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26 pages, 2143 KB  
Review
From Nature to Pharmacy: A Review of Tectoridin for Modern Therapeutics
by Shengxi Zhang, Jinxi Huang, Xiaoming Li, Ziling Zhou, Shichang Bai, Dan Zhang, Tao Song, Xianyao Wang, Jun Tan, Qinghong Kong, Jidong Zhang and Changxin Li
Pharmaceuticals 2026, 19(5), 703; https://doi.org/10.3390/ph19050703 (registering DOI) - 29 Apr 2026
Abstract
Background: Tectoridin is a prominent isoflavone glycoside found in herbs such as Belamcanda chinensis (L.) DC and Iris tectorum Maxim. It has drawn increasing research interest due to its promising pharmacological activities. However, no critical review to date has determined whether its broad [...] Read more.
Background: Tectoridin is a prominent isoflavone glycoside found in herbs such as Belamcanda chinensis (L.) DC and Iris tectorum Maxim. It has drawn increasing research interest due to its promising pharmacological activities. However, no critical review to date has determined whether its broad pharmacological activity stems from binding to specific targets or from the non-specific, broad-spectrum activity commonly associated with flavonoids. This paper provides a comprehensive review of tectoridin, covering its plant sources, pharmacological effects, pharmacokinetics, and toxicity, alongside an in-depth analysis of the mechanisms underlying its pharmacological effects and strategic recommendations for advancing its clinical translation. Methods: A systematic literature search was conducted in PubMed, Web of Science, Google Scholar, SciFinder, and CNKI for publications from 1968 to 2025 using keywords including tectoridin, tectorigenin 7-O-glucoside, traditional uses, ethnopharmacology, pharmacology, bioactive compounds, biological activity, pharmacokinetics and toxicity. Results: Tectoridin exhibits a broad spectrum of pharmacological activities, including anticancer, anti-inflammatory, hepatoprotective, antidiabetic, antioxidant, cardiovascular, and estrogenic effects. Pharmacokinetic studies have shown rapid tissue distribution and slow elimination; the aglycone metabolite tectorigenin often displays enhanced bioactivity, and chemical modifications may further improve efficacy. Toxicity data suggest relative safety in medicinal food contexts, but comprehensive in vivo studies remain limited. Tectoridin shows promise for treating cancer and inflammatory diseases; however, further research is needed to elucidate its molecular mechanisms, clarify toxicity, and optimize bioactivity. Conclusions: This review bridges natural products and modern therapeutics by focusing on tectoridin, highlighting its therapeutic potential, addressing challenges, and offering new perspectives for treating various diseases. Full article
(This article belongs to the Section Natural Products)
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13 pages, 2630 KB  
Article
High-Performance Porous Ceramics from Red Mud via Foam-Gelcasting for Efficient Waste Utilization
by Yanxiu Wang, Fan Wang, Ling Zhang, Shipei Wang, Anqi Yang, Chengwen Wang, Li Wang, Haisheng Han and Wei Sun
Materials 2026, 19(9), 1817; https://doi.org/10.3390/ma19091817 (registering DOI) - 29 Apr 2026
Abstract
Red mud, as a by-product of alkaline regeneration of alumina, has limited application due to its strong alkalinity, fine particle size, and complex composition. In this work, red mud porous ceramics with uniform pore size distribution and high mechanical strength were prepared using [...] Read more.
Red mud, as a by-product of alkaline regeneration of alumina, has limited application due to its strong alkalinity, fine particle size, and complex composition. In this work, red mud porous ceramics with uniform pore size distribution and high mechanical strength were prepared using a foam-gel casting method. The effects of solid loading and sintering temperature on the microstructure of porous ceramics were systematically investigated. The porosity of red mud-based porousceramics sintered at 1150 °C with a solid content of 60.4% was 33.7%, and the maximum compressive strength was 54.70 MPa, while the porousceramics prepared with a solid loading of 34.1% and sintered at 1050 °C achieved a maximum porosity of 79.7% and a compressive strength of 2.36 MPa. Increasing the solid loading reduced porosity and enhanced compressive strength, allowing for the tailoring of mechanical properties to meet specific application requirements. Higher sintering temperature promoted the formation of the liquid phase, enhanced particle bonding, and further improved the compressive strength. Additionally, toxicity leaching tests confirmed that the ceramics are environmentally safe, with leachate levels well within regulated limits. These results demonstrate the potential of foam-gel casting as an effective route for transforming red mud into value-added porous ceramics, thereby contributing to sustainable waste utilization and broadening the application prospects of red mud-based materials. Full article
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31 pages, 1014 KB  
Review
Inducing Ferroptosis to Enhance Radiotherapy in Head and Neck Cancer: Mechanisms, Radiosensitization Strategies, and Normal Tissue Considerations
by Jaewang Lee and Jong-Lyel Roh
Cells 2026, 15(9), 812; https://doi.org/10.3390/cells15090812 (registering DOI) - 29 Apr 2026
Abstract
Ferroptosis is an iron-dependent form of regulated cell death characterized by lipid peroxidation and failure of cellular antioxidant defenses. Increasing evidence indicates that ferroptosis contributes to the biological effects of radiotherapy and influences both tumor radiosensitivity and normal tissue injury. Because radiotherapy is [...] Read more.
Ferroptosis is an iron-dependent form of regulated cell death characterized by lipid peroxidation and failure of cellular antioxidant defenses. Increasing evidence indicates that ferroptosis contributes to the biological effects of radiotherapy and influences both tumor radiosensitivity and normal tissue injury. Because radiotherapy is a central treatment modality for many head and neck cancers, understanding how ferroptosis interacts with radiation responses has important translational implications. Ionizing radiation can induce ferroptosis through reactive oxygen species generation, disruption of glutathione metabolism, suppression of the SLC7A11–GSH–GPX4 antioxidant axis, and remodeling of membrane lipid composition. Conversely, tumor cells frequently develop radioresistance by reinforcing ferroptosis-suppressive pathways, including enhanced cystine transport, lipid desaturation, and metabolic adaptation. In head and neck cancers such as head and neck squamous cell carcinoma, nasopharyngeal carcinoma, oral squamous cell carcinoma, and thyroid malignancies, experimental studies show that modulation of ferroptosis significantly alters radiation response. Strategies that promote ferroptosis—including inhibition of antioxidant defenses, targeting of lipid metabolism, and modulation of iron homeostasis—have demonstrated radiosensitizing effects in preclinical models. However, ferroptosis may also contribute to radiation-induced normal tissue injury, particularly in oxidative stress-sensitive organs such as the salivary glands. This review summarizes the molecular basis of ferroptosis in radiotherapy, examines its role in radiosensitivity and radioresistance in head and neck cancers, and discusses therapeutic strategies to exploit ferroptosis while minimizing normal tissue toxicity. Full article
15 pages, 6751 KB  
Article
Transcriptomics, Proteomics and Network Pharmacology Reveal the Mechanisms of Cantharidin-Induced Kidney Injury in Rats
by Xiaotong Duan, Cancan Zhao, Sali Li, Liu Liu, Ming Yu, Yuanming Wu, Jianyong Zhang and Xiaofei Li
Curr. Issues Mol. Biol. 2026, 48(5), 460; https://doi.org/10.3390/cimb48050460 (registering DOI) - 29 Apr 2026
Abstract
Cantharidin (CTD), the principal active constituent of the traditional Chinese medicine (TCM) Mylabris, exhibits potent antitumor activity. However, its clinical application is limited by organ toxicity (especially nephrotoxicity), and the underlying mechanisms remain incompletely defined. This research endeavored to elucidate the nephrotoxic effects [...] Read more.
Cantharidin (CTD), the principal active constituent of the traditional Chinese medicine (TCM) Mylabris, exhibits potent antitumor activity. However, its clinical application is limited by organ toxicity (especially nephrotoxicity), and the underlying mechanisms remain incompletely defined. This research endeavored to elucidate the nephrotoxic effects and molecular mechanisms of CTD in rats using serum biochemical assays, histopathological examinations, and a multi-omics strategy. CTD treatment significantly increased levels of urea nitrogen and creatinine and induced histopathological injury in the kidneys. Transcriptomics, proteomics, and network pharmacology integrated analysis have revealed 14 common targets, mainly involved in the glutathione metabolic pathway. Further verification showed that CTD markedly upregulated protein expression of glutaminase (GLS), while downregulating homogentisate 1,2-dioxygenase (HGD), glutamate-cysteine ligase catalytic subunit (GCLC), and regulatory subunit (GCLM), thereby suppressing the glutathione metabolic pathway and exacerbating kidney injury. Our results indicate that CTD induces oxidative stress and consequent nephrotoxicity by inhibiting the glutathione metabolic pathway, providing a mechanistic basis for optimizing clinical strategies to mitigate CTD-induced kidney injury. Full article
20 pages, 717 KB  
Article
Changing Patterns in Hospitalisations of Patients with Systemic Lupus Erythematosus over Three Decades at a Tertiary Referral Centre in Catalonia
by Jesús Cívico-Ortega, Sergio Prieto-González, Olga Araújo, Georgina Espígol-Frigolé, Verónica Gómez-Caverzaschi, Maria Cecilia Garbarino, Ignasi Rodríguez-Pintó, Maria Cinta Cid, Xavier Crespo-Timoner, Rita Reig-Viader, José Hernández-Rodríguez, Gerard Espinosa and Ricard Cervera
J. Clin. Med. 2026, 15(9), 3407; https://doi.org/10.3390/jcm15093407 (registering DOI) - 29 Apr 2026
Abstract
Background/Objectives: Hospitalisations in systemic lupus erythematosus (SLE) reflect disease severity, accumulated damage, and the burden of comorbidity, remaining a major determinant of healthcare utilisation. Recent evidence suggests a shift from flare-driven admissions toward complications related to infections, comorbidities, and long-term treatment effects. [...] Read more.
Background/Objectives: Hospitalisations in systemic lupus erythematosus (SLE) reflect disease severity, accumulated damage, and the burden of comorbidity, remaining a major determinant of healthcare utilisation. Recent evidence suggests a shift from flare-driven admissions toward complications related to infections, comorbidities, and long-term treatment effects. We aimed to analyse the causes, characteristics, and outcomes of hospital admissions in patients with systemic lupus erythematosus (SLE) over a 30-year period in a tertiary referral centre in Catalonia (Spain) and to evaluate changes over time and prognostic factors associated with adverse outcomes. Methods: A retrospective observational study was conducted including all SLE patients admitted to the Department of Autoimmune Diseases at Hospital Clínic de Barcelona between June 1995 and December 2024. Admissions lasting less than 48 h or lacking clinical documentation were excluded. Variables analysed included demographics, disease duration, comorbidities, cause of admission, treatments, and outcomes. A composite outcome was defined as intensive care unit (ICU) admission, 30-day readmission, or prolonged hospital stay. Statistical analyses included univariate and multivariate regression models. Results: Among the 1216 hospital admissions, SLE flares and infections were the most frequent causes. Over the study period, admissions due to infections increased significantly and, in the last five years, exceeded those related to disease flares (33.7% vs. 26.1%). Patients hospitalized for flares were younger and had a shorter disease duration, whereas infection-related admissions were more common among older patients, those with overlap syndromes, and those with higher damage scores. Vascular events and SLE flares were independently associated with poorer outcomes. Although antimalarial use increased over time, it remained suboptimal, largely due to drug toxicity and newly diagnosed cases (from 45.2% to 69.7%; p < 0.001). Treatment strategies also evolved, with a shift toward lower glucocorticoid doses (from 14.5% to 38.3%; p < 0.001), and mycophenolate mofetil replacing cyclophosphamide as the preferred immunosuppressive agent. Conclusions: Hospitalisation patterns in SLE have shifted over time, with infections emerging as the leading cause of admission. This trend reflects an evolving patient profile characterized by older age, greater accumulated damage, comorbidities, and increased exposure to immunosuppressive therapies. These findings underscore the need for optimized infection prevention strategies and individualized treatment approaches to improve outcomes in contemporary SLE care. Full article
19 pages, 1030 KB  
Article
Distinct Echocardiographic Phenotypes in Primary vs. Secondary Iron Overload Cardiomyopathy: A Pilot Study on Myocardial Work Indices
by Luis Andrés Vega-Quesada, Zuilma Yurith Vásquez-Ortiz, María Elena Soto-López, Gerardo Marín and Cristofer Zarate-Calderon
Med. Sci. 2026, 14(2), 223; https://doi.org/10.3390/medsci14020223 (registering DOI) - 29 Apr 2026
Abstract
Background: Iron overload cardiomyopathy (IOC) is a major determinant of outcomes in hemochromatosis, and conventional echocardiography may miss early myocardial toxicity. Comparative data on primary (PH) versus secondary hemochromatosis (SH) using myocardial work (MW) indices are limited. Methods: We performed a retrospective cross-sectional [...] Read more.
Background: Iron overload cardiomyopathy (IOC) is a major determinant of outcomes in hemochromatosis, and conventional echocardiography may miss early myocardial toxicity. Comparative data on primary (PH) versus secondary hemochromatosis (SH) using myocardial work (MW) indices are limited. Methods: We performed a retrospective cross-sectional study of 34 adults (16 PH and 18 SH patients) at a tertiary center. They all underwent echocardiography with speckle-tracking to obtain LV global longitudinal strain (GLS) and non-invasive MW indices from pressure-strain loops: global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). Echocardiographic phenotypes were classified as a Normal, Dilated, Restrictive, or right ventricular/pulmonary hypertension (RVPH) phenotype. Results: SH patients showed higher iron burden and neurohormonal activation than PH patients (maximum ferritin 2954 vs. 444 ng/mL; BNP 93 vs. 13.5 pg/mL; both p < 0.001) and accounted for all deaths (33% vs. 0%) despite similar 3D LVEFs and GLSs. PH patients predominantly exhibited Normal phenotypes (81%), whereas SH patients more often showed advanced phenotypes, mainly RVPH and Dilated. GWI correlated inversely with ferritin (ρ ≈ −0.40), particularly ferritin at echocardiography in SH patients, while PH patients showed no significant correlations. GWW was higher in Dilated/RVPH compared to Normal phenotypes, and in SH patients, higher maximum ferritin was associated with impaired right ventricular free-wall strain. Conclusions: PH and SH patients exhibit distinct IOC phenotypes, with SH patients showing more advanced remodeling and worse outcomes. In this exploratory analysis, MW indices showed modest associations with iron burden markers, suggesting they may provide complementary information beyond LVEF and GLS. These preliminary findings require validation in larger, prospective studies. Full article
(This article belongs to the Section Cardiovascular Disease)
18 pages, 2807 KB  
Article
Multi-Dimensional Assessment Approach to Assess Pesticide Manufacturing Industry Wastewater Toxicity
by Deling Fan, Jian Wang, Lili Shi, Lei Wang and Zheng Fang
Biology 2026, 15(9), 700; https://doi.org/10.3390/biology15090700 (registering DOI) - 29 Apr 2026
Abstract
Pesticide manufacturing industry wastewater is a complex mixture of potentially harmful components. If not properly treated, discharged effluents may pose serious risks to environment and organisms. In this study, influent and effluent wastewater samples from a pesticide factory were comprehensively non-screened by liquid [...] Read more.
Pesticide manufacturing industry wastewater is a complex mixture of potentially harmful components. If not properly treated, discharged effluents may pose serious risks to environment and organisms. In this study, influent and effluent wastewater samples from a pesticide factory were comprehensively non-screened by liquid chromatography high-resolution mass spectrometry, coupled with zebrafish embryo toxicity testing to assess whole effluent toxicity. A total of eight chemical groups were identified, including pesticides, antibiotics, nitrogen compounds, ketones, esters, amines and derivatives, other drugs, and other organic compounds. While wastewater treatment processes reduced most of the analyzed groups of compounds, compounds (e.g., 2-aminophenol, N-Nitrosodipropylamine, and carbamazepine) increased during the treatments. The influent samples were more toxic to zebrafish than the effluent samples in terms of lethality, teratogenic effects, developmental impacts, locomotor behavior, and neurotoxicity. The results showed that locomotor behavior was the most sensitive phenotypic toxicity endpoint, with significantly higher sensitivity than traditional acute lethal or teratogenic endpoints. Through a multi-dimensional assessment approach combining chemical screening, literature-based, risk ranking, and targeted quantification, we identified three predominant pesticide residues in the wastewater samples (both influents and effluents): hexaconazole, fenobucarb and isoprocarb. All three compounds exhibited additive or synergistic toxicity in zebrafish embryos. Exposure to ≥0.08% influent or ≥2% effluent increased inflammation (interleukin-1 beta, IL-1β), oxidative stress (copper/zinc superoxide dismutase, Cu/Zn-Sod), apoptosis (tumor protein p53, p53), and significantly impaired neurodevelopment in zebrafish larvae by altering the expression of sonic hedgehog a (shha), synapsin IIa (syn2a), and glial fibrillary acidic protein (gfap). This study suggests the necessity of incorporating non-apical endpoint (locomotor behavior) into whole effluent toxicity test, as this approach is essential for reducing the environmental risks posed by pesticide factory wastewater. Full article
(This article belongs to the Special Issue Advances in Ecotoxicology and Environmental Toxicology)
38 pages, 3263 KB  
Article
Thiazolyl-Methylthio-1,3,4-Thiadiazole Hybrids as Halicin Analogues with Antimicrobial and Antibiofilm Activities: Chemical Development, Biological Assessment, and 2D-QSAR Study
by Daniel Ungureanu, Gabriel Marc, Mihaela Niculina Duma, Dan Cristian Vodnar, Gheorghe-Adrian Martău, Laurian Vlase, Adrian Pîrnău, Brîndușa Tiperciuc, Cristina Moldovan, Ioana Ionuț, Anca Stana, Ilioara Oniga and Ovidiu Oniga
Antibiotics 2026, 15(5), 448; https://doi.org/10.3390/antibiotics15050448 (registering DOI) - 29 Apr 2026
Abstract
Background/Objectives: The purpose of this study was the chemical design, synthesis, and evaluation of the antimicrobial and antibiofilm potentials of 20 novel thiazolyl-methylthio-thiadiazole hybrid compounds (6aj and 8aj). Methods: The compounds were designed as structural [...] Read more.
Background/Objectives: The purpose of this study was the chemical design, synthesis, and evaluation of the antimicrobial and antibiofilm potentials of 20 novel thiazolyl-methylthio-thiadiazole hybrid compounds (6aj and 8aj). Methods: The compounds were designed as structural analogues of halicin with two points of variation and were synthesized through a process with multiple condensation steps. The compounds were evaluated in vitro through MIC determinations for the antimicrobial activity and percentage of biofilm inhibition, and in silico, respectively, through molecular docking, druggability, and ADMETox prediction. A 2D-QSAR study was conducted for antimicrobial activity using the Free-Wilson model. Results: In terms of antibacterial activity, all compounds displayed important activity on the tested strains (MICs = 15.62–250 μg/mL), except against Staphylococcus aureus. Regarding the antifungal activity, the effect against Candida albicans was similar to fluconazole in most cases (MIC = 15.62 μg/mL). With respect to the antibiofilm activity, the most effective activity was registered against the Pseudomonas aeruginosa biofilm. The in vitro results for the antibacterial activity against Escherichia coli were correlated with the observations drawn in the molecular docking study on the ATPase domain of the GyrB subunit of E. coli. The in silico predictions of the molecular properties concluded that all compounds have good druggability properties, while the ADMETox predictions concluded that the compounds could have low gastrointestinal absorption and blood–brain barrier permeation capacity, but raised safety flags (e.g., hepatotoxicity and high acute oral toxicity). The 2D-QSAR study concluded that the thiazolyl-methylthio-thiadiazole scaffold had the highest contribution to antimicrobial activity in almost all cases. Conclusions: The two series of compounds highlight the impact of structural modulations of the scaffold and its substituents on the investigated biological activities. Full article
(This article belongs to the Special Issue Antibiotic Synthesis, 2nd Edition)
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39 pages, 1103 KB  
Review
Quorum Sensing and Quorum Quenching in Pseudomonas aeruginosa and Staphylococcus aureus Infections: Therapeutic Potential, Limitations and Clinical Challenges
by Emilia Nowak, Matylda Korgiel, Karolina Pawłuszkiewicz, Jarosław Widelski, Bachar Cheaib and Emil Paluch
Antibiotics 2026, 15(5), 447; https://doi.org/10.3390/antibiotics15050447 - 29 Apr 2026
Abstract
Antimicrobial resistance (AMR) represents a major global health threat, largely driven by antibiotic overuse and the protective role of bacterial biofilms. Quorum sensing (QS), a bacterial communication system regulating virulence and biofilm formation, has emerged as a promising therapeutic target. Quorum quenching (QQ), [...] Read more.
Antimicrobial resistance (AMR) represents a major global health threat, largely driven by antibiotic overuse and the protective role of bacterial biofilms. Quorum sensing (QS), a bacterial communication system regulating virulence and biofilm formation, has emerged as a promising therapeutic target. Quorum quenching (QQ), which disrupts QS without directly inhibiting bacterial growth, is considered a potential anti-virulence strategy that may reduce selective pressure for resistance. This review critically evaluates recent advances in QQ research, focusing on its clinical applicability, limitations, and risks. We analyzed studies from the last five years involving natural compounds, synthetic molecules, nanoparticles (NPs), and combination therapies targeting key pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus in models of lung diseases, mainly cystic fibrosis, chronic wounds, burns, and implant-associated infections. While numerous compounds demonstrate significant in vitro anti-biofilm and anti-virulence activity, major challenges remain, including limited in vivo validation, pharmacokinetic constraints, toxicity concerns, microbiome disruption, and the potential development of tolerance or functional resistance. Although QQ offers a promising adjunctive approach to conventional antibiotics, its long-term clinical feasibility requires comprehensive evaluation of evolutionary dynamics, host–microbe interactions, and safety profiles. Full article
(This article belongs to the Special Issue Limits and Risks of Quorum Quenching in Medicine)
19 pages, 928 KB  
Article
Household Pharmaceutical Accumulation in Southeastern Mexico: A Multidimensional Pharmacoepidemiological Risk Assessment Framework
by Rafael Manuel de Jesús Mex-Álvarez, María Magali Guillen-Morales, Patricia Garma-Quen, David Yanez-Nava, Diana Andrea Luna-Salazar and Roger Enrique Chan-Martínez
Pharmacoepidemiology 2026, 5(2), 13; https://doi.org/10.3390/pharma5020013 - 29 Apr 2026
Abstract
Background/Objectives: The accumulation of unused and expired pharmaceuticals in households is a growing public health concern with implications for patient safety, rational drug use, and environmental health. However, systematic risk characterization integrating clinical and environmental perspectives at the community level remains limited, [...] Read more.
Background/Objectives: The accumulation of unused and expired pharmaceuticals in households is a growing public health concern with implications for patient safety, rational drug use, and environmental health. However, systematic risk characterization integrating clinical and environmental perspectives at the community level remains limited, particularly in low- and middle-income settings. This study aimed to develop and apply a composite risk index, grounded in an eco-pharmacovigilance framework, for the assessment of health risks associated with accumulated household pharmaceuticals in southeastern Mexico. Methods: A cross-sectional study was conducted in 526 randomly selected households using stratified sampling. Guided in-home medication inventories were performed with participant collaboration, and pharmaceuticals were classified according to the Anatomical Therapeutic Chemical (ATC) system. A composite risk index (CRI = Fr × PR) was developed within an eco-pharmacovigilance framework. The frequency of accumulation (Fr) for each therapeutic group was multiplied by a potential risk score (PR) derived through a structured multidisciplinary expert consensus process integrating clinical toxicity, environmental persistence, and antimicrobial resistance potential. Results: A total of 2184 pharmaceutical units were recorded during the household inventories, of which 28.7% were expired. Expired medications were primarily retained rather than actively used, representing a latent risk for inappropriate self-medication and accidental exposure. The therapeutic groups with the highest CRI values were antihypertensives (CRI = 42.3), antidiabetics (CRI = 37.8), and antibiotics (CRI = 31.5), indicating a relatively higher contribution within the composite risk index framework to overall household pharmaceutical risk. These findings highlight priority therapeutic groups driven by the combined effect of high accumulation frequency, distinct accumulation patterns, and intrinsic hazard. Conclusions: Household pharmaceutical accumulation can be characterized using a composite, eco-pharmacovigilance-based approach that integrates exposure and hazard dimensions. The proposed framework functions as a prioritization tool rather than a precise quantitative measure, enabling the identification of therapeutic groups requiring targeted intervention. Findings should be interpreted as indicative of relative risk patterns rather than precise estimates, given the exploratory design and guided data collection approach. The proposed framework provides a practical tool for prioritizing interventions aimed at improving rational drug use, reducing accumulation, and mitigating environmental impact. Further validation in diverse settings is warranted to strengthen its applicability. Full article
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15 pages, 10771 KB  
Article
Exogenous Ganglioside GM3 Attenuates Atherosclerosis via Multi-Organ Modulation of Lipid Metabolism
by Jinhua Zhou, Hongda Zhuang, Qinghua Sheng, Zhitao Qiu and Yong Chen
Pharmaceutics 2026, 18(5), 547; https://doi.org/10.3390/pharmaceutics18050547 - 29 Apr 2026
Abstract
Background: Atherosclerosis (AS) remains a leading cause of cardiovascular mortality worldwide and is significantly driven by hyperlipidemia. While ganglioside GM3 is known to regulate cellular lipid metabolism, its systemic pharmacological effects on atherosclerosis remain unclear. This study aims to evaluate the anti-atherosclerotic efficacy [...] Read more.
Background: Atherosclerosis (AS) remains a leading cause of cardiovascular mortality worldwide and is significantly driven by hyperlipidemia. While ganglioside GM3 is known to regulate cellular lipid metabolism, its systemic pharmacological effects on atherosclerosis remain unclear. This study aims to evaluate the anti-atherosclerotic efficacy of exogenous GM3 and elucidate its underlying systemic mechanisms. Methods: C57BL/6N ApoE−/− mice fed a high-fat diet were intravenously treated with exogenous GM3 (1 or 4 mg/kg) every three days for 12 weeks. Atherosclerotic progression and lipid profiles were evaluated through histological analyses of the aortic arch and aortic sinus, alongside biochemical and molecular assessments of plasma, hepatic, and intestinal tissues. Results: GM3 treatment significantly reduced plaque formation in the aortic arch and aortic sinus, along with decreased plasma levels of triglycerides, total cholesterol, and LDL-C. Mechanistically, GM3 suppressed hepatic VLDL secretion by downregulating ApoB100 and MTTP expression. Concurrently, hepatic lipid clearance was enhanced via the upregulation of Ldlr, Scarb1, and Lrp1. GM3 also lowered circulating PCSK9 levels and reduced intestinal cholesterol absorption by decreasing NPC1L1 expression. Although GM3 promoted lipid accumulation in the liver, no evidence of liver dysfunction or systemic toxicity was observed. Conclusions: Exogenous GM3 acts as a potent multi-target modulator that attenuates atherosclerosis by coordinating hepatic lipoprotein metabolism and restricting intestinal cholesterol uptake. This multi-organ metabolic partitioning strategy highlights the potential of GM3-based therapeutics for managing complex dyslipidemia. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
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17 pages, 11118 KB  
Article
Comparative Hepatotoxicity Assessment of PFOS and Its Alternative 6:2 FTSA in Adult Female Zebrafish
by Wenying Zhang, Yunru Dong, Yanmin Jian, Yazhe Jia, Keyi Yang, Yang Chen, Yuan Cao, Lulu Guo, Shujing Zhang, Dongwu Liu, Qiuxiang Pang and Shuang Jiao
Animals 2026, 16(9), 1368; https://doi.org/10.3390/ani16091368 - 29 Apr 2026
Abstract
As an alternative to perfluorooctane sulfonate (PFOS), 6:2 fluorotelomer sulfonic acid (6:2 FTSA) has been increasingly produced and detected in aquatic environments, yet its toxicological effects in fish remain incompletely characterized. In this study, adult female zebrafish were exposed for 30 days to [...] Read more.
As an alternative to perfluorooctane sulfonate (PFOS), 6:2 fluorotelomer sulfonic acid (6:2 FTSA) has been increasingly produced and detected in aquatic environments, yet its toxicological effects in fish remain incompletely characterized. In this study, adult female zebrafish were exposed for 30 days to solvent control (CK), 50 μg/L PFOS (P50), 50 μg/L 6:2 FTSA (F50), and 500 μg/L 6:2 FTSA (F500), respectively. Histopathological analysis revealed that both compounds induced hepatic injury, with the most severe damage observed in the F500 group. Hepatic transcriptomic analysis identified 645, 191, and 85 differentially expressed genes (DEGs) in the P50, F50, and F500 groups versus CK, respectively. Functional enrichment analysis further demonstrated distinct toxic profiles: PFOS at 50 μg/L primarily disrupted pathways related to the cell cycle, DNA replication, and reproduction. In contrast, 50 μg/L 6:2 FTSA predominantly activated PPAR-mediated lipid metabolism pathways, consistent with a “metabolic toxicity” phenotype. Notably, at 500 μg/L, 6:2 FTSA induced the most severe injury accompanied by a distinct transcriptomic signature—characterized by fewer DEGs but a pronounced enrichment of endoplasmic reticulum stress pathways—suggestive of a shift from metabolic perturbation to overwhelming cellular stress. Biochemical analysis confirmed a significant increase in malondialdehyde (MDA) only in the F50 group, supporting oxidative stress-mediated metabolic toxicity. Collectively, these findings demonstrate that 6:2 FTSA is not a safe alternative to PFOS but exhibits a dose-dependent and multifaceted toxicological profile, with high-dose effects indicative of acute cellular stress. This study underscores the need for case-specific, dose-range inclusive risk assessment of emerging PFAS alternatives. Full article
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11 pages, 250 KB  
Article
Neoadjuvant Chemotherapy and Stereotactic Body Radiation Therapy in Patients with Early-Onset Pancreatic Cancer: Clinical Outcomes and Toxicity
by Shuchi Sehgal, Abhinav V. Reddy, Suqi Ke, Colin S. Hill, Timothy A. Lin, Serena Mao, Lei Zheng, Jin He, Joseph M. Herman, Chen Hu, Jeffrey J. Meyer and Amol K. Narang
Cancers 2026, 18(9), 1418; https://doi.org/10.3390/cancers18091418 - 29 Apr 2026
Abstract
Purpose/Objective: This purpose of this study is to report on a cohort of patients with Early-onset pancreatic cancer (EOPC) (age < 55 years) who were treated with neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT) with or without surgical resection. Materials/Methods: [...] Read more.
Purpose/Objective: This purpose of this study is to report on a cohort of patients with Early-onset pancreatic cancer (EOPC) (age < 55 years) who were treated with neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT) with or without surgical resection. Materials/Methods: This was a single-institution, retrospective review of patients with EOPC that was staged as either borderline resectable (BRPC) or locally advanced (LAPC) based on NCCN criteria and who were treated with upfront chemotherapy followed by SBRT, with or without subsequent surgical resection. Endpoints included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and treatment-related toxicity. Results: From 2016 to 2021, 47 patients met the inclusion criteria. The median age was 50.4 years (range, 36.4–54.7 years). The median duration of induction chemotherapy was 4 months (range, 2.5–9.0 months). The SBRT dose for the majority (46/47, 97.9%) of patients was 33 Gy in five fractions. Surgical resection was performed in 33 patients (70.2%). The median OS, LPFS, DMFS, and PFS were 14.2 months, 11.6 months, 8.9 months, and 8.1 months respectively. Six-month and 1-year LPFS were 88.3% and 45.4%, respectively. Chemotherapy duration (≥4 months) was associated with improved median OS (16.5 vs. 10.1 months, p = 0.005), LPFS (10.1 vs. 4.9 months, p = 0.002), DMFS (9.7 vs. 5.2 months, p = 0.014), and PFS (9.7 vs. 5.2 months, p = 0.020). The normalization of CA 19-9 (≤34 vs. >34 U/mL) after chemotherapy was associated with improved median DMFS (not reached vs. 5.6 months, p = 0.003) and PFS (11.3 vs. 5.6 months, p = 0.022). Grade 3+ rates of chemotherapy and radiation-related toxicity were 14.9% and 2.1% respectively. The Clavien–Dindo 3b toxicity rate was 3.0%. Conclusions: In EOPC, an induction chemotherapy duration ≥4 months and the normalization of CA 19-9 after chemotherapy were associated with improved outcomes, suggesting a role for extended durations of systemic therapy titrated to CA 19-9 response before transitioning to local therapy. The high rate of local failure and the low rate of grade 3+ toxicity also suggest a role for intensifying local therapy in this population. Full article
40 pages, 7342 KB  
Review
Traditional Uses, Phytochemicals, Biological Activities, and Biotechnological Applications of Serjania Species: A Review of Current Knowledge and Future Prospects
by Ana Belem Rubio-García, Cecilia Guadalupe de Loza-García, Jorge Manuel Silva-Jara, Napoleón González-Silva, Luis Antonio Ramirez-Contreras, Zuamí Villagran, Omar Graciano-Machuca, Jessica del Pilar Ramírez-Anaya, Fernando Martínez-Esquivias and Luis Miguel Anaya-Esparza
Molecules 2026, 31(9), 1477; https://doi.org/10.3390/molecules31091477 - 29 Apr 2026
Abstract
The genus Serjania (family Sapindaceae) comprises more than 240 species, primarily distributed in Brazil and Mexico, and it exhibits considerable ethnobotanical and therapeutic potential. Ethnobotanical evidence documents the widespread use of decoctions prepared from the leaves, stems, and roots of Serjania species for [...] Read more.
The genus Serjania (family Sapindaceae) comprises more than 240 species, primarily distributed in Brazil and Mexico, and it exhibits considerable ethnobotanical and therapeutic potential. Ethnobotanical evidence documents the widespread use of decoctions prepared from the leaves, stems, and roots of Serjania species for the treatment of gastrointestinal disorders, renal pain, inflammatory conditions, and infections. Among the most extensively studied species are S. marginata, S. erecta, S. lethalis, S. caracasana, S. goniocarpa, S. schiedeana, S. yucatenensis, S. triquetra, and S. racemose. Phytochemical research has identified a diverse array of bioactive secondary metabolites, including saponins, flavonoids, phenolic acids, tannins, and terpenoids. Significant experimental evidence supports the broad spectrum of biological activities of these Serjania species, including antimicrobial, anti-inflammatory, antioxidant, gastroprotective, antihypertensive, analgesic, antivenom, cytotoxic, antimutagenic, anti-ulcer, photoprotective, antiparasitic, and vasorelaxant effects, as demonstrated in both in vitro and in vivo models. Although preliminary toxicity assessments of extracts from some Serjania species in murine models, Oreochromis niloticus (Nile tilapia), and Artemia salina suggest a favorable safety profile, significant research gaps remain. Additionally, several Serjania species have shown potential as natural pesticides and bioherbicides, highlighting their relevance in agricultural applications. Future studies should prioritize the isolation and structural characterization of individual bioactive compounds, as well as the elucidation of their molecular mechanisms of action, moving beyond crude extract-based screening approaches. Overall, this review summarizes current knowledge on traditional uses, phytochemical composition, biological activities, and biotechnological applications of Serjania species. Full article
(This article belongs to the Special Issue Natural Products and Microbiology in Human Health, 2nd Edition)
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16 pages, 28414 KB  
Article
PLGA Microparticles as a Stable and Biocompatible Carrier for Adiponectin Delivery to Enhance Bone Regeneration
by Pengxin Zhang, Yang Wang, Fan Hu and Yanping Gong
Pharmaceutics 2026, 18(5), 546; https://doi.org/10.3390/pharmaceutics18050546 - 29 Apr 2026
Abstract
Background: Adiponectin (ADPN) is a key adipokine with osteogenic potential, but its clinical translation for bone regeneration is hindered by poor in vivo stability. This study aimed to develop poly lactic-co-glycolic acid (PLGA) microparticles as a stable and biocompatible carrier for sustained [...] Read more.
Background: Adiponectin (ADPN) is a key adipokine with osteogenic potential, but its clinical translation for bone regeneration is hindered by poor in vivo stability. This study aimed to develop poly lactic-co-glycolic acid (PLGA) microparticles as a stable and biocompatible carrier for sustained ADPN delivery to enhance bone repair. Methods: ADPN-loaded PLGA microparticles (ADPN-MPs) were fabricated via emulsion solvent evaporation. Their physicochemical properties were characterized using scanning electron microscopy (SEM) and circular dichroism (CD) spectroscopy. Loading efficiency and drug loading were quantified. In vitro release kinetics and stability under physiological conditions were assessed. Biocompatibility was evaluated using MC3T3-E1 osteoblasts and BMSCs, and in vivo efficacy was tested in a fracture model via gait analysis. Results: Employing CD to evaluate the secondary structure of ADPN, emulsion solvent evaporation for microparticles preparation, and SEM for morphological analysis, we quantitatively assessed the loading efficiency (69.83 ± 4.24%) and drug loading (0.97 ± 0.06%) of ADPN-MPs. Results indicated that ADPN-MPs maintained significant stability under varied pH and temperature conditions and exhibited a controlled release profile, with an average initial rapid release of 14.25% within 24 h and an average cumulative release of 55.00% by day 28. Furthermore, ADPN-MPs promoted the proliferation of MC3T3-E1 and BMSCs without toxicity, demonstrating excellent biocompatibility. Notably, gait analysis in a fracture model showed improved healing in both ADPN and ADPN-MPs groups compared to controls, with ADPN-MPs demonstrating comparable efficacy to free ADPN, supporting its potential as a stable delivery system for bone regeneration. Conclusions: PLGA microparticles serve as an effective, stable, and biocompatible delivery platform for ADPN, significantly promoting bone regeneration in vitro and in vivo. This delivery system enhances the therapeutic potential of ADPN for clinical bone repair applications. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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