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27 pages, 1800 KB  
Review
The Research Landscape of Spirulina platensis (2016–2025): A Bibliometric Analysis and Scoping Review of Therapeutic Trends and Biotechnological Applications
by Florina Miere (Groza), Andrada Pop, Luminita Fritea, Florin Banica, Angela Antonescu and Daniela Simona Cavalu
Appl. Sci. 2026, 16(9), 4203; https://doi.org/10.3390/app16094203 (registering DOI) - 24 Apr 2026
Abstract
Objectives: This study evaluates the research landscape of the cyanobacterium Spirulina (recently reclassified as Limnospira), a strategic resource in the nutraceutical, pharmaceutical, and functional food industries. The central objective is to transition from the traditional “superfood” narrative to a structured analysis [...] Read more.
Objectives: This study evaluates the research landscape of the cyanobacterium Spirulina (recently reclassified as Limnospira), a strategic resource in the nutraceutical, pharmaceutical, and functional food industries. The central objective is to transition from the traditional “superfood” narrative to a structured analysis of its modern therapeutic potential as reflected in current scientific literature. This study employs bibliometric analysis to highlight research trends and thematic directions in Spirulina-related studies, rather than to experimentally validate therapeutic effects. Methods: The investigation employed an exploratory bibliometric analysis of 996 peer-reviewed articles indexed in the Web of Science (2016–2025). Using VOSviewer software, we mapped keyword co-occurrence networks, international collaborations, and institutional clusters to identify dominant thematic directions and emerging research frontiers in biotechnology and medicine. Results: Bibliometric mapping illustrates research trends and thematic associations reported in the scientific literature centered on pathophysiological mechanisms, particularly oxidative stress, inflammation, and hepatoprotection. While often referred to as “microalgae”, Spirulina is biologically a photosynthetic prokaryote with a unique lipid profile characterized by high gamma-linolenic acid (GLA) content, although clinical evidence remains heterogeneous. The analysis highlights a robust regional research hub in the Middle East and North Africa, led by Egypt and Saudi Arabia, in contrast to fragmented inter-continental collaboration. Conclusions: The steady upward trend in publications confirms expanding academic interest in Spirulina as a functional ingredient. However, this study underscores a persistent gap between in vitro bioactivity and standardized clinical validation. These findings provide a roadmap for future biotechnological developments, emphasizing the need for more rigorous, multi-center clinical trials to bridge the “superfood” perception with evidence-based therapeutic applications. Full article
20 pages, 1336 KB  
Review
C/EBPδ as a Regulatory Node in Adipocytes: Roles in Differentiation, Metabolism, and Immune Function
by Suining Ma, Meiting Lai, Tongjun Li, Lexun Wang and Xianglu Rong
Biomolecules 2026, 16(5), 641; https://doi.org/10.3390/biom16050641 - 24 Apr 2026
Abstract
CCAAT/enhancer-binding protein δ (C/EBPδ) is a rapidly responsive transcription factor that occupies an important regulatory position in adipocytes. Induced during the early stage of adipocyte differentiation, C/EBPδ integrates hormonal, inflammatory, metabolic, and stress-related cues and contributes to the coordination of downstream transcriptional and [...] Read more.
CCAAT/enhancer-binding protein δ (C/EBPδ) is a rapidly responsive transcription factor that occupies an important regulatory position in adipocytes. Induced during the early stage of adipocyte differentiation, C/EBPδ integrates hormonal, inflammatory, metabolic, and stress-related cues and contributes to the coordination of downstream transcriptional and functional programs. Beyond its role in the initiation of differentiation, C/EBPδ is also involved in adipogenic progression, metabolic regulation, and immune-related functions in adipocytes. Current evidence indicates that C/EBPδ participates in early adipogenic regulatory networks, contributes to lipid metabolic programs, and is associated with immune-regulatory processes linked to lipid antigen presentation. Notably, the biological output of C/EBPδ is strongly shaped by tissue type, developmental stage, and microenvironmental context, ranging from promotion of adipogenic differentiation to regulation of inflammatory, metabolic, and adaptive stress responses under distinct physiological and pathological conditions. This review summarizes the upstream regulatory network, downstream functional framework, and context-dependent roles of C/EBPδ in adipocytes, and further discusses its potential relevance to adipose-related diseases as well as the opportunities and challenges for future precision intervention strategies. Full article
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18 pages, 921 KB  
Article
Colloidal Hydroxyapatite Nanoparticles as a Carrier for Cannabinol: The Effect on Model Langmuir Monolayers and Bilayer Lipid Membranes
by Emilia Świątek, Jan Taudul, Daria Kępińska, Dorota Nieciecka and Paweł Krysiński
Colloids Interfaces 2026, 10(3), 33; https://doi.org/10.3390/colloids10030033 - 24 Apr 2026
Abstract
Cannabinol (CBN) is a highly lipophilic phytocannabinoid whose biomedical application is limited by poor water solubility. In this study, colloidal hydroxyapatite nanoparticles (nHAp) were evaluated as a carrier for CBN, and their effect on model lipid membranes was investigated. Interactions between CBN and [...] Read more.
Cannabinol (CBN) is a highly lipophilic phytocannabinoid whose biomedical application is limited by poor water solubility. In this study, colloidal hydroxyapatite nanoparticles (nHAp) were evaluated as a carrier for CBN, and their effect on model lipid membranes was investigated. Interactions between CBN and lipids were examined using Langmuir monolayers and lipid bilayers (black lipid membranes, BLMs). Langmuir monolayer studies revealed strong interactions between CBN and lipids, resulting in changes in isotherms, compressibility, and monolayer stability. BLM measurements indicated that delivery of CBN via nHAp modifies the electrical properties and stability of the lipid bilayer, suggesting alterations in membrane organization and permeability. These results demonstrate that hydroxyapatite nanoparticles can effectively serve as a carrier for cannabinol while modulating its interactions with lipid membranes. Full article
31 pages, 1156 KB  
Review
Edible Plant-Derived Exosome-like Nanoparticles as Prebiotic Nanocarriers: Gut Microbiota Modulation and Functional Food Potential
by Yağız Alkan, Yalçın Mert Yalçıntaş, Mikhael Bechelany and Sercan Karav
Pharmaceutics 2026, 18(5), 520; https://doi.org/10.3390/pharmaceutics18050520 (registering DOI) - 24 Apr 2026
Abstract
The gut microbiota takes charge in a pivotal role in metabolic equilibrium, immune response, and modulating gut lining stability and has become the main focus of nutrition and functional food research. In this regard, the definition of prebiotics has progressed past the traditional [...] Read more.
The gut microbiota takes charge in a pivotal role in metabolic equilibrium, immune response, and modulating gut lining stability and has become the main focus of nutrition and functional food research. In this regard, the definition of prebiotics has progressed past the traditional approach limited to indigestible dietary fibers, embracing more targeted, biologically active, and functional delivery systems. In recent years, plant-derived exosomes (PDEs), a subclass of exosomes defined as extracellular vesicles (EVs) in the 30–150 nm size range, have emerged as an innovative class of nanostructures supporting this transformation. Plant-derived exosome-like nanoparticles (PELNs) have been taken into account as natural nanocarriers which are suitable for the gastrointestinal system with the help of their high biocompatibility, low immunogenicity profiles and rich bioactive cargo contents. This review discusses structural features of PELNs, molecular cargo content, and biological roles comprehensively and focuses especially on gut microbiota interactions. MicroRNAs, proteins, lipids, polyphenols, and glycans which PELNs contain are discussed with regard to shaping the microbial composition, regulating microbial metabolic activity, and modulating host-microbe communication. Findings derived from in vitro, in vivo, and limited translational studies indicate that PELNs can modulate specific microbial taxa, increase short-chain fatty acid (SCFA) yield, strengthen mucosal immune homeostasis, and induce source-dependent responses in the gut microbiota. In their traditional definition, prebiotics are taken into account as food components which selectively support proliferation and metabolism of helpful microbes, especially Bifidobacteria and Lactobacilli. Within this framework, PELNs are not only passive carriers of functional components but also evaluated as active systems which can directly affect microbiota composition and metabolic functions. Thus, they are repositioned as “prebiotic nanocarriers.” Also this review evaluates the potential of functional food and integration of major edible PELNs into synbiotic formulations by discussing their isolation and characterization methods and stabilities in the gastrointestinal environment. Limitations of clinical applications and lack of research from a prebiotic nanocarrier perspective of PELNs show that this field still contains important research gaps. The novelty of the study lies in its integration of PELN research with nutrition-based approaches to microbiota modulation and innovative functional food strategies under a single multidisciplinary conceptual framework. Full article
16 pages, 2501 KB  
Article
Spatially Resolved Metabolomic Profiling Reveals Progression-Associated Metabolic Reprogramming in Colorectal Liver Metastasis
by Ying Zhu, Yixuan Cai, Qianyu Wang, Hanchuan Guo, Qianqian Xie, Yingshi Xiang, Songlin Yu, Bin Wu and Ling Qiu
Metabolites 2026, 16(5), 293; https://doi.org/10.3390/metabo16050293 - 24 Apr 2026
Abstract
Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with colorectal liver metastasis (CRLM) being the major determinant of poor prognosis. Tumor metabolic reprogramming and spatial heterogeneity complicate biomarker discovery and clinical management. This study aimed to characterize the spatial [...] Read more.
Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with colorectal liver metastasis (CRLM) being the major determinant of poor prognosis. Tumor metabolic reprogramming and spatial heterogeneity complicate biomarker discovery and clinical management. This study aimed to characterize the spatial metabolomic landscape of CRC and identify progression-associated metabolic alterations and potential metabolic signatures for liver metastasis. Methods: A total of 23 tissue samples were collected from patients with CRC, with and without liver metastasis. Air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was used to map the spatial metabolite distributions. Region-of-interest analysis guided by histopathology enabled comparative metabolomic profiling across different tissue types. Multivariate statistical analysis, pathway enrichment, and receiver operating characteristic (ROC) curve analyses were performed to identify key metabolic alterations and evaluate potential biomarker performance. Results: Distinct spatial metabolomic profiles were observed across normal mucosa, primary tumors, liver metastases, and normal liver tissues. In primary colorectal tumors, amino acid, purine, and choline metabolism were significantly upregulated, whereas liver metastases were characterized by elevated levels of triglycerides, diglycerides, cholesteryl esters, and acylcarnitines, indicating enhanced lipid synthesis, incomplete fatty acid oxidation, and/or mitochondrial dysfunction. Progression-associated analyses across tissue types revealed consistently increasing trends in glycerides and acylcarnitines, along with heterogeneous alterations in amino acids and phospholipids. Furthermore, 122 differential metabolites were identified between metastatic and non-metastatic CRC, and a four-lipid panel demonstrated strong discriminatory performance. Conclusions: This study provides a spatially resolved characterization of metabolic reprogramming during CRC progression and liver metastasis, highlighting lipid and amino acid metabolism as key features and revealing the metabolic signatures of CRLM. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
26 pages, 728 KB  
Review
Extracellular Vesicles as Mediators of Endothelial and Tubular Injury in Cardiac Surgery-Associated Acute Kidney Injury
by Elena Grossini, Teresa Esposito, Mohammad Mostafa Ola Pour, Carlo Smirne, Giovanni Casali, Mario Pirisi, Vincenzo Cantaluppi, Daniele Pierelli, Rosanna Vaschetto and Sakthipriyan Venkatesan
Biomedicines 2026, 14(5), 982; https://doi.org/10.3390/biomedicines14050982 - 24 Apr 2026
Abstract
Cardiac surgery represents a cornerstone of modern cardiovascular medicine, yet it is intrinsically linked to significant systemic stress responses that can compromise remote organ function. Among postoperative complications, cardiac surgery-associated acute kidney injury (CSA-AKI) remains a significant clinical challenge characterized by high morbidity [...] Read more.
Cardiac surgery represents a cornerstone of modern cardiovascular medicine, yet it is intrinsically linked to significant systemic stress responses that can compromise remote organ function. Among postoperative complications, cardiac surgery-associated acute kidney injury (CSA-AKI) remains a significant clinical challenge characterized by high morbidity and complex pathophysiology. While hemodynamic instability and ischemia–reperfusion injury are established risk factors, renal dysfunction frequently persists despite optimal perfusion. This observation suggests the involvement of potent circulating mediators in cellular injury. Extracellular vesicles (EVs) are essential for intercellular communication and serve as central hubs for transporting bioactive lipids, proteins, and genetic material. Accumulating evidence indicates that the mechanical and oxidative stress inherent to cardiopulmonary bypass triggers substantial release of EVs from platelets, erythrocytes, and injured vascular tissues. These vesicles may function as vectors that traffic oxidized mitochondrial components and pro-inflammatory cargo to the renal parenchyma. This signaling cascade appears to disrupt renal homeostasis through a proposed “dual-hit” mechanism involving the induction of endothelial dysfunction and endothelial-to-mesenchymal transition (EndMT), followed by tubular epithelial injury via mitochondrial fragmentation, redox imbalance, and downregulation of anti-aging factors. The complexity of these EV-mediated interactions may contribute to an incomplete understanding of why specific patient phenotypes fail to recover. This narrative review examines the mechanisms of surgery-induced EV biogenesis, the molecular pathogenesis of endothelial and tubular damage, and the role of intercellular crosstalk. Additionally, we discuss future perspectives on targeting the “EV vector” through therapeutic apheresis and mitochondrial pharmacotherapy to potentially improve clinical outcomes in high-risk surgical patients. Full article
15 pages, 2873 KB  
Article
Developmental Toxicity and Stress Response Profiles of a Commercial Aloe vera Extract in Zebrafish Embryos
by Cláudia A. Rocha, João Pereira, Enrique Moreira, Bruno Sousa, Ana Luzio, Sandra M. Monteiro, Carlos Venâncio and Luís Félix
Toxics 2026, 14(5), 362; https://doi.org/10.3390/toxics14050362 - 24 Apr 2026
Abstract
Despite the widespread use of Aloe vera extracts, their developmental toxicity in aquatic organisms remains poorly understood. This study investigated the effects of a commercial Aloe vera extract on zebrafish embryogenesis, focusing on developmental, morphological, behavioural, and oxidative stress-related endpoints. The 96 h-LC [...] Read more.
Despite the widespread use of Aloe vera extracts, their developmental toxicity in aquatic organisms remains poorly understood. This study investigated the effects of a commercial Aloe vera extract on zebrafish embryogenesis, focusing on developmental, morphological, behavioural, and oxidative stress-related endpoints. The 96 h-LC50 was determined to be 0.03%. Embryos at 2 h post-fertilization (hpf) were exposed for 96 h to 0.0004% (LC10) and 0.03% (LC50). Exposure to 0.0004% caused no significant effects compared to controls. In contrast, exposure to 0.03% significantly increased mortality, reduced heart rate, impaired locomotion, and induced multiple malformations. Biochemical analyses revealed alterations in redox-associated biomarkers, characterized by unchanged ROS levels and mitochondrial activity, increased antioxidant enzyme activities (SOD, GPx, GR), and a decreased GSH:GSSG ratio. Lipid peroxidation levels were reduced, while a significant increase in DNA double-strand breaks (DSBs) was observed. Additionally, Nrf2 protein expression was upregulated at 0.03%. Together, these findings suggest concentration-dependent developmental toxicity correlated with alterations in redox homeostasis and genomic stability during early zebrafish development. This study provides new insight into the developmental hazard potential of a commercial Aloe vera extract in an aquatic vertebrate model. Full article
(This article belongs to the Section Ecotoxicology)
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17 pages, 880 KB  
Review
Targeting Neuroinflammation and Oxidative Stress to Slow Neurodegeneration in the Visual System
by Nara Shakaki and Minzhong Yu
J. Clin. Med. 2026, 15(9), 3254; https://doi.org/10.3390/jcm15093254 - 24 Apr 2026
Abstract
Purpose: Neuroinflammation and oxidative stress are increasingly recognized as central, interconnected drivers of neurodegeneration in the visual system. This review examines the pathogenic mechanisms shared across glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and Alzheimer’s disease (AD), and evaluates the therapeutic rationale [...] Read more.
Purpose: Neuroinflammation and oxidative stress are increasingly recognized as central, interconnected drivers of neurodegeneration in the visual system. This review examines the pathogenic mechanisms shared across glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and Alzheimer’s disease (AD), and evaluates the therapeutic rationale for targeting both pathways simultaneously. Methods: A narrative review of peer-reviewed literature was conducted using PubMed. Searches included the following MeSH terms: neuroinflammation, oxidative stress, retinal neurodegeneration, microglia, Müller glia, mitochondrial dysfunction, glaucoma, age-related macular degeneration, diabetic retinopathy, and Alzheimer’s disease. Priority was given to original research, systematic reviews, and high-impact publications from 2000 through 2025. However, seminal foundational works were included regardless of publication date. Studies were selected based on relevance to glial activation, mitochondrial dysfunction, reactive oxygen and nitrogen species, and disease-specific neuronal outcomes. Results: Across all four diseases, persistent microglial and Müller glial activation, mitochondrial electron transport chain dysfunction, and excess reactive oxygen species (ROS) and reactive nitrogen species (RNS) production form a self-amplifying feed-forward loop that accelerates neuronal injury. In glaucoma, these mechanisms drive intraocular pressure-independent retinal ganglion cell loss. In AMD and DR, lipid dysregulation, complement activation, and chronic hyperglycemia sustain oxidative-inflammatory injury to the retinal pigment epithelium, photoreceptors, and neurovasculature. In AD, retinal amyloid deposition and oxidative burden mirror cortical pathology, positioning the retina as a noninvasive biomarker site. Conclusions: Neuroinflammation and oxidative stress constitute unifying upstream mechanisms across major vision-threatening neurodegenerative diseases. Combination therapeutic strategies that simultaneously modulate glial activation and restore redox homeostasis may offer superior neuroprotective efficacy compared to approaches targeting isolated downstream mediators. Full article
23 pages, 1287 KB  
Article
Lutein Modulates Stress-Responsive Signaling Pathways in THLE-2 Human Hepatocytes Under Intestinal Failure–Associated Liver Disease Conditions
by Izabela Żółnowska, Violetta Krajka-Kuźniak, Marta Belka, Grzegorz Adamek and Maciej Stawny
Molecules 2026, 31(9), 1413; https://doi.org/10.3390/molecules31091413 - 24 Apr 2026
Abstract
Intestinal dysfunction and parenteral nutrition (PN) can trigger a spectrum of liver disorders collectively referred to as intestinal failure-associated liver disease (IFALD), for which therapeutic options remain limited. In the present study, we investigated the modulatory effects of the bioactive xanthophyll carotenoid lutein [...] Read more.
Intestinal dysfunction and parenteral nutrition (PN) can trigger a spectrum of liver disorders collectively referred to as intestinal failure-associated liver disease (IFALD), for which therapeutic options remain limited. In the present study, we investigated the modulatory effects of the bioactive xanthophyll carotenoid lutein in an in vitro IFALD model utilizing human THLE-2 hepatocytes exposed to lipopolysaccharide and Intralipid to mimic PN–associated inflammatory and metabolic stress. Because lutein is poorly water-soluble and patients receiving PN lack enteral intake of this compound, we also evaluated the cyto- and hemocompatibility of a human serum albumin–based lutein nanoformulation developed to enable intravenous administration. A bead-based multiplex immunoassay revealed that lutein attenuated dysregulation of inflammatory and metabolic signaling by modulating total and phosphorylated levels of MAPKs, NF-κB, Akt, STAT5, CREB, and p70S6K. Lutein also affected lipid metabolism–related gene expression, decreasing SREBF2 and restoring ABCA1 and PRKAA2 mRNA toward control levels, as determined by qPCR. Nanoformulated lutein, with a mean particle size of approximately 160 nm, was non-toxic in THLE-2 cells and exhibited hemocompatibility in a human erythrocyte hemolysis assay. Together, our findings provide both biological and technological rationale for further exploration of lutein-based strategies to mitigate IFALD in patients receiving PN. Full article
(This article belongs to the Special Issue Bioactive Compounds in Plants: Extraction and Application)
22 pages, 1165 KB  
Article
Characterization of the Klebsiella pneumoniae Secretome Using Size-Exclusion Chromatography and Raman Spectroscopy
by Elizaveta Denisova, Anastasia Avdyusheva, Elizaveta Tyshchuk, Polina Grebenkina, Andrey Korenevsky, Ivan Chelibanov, Vladimir Chelibanov, Areg Totolian, Lyudmila Kraeva, Vitaly Nazarov and Dmitry Sokolov
Int. J. Mol. Sci. 2026, 27(9), 3797; https://doi.org/10.3390/ijms27093797 - 24 Apr 2026
Abstract
The secretome of ESKAPE pathogens, including Klebsiella pneumoniae, comprises a diverse array of bioactive molecules that govern virulence, antibiotic resistance, and the establishment of an immunosuppressive microenvironment. However, the high chemical complexity of the secretome impedes the identification of key metabolites mediating [...] Read more.
The secretome of ESKAPE pathogens, including Klebsiella pneumoniae, comprises a diverse array of bioactive molecules that govern virulence, antibiotic resistance, and the establishment of an immunosuppressive microenvironment. However, the high chemical complexity of the secretome impedes the identification of key metabolites mediating pathogenesis. In this study, we profiled the metabolite composition of cell-free K. pneumoniae supernatant using a combined approach of chromatographic fractionation and Raman spectroscopy. Chromatographic separation enabled the resolution of the complex secretome and revealed fractions with distinct biochemical signatures. A key finding was the identification of Fraction 3, characterized by a unique metabolic profile: it was enriched in nucleic acid fragments, peptides containing tyrosine and methionine, polysaccharides, and stress-response metabolites (e.g., citrate), while notably lacking markers of tryptophan and sterol-like lipids. These spectral signatures suggest a potential role for Fraction 3 metabolites in intercellular communication, biofilm formation, and protection against oxidative stress. The remaining fractions also exhibited distinct biochemical profiles, defined by unique profiles of lipids, nucleotides, and amino acids. Collectively, these data underscore the critical role of specific K. pneumoniae secreted metabolites to pathogen survival and host immune modulation. The combined approach effectively resolves functionally relevant secretome fractions, offering new avenues for identifying diagnostic and therapeutic targets for multidrug-resistant infections. Full article
(This article belongs to the Section Molecular Biophysics)
38 pages, 2590 KB  
Review
Coronary Artery-Specific Changes in Patients with Chronic Kidney Disease
by Julia Hanke, Katarzyna Romejko and Stanisław Niemczyk
Cells 2026, 15(9), 765; https://doi.org/10.3390/cells15090765 - 24 Apr 2026
Abstract
Cardiovascular disease represents the primary cause of morbidity and mortality among patients with chronic kidney disease (CKD). Emerging evidence suggests that coronary artery pathology in CKD diverges from the traditional atherosclerotic phenotype seen in individuals with maintained renal function. This review delineates coronary [...] Read more.
Cardiovascular disease represents the primary cause of morbidity and mortality among patients with chronic kidney disease (CKD). Emerging evidence suggests that coronary artery pathology in CKD diverges from the traditional atherosclerotic phenotype seen in individuals with maintained renal function. This review delineates coronary artery-specific alterations in CKD, focusing on mechanisms that expedite atherogenesis, characteristics of plaques, calcific remodeling, and dysfunction of the coronary microvasculature. CKD fosters a pro-inflammatory, pro-oxidative, and pro-calcific environment, which results in endothelial damage and vascular calcification remodeling. Furthermore, coronary plaques in CKD are more likely to exhibit larger lipid-rich necrotic cores, heightened inflammatory cell infiltration, a significant calcific burden, and vulnerability indicators such as cholesterol crystals and microdisruptions. Impaired coronary microvascular function is also prevalent and may account for ischemia with non-obstructive coronary arteries. In summary, CKD is linked to a rapid, calcification- and inflammation-driven form of coronary disease characterized by both macrovascular plaque remodeling and microvascular dysfunction. This underscores the necessity of early identification and prevention of cardiovascular risk, targeting CKD-specific mechanisms in conjunction with conventional risk factors. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Vascular-Related Diseases)
32 pages, 3103 KB  
Article
The Invasive Blue Crab Callinectes sapidus as a Model for Assessing Sub-Lethal Effects of Polyvinyl Alcohol
by Alessandra Maganza, Giorgia Zicarelli, Giuseppe Esposito, Annalisa Cotugno, Alice Gabetti, Camilla Mossotto, Alessia Merialdi, Francesca Provenza, Serena Anselmi, Marzia Pezzolato, Elena Bozzetta, Monia Renzi, Marino Prearo, Caterina Faggio, Edoardo Turolla, Antonia Concetta Elia and Paolo Pastorino
Toxics 2026, 14(5), 358; https://doi.org/10.3390/toxics14050358 - 24 Apr 2026
Abstract
Polyvinyl alcohols (PVAs) are synthetic, water-soluble polymers widely used in industrial, medical, and personal care products. Their slow biodegradation raises concerns about potential impacts on marine ecosystems. This study examined how PVA exposure affects the blue crab Callinectes sapidus, an invasive species [...] Read more.
Polyvinyl alcohols (PVAs) are synthetic, water-soluble polymers widely used in industrial, medical, and personal care products. Their slow biodegradation raises concerns about potential impacts on marine ecosystems. This study examined how PVA exposure affects the blue crab Callinectes sapidus, an invasive species in the Mediterranean Sea. Crabs were exposed to three PVA concentrations (0.5, 5, and 25 mg L−1) along with a control group, for periods of 10 and 20 days. Oxidative stress was assessed by measuring antioxidant enzyme activities, including superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione peroxidase (GPx), and lipid peroxidation levels in muscle, gill, and hepatopancreas. Cell viability in the hemolymph and hepatopancreas was also evaluated. The results showed that hepatopancreas cells were more sensitive than hemolymph cells. Oxidative stress increased with exposure time and concentration, as indicated by elevated antioxidant enzyme activity and lipid peroxidation. After 10 days, early detoxification responses were observed, while after 20 days of exposure, clear dose- and time-dependent trends were evident, highlighting an intensification of physiological dysfunctions with increasing PVA concentrations and prolonged exposure duration. The histopathological observations showed limited alterations in muscle and hepatopancreas tissue but evident structural changes in gill tissues, particularly after prolonged exposure. The findings reveal a concentration- and time-dependent biological response to PVA, highlighting physiological changes at higher exposure levels and the need for further research on environmental consequences. Full article
(This article belongs to the Special Issue Toxic Effects of Emerging Pollutants on Aquatic Organisms and Human)
27 pages, 8132 KB  
Review
Delivery of mRNA Therapeutics Beyond Infectious Diseases: Design Innovations and Applications in Oncology, Cardiovascular, and Rare Genetic Diseases
by Snehitha Akkineni, Mahek Gulani, Samir A. Kouzi, Martin J. D’Souza and Mohammad N. Uddin
Pharmaceuticals 2026, 19(5), 663; https://doi.org/10.3390/ph19050663 - 24 Apr 2026
Abstract
Empowered by nanotechnology, messenger RNA (mRNA) therapeutics have shown a rapid evolution post COVID-19 from a conceptual platform to a clinically validated modality, and they diversified into oncology, cardiovascular diseases, and rare disorders. As a template for in situ protein production, it offers [...] Read more.
Empowered by nanotechnology, messenger RNA (mRNA) therapeutics have shown a rapid evolution post COVID-19 from a conceptual platform to a clinically validated modality, and they diversified into oncology, cardiovascular diseases, and rare disorders. As a template for in situ protein production, it offers several advantages over traditional proteins and DNA drugs. The intrinsic stability of mRNA and its sensitivity to innate immune sensing hinder its capacity for immediate cellular entry, necessitating its need for a delivery system to obtain optimal therapeutic potential. This review explores the innovations in nanocarrier engineering, design principles for lipid nanoparticles-mRNA (LNPs) platforms, and their clinical translation across the prominent indications. It also addresses their safety, immunogenicity, and scalability while addressing the key limitations and manufacturing scalability through comparative platform analysis. Although LNPs usually dominate their delivery through encapsulation and manufacturability, their limitations, like repeat dose reactogenicity and liver tropism, require next-generation designs like SORT lipids, stimuli-responsive hybrids for extrahepatic targeting. In oncology, LNP-mRNA drives the neoantigen vaccines, and rare diseases leverage the transient enzyme replacement. While the safety profiles highlight the innate immune tuning through nucleoside mods and lipid biodegradability, chronic administration risks are still persistent. While there are novel scalability options like microfluidic mixing to support the production gaps in organ selectivity and durability, their adoption is hindered. We outline the future directions to perceive mRNA’s full potential as a broader therapeutic class. Full article
(This article belongs to the Collection Feature Review Collection in Biopharmaceuticals)
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31 pages, 1906 KB  
Article
Transcriptomic and Metabolomic Profiling Reveals Differential Responses of Soybean Germination to Neutral and Alkaline Salt Stresses
by Yujie Jin, Lijun Pan, Dingkun Qian, Yuntian Zhao, Shengbo Xu, Hongtian Wang, Zhuo Zhang and Jian Wei
Biology 2026, 15(9), 670; https://doi.org/10.3390/biology15090670 - 24 Apr 2026
Abstract
Saline–alkali stress severely limits crop production worldwide. Soybean [Glycine max (L.) Merr.] is particularly sensitive during seed germination, a stage critical for stand establishment. This complex stress environment encompasses two distinct yet equally critical dimensions: neutral salt stress and alkaline salt stress, [...] Read more.
Saline–alkali stress severely limits crop production worldwide. Soybean [Glycine max (L.) Merr.] is particularly sensitive during seed germination, a stage critical for stand establishment. This complex stress environment encompasses two distinct yet equally critical dimensions: neutral salt stress and alkaline salt stress, each eliciting specialized physiological and metabolic responses. Here, a comparative assessment of four genotypes (tolerant: CN16, CN17; sensitive: Williams 82, K18) under 100 mmol/L Na+ revealed that alkaline salt stress exerts a significantly more potent inhibitory effect than neutral salt stress. Tolerant cultivars maintained 75–80% germination under alkaline conditions, whereas sensitive ones dropped below 15%, a divergence primarily driven by superior oxidative mitigation capacity. Integrated multi-omics analysis of the tolerant variety CN16 identified stage-specific regulatory shifts: early alkaline salt stress (60 h) triggers extensive transcriptional reprogramming focused on physical barrier reinforcement, including cell walls and lipid remodeling. By 96 h, regulatory modes between the two stress types diverged: neutral salt elicited a transcriptional surge, while alkaline salt transitioned to a metabolically dominant regulation, shifting flux from growth-related isoflavonoids to defense-related anthocyanins. Crucially, this study uncovers the distinct bioenergetic trade-offs governing these responses: whereas adaptation to neutral salt relies on low-energy galactose metabolism, tolerance to alkaline salt demands energy-intensive processes, specifically the active vacuolar compartmentalization of organic acids and anthocyanins for intracellular buffering. This obligatory energy expenditure restricts biomass accumulation, explaining the severe growth penalties observed in complex saline-alkali environments. Finally, the identification of a core regulatory module driven by key genes, including GmPHOT2b, GmLOG, and GmSHMT08, enriches the metabolic regulatory network under saline-alkali stress, providing core targets and a theoretical framework for precisely balancing metabolic expenditure with biomass accumulation in breeding practice. Full article
(This article belongs to the Section Plant Science)
22 pages, 1713 KB  
Article
Protective Effects of Myrtus communis Essential Oil Against Bisphenol A-Induced Sperm Dysfunction: Insights from Lipidomic, Amino Acid Profiling, Oxidative Stress and Molecular Docking
by Mariem Mhimdi, Slimen Selmi, Wael Taamalli, Stefania Sut, Hichem Sebai and Stefano Dall’acqua
Antioxidants 2026, 15(5), 536; https://doi.org/10.3390/antiox15050536 (registering DOI) - 24 Apr 2026
Abstract
BisphenolA (BPA) is a common endocrine disruptor that impairs male fertility through oxidative stress and alterations in membrane lipids. This study evaluated the protective effects of Myrtus communis L. essential oil (EOMC) on BPA-induced sperm toxicity in Wistar rats in vitro. BPA significantly [...] Read more.
BisphenolA (BPA) is a common endocrine disruptor that impairs male fertility through oxidative stress and alterations in membrane lipids. This study evaluated the protective effects of Myrtus communis L. essential oil (EOMC) on BPA-induced sperm toxicity in Wistar rats in vitro. BPA significantly decreased sperm motility and viability. It also increased lipid peroxidation, depleted thiols, and reduced the activity of antioxidant enzymes (SOD, CAT-like and GPx-like). Concomitant treatment with low and intermediate doses of EOMC (0.5–1 µL/mL) restored sperm function, reduced oxidative stress, and preserved membrane phospholipids. However, the highest dose (5 µL/mL) further impaired sperm function and disrupted membrane phospholipids. BPA also altered amino acid profiles and accumulated intracellularly, effects partially reversed by EOMC, which redistributed free BPA into the culture medium. Bioavailability analysis revealed selective absorption of α-pinene, while d-limonene and 1,8-cineole were undetectable. Molecular modeling indicated strong binding of BPA to antioxidant enzymes, potentially disrupting their structure and activity. Overall, these results show that EOMC protects sperm from BPA-induced damage in a dose-dependent manner through antioxidant, membrane-stabilizing, and redistribution mechanisms. This highlights its potential application in phytotherapy for male reproductive health. Full article
(This article belongs to the Section Antioxidant Enzyme Systems)
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