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Search Results (16,928)

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16 pages, 2267 KiB  
Article
Placenta-Derived Mesenchymal Stem Cells (pMSCs) Reverse Diabetes-Associated Endothelial Complications in a Preclinical Animal Model
by Yasser Basmaeil, Ahmed Bakillah, Abdullah Mohammed Al Subayyil, Haya Nasser Bin Kulayb, Maha Abdullah AlRodayyan, Abeer Al Otaibi, Sindiyan Al Shaikh Mubarak, Hassan S. Alamri, Altaf A. Kondkar, Jahangir Iqbal and Tanvir Khatlani
Int. J. Mol. Sci. 2025, 26(16), 8057; https://doi.org/10.3390/ijms26168057 (registering DOI) - 20 Aug 2025
Abstract
Diabetes is increasingly recognized as a chronic inflammatory disease marked by systemic metabolic disturbances, with endothelial dysfunction playing a central role in its complications. Hyperglycemia, a hallmark of diabetes, drives endothelial damage by inducing excessive reactive oxygen species (ROS) production, particularly hydrogen peroxide [...] Read more.
Diabetes is increasingly recognized as a chronic inflammatory disease marked by systemic metabolic disturbances, with endothelial dysfunction playing a central role in its complications. Hyperglycemia, a hallmark of diabetes, drives endothelial damage by inducing excessive reactive oxygen species (ROS) production, particularly hydrogen peroxide (H2O2). This oxidative stress impairs endothelial cells, which are vital for vascular health, leading to severe complications such as diabetic nephropathy, retinopathy, and coronary artery disease—major causes of morbidity and mortality in diabetic patients. Recent studies have highlighted the therapeutic potential of placenta-derived mesenchymal stem cells (pMSCs), in mitigating these complications. pMSCs exhibit anti-inflammatory, antioxidant, and tissue-repair properties, showing promise in reversing endothelial damage in laboratory settings. To explore their efficacy in a more physiologically relevant context, we used a streptozotocin (STZ)-induced diabetic mouse model, which mimics type 1 diabetes by destroying pancreatic beta cells and causing hyperglycemia. pMSCs were administered via intra-peritoneal injections, and their effects on endothelial injury and tissue damage were assessed. Metabolic tests, including glucose tolerance tests (GTTs) and insulin tolerance tests (ITTs) revealed that pMSCs did not restore metabolic homeostasis or improve glucose regulation. However, histopathological kidney, heart, and eye tissue analyses demonstrated significant protective effects. pMSCs preserved glomerular structure in the kidneys, protected cardiac blood vessels, and maintained retinal integrity, suggesting their potential to address diabetes-related tissue injuries. Although these findings underscore the therapeutic potential of pMSCs for diabetic complications, further research is needed to optimize dosing, elucidate molecular mechanisms, and evaluate long-term safety and efficacy. Combining pMSCs with other therapies may enhance their benefits, paving the way for future clinical applications. Full article
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22 pages, 956 KiB  
Review
Photodithazine-Mediated Antimicrobial Photodynamic Therapy: A Systematic Review of Efficacy and Applications
by Rafał Wiench, Jakub Fiegler-Rudol, Kinga Grzech-Leśniak, Dariusz Skaba and Josep Arnabat-Dominguez
Int. J. Mol. Sci. 2025, 26(16), 8049; https://doi.org/10.3390/ijms26168049 (registering DOI) - 20 Aug 2025
Abstract
Antimicrobial resistance is a critical global health issue exacerbated by biofilm-associated infections that often resist conventional therapies. Photodithazine-mediated antimicrobial photodynamic therapy (PDZ-aPDT) has emerged as a promising alternative, demonstrating a broad-spectrum antimicrobial efficacy against multidrug-resistant bacteria and fungi, including those in biofilms. This [...] Read more.
Antimicrobial resistance is a critical global health issue exacerbated by biofilm-associated infections that often resist conventional therapies. Photodithazine-mediated antimicrobial photodynamic therapy (PDZ-aPDT) has emerged as a promising alternative, demonstrating a broad-spectrum antimicrobial efficacy against multidrug-resistant bacteria and fungi, including those in biofilms. This systematic review evaluates the efficacy, safety, and clinical applications of PDZ-aPDT by synthesizing evidence from preclinical and clinical studies. Databases including PubMed, Embase, Scopus, and Cochrane were systematically searched, resulting in the inclusion of 13 studies for qualitative analysis. PDZ-aPDT consistently reduced the microbial burden in various models, including oral candidiasis, denture stomatitis, acne, and infections related to medical devices. Synergistic combinations with conventional antimicrobials and adjunctive therapies (e.g., DNase I) further enhanced its effectiveness. However, the evidence base remains limited by methodological variability, small sample sizes, and short follow-up periods. Future research should focus on rigorous clinical trials with standardized protocols and extended follow-up to establish definitive efficacy and safety profiles, facilitating a broader clinical implementation in combating antimicrobial resistance. Full article
(This article belongs to the Special Issue Photodynamic Therapy and Photodetection, 2nd Edition)
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21 pages, 2829 KiB  
Systematic Review
Comparative Safety of Anticoagulant, Antiplatelet and the Combination of Both for Acute Coronary Syndrome: A Systematic Review and Network Meta-Analysis
by Qingsheng Niu, Ziyi Zhu, Fulin Wang and Yaowen Jiang
Biomedicines 2025, 13(8), 2027; https://doi.org/10.3390/biomedicines13082027 - 20 Aug 2025
Abstract
Background: Antithrombotic therapy plays an important role in acute coronary syndrome (ACS). The combination of anticoagulant and antiplatelet therapy resulted in fewer complications and stronger potency compared to traditional monotherapy. Our net meta-analysis aimed to compare and rank the safety of different treatments [...] Read more.
Background: Antithrombotic therapy plays an important role in acute coronary syndrome (ACS). The combination of anticoagulant and antiplatelet therapy resulted in fewer complications and stronger potency compared to traditional monotherapy. Our net meta-analysis aimed to compare and rank the safety of different treatments used in patients with ACS. Method: We conducted a search for trials in three prominent databases. The main objective of our investigation was to assess hemorrhage. Additional outcomes included mortality, myocardial infarction, stroke, and embolism. We used a frequentist network meta-analysis with a random-effects model to, directly and indirectly, compare safety across different antithrombotic strategies. Result: A total of 30 randomized clinical trials were included in this net meta-analysis with 135,471 ACS patients. In these eight different antithrombotic therapies, SAPT (single-agent platelet inhibitor therapy) showed the lowest risk of bleeding (SUCRA = 0.5%). The highest risk of bleeding was observed in VKA (vitamin K antagonists) + DAPT (dual antiplatelet therapy) (SUCRA = 99.8%). Bleeding among NOAC (non-vitamin K antagonist oral anticoagulants) + DAPT was found to be higher than DAPT (OR = 1.94, 95% CI = 1.42–2.65). NOAC + SAPT significantly reduced the embolism (OR = 1.50, 95% CI = 1.16–1.94) and myocardial infarction (OR = 1.22, 95% CI = 1.08–1.37) events compared with SAPT. In addition, VKA significantly reduced the rate of stroke compared with SAPT (OR = 3.45, 95% CI = 1.17–10.18). However, no significant difference was observed in death events among these eight antithrombotic therapies. Conclusions: We advise against the use of SAPT in ACS due to its elevated risk of embolism, myocardial infarction, and stroke. It is important to mention that the combination of NOAC and SAPT has a lower incidence of myocardial infarction, bleeding and embolism problems. Therefore, the combination of NOAC and SAPT may be the optimal approach to achieve a balance between the risks of bleeding and embolism. This meta-analysis was registered in PROSPERO with the registration number CRD42024542826. Full article
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32 pages, 4089 KiB  
Review
Latest Advances in Inhalable Dry Powder Bacteriophage Therapy for Pulmonary Infections
by David Encinas-Basurto, Patricia Dolores Martinez-Flores, Joselyn García, Marco Antonio Lopez-Mata, Gerardo García-González, Gerardo E. Rodea, Basanth Babu Eedara, Heidi M. Mansour and Josue Juarez
Pharmaceutics 2025, 17(8), 1077; https://doi.org/10.3390/pharmaceutics17081077 - 20 Aug 2025
Abstract
The concerning increase in respiratory infections that are resistant to multiple drugs has led to a growing interest in bacteriophage therapy as a potential alternative to conventional antibiotics. Effective phage delivery to the lungs, however, presents several formulation and stability issues, particularly for [...] Read more.
The concerning increase in respiratory infections that are resistant to multiple drugs has led to a growing interest in bacteriophage therapy as a potential alternative to conventional antibiotics. Effective phage delivery to the lungs, however, presents several formulation and stability issues, particularly for inhalation-based methods. This review highlights current developments in the creation of dry powder formulations that can be inhaled for pulmonary phage therapy, with a focus on encapsulation methods based on nanoparticles, such as solid lipid nanoparticles (SLNs) and polymer-based nanoparticles. These carriers enhance the aerodynamic characteristics of phages, making them suitable for deep lung deposition, while also protecting them during processing and storage. Several drying methods have been investigated to create powders with optimal morphologies, porosity, and dispersibility, including spray drying and spray freeze drying. The review also emphasizes how the phage morphotype affects stability, especially when nebulization stress is present. Furthermore, the advantages of nanoparticle matrices are confirmed by the reduced viability loss (usually < 0.5 log PFU) of encapsulated phages. Standardizing production processes, scaling up, and ensuring regulatory compliance remain challenging despite encouraging preclinical results. The combination of phage therapy with nanotechnology creates new avenues for the utilization of inhalable delivery methods to treat multidrug-resistant pulmonary infections. To translate these novel formulations from preclinical development to clinical application, sustained multidisciplinary collaboration across pharmaceutical sciences, microbiology, and clinical pharmacology is essential. Full article
29 pages, 1172 KiB  
Review
Oncolytic Herpes Simplex Virus Therapy: Latest Advances, Core Challenges, and Future Outlook
by Yiyang Zheng, Yusheng Pei, Chunyan Dong, Jinghui Liang, Tong Cai, Yuan Zhang, Dejiang Tan, Junzhi Wang and Qing He
Vaccines 2025, 13(8), 880; https://doi.org/10.3390/vaccines13080880 (registering DOI) - 20 Aug 2025
Abstract
Oncolytic virus (OV) immunotherapy, particularly with oncolytic herpes simplex virus (oHSV), has become a promising new strategy in cancer treatment. This field has achieved significant clinical milestones, highlighted by the FDA approval of Talimogene laherparepvec (T-VEC) for melanoma in 2015 and the approval [...] Read more.
Oncolytic virus (OV) immunotherapy, particularly with oncolytic herpes simplex virus (oHSV), has become a promising new strategy in cancer treatment. This field has achieved significant clinical milestones, highlighted by the FDA approval of Talimogene laherparepvec (T-VEC) for melanoma in 2015 and the approval of Teserpaturev/G47Δ for malignant glioma in Japan in 2021. This review synthesizes the key preclinical and clinical advancements in oHSV therapy over the last decade, critically analyzing the core challenges in target selection, genetic modification, administration routes, and targeted delivery. Key findings indicate that arming oHSV with immunomodulatory transgenes, such as cytokines and antibodies, and combining it with immune checkpoint inhibitors are critical strategies for enhancing therapeutic efficacy. Future research will focus on precision engineering using CRISPR/Cas9, the development of novel delivery vehicles like nanoparticles and mesenchymal stem cells (MSCs), and biomarker-guided personalized medicine, aiming to provide safer and more effective solutions for refractory cancers. This review synthesizes oHSV advances and analyzes novel delivery and gene-editing strategies. Full article
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35 pages, 1045 KiB  
Review
Biomarkers in Heart Failure: A Review and a Wish
by Laura Asta, Calogera Pisano, Adriana Sbrigata, Giuseppe Maria Raffa, Letizia Scola and Carmela Rita Balistreri
Int. J. Mol. Sci. 2025, 26(16), 8046; https://doi.org/10.3390/ijms26168046 (registering DOI) - 20 Aug 2025
Abstract
Natriuretic peptides (NPs) have significantly improved the assessment and management of patients with heart failure (HF), but they present several limitations. It is now clear that no single biomarker can adequately guide the diagnosis, prognosis, and outcomes of HF. Therefore, the use of [...] Read more.
Natriuretic peptides (NPs) have significantly improved the assessment and management of patients with heart failure (HF), but they present several limitations. It is now clear that no single biomarker can adequately guide the diagnosis, prognosis, and outcomes of HF. Therefore, the use of multiple biomarkers, correlated with HF pathophysiology, may improve HF management. An exponential number of emerging biomarkers have been reported in the literature, and when combined, they demonstrate greater clinical relevance than when used alone. They are also increasingly used as targets in the development of innovative treatments, such as targeted and personalized therapies. Their identification and clinical relevance could also be facilitated by the application of artificial intelligence models and the use of multi-omics approaches. This article presents a detailed overview of emerging biomarkers, potential targets, and innovative therapies, illustrating their advantages and limitations, as well as possible solutions to overcome them, and highlighting their strong, promising potential. This could enable the prediction of the spread of this disease in the general population, enabling early diagnosis and limiting complications and mortality. The path to achieving this goal is arduous, but it is achievable. This will require further efforts by researchers and clinicians with diverse multidisciplinary expertise. Full article
33 pages, 2196 KiB  
Review
Redefining Chemoresistance: Natural Bioactives as Molecular Modulators at the Cancer–Tumor Microenvironment Interface
by Claudia Reytor-González, Emilia Jiménez-Flores, Natalí González and Daniel Simancas-Racines
Int. J. Mol. Sci. 2025, 26(16), 8037; https://doi.org/10.3390/ijms26168037 (registering DOI) - 20 Aug 2025
Abstract
Therapeutic resistance remains a critical barrier in effective cancer treatment, contributing to disease recurrence, progression, and reduced patient survival. In recent years, natural bioactive compounds have emerged as promising adjuncts in oncology due to their ability to modulate multiple biological processes involved in [...] Read more.
Therapeutic resistance remains a critical barrier in effective cancer treatment, contributing to disease recurrence, progression, and reduced patient survival. In recent years, natural bioactive compounds have emerged as promising adjuncts in oncology due to their ability to modulate multiple biological processes involved in resistance. This review explores current evidence on the role of natural compounds in influencing cancer cell behavior and their interactions with the tumor microenvironment. By organizing these compounds into chemical families, we provide a structured overview of their potential to enhance the efficacy of standard chemotherapy and reduce resistance-related mechanisms. We also highlight innovative strategies, including combination therapies and advanced drug delivery systems, that aim to improve their clinical applicability. Overall, this work underscores the relevance of integrating natural bioactives into modern cancer therapy and calls for further translational research to bridge preclinical findings with clinical implementation. Full article
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23 pages, 1615 KiB  
Review
Current Mechanobiological Pathways and Therapies Driving Spinal Health
by Rahul Kumar, Kyle Sporn, Harlene Kaur, Akshay Khanna, Phani Paladugu, Nasif Zaman and Alireza Tavakkoli
Bioengineering 2025, 12(8), 886; https://doi.org/10.3390/bioengineering12080886 (registering DOI) - 20 Aug 2025
Abstract
Spinal health depends on the dynamic interplay between mechanical forces, biochemical signaling, and cellular behavior. This review explores how key molecular pathways, including integrin, yeas-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), Piezo, and Wingless/Integrated (Wnt) with β-catenin, actively shape the [...] Read more.
Spinal health depends on the dynamic interplay between mechanical forces, biochemical signaling, and cellular behavior. This review explores how key molecular pathways, including integrin, yeas-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), Piezo, and Wingless/Integrated (Wnt) with β-catenin, actively shape the structural and functional integrity of spinal tissues. These signaling mechanisms respond to physical cues and interact with inflammatory mediators such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α), driving changes that lead to disc degeneration, vertebral fractures, spinal cord injury, and ligament failure. New research is emerging that shows scaffold designs that can directly harness these pathways. Further, new stem cell-based therapies have been shown to promote disc regeneration through targeted differentiation and paracrine signaling. Interestingly, many novel bone and ligament scaffolds are modulating anti-inflammatory signals to enhance tissue repair and integration, as well as prevent scaffold degradation. Neural scaffolds are also arising. These mimic spinal biomechanics and activate Piezo signaling to guide axonal growth and restore motor function. Scientists have begun combining these biological platforms with brain–computer interface technology to restore movement and sensory feedback in patients with severe spinal damage. Although this technology is not fully clinically ready, this field is advancing rapidly. As implantable technology can now mimic physiological processes, molecular signaling, biomechanical design, and neurotechnology opens new possibilities for restoring spinal function and improving the quality of life for individuals with spinal disorders. Full article
(This article belongs to the Special Issue Biomechanics and Mechanobiology in Cell and Tissue Engineering)
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25 pages, 2729 KiB  
Article
Therapeutic Effects of Neuro-Cells on Amyloid Pathology, BDNF Levels, and Insulin Signalling in APPswe/PSd1E9 Mice
by Johannes P. J. M. de Munter, Andrey Tsoy, Kseniia Sitdikova, Erik Ch. Wolters, Kirill Chaprov, Konstantin B. Yenkoyan, Hamlet Torosyan, Sholpan Askarova, Daniel C. Anthony and Tatyana Strekalova
Cells 2025, 14(16), 1293; https://doi.org/10.3390/cells14161293 - 20 Aug 2025
Abstract
Stem cell therapies, including mesenchymal (MSCs) and haematopoietic stem cells (HSCs), have shown promise in neurodegenerative diseases. Here, we investigated the therapeutic effects of a defined combination of unmanipulated MSCs and CD34+ HSCs, termed Neuro-Cells (NC), in a murine model of Alzheimer’s [...] Read more.
Stem cell therapies, including mesenchymal (MSCs) and haematopoietic stem cells (HSCs), have shown promise in neurodegenerative diseases. Here, we investigated the therapeutic effects of a defined combination of unmanipulated MSCs and CD34+ HSCs, termed Neuro-Cells (NC), in a murine model of Alzheimer’s disease (AD), the APPswe/PS1dE9 mouse. At 12 months of age, mice received intracisternal injections of NC (1.39 × 106 MSCs + 5 × 105 HSCs) or vehicle. After 45 days, behavioural testing, immunohistochemical analyses of amyloid plaque density (APD), and cortical gene expression profiling were conducted. NC-treated APP/PS1 mice exhibited preserved object recognition memory and reduced anxiety-like behaviours, contrasting with deficits observed in untreated transgenic controls. Histologically, NC treatment significantly reduced the density of small amyloid plaques (<50 μm2) in the hippocampus and thalamus, and total plaque burden in the thalamus. Gene expression analysis revealed that NC treatment normalised or reversed disease-associated changes in insulin receptor (IR) signalling and neurotrophic pathways. Specifically, NC increased expression of Bdnf, Irs2, and Pgc-1α, while attenuating aberrant upregulation of Insr, Igf1r, and markers of ageing and AD-related pathology (Sirt1, Gdf15, Arc, Egr1, Cldn5). These findings indicate that NC therapy mitigates behavioural and molecular hallmarks of AD, potentially via restoration of BDNF and insulin receptor-mediated signalling. Full article
(This article belongs to the Section Cells of the Nervous System)
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21 pages, 1385 KiB  
Review
Mistletoe in Cancer Cell Biology: Recent Advances
by Chang-Eui Hong and Su-Yun Lyu
Curr. Issues Mol. Biol. 2025, 47(8), 672; https://doi.org/10.3390/cimb47080672 - 20 Aug 2025
Abstract
Mistletoe (Viscum album L.) has been used in complementary cancer therapy for decades, but its mechanisms remained poorly understood until recently. This review synthesizes transformative advances in mistletoe cancer research from 2020 to 2025, focusing on newly discovered molecular mechanisms, immunomodulatory properties, [...] Read more.
Mistletoe (Viscum album L.) has been used in complementary cancer therapy for decades, but its mechanisms remained poorly understood until recently. This review synthesizes transformative advances in mistletoe cancer research from 2020 to 2025, focusing on newly discovered molecular mechanisms, immunomodulatory properties, and clinical applications. We conducted a comprehensive analysis of controlled studies, mechanistic investigations, and real-world evidence published between 2020 and 2025. The discovery of mistletoe-induced immunogenic cell death (ICD) represents a paradigm shift in understanding its anticancer effects. Mistletoe extracts trigger endoplasmic reticulum stress, leading to calreticulin exposure in 18–51% of cancer cells and a 7-fold increase in adenosine triphosphate (ATP) release. Three-dimensional culture models revealed enhanced macrophage reprogramming effects, with a 15.8% increase in pro-inflammatory interleukin (IL)-6 and a 26.4% reduction in immunosuppressive IL-10. Real-world evidence from over 400 non-small-cell lung cancer patients shows that combining mistletoe with programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors doubles median overall survival (6.8 to 13.8 months), with biomarker-selected populations experiencing up to a 91.2% reduction in death risk. The Johns Hopkins Phase I trial established intravenous administration safety at 600 mg three times weekly. Advanced analytical approaches including metabolomics, chronobiology, and machine learning are enabling precision medicine applications. These findings position mistletoe as a scientifically validated component of integrative oncology, bridging traditional medicine with evidence-based cancer care. Future research should focus on ferroptosis mechanisms, single-cell immune profiling, and standardized clinical protocols. Full article
(This article belongs to the Special Issue Phytochemicals in Cancer Chemoprevention and Treatment: 2nd Edition)
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14 pages, 1831 KiB  
Article
Evaluation of Compatibility of Different Attachment Types Used in Orthodontic Clear Aligners with Electron Microscopy
by Can Sever and Can Arslan
Dent. J. 2025, 13(8), 379; https://doi.org/10.3390/dj13080379 - 20 Aug 2025
Abstract
Background/Objectives: The effectiveness of clear aligner therapy depends significantly on the precision of force delivery through the aligner–attachment interface. This study aimed to evaluate the microscopic compatibility between different orthodontic clear aligner materials (Duran+ and Zendura FLX) and attachment designs (rectangular and [...] Read more.
Background/Objectives: The effectiveness of clear aligner therapy depends significantly on the precision of force delivery through the aligner–attachment interface. This study aimed to evaluate the microscopic compatibility between different orthodontic clear aligner materials (Duran+ and Zendura FLX) and attachment designs (rectangular and optimized) using scanning electron microscopy (SEM). Methods: Fifty-six samples were divided into four groups: rectangular attachments with Duran+ aligners (n = 14), rectangular attachments with Zendura FLX aligners (n = 14), optimized attachments with Duran+ aligners (n = 14), and optimized attachments with Zendura FLX aligners (n = 14). Attachments were bonded to bovine incisors using standardized protocols. Clear aligners were thermoformed at 220 °C for 40 s. Cross-sectional samples were analyzed using SEM at 250× magnification. Gap measurements were taken at seven points for rectangular attachments and five points for optimized attachments. Results: Gap measurements ranged from 14.75 ± 1.41 µm to 91.07 ± 3.11 µm. Zendura FLX demonstrated significantly better adaptation than Duran+ with rectangular attachments (42.10 ± 1.07 µm vs. 44.52 ± 1.51 µm, p < 0.001). Optimized attachments showed better overall adaptation than rectangular attachments. All combinations showed regional variation with the largest gaps at gingival borders (67.18–91.07 µm) and the smallest at flat buccal surfaces (14.75–20.98 µm). Conclusions: Perfect adaptation was not achieved with any material–attachment combination tested. Material selection and attachment design significantly influence microscopic adaptation, with multi-layer materials and optimized geometries showing superior performance. These findings provide mechanical explanations for clinical limitations in clear aligner therapy. Full article
(This article belongs to the Special Issue Malocclusion: Treatments and Rehabilitation)
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18 pages, 930 KiB  
Article
Adding L-Carnitine and Selenium to Methimazole in Graves’ Disease: A Prospective Randomized Trial on Thyroid Markers and Quality of Life
by Mattia Rossi, Letizia Meomartino, Marco Zavattaro, Gloria Selvatico, Ruth Rossetto Giaccherino and Loredana Pagano
Nutrients 2025, 17(16), 2693; https://doi.org/10.3390/nu17162693 - 20 Aug 2025
Abstract
Background: The therapeutic response in Graves’ Disease (GD) remains largely unpredictable. Patients often experience persistent symptoms that are poorly correlated with thyroid hormone levels, an undefined treatment duration, and the need for long-term or definitive therapies. Based on the nuclear antagonistic properties [...] Read more.
Background: The therapeutic response in Graves’ Disease (GD) remains largely unpredictable. Patients often experience persistent symptoms that are poorly correlated with thyroid hormone levels, an undefined treatment duration, and the need for long-term or definitive therapies. Based on the nuclear antagonistic properties of L-carnitine (LCT) on thyroid hormone action and the immunomodulatory role of selenium (Se), we aimed to assess the impact of adding a combined LCT and Se supplement to standard methimazole (MMI) therapy on the biochemical profile and quality of life (QoL) of patients with overt GD. Methods: This multicenter prospective randomized trial enrolled 60 consecutive patients with newly diagnosed overt GD. Participants were randomized to receive either standard treatment with MMI alone (Control Group) or MMI plus the combined LCT/Se supplement (Intervention Group). TSH, fT3, fT4, and TSH–receptor antibodies (TRAb) levels were evaluated every two months for up to 24 months or until spontaneous remission or definitive therapy. At each visit, patients completed a symptom questionnaire addressing the frequency of typical thyrotoxic symptoms. Results: No significant differences were observed between groups in the trend or time-to-normalization of TSH, fT3, and fT4 levels. However, the Intervention Group reached TRAb negativity significantly earlier (HR = 2.35 (1.14–4.81), p = 0.016), with a synergistic interaction with MMI therapy. MMI requirements were consistently lower in the Intervention Group, both in average dosage (p = 0.013) and cumulative dose (p = 0.020). The rate of spontaneous remission was significantly higher (OR = 11.22 (3.35–46.11), p < 0.001). Overall symptom burden did not differ significantly between groups; however, the supplement exerted an independent effect in reducing the severity of tremor, irritability, mood lability, heat intolerance, and exertional dyspnea. Conclusions: Our findings suggest the clinical benefits of adding combined LCT and Se supplementation to MMI in the treatment of overt GD, including shorter disease duration, lower cumulative MMI exposure and earlier TRAb normality, that could positively influence TRAb-related prognostic outcomes. Full article
(This article belongs to the Section Nutrition and Metabolism)
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13 pages, 2063 KiB  
Article
SIRT1 Modulates the Photodynamic Anticancer Activity of 5,10,15-Triethoxycarbonyl P(V) Corrole in Hepatocellular Carcinoma
by Yan Liu, Jian Zheng, Jiayi Zhu, Xuemin Xian, Zhao Zhang and Haitao Zhang
Pharmaceuticals 2025, 18(8), 1226; https://doi.org/10.3390/ph18081226 - 20 Aug 2025
Abstract
Background: Hepatocellular carcinoma (HCC) remains a global health challenge with limited therapeutic efficacy. Photodynamic therapy (PDT) using 5,10,15-triethoxycarbonyl P(V) corrole (1-P) shows promise, but its molecular mechanisms and regulatory factors, particularly the role of SIRT1, are poorly understood. Methods: [...] Read more.
Background: Hepatocellular carcinoma (HCC) remains a global health challenge with limited therapeutic efficacy. Photodynamic therapy (PDT) using 5,10,15-triethoxycarbonyl P(V) corrole (1-P) shows promise, but its molecular mechanisms and regulatory factors, particularly the role of SIRT1, are poorly understood. Methods: The effects of 1-P combined with red light irradiation (625 nm) on HCC cells (HepG2, PLC/PRF5, MHCC97H) were evaluated via MTT, clonogenic assays, flow cytometry (apoptosis, mitochondrial membrane potential, ROS), and Western blotting (p53, Bax, Bcl-2, cleaved caspase-3, SIRT1). SIRT1-overexpressing cells and xenograft mouse models were used to validate its regulatory role. Results: 1-P with irradiation dose-dependently inhibited cell viability (IC50: 0.965–1.478 μM), suppressed clonogenicity, induced apoptosis (up to 68.8%), reduced mitochondrial membrane potential, and elevated ROS. Mechanistically, 1-P upregulated Bax/p53/cleaved caspase-3 and downregulated Bcl-2/SIRT1. SIRT1 overexpression rescued 1-P-induced apoptosis (30–50% reduction), restored mitochondrial function, and attenuated ROS accumulation. In vivo, 1-P significantly inhibited tumor growth in mice, but SIRT1 overexpression diminished this effect (p < 0.05). Conclusions: 1-P exerts potent photodynamic anticancer effects via mitochondrial dysfunction, oxidative stress, and apoptosis induction. SIRT1 is a critical modulator of 1-P activity, highlighting its potential as a therapeutic target to enhance PDT efficacy in HCC. Full article
(This article belongs to the Section Pharmacology)
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24 pages, 4816 KiB  
Article
Formulation of Honokiol- and Magnolol-Loaded Nanoemulsions for Head and Neck Cancer Adjuvant Therapy: Evaluation of Radiation Sterilization Effects on Active Substance Properties
by Katarzyna Dominiak, Aleksandra Gostyńska-Stawna, Agnieszka Sobczak, Jarosław Paluszczak, Aneta Woźniak-Braszak, Mikołaj Baranowski, Paweł Bilski, Barbara Wicher, Ewa Tykarska, Anna Jelińska and Maciej Stawny
Int. J. Mol. Sci. 2025, 26(16), 8032; https://doi.org/10.3390/ijms26168032 (registering DOI) - 20 Aug 2025
Abstract
Honokiol (HON) and magnolol (MAG), structural isomers from Magnolia officinalis, exhibit notable anticancer activity, particularly against head and neck squamous cell carcinoma (HNSCC). However, due to their high lipophilicity, their intravenous administration is challenging. This study aimed to develop HON- and MAG-loaded [...] Read more.
Honokiol (HON) and magnolol (MAG), structural isomers from Magnolia officinalis, exhibit notable anticancer activity, particularly against head and neck squamous cell carcinoma (HNSCC). However, due to their high lipophilicity, their intravenous administration is challenging. This study aimed to develop HON- and MAG-loaded intravenous (IV) nanoemulsions using commercial lipid preparations with varying fatty acid compositions. The formulations were physicochemically characterized and evaluated in vitro using FaDu and SCC-040 HNSCC cell lines. HON and MAG were sterilized via ionizing radiation at doses of 25, 100, and 400 kGy. Their suitability for IV use was assessed through PXRD, DSC, TGA, EPR, FT-IR, NMR, and HPLC analyses. All formulations met safety criteria for IV administration, with mean droplet diameters below 241 nm and encapsulation efficiencies exceeding 95%. They significantly reduced cancer cell viability, with a synergistic effect observed in combined HON and MAG formulations compared to single-compound nanoemulsions. Clinoleic-based formulations showed enhanced anticancer efficacy, likely due to the pro-apoptotic properties of oleic acid. Notably, radiation sterilization at the standard 25 kGy dose preserved the thermal, crystalline, and structural stability of HON and MAG, whereas higher doses (400 kGy) induced degradation. Although free radicals were detected via EPR, their transient nature and rapid decay confirmed the method’s safety. HON/MAG-loaded nanoemulsions exhibited strong anticancer potential, while radiation sterilization at 25 kGy ensured sterility without compromising stability. These findings provide a preliminary in vitro basis for future in vivo studies investigating HON and MAG as potential adjuvant therapies for HNSCC. Full article
(This article belongs to the Special Issue Drug Discovery: Natural Products and Compounds)
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27 pages, 1363 KiB  
Review
Promising Nanotechnology-Based Strategies for Melanoma Treatment
by Letícia Sias-Fonseca, Paulo C. Costa, Lucília Saraiva, Ana Alves and Maria Helena Amaral
Colloids Interfaces 2025, 9(4), 53; https://doi.org/10.3390/colloids9040053 - 20 Aug 2025
Abstract
Melanoma is a type of skin cancer with high lethality and increasing incidence. Current treatments typically involve surgery as the first step, followed by adjuvant treatments, which are necessary in most cases. These adjuvant treatments may include radiotherapy, phototherapy, chemotherapy, immunotherapy, and combined [...] Read more.
Melanoma is a type of skin cancer with high lethality and increasing incidence. Current treatments typically involve surgery as the first step, followed by adjuvant treatments, which are necessary in most cases. These adjuvant treatments may include radiotherapy, phototherapy, chemotherapy, immunotherapy, and combined therapies. However, patients with melanoma still face great difficulties, such as the inefficiency of therapies and serious side effects, in addition to uncomfortable scars. Most of these problems are related to limitations of antitumor therapies, such as the low bioavailability of drugs, degradation in biological fluids, rapid clearance, difficulty in reaching the tumors, the low capacity for accumulation and infiltration in tumor cells, toxicity to healthy cells, and systemic action. Thus, antitumor therapy for melanoma remains a challenge. In this line, nanotechnology has brought new perspectives and has been the subject of intensive research on the use of nanoparticles (liposomes, lipid nanoparticles, polymeric nanoparticles, inorganic nanoparticles, carbon nanotubes, dendrimers, nanogels, and biomimetic nanoparticles, among others) as carriers for the controlled release of drugs and tumor diagnosis. This work outlines the main limitations of current melanoma therapies and explores how nanoparticle-based drug delivery systems can overcome these challenges, highlighting recent research and clinical developments. Full article
(This article belongs to the Special Issue Feature Reviews in Colloids and Interfaces)
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