloma. However, [...] Read more.
Background: Plasma cell myeloma is an incurable malignancy of clonal plasma cells. Recent success in immunotherapeutic strategies has altered the landscape of myeloma treatment. Daratumumab is an anti-CD38 IgG kappa monoclonal antibody that has shown great efficacy in the treatment of myeloma. However, Daratumumab brought with it new challenges in post-therapeutic laboratory assessment, including therapeutic antibody interference with serum protein electrophoresis and serum immunofixation electrophoresis assays. In this study, we highlight the interference identified in post-therapeutic flow cytometry analysis related to bound Daratumumab on normal hematopoietic cells. We also highlight the methods of detection of residual plasma cell neoplasm, post-Daratumumab therapy.: A total of 28 patients with refractory plasma cell myeloma who received Daratumumab (2016–2018) were included in this study. Flow cytometry was performed using 4- or 10-color antibody panels (BD FASC Canto) and analyzed by cluster analysis (Cytopaint Classic software) using four tube panels including VS38c for measurable residual disease (MRD) testing. Pretreatment and post-Daratumumab follow-up bone marrow flow cytometry samples were analyzed. In addition, 10 multiple myeloma patient samples were reflexed to multi-epitope CD38 analysis by flow cytometric analysis of post-Daratumumab residual disease. When discussing CD38 expression, we will refer to CD38 as being detected by conventional reagents. Results: All post-Daratumumab-treated cases (100%) showed negative staining for CD38 using conventional reagents on all plasma cells in the specimens. MRD testing successfully identified small clonal plasma cell populations using VS38C and multi-epitope CD38 (meCD38) antibodies, despite the absence of demonstrable CD38 expression. Additionally, all cases exhibited weak kappa light chain staining on hematogones, attributed to the binding of Daratumumab kappa monoclonal antibody. This interaction can create the appearance of a CD10+ monotypic B-cell population. We also noted diminished CD38 staining on myeloblasts, resulting in an atypical CD34/CD38 staining pattern. This alteration could potentially be misinterpreted as indicative of a myelodysplastic neoplasm (MDS). Furthermore, decreased staining of CD38 was noted on T cells, natural killer (NK) cells, basophils, monocytes, and plasmacytoid dendritic cells. Conclusions: With the emergence of successfully targeted immunotherapies, such as anti-CD38 antibodies, it is important to understand and correctly interpret variations in flow cytometry that may arise from the therapy. Hematogones exhibit high-intensity levels of CD38 expression; thus, Daratumumab binds to them, creating the appearance of kappa expression on all hematogones. Stage I/early stage II hematogones normally lack surface immunoglobulin light chain expression, but in the presence of Daratumumab, they appear to be a CD10(+) monotypic population of B cells. The misinterpretation of these normal cells as a CD10(+) B-cell clone can lead to inaccurate assessment, unnecessary bone marrow immunohistochemical evaluation, and unwarranted anxiety. Additionally, artefacts on various other hematopoietic cells can result in inaccurate assessments of immunophenotypic aberrancy due to binding of the drug. This may lead to the false interpretation of a secondary/therapy-related myeloid neoplasm. This study highlights in detail the interferences that must be considered when assessing residual disease in the era of targeted drug therapies. Full article
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13 pages, 3198 KiB  
Article
A Sequential Ultrafiltration Method to Enhance the Accuracy and Throughput in Plasma Protein Binding Tests
by Sang Ho Jeon, Min Chang Kim, Haejun Lee, Ju-Hee Oh, Hyun Seo Kim, Heawon Lee, Taehoon Park and Young-Joo Lee
Pharmaceutics 2025, 17(2), 273; https://doi.org/10.3390/pharmaceutics17020273 - 18 Feb 2025
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Abstract
Objectives: Ultrafiltration (UF) is widely accepted as a method for assessing the plasma protein binding (PPB) of drugs. However, it is vulnerable to non-specific binding (NSB) to the device, which can result in inaccuracies. This study presents a straightforward, high-throughput modified UF [...] Read more.
Objectives: Ultrafiltration (UF) is widely accepted as a method for assessing the plasma protein binding (PPB) of drugs. However, it is vulnerable to non-specific binding (NSB) to the device, which can result in inaccuracies. This study presents a straightforward, high-throughput modified UF method aimed at minimizing bias due to NSB. Methods: The modified UF method, sequential UF, features the addition of a 2 min pre-UF phase designed to saturate the NSB in the device, followed by the main 20 min UF procedure, compared to the conventional UF method. To evaluate the feasibility of this sequential UF method, we measured the PPB of nine compounds using sequential UF and compared these results to those obtained with the conventional mass balance UF method, recognized as a standard for NSB correction. Results: The PPB values determined through sequential UF were generally consistent with those derived from the mass balance UF method. The fold differences ranged from 97.9% to 113.8%, with an average of 103.5%. No significant differences were observed between the two methods for all compounds, with the exception of quercetin, which showed an unusually high PPB. Conclusions: Sequential UF was effective in correcting NSB to the device while providing advantages in terms of simplicity and efficiency. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
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