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20 pages, 1340 KB  
Systematic Review
The Effects of Exercise Training on Functional Aerobic Capacity and Quality of Life in Patients with Systemic Lupus Erythematosus: A Systematic Review of Randomized Controlled Trials
by Virginia Zouganeli, Stavros Dimopoulos, Alexandros Briasoulis, Achilleas Karkamanis, Panagiotis Panagiotopoulos, Eleftherios Karatzanos, Dimitrios T. Boumpas, Ioannis Vasileiadis, Serafim Nanas and Christos Kourek
J. Clin. Med. 2025, 14(19), 7031; https://doi.org/10.3390/jcm14197031 (registering DOI) - 4 Oct 2025
Abstract
Background/Objectives: Systemic lupus erythematosus (SLE) is associated with impaired functional capacity, persistent fatigue, and poor health-related quality of life despite advances in pharmacological therapy. Exercise training has been proposed as a non-pharmacological intervention, but its efficacy and safety remain incompletely defined. This [...] Read more.
Background/Objectives: Systemic lupus erythematosus (SLE) is associated with impaired functional capacity, persistent fatigue, and poor health-related quality of life despite advances in pharmacological therapy. Exercise training has been proposed as a non-pharmacological intervention, but its efficacy and safety remain incompletely defined. This systematic review aimed to evaluate the effects of exercise training on functional aerobic capacity and quality of life in adults with SLE. Methods: A comprehensive search of PubMed, EMBASE, Cochrane Library, and PEDro was conducted to identify randomized controlled trials published up to October 2022, in accordance with the PRISMA guidelines. Results: Twelve randomized controlled trials involving 619 participants were included. Exercise interventions were heterogeneous and comprised aerobics, resistance, combined programs, vibration training, home-based protocols, and counseling strategies, with durations ranging from 6 weeks to 12 months. Supervised aerobic and combined interventions consistently improved functional aerobic capacity, while quality of life benefits were reported across several domains, particularly physical health, vitality, and fatigue. Additional positive effects were observed on fatigue, depression, pain, sleep, insulin sensitivity, and self-care ability, without evidence of increased disease activity. Conclusions: Structured exercise is safe and can meaningfully enhance functional capacity and quality of life in patients with SLE, supporting its incorporation into multidisciplinary clinical management. Full article
(This article belongs to the Special Issue New Advances in Systemic Lupus Erythematosus (SLE))
36 pages, 5429 KB  
Review
Nanoceria as Next-Generation Immunotherapeutics: Applications in Chronic Inflammation, Cancer, and Tissue Repair
by Kay Hadrick, Panangattukara Prabhakaran Praveen Kumar and Taeho Kim
J. Nanotheranostics 2025, 6(4), 28; https://doi.org/10.3390/jnt6040028 (registering DOI) - 4 Oct 2025
Abstract
The immune system is crucial in protecting against disease, but it can also contribute to chronic illnesses when it malfunctions, with different conditions involving either inflammation or immune suppression. Current treatments often fall short due to limited effectiveness and side effects. Nanomedicine, particularly [...] Read more.
The immune system is crucial in protecting against disease, but it can also contribute to chronic illnesses when it malfunctions, with different conditions involving either inflammation or immune suppression. Current treatments often fall short due to limited effectiveness and side effects. Nanomedicine, particularly cerium oxide nanoparticles (nanoceria), offers promising potential due to its unique therapeutic properties and role in modulating macrophages. Nanoceria (<5 nm) possess the catalytic ability to mimic natural enzymes such as superoxide dismutase, peroxidase, and catalase, enabling effective scavenging of reactive oxygen species (ROS), which play a central role in the pathogenesis of chronic inflammation and cancer. This review comprehensively summarizes the current advances in the application of nanoceria for inflammatory and anti-inflammatory therapy, including their modulatory effects on immune cell activation, cytokine production, and resolution of inflammatory responses. We discuss the mechanisms underlying their immunomodulatory actions in various disease contexts, such as rheumatoid arthritis, women’s health conditions (e.g., endometriosis), wound healing, and cancer. Additionally, the review highlights biocompatibility, therapeutic efficacy, adaptability in imaging (theranostics), and challenges in translating nanoceria-based therapies into clinical practice. The multifunctionality of nanoceria positions them as innovative candidates for next-generation immunotherapy aimed at efficiently controlling inflammation and promoting tissue repair. Full article
14 pages, 2579 KB  
Article
Targeted Delivery of VEGF-siRNA to Glioblastoma Using Orientation-Controlled Anti-PD-L1 Antibody-Modified Lipid Nanoparticles
by Ayaka Matsuo-Tani, Makoto Matsumoto, Takeshi Hiu, Mariko Kamiya, Longjian Geng, Riku Takayama, Yusuke Ushiroda, Naoya Kato, Hikaru Nakamura, Michiharu Yoshida, Hidefumi Mukai, Takayuki Matsuo and Shigeru Kawakami
Pharmaceutics 2025, 17(10), 1298; https://doi.org/10.3390/pharmaceutics17101298 (registering DOI) - 4 Oct 2025
Abstract
Background/Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor with limited therapeutic options despite multimodal treatment. Small interfering RNA (siRNA)-based therapeutics can silence tumor-promoting genes, but achieving efficient and tumor-specific delivery remains challenging. Lipid nanoparticles (LNPs) are promising siRNA carriers; however, conventional [...] Read more.
Background/Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor with limited therapeutic options despite multimodal treatment. Small interfering RNA (siRNA)-based therapeutics can silence tumor-promoting genes, but achieving efficient and tumor-specific delivery remains challenging. Lipid nanoparticles (LNPs) are promising siRNA carriers; however, conventional antibody conjugation can impair antigen recognition and complicate manufacturing. This study aimed to establish a modular Fc-binding peptide (FcBP)-mediated post-insertion strategy to enable PD-L1-targeted delivery of VEGF-siRNA via LNPs for GBM therapy. Methods: Preformed VEGF-siRNA-loaded LNPs were functionalized with FcBP–lipid conjugates, enabling non-covalent anchoring of anti-PD-L1 antibodies through Fc interactions. Particle characteristics were analyzed using dynamic light scattering and encapsulation efficiency assays. Targeted cellular uptake and VEGF gene silencing were evaluated in PD-L1-positive GL261 glioma cells. Anti-tumor efficacy was assessed in a subcutaneous GL261 tumor model following repeated intratumoral administration using tumor volume and bioluminescence imaging as endpoints. Results: FcBP post-insertion preserved LNP particle size (125.2 ± 1.3 nm), polydispersity, zeta potential, and siRNA encapsulation efficiency. Anti-PD-L1–FcBP-LNPs significantly enhanced cellular uptake (by ~50-fold) and VEGF silencing in PD-L1-expressing GL261 cells compared to controls. In vivo, targeted LNPs reduced tumor volume by 65% and markedly suppressed bioluminescence signals without inducing weight loss. Final tumor weight was reduced by 63% in the anti-PD-L1–FcBP–LNP group (656.9 ± 125.4 mg) compared to the VEGF-siRNA LNP group (1794.1 ± 103.7 mg). The FcBP-modified LNPs maintained antibody orientation and binding activity, enabling rapid functionalization with targeting antibodies. Conclusions: The FcBP-mediated post-insertion strategy enables site-specific, modular antibody functionalization of LNPs without compromising physicochemical integrity or antibody recognition. PD-L1-targeted VEGF-siRNA delivery demonstrated potent, selective anti-tumor effects in GBM murine models. This platform offers a versatile approach for targeted nucleic acid therapeutics and holds translational potential for treating GBM. Full article
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28 pages, 4335 KB  
Perspective
Time-Restricted Eating, ANGPTL4, and Reduction in Residual Cardiovascular Risk
by Alejandro Gugliucci
J. Clin. Med. 2025, 14(19), 7026; https://doi.org/10.3390/jcm14197026 - 3 Oct 2025
Abstract
Atherosclerotic cardiovascular disease treatment is being reevaluated, since a residual cardiovascular risk (RCR) persists even in patients who achieve optimal LDL-C values. Underlying causes are metabolic dysfunction, lipoprotein(a), inflammation, and triglyceride-rich lipoproteins and their remnants. Dietary treatment options like time-restricted eating (TRE) are [...] Read more.
Atherosclerotic cardiovascular disease treatment is being reevaluated, since a residual cardiovascular risk (RCR) persists even in patients who achieve optimal LDL-C values. Underlying causes are metabolic dysfunction, lipoprotein(a), inflammation, and triglyceride-rich lipoproteins and their remnants. Dietary treatment options like time-restricted eating (TRE) are becoming more widely acknowledged for their potential advantages in metabolic health and weight control, as a treatment of atherosclerosis expanding beyond LDL-C medication. Beyond weight loss, TRE (which restricts meals to a window of 6 to 8 h) appears as the most accessible treatment, and has been shown to improve blood pressure, lipid profiles, and glucose regulation through mechanisms like metabolic switching and circadian synchronization. We hypothesize, and will present our arguments, that a key mechanism underlying the cardiovascular and weight-related benefits of TRE is its impact on the circadian regulation of angiopoietin-like protein 4 (ANGPTL4) activity within adipose tissue. Additionally, lipolysis is accelerated by ANGPTL4 activation. TRE, via its actions on ANGPTL4, therefore not only inhibits adipose fatty acid uptake but stimulates their release as well. Additionally, TRE may increase intravascular very low-density lipoprotein (VLDL) catabolism by muscle due to the reduced exposure of lipoprotein lipase (LPL) to competing chylomicrons, known to slow the rate of VLDL catabolism. During the prolonged fasting, VLDL residence time is thus shortened, limiting the exposure to endothelium and hepatic lipases and thus reducing the amount of atherogenic remnant particles. Larger, longer-term randomized controlled studies in a variety of groups are required to further clarify TRE’s function in RCR prevention and therapy. As knowledge of triglyceride lipoprotein (TRL) metabolism expands, a comprehensive strategy for the management of RCR emerges, and a broader spectrum of LPL regulator-based therapeutics is created. Consequently, it is advisable to prioritize further research into the influence of TRE on LPL modulation via ANGPTL4 and ANGPTL8, which provides a natural, accessible, and low-cost alternative. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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15 pages, 1628 KB  
Article
CT Brain Perfusion Imaging Utilization Following Widening of the Intracranial Mechanical Thrombectomy Treatment Window in a Cosmos Multi-Institutional Population
by Yusuf Rasheed, Colin Berkheimer, Zarar Ajam and Xuan V. Nguyen
Appl. Sci. 2025, 15(19), 10680; https://doi.org/10.3390/app151910680 - 2 Oct 2025
Abstract
The goal of this study is to analyze trends in clinical utilization of CT brain perfusion (CTP) across the past 10 years, during which there have been substantial changes in neuro-interventional and neuroimaging guidelines related to emergent stroke therapy, particularly intra-arterial mechanical thrombectomy. [...] Read more.
The goal of this study is to analyze trends in clinical utilization of CT brain perfusion (CTP) across the past 10 years, during which there have been substantial changes in neuro-interventional and neuroimaging guidelines related to emergent stroke therapy, particularly intra-arterial mechanical thrombectomy. The Cosmos platform, a multi-institutional data aggregation tool containing health record data from billions of encounters, was used to retrospectively identify millions of patients with active clinical encounters during the study period (2015–2024). For each calendar quarter, numbers and proportions of active patients undergoing mechanical thrombectomy or brain CTP were obtained using billing code queries. CTP utilization per 100,000 active patients grew slowly from Q1-2015 to Q3-2017, ranging from 4.32 to 9.45, but beginning in Q4-2017, coinciding with the publication of landmark stroke trials, CTP utilization began to increase more rapidly, almost 4-fold higher as determined through segmented linear regression, reaching 61.24 per 100,000 in Q4-2024. Although causation cannot be proven in this study, the observed increases in CTP utilization likely reflect rapid adoption of evidence-based adjustments to stroke triage guidelines after eligibility for mechanical neurointervention had been widened to 24 h from symptom onset. Full article
(This article belongs to the Special Issue Advances in Diagnostic Radiology)
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17 pages, 551 KB  
Systematic Review
Post-Exercise Recovery Modalities in Male and Female Soccer Players of All Ages and Competitive Levels: A Systematic Review
by Emaly Vatne, Jose M. Oliva-Lozano, Catherine Saenz, Rick Cost and Josh Hagen
Sports 2025, 13(10), 343; https://doi.org/10.3390/sports13100343 - 2 Oct 2025
Abstract
Optimal recovery supports health and enhances performance in soccer players, yet the empirical evidence on various recovery strategies in soccer is complex to interpret. This review aimed to summarize the literature on post-exercise recovery modalities in male and female soccer players of all [...] Read more.
Optimal recovery supports health and enhances performance in soccer players, yet the empirical evidence on various recovery strategies in soccer is complex to interpret. This review aimed to summarize the literature on post-exercise recovery modalities in male and female soccer players of all ages and competition levels. Following PRISMA guidelines, PubMed, SPORTDiscuss, and Web of Science were systematically searched until 17 October 2023. Randomized controlled trials or within-subjects crossover design studies that examined the effects of post-exercise recovery interventions on physical, psychological, or performance outcomes in soccer players were included. A single reviewer extracted data and assessed study quality using the Physiotherapy Evidence Database (PEDro) scale. Overall, 41 studies were included in the final review. The recovery strategies represented in these studies were organized into the following categories: active recovery, blood flow restriction, cold water immersion, contrast water therapy, compression garments, active cool-down, cryotherapy, cold garments, sleep and daytime nap, pneumatic cooling, foam rolling, mindfulness interventions, nutritional intervention, and static stretching. The findings demonstrated that cold-water immersion consistently improved jump performance and perceptions of fatigue, soreness, and overall well-being. Other recovery strategies, such as active recovery, compression therapy, sleep interventions, and nutrition supplementation, also positively impacted recovery, albeit with varying levels of effectiveness and evidence. However, the studies exhibited heterogeneity in methods, outcome measures, and recovery intervention protocols, posing challenges for generalizability. This review summarizes recovery strategies for soccer players, emphasizing the need for practitioners, coaches, and athletes to individualize interventions based on athletes’ needs, preferences, and competition level. Full article
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25 pages, 5895 KB  
Article
Oral Gel Formulation of Cotinus coggygria Scop. Stem Bark Extract: Development, Characterization, and Therapeutic Efficacy in a Rat Model of Aphthous Stomatitis
by Jovana Bradic, Miona Vuletic, Vladimir Jakovljevic, Jasmina Sretenovic, Suzana Zivanovic, Marina Tomovic, Jelena Zivkovic, Aleksandar Kocovic and Nina Dragicevic
Pharmaceutics 2025, 17(10), 1293; https://doi.org/10.3390/pharmaceutics17101293 - 2 Oct 2025
Abstract
Background/Objectives: Encouraged by the traditional use of Cotinus coggygria Scop. (European smoketree) for its anti-inflammatory and antioxidant properties, and considering the limitations of current therapies for recurrent aphthous stomatitis (RAS), we aimed to develop and evaluate a mucoadhesive oral gel containing C. coggygria [...] Read more.
Background/Objectives: Encouraged by the traditional use of Cotinus coggygria Scop. (European smoketree) for its anti-inflammatory and antioxidant properties, and considering the limitations of current therapies for recurrent aphthous stomatitis (RAS), we aimed to develop and evaluate a mucoadhesive oral gel containing C. coggygria stem bark extract. Methods: A thermosensitive gel was formulated using Carbopol® 974P NF and poloxamer 407, enriched with 5% C. coggygria extract (CC gel), and characterized for its organoleptic properties, pH, electrical conductivity, and storage stability over six months. Therapeutic efficacy was assessed in a Wistar albino rat model of chemically induced oral ulcers. Animals were divided into three groups: untreated controls (CTRL), rats treated with gel base (GB), and those treated with CC gel over a 10-day period. Healing progression was monitored macroscopically (ulcer size reduction), biochemically (oxidative stress markers in plasma and tissue), and histologically. Results: The CC gel demonstrated satisfactory physicochemical stability and mucosal compatibility. Moreover, it significantly accelerated ulcer contraction and achieved complete re-epithelialization by day 6. Biochemical analyses revealed reduced TBARS and increased SOD, CAT, and GSH levels in ulcer tissue, indicating enhanced local antioxidant defense. Histological evaluation confirmed early resolution of inflammation, pronounced fibroblast activity, capillary proliferation, and full epithelial regeneration in the CC group, in contrast to delayed healing and persistent inflammatory infiltration in the GB and CTRL groups. Conclusions: These findings indicate that the CC gel has potential as a natural, topical formulation with antioxidant and regenerative properties for RAS, although further studies, including clinical evaluation, are required to confirm its overall efficacy and long-term safety. Full article
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13 pages, 866 KB  
Article
Phenotype-Guided Outpatient Levosimendan as a Bridge-to-Transplant in Low-Output Advanced Heart Failure: A Single-Center Cohort
by Ricardo Carvalheiro, Ana Raquel Santos, Ana Rita Teixeira, João Ferreira Reis, António Valentim Gonçalves, Rita Ilhão Moreira, Tiago Pereira da Silva, Valdemar Gomes, Pedro Coelho and Rui Cruz Ferreira
J. Pers. Med. 2025, 15(10), 473; https://doi.org/10.3390/jpm15100473 - 2 Oct 2025
Abstract
Background: Advanced heart failure (HF) carries high morbidity and mortality, and deterioration on the heart transplantation (HT) waiting list remains a major challenge. Intermittent outpatient levosimendan has been proposed as a bridge strategy, but the optimal regimen and its impact on peri-transplant [...] Read more.
Background: Advanced heart failure (HF) carries high morbidity and mortality, and deterioration on the heart transplantation (HT) waiting list remains a major challenge. Intermittent outpatient levosimendan has been proposed as a bridge strategy, but the optimal regimen and its impact on peri-transplant outcomes remain uncertain. Within a personalized-medicine framework, we targeted a low-output/INTERMACS 3 phenotype and operationalized an adaptable, protocolized levosimendan pathway focused on perfusion/congestion stabilization to preserve transplant candidacy. Methods: We conducted a single-center, retrospective cohort study of 25 consecutive adults actively listed for HT between 2019 and 2024, treated with a standardized outpatient program of a 14-day interval of 6 h intravenous levosimendan infusions (target 0.2 μg/kg/min infusions) continued until transplant. Personalization in this program was operationalized through (i) phenotype-based eligibility (low CI and elevated filling pressures despite GDMT), (ii) predefined titration and safety rules for blood pressure, arrhythmias, and renal function, and (iii) individualized continuation until transplant with nurse-supervised monitoring and review of patient trajectories. Baseline characteristics, treatment exposure and safety, changes in hospitalizations and biomarkers, and peri-transplant outcomes were analyzed. Results: Patients were predominantly male (68%), with a mean age of 47.9 ± 17.5 years and severe LV dysfunction (LVEF 30.6 ± 9.8%). Median treatment duration was 131 days (IQR 60–241). No infusions required discontinuation for hypotension or arrhythmia, and no adverse events were directly attributed to levosimendan. Two patients (8%) died on the waiting list, both unrelated to therapy. During treatment, HF hospitalizations decreased significantly compared with the previous 6 months (48% vs. 20%, p = 0.033), renal function remained stable, and NT-proBNP trended downward. Of the 23 patients transplanted, two (9%) underwent urgent HT during decompensation. Post-transplant, vasoplegia occurred in 26% (n = 6 of 23), and 30-day mortality was 9% (n = 2 of 23). Conclusions: By defining the target phenotype, therapeutic goals, and adaptation rules, this study shows how a standardized but flexible outpatient levosimendan regimen can function as a personalized bridge strategy for low-output advanced HF. The approach was associated with fewer hospitalizations, stable renal function, and acceptable peri-transplant outcomes, and merits confirmation in multicenter cohorts with attention to patient heterogeneity and treatment effect refinement. Full article
(This article belongs to the Special Issue Personalized Treatment for Heart Failure)
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14 pages, 1992 KB  
Article
Riociguat Alleviates Cisplatin-Caused Kidney Injury by Suppressing Oxidative Stress and Inflammation
by Yousuf M. Al Suleimani, Yousra Nomeir, Raya Al Maskari, Haytham Ali, Priyadarsini Manoj and Aly M. Abdelrahman
Biology 2025, 14(10), 1346; https://doi.org/10.3390/biology14101346 - 2 Oct 2025
Abstract
Background: Cisplatin (CP), a platinum-based chemotherapeutic agent, is widely used to treat cancer but causes nephrotoxicity. Riociguat, a soluble guanylate cyclase (sGC) stimulator that enhances the nitric oxide–sGC–cGMP signaling pathway, was investigated for its potential protective effects against cisplatin-induced nephrotoxicity. Materials and Methods: [...] Read more.
Background: Cisplatin (CP), a platinum-based chemotherapeutic agent, is widely used to treat cancer but causes nephrotoxicity. Riociguat, a soluble guanylate cyclase (sGC) stimulator that enhances the nitric oxide–sGC–cGMP signaling pathway, was investigated for its potential protective effects against cisplatin-induced nephrotoxicity. Materials and Methods: Rats were randomly divided into four equal groups (six rats each) and treated for nine consecutive days. The first and second groups were given oral carboxymethylcellulose 0.5% (vehicle) for 9 days, and on day 6 were injected intraperitoneally with saline or CP, respectively. The third and fourth groups were treated orally with two doses of riociguat (3 and 10 mg/kg/day) for 9 days, and received intraperitoneal injections of CP on day 6. Blood, urine, and kidney tissues were analyzed 24 h after the last treatment. Results: CP significantly elevated the markers of kidney function, including uric acid, serum creatinine, and urea. CP also caused histological kidney damage. Antioxidant markers, including catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), and total antioxidant capacity (TAC) were significantly reduced, while inflammatory cytokines (IL-1β, IL-6, and TNF-α) and lipid peroxidation (MDA) were markedly increased. Riociguat improved kidney structure and significantly reduced kidney function markers, MDA, and inflammatory cytokines while restoring GR, TAC, SOD, and CAT activities. Conclusions: These results indicate that riociguat exerts protection of the kidneys from CP-caused kidney damage by antioxidation and anti-inflammation. Riociguat may have potential as an adjunct therapy to mitigate CP-associated nephrotoxicity. Full article
(This article belongs to the Special Issue Physiology and Pathophysiology of the Kidney)
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16 pages, 2918 KB  
Article
Surface Engineering of Natural Killer Cells with Lipid-Based Antibody Capture Platform for Targeted Chemoimmunotherapy
by Su Yeon Lim, Yeongbeom Kim, Hongbin Kim, Seungmin Han, Jina Yun, Hyun-Ouk Kim, Suk-Jin Ha, Sehyun Chae, Young-Wook Won and Kwang Suk Lim
Pharmaceutics 2025, 17(10), 1285; https://doi.org/10.3390/pharmaceutics17101285 - 1 Oct 2025
Abstract
Next-generation cancer immunotherapy increasingly combines tumor-targeting antibodies or antibody–drug conjugates (ADCs) with immune effector cells to enhance therapeutic precision. However, many existing approaches rely on genetic modification or complex manufacturing, limiting their clinical scalability and rapid deployment. To address this issue, we developed [...] Read more.
Next-generation cancer immunotherapy increasingly combines tumor-targeting antibodies or antibody–drug conjugates (ADCs) with immune effector cells to enhance therapeutic precision. However, many existing approaches rely on genetic modification or complex manufacturing, limiting their clinical scalability and rapid deployment. To address this issue, we developed an antibody capture protein (ACP)-based surface engineering platform that enables the rapid, reversible, and non-genetic functionalization of NK cells with therapeutic antibodies or ADCs. This approach uses a DMPE-PEG-lipid conjugate to anchor thiolated protein A (ACP) to the NK cell membrane via hydrophobic insertion, thereby stably and selectively binding to the Fc region of IgG molecules. Using this strategy, we developed ACP-modified NK cells (AC-NKs) that can selectively capture therapeutic antibodies (trastuzumab (TZ), trastuzumab-emtansine (T-DM1), and sacituzumab (SZ)) pre-bound to each target antigen on tumor cells and induce antigen-specific cytotoxic responses. The resulting AC-NKs exhibited enhanced tumor recognition and cytotoxicity against HER2-positive and Trop-2-positive cancer cells in vitro. Compared with conventional combination therapies, AC-NKs enhanced immune activation, as demonstrated by effective delivery of cytotoxic agents, enhanced cancer cell engagement, and upregulation of CD107a expression. Notably, the system supports multiple antigen targeting and tunable antibody loading, enabling adaptation to tumor heterogeneity and resistant phenotypes. This platform might also provide a simple, scalable, and safe method for rapidly developing programmable immune cell therapies without genetic modification. Its versatility supports multi-antigen targeting and broad applicability across NK and T cell therapies, offering a promising path toward personalized, off-the-shelf chemoimmunotherapy. Full article
(This article belongs to the Special Issue Advanced Drug Delivery Systems for Targeted Immunotherapy)
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22 pages, 1386 KB  
Article
Pharmacokinetic Profile of Extracts from the Chayote (Sechium edule) H387 07 Hybrid and Phytochemical Characterization of Its Segregant H387 M16 for Potential Therapeutic Applications
by Eugenia Elisa Delgado-Tiburcio, Ramón Marcos Soto-Hernández, Itzen Aguiñiga-Sánchez, Jorge Cadena-Iñiguez, Lucero del Mar Ruiz-Posadas, Cecilia B. Peña-Valdivia and Héctor Gómez-Yáñez
Molecules 2025, 30(19), 3948; https://doi.org/10.3390/molecules30193948 - 1 Oct 2025
Abstract
The hybrid Sechium edule H387 07, commonly known as chayote, has shown potential as an antiproliferative, cytotoxic, and pro-apoptotic agent in the murine leukemia cell lines P388 (macrophagic) and J774 (monocytic) and in the myelomonocytic leukemia cell line WEHI-3. However, despite these reported [...] Read more.
The hybrid Sechium edule H387 07, commonly known as chayote, has shown potential as an antiproliferative, cytotoxic, and pro-apoptotic agent in the murine leukemia cell lines P388 (macrophagic) and J774 (monocytic) and in the myelomonocytic leukemia cell line WEHI-3. However, despite these reported bioactivities, its pharmacokinetic profile remains largely unexplored. Understanding the absorption, distribution, and elimination of this hybrid is critical for addressing unmet therapeutic needs and for advancing the development of natural product-based therapies. These effects are attributed to the presence of phenols, flavonoids, and cucurbitacins in its organic extracts. In this study, the pharmacokinetic parameters of secondary metabolites from methanolic extracts of Sechium H387 07 were evaluated after oral administration in mice, while its segregant H387 M16 was subjected to complementary phytochemical characterization. Methanolic extracts of Sechium edule H387 07 were orally administered to mice at doses of 8, 125, and 250 mg/kg, and plasma, liver, and urine samples were collected at 1, 6, 24, and 48 h post-treatment. High-performance liquid chromatography (HPLC) identified polyphenols and cucurbitacins, notably cucurbitacin B (CuB) and cucurbitacin IIA (CuIIA), in the biological samples, and pharmacokinetic variables such as the maximum plasma concentration (Cmax), time to reach maximum concentration (Tmax), half-life (T1/2), and volume of distribution (Vd) were determined. For instance, CuB exhibited a Cmax of 37.56 µg/mL at 1 h post-dose after oral administration of 125 mg/kg, confirming its rapid absorption and systemic distribution. Notably, the presence of CuIIA in plasma was documented for the first time, along with the pharmacokinetic profiles of apigenin, phloretin, CuB, CuE, and CuI. In parallel, the segregant H387 M16 was characterized via colorimetric assays, thin-layer chromatography (TLC), HPLC, and antioxidant activity tests, which revealed high levels of flavonoids, phenols, and cucurbitacins, with an antioxidant activity of approximately 75% at the highest tested dose (1 mg/mL), supporting its suitability for future bioassays. Overall, these findings not only provide novel pharmacokinetic data for key metabolites of the H387 07 hybrid but also establish the phytochemical and antioxidant profile of its segregant H387 M16. This dual characterization strengthens the evidence of the therapeutic potential of Sechium genotypes and provides a valuable foundation for future studies aiming to develop standardized protocols and explore translational applications in drug development and natural product-based therapies. Full article
(This article belongs to the Section Natural Products Chemistry)
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15 pages, 1939 KB  
Review
Challenges of Ozone Therapy in Periodontal Regeneration: A Narrative Review and Possible Therapeutic Improvements
by Nada Tawfig Hashim, Rasha Babiker, Vivek Padmanabhan, Md Sofiqul Islam, Sivan Padma Priya, Nallan C. S. K. Chaitanya, Riham Mohammed, Shahistha Parveen Dasnadi, Ayman Ahmed, Bakri Gobara Gismalla and Muhammed Mustahsen Rahman
Curr. Issues Mol. Biol. 2025, 47(10), 811; https://doi.org/10.3390/cimb47100811 - 1 Oct 2025
Abstract
Ozone (O3) has re-emerged in periodontology for its antimicrobial, oxygenating, and immunomodulatory actions, yet its role in regeneration remains contentious. This narrative review synthesizes current evidence on adjunctive ozone use in periodontal therapy, delineates cellular constraints—especially in periodontal ligament fibroblasts (PDLFs)—and [...] Read more.
Ozone (O3) has re-emerged in periodontology for its antimicrobial, oxygenating, and immunomodulatory actions, yet its role in regeneration remains contentious. This narrative review synthesizes current evidence on adjunctive ozone use in periodontal therapy, delineates cellular constraints—especially in periodontal ligament fibroblasts (PDLFs)—and explores mitigation strategies using bioactive compounds and advanced delivery platforms. Two recent meta-analyses indicate that adjunctive ozone with scaling and root planing yields statistically significant reductions in probing depth and gingival inflammation, with no significant effects on bleeding on probing, plaque control, or clinical attachment level; interpretation is limited by heterogeneity of formulations, concentrations, and delivery methods. Mechanistically, ozone imposes a dose-dependent oxidative burden that depletes glutathione and inhibits glutathione peroxidase and superoxide dismutase, precipitating lipid peroxidation, mitochondrial dysfunction, ATP depletion, and PDLF apoptosis. Concurrent activation of NF-κB and upregulation of IL-6/TNF-α, together with matrix metalloproteinase-mediated extracellular matrix degradation and tissue dehydration (notably with gaseous applications), further impairs fibroblast migration, adhesion, and ECM remodeling, constraining regenerative potential. Emerging countermeasures include co-administration of polyphenols (epigallocatechin-3-gallate, resveratrol, curcumin, quercetin), coenzyme Q10, vitamin C, and hyaluronic acid to restore redox balance, stabilize mitochondria, down-modulate inflammatory cascades, and preserve ECM integrity. Nanocarrier-based platforms (nanoemulsions, polymeric nanoparticles, liposomes, hydrogels, bioadhesive films) offer controlled ozone release and co-delivery of protectants, potentially widening the therapeutic window while minimizing cytotoxicity. Overall, current evidence supports ozone as an experimental adjunct rather than a routine regenerative modality. Priority research needs include protocol standardization, dose–response definition, long-term safety, and rigorously powered randomized trials evaluating bioactive-ozone combinations and nanocarrier systems in clinically relevant periodontal endpoints. Full article
(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2025)
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14 pages, 842 KB  
Review
Biological Augmentation of Meniscal Repair: A Review with Insights into Injectable Hydrogel Delivery
by Marta Tuszynska, Joanna Skopinska-Wisniewska and Anna Bajek
Gels 2025, 11(10), 786; https://doi.org/10.3390/gels11100786 - 1 Oct 2025
Abstract
Meniscal injuries are common and often lead to chronic pain, joint instability, and an increased risk of osteoarthritis. Traditional treatments, such as partial meniscectomy, may accelerate joint degeneration. In recent years, biologically active therapies, including platelet-rich plasma (PRP), mesenchymal stem cells (MSCs), hyaluronic [...] Read more.
Meniscal injuries are common and often lead to chronic pain, joint instability, and an increased risk of osteoarthritis. Traditional treatments, such as partial meniscectomy, may accelerate joint degeneration. In recent years, biologically active therapies, including platelet-rich plasma (PRP), mesenchymal stem cells (MSCs), hyaluronic acid (HA), bone marrow aspirate concentrate (BMAC), collagen, growth factors (GFs), and silk fibroin (SF), have emerged as promising strategies to enhance meniscal healing. This review evaluates the efficiency of these biological agents in promoting meniscal repair, with a particular focus on their potential integration into injectable hydrogel systems for targeted, minimally invasive delivery. Recent literature from 2015 to 2025 has provided growing insights into the role of biologically active agents and biomaterials in meniscal repair. Among the agents studied, PRP, MSCs, and HA have shown particular promise in modulating inflammation and supporting tissue regeneration. While biological therapies alone may not replace surgery for complex tears, they offer promising, less invasive alternatives that support tissue preservation. However, variability in study design, agent quality, and treatment protocols remains challenging. Further long-term research will be essential to confirm clinical benefits and optimize hydrogel-based delivery methods. Full article
(This article belongs to the Special Issue Research and Application of Injectable Hydrogels)
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14 pages, 673 KB  
Review
Is Vitamin B6 a Precision Therapy for Neonatal Seizures?
by Raffaele Falsaperla, Vincenzo Sortino, Bruna Scalia and Marco Andrea Nicola Saporito
Neurol. Int. 2025, 17(10), 157; https://doi.org/10.3390/neurolint17100157 - 1 Oct 2025
Abstract
Background: Neonatal seizures are critical neurological events with long-term implications for brain development. Standard antiseizure medications, such as phenobarbital, often yield suboptimal seizure control and may be associated with neurotoxicity. This narrative review explores the role of vitamin B6 as a precision [...] Read more.
Background: Neonatal seizures are critical neurological events with long-term implications for brain development. Standard antiseizure medications, such as phenobarbital, often yield suboptimal seizure control and may be associated with neurotoxicity. This narrative review explores the role of vitamin B6 as a precision therapy in neonatal seizure syndromes, particularly in pyridoxine-responsive conditions. Methods: We conducted a narrative review of the biochemical functions of vitamin B6, focusing on its active form, pyridoxal 5′-phosphate (PLP), and its role as a coenzyme in neurotransmitter synthesis. We examined the genetic and metabolic disorders linked to vitamin B6 deficiency, such as mutations in pyridox(am)ine 5’-phosphate oxidase (PNPO), Aldehyde Dehydrogenase 7 Family Member A1 (ALDH7A1), alkaline locus phosphatase (ALPL), and cystathionine β-synthase (CBS), and discussed the clinical rationale for empirical administration in acute neonatal seizure settings. Results: Vitamin B6 is essential for the synthesis of gamma-aminobutyric acid (GABA), dopamine, and serotonin, with PLP-dependent enzymes such as glutamic acid decarboxylase and aromatic L-amino acid decarboxylase playing central roles. Deficiencies in PLP due to genetic mutations or metabolic disruptions can result in treatment-resistant neonatal seizures. Early supplementation, especially in suspected vitamin B6-dependent epilepsies, may provide both diagnostic clarity and seizure control, potentially reducing exposure to conventional antiseizure medications. Conclusions: Vitamin B6-responsive epilepsies highlight the clinical value of mechanism-based, individualized treatment approaches in neonatology. Incorporating genetic and metabolic screening into seizure management may improve outcomes and aligns with the principles of precision medicine. Full article
(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)
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11 pages, 624 KB  
Communication
Therapeutic Monitoring of Post-COVID-19 Cognitive Impairment Through Novel Brain Function Assessment
by Veronica Buonincontri, Chiara Fiorito, Davide Viggiano, Mariarosaria Boccellino and Ciro Pasquale Romano
COVID 2025, 5(10), 166; https://doi.org/10.3390/covid5100166 - 1 Oct 2025
Abstract
 COVID-19 infection is often accompanied by psychological symptoms, which may persist long after the end of the infection (long COVID). The symptoms include fatigue, cognitive impairment, and anxiety. The reason for these long-term effects is currently unclear. Therapeutic approaches have included cognitive rehabilitation [...] Read more.
 COVID-19 infection is often accompanied by psychological symptoms, which may persist long after the end of the infection (long COVID). The symptoms include fatigue, cognitive impairment, and anxiety. The reason for these long-term effects is currently unclear. Therapeutic approaches have included cognitive rehabilitation therapy, physical activity, and serotonin reuptake inhibitors (SSRIs) if depression co-exists. The neuropsychological evaluation of subjects with suspected cognitive issues is essential for the correct diagnosis. Most of the COVID-19 studies used the Montreal Cognitive Assessment (MoCA) or the Mini Mental State Examination (MMSE). However, MoCA scores can be confusing if not interpreted correctly. For this reason, we have developed an original technique to map cognitive domains and motor performance on various brain areas in COVID-19 patients aiming at improving the follow-up of long-COVID-19 symptoms. To this end, we retrospectively reanalyzed data from a cohort of 40 patients hospitalized for COVID-19 without requiring intubation or hemodialysis. Cognitive function was tested during hospitalization and six months after. Global cognitive function and cognitive domains were retrieved using MoCA tests. Laboratory data were retrieved regarding kidney function, electrolytes, acid–base, blood pressure, TC score, and P/F ratio. The dimensionality of cognitive functions was represented over cortical brain structures using a transformation matrix derived from fMRI data from the literature and the Cerebroviz mapping tool. Memory function was linearly dependent on the P/F ratio. We also used the UMAP method to reduce the dimensionality of the data and represent them in low-dimensional space. Six months after hospitalization, no cases of severe cognitive deficit persisted, and the number of moderate cognitive deficits reduced from 14% to 4%. Most cognitive domains (visuospatial abilities, executive functions, attention, working memory, spatial–temporal orientation) improved over time, except for long-term memory and language skills, which remained reduced or slightly decreased. The Cerebroviz algorithm helps to visualize which brain regions might be involved in the process. Many patients with COVID-19 continue to suffer from a subclinical cognitive deficit, particularly in the memory and language domains. Cerebroviz’s representation of the results provides a new tool for visually representing the data.  Full article
(This article belongs to the Special Issue Exploring Neuropathology in the Post-COVID-19 Era)
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