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33 pages, 4366 KiB  
Review
Progress and Prospects of Biomolecular Materials in Solar Photovoltaic Applications
by Anna Fricano, Filippo Tavormina, Bruno Pignataro, Valeria Vetri and Vittorio Ferrara
Molecules 2025, 30(15), 3236; https://doi.org/10.3390/molecules30153236 (registering DOI) - 1 Aug 2025
Abstract
This Review examines up-to-date advancements in the integration of biomolecules and solar energy technologies, with a particular focus on biohybrid photovoltaic systems. Biomolecules have recently garnered increasing interest as functional components in a wide range of solar cell architectures, since they offer a [...] Read more.
This Review examines up-to-date advancements in the integration of biomolecules and solar energy technologies, with a particular focus on biohybrid photovoltaic systems. Biomolecules have recently garnered increasing interest as functional components in a wide range of solar cell architectures, since they offer a huge variety of structural, optical, and electronic properties, useful to fulfill multiple roles within photovoltaic devices. These roles span from acting as light-harvesting sensitizers and charge transport mediators to serving as micro- and nanoscale structural scaffolds, rheological modifiers, and interfacial stabilizers. In this Review, a comprehensive overview of the state of the art about the integration of biomolecules across the various generations of photovoltaics is provided. The functional roles of pigments, DNA, proteins, and polysaccharides are critically reported improvements and limits associated with the use of biological molecules in optoelectronics. The molecular mechanisms underlying the interaction between biomolecules and semiconductors are also discussed as essential for a functional integration of biomolecules in solar cells. Finally, this Review shows the current state of the art, and the most significant results achieved in the use of biomolecules in solar cells, with the main scope of outlining some guidelines for future further developments in the field of biohybrid photovoltaics. Full article
(This article belongs to the Special Issue Thermal and Photocatalytic Analysis of Nanomaterials: 2nd Edition)
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12 pages, 3016 KiB  
Case Report
Blue Nevi and Melanoma Arising in Blue Nevus: A Comparative Histopathological Case Series
by Hristo Popov, Pavel Pavlov and George S. Stoyanov
Reports 2025, 8(3), 131; https://doi.org/10.3390/reports8030131 (registering DOI) - 1 Aug 2025
Abstract
Background and Clinical Significance: Blue nevi are a dubious pigmented lesion. While somewhat common throughout the population, they are significantly less common than other melanocytic neoplasms, and both their morphology and development bring them closer to true hamartomas than neoplasms. An exceedingly rare [...] Read more.
Background and Clinical Significance: Blue nevi are a dubious pigmented lesion. While somewhat common throughout the population, they are significantly less common than other melanocytic neoplasms, and both their morphology and development bring them closer to true hamartomas than neoplasms. An exceedingly rare occurrence is the development of melanoma from a preexisting blue nevus. This nosological unit, defined as melanoma arising in a blue nevus, also known as malignant blue nevus, blue naevus–like melanoma, melanoma ex-blue naevus, and melanoma mimicking cellular blue naevus, is required to either originate from an area of previously excised blue nevus or have a blue nevus remnant adjacent to it. Due to the spindle cell morphology of melanoma arising in blue nevus, the terminology is often misused by some authors to include spindle cell melanomas, which exhibit a distinct pathogenesis and, although morphologically similar, have differing molecular profiles as well. Case presentations: The following manuscript discusses comparative morphological features in a case series of blue nevi and melanoma arising in blue nevi. Discussion: Blue nevi present with unique morphological features, with melanomas originating from them having a unique molecular pathology profile, which significantly differs from other cutaneous melanomas and is closer to that of uveal melanomas. Full article
(This article belongs to the Section Dermatology)
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16 pages, 4054 KiB  
Article
Uncovering Fibrocapsa japonica (Raphidophyceae) in South America: First Taxonomic and Toxicological Insights from Argentinean Coastal Waters
by Delfina Aguiar Juárez, Inés Sunesen, Ana Flores-Leñero, Luis Norambuena, Bernd Krock, Gonzalo Fuenzalida and Jorge I. Mardones
Toxins 2025, 17(8), 386; https://doi.org/10.3390/toxins17080386 (registering DOI) - 31 Jul 2025
Abstract
Fibrocapsa japonica (Raphidophyceae) is a cosmopolitan species frequently associated with harmful algal blooms (HABs) and fish mortality events, representing a potential threat to aquaculture and coastal ecosystems. This study provides the first comprehensive morphological, phylogenetic, pigmentary, and toxicological characterization of F. japonica strains [...] Read more.
Fibrocapsa japonica (Raphidophyceae) is a cosmopolitan species frequently associated with harmful algal blooms (HABs) and fish mortality events, representing a potential threat to aquaculture and coastal ecosystems. This study provides the first comprehensive morphological, phylogenetic, pigmentary, and toxicological characterization of F. japonica strains isolated from Argentina. Light and transmission electron microscopy confirmed key diagnostic features of the species, including anterior flagella and the conspicuous group of mucocyst in the posterior region. Phylogenetic analysis based on the LSU rDNA D1–D2 region revealed monophyletic relationships with strains from geographically distant regions. Pigment analysis by HPLC identified chlorophyll-a (62.3 pg cell−1) and fucoxanthin (38.4 pg cell−1) as the main dominant pigments. Cytotoxicity assays using RTgill-W1 cells exposed for 2 h to culture supernatants and intracellular extracts showed strain-specific effects. The most toxic strain (LPCc049) reduced gill cell viability down to 53% in the supernatant exposure, while LC50 values ranged from 1.6 × 104 to 4.7 × 105 cells mL−1, depending directly on the strain and treatment type. No brevetoxins (PbTx-1, -2, -3, -6, -7, -8, -9, -10, BTX-B1 and BTX-B2) were detected by LC–MS/MS, suggesting that the cytotoxicity may be linked to the production of reactive oxygen species (ROS), polyunsaturated fatty acids (PUFAs), or hemolytic compounds, as previously hypothesized in the literature. These findings offer novel insights into the toxic potential of F. japonica in South America and underscore the need for further research to elucidate the mechanisms underlying its ichthyotoxic effect. Full article
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32 pages, 2108 KiB  
Review
Phytochemical Composition and Multifunctional Applications of Ricinus communis L.: Insights into Therapeutic, Pharmacological, and Industrial Potential
by Tokologo Prudence Ramothloa, Nqobile Monate Mkolo, Mmei Cheryl Motshudi, Mukhethwa Michael Mphephu, Mmamudi Anna Makhafola and Clarissa Marcelle Naidoo
Molecules 2025, 30(15), 3214; https://doi.org/10.3390/molecules30153214 (registering DOI) - 31 Jul 2025
Viewed by 28
Abstract
Ricinus communis (Euphorbiaceae), commonly known as the castor oil plant, is prized for its versatile applications in medicine, industry, and agriculture. It features large, deeply lobed leaves with vibrant colours, robust stems with anthocyanin pigments, and extensive root systems for nutrient absorption. Its [...] Read more.
Ricinus communis (Euphorbiaceae), commonly known as the castor oil plant, is prized for its versatile applications in medicine, industry, and agriculture. It features large, deeply lobed leaves with vibrant colours, robust stems with anthocyanin pigments, and extensive root systems for nutrient absorption. Its terminal panicle-like inflorescences bear monoecious flowers, and its seeds are enclosed in prickly capsules. Throughout its various parts, R. communis harbours a diverse array of bioactive compounds. Leaves contain tannins, which exhibit astringent and antimicrobial properties, and alkaloids like ricinine, known for anti-inflammatory properties, as well as flavonoids like rutin, offering antioxidant and antibacterial properties. Roots contain ellagitannins, lupeol, and indole-3-acetic acid, known for anti-inflammatory and liver-protective effects. Seeds are renowned for ricin, ricinine, and phenolic compounds crucial for industrial applications such as biodegradable polymers. Pharmacologically, it demonstrates antioxidant effects from flavonoids and tannins, confirmed through minimum inhibitory concentration (MIC) assays for antibacterial activity. It shows potential in managing diabetes via insulin signalling pathways and exhibits anti-inflammatory properties by activating nuclear factor erythroid 2-related factor 2 (Nrf2). Additionally, it has anti-fertility effects and potential anticancer activity against cancer stem cells. This review aims to summarize Ricinus communis’s botanical properties, therapeutic uses, chemical composition, pharmacological effects, and industrial applications. Integrating the current knowledge offers insights into future research directions, emphasizing the plant’s diverse roles in agriculture, medicine, and industry. Full article
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22 pages, 1916 KiB  
Article
Freeze-Dried Probiotic Fermented Camel Milk Enriched with Ajwa Date Pulp: Evaluation of Functional Properties, Probiotic Viability, and In Vitro Antidiabetic and Anticancer Activities
by Sally S. Sakr and Hassan Barakat
Foods 2025, 14(15), 2698; https://doi.org/10.3390/foods14152698 (registering DOI) - 31 Jul 2025
Viewed by 54
Abstract
Noncommunicable diseases (NCDs) like diabetes and cancer drive demand for therapeutic functional foods. This study developed freeze-dried fermented camel milk (FCM) with Ajwa date pulp (ADP), evaluating its physical and functional properties, probiotic survival, and potential benefits for diabetes and cancer. To achieve [...] Read more.
Noncommunicable diseases (NCDs) like diabetes and cancer drive demand for therapeutic functional foods. This study developed freeze-dried fermented camel milk (FCM) with Ajwa date pulp (ADP), evaluating its physical and functional properties, probiotic survival, and potential benefits for diabetes and cancer. To achieve this target, six FCM formulations were prepared using ABT-5 starter culture (containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Streptococcus thermophilus) with or without Lacticaseibacillus rhamnosus B-1937 and ADP (12% or 15%). The samples were freeze-dried, and their functional properties, such as water activity, dispersibility, water absorption capacity, water absorption index, water solubility index, insolubility index, and sedimentation, were assessed. Reconstitution properties such as density, flowability, air content, porosity, loose bulk density, packed bulk density, particle density, carrier index, Hausner ratio, porosity, and density were examined. In addition, color and probiotic survivability under simulated gastrointestinal conditions were analyzed. Also, antidiabetic potential was assessed via α-amylase and α-glucosidase inhibition assays, while cytotoxicity was evaluated using the MTT assay on Caco-2 cells. The results show that ADP supplementation significantly improved dispersibility (up to 72.73% in FCM15D+L). These improvements are attributed to changes in particle size distribution and increased carbohydrate and mineral content, which facilitate powder rehydration and reduce clumping. All FCM variants demonstrated low water activity (0.196–0.226), indicating good potential for shelf stability. The reconstitution properties revealed that FCM powders with ADP had higher bulk and packed densities but lower particle density and porosity than controls. Including ADP reduced interstitial air and increased occluded air within the powders, which may minimize oxidation risks and improve packaging efficiency. ADP incorporation resulted in a significant decrease in lightness (L*) and increases in redness (a*) and yellowness (b*), with greater pigment and phenolic content at higher ADP levels. These changes reflect the natural colorants and browning reactions associated with ADP, leading to a more intense and visually distinct product. Probiotic survivability was higher in ADP-fortified samples, with L. acidophilus and B. bifidum showing resilience in intestinal conditions. The FCM15D+L formulation exhibited potent antidiabetic effects, with IC50 values of 111.43 μg mL−1 for α-amylase and 77.21 μg mL−1 for α-glucosidase activities, though lower than control FCM (8.37 and 10.74 μg mL−1, respectively). Cytotoxicity against Caco-2 cells was most potent in non-ADP samples (IC50: 82.22 μg mL−1 for FCM), suggesting ADP and L. rhamnosus may reduce antiproliferative effects due to proteolytic activity. In conclusion, the study demonstrates that ADP-enriched FCM is a promising functional food with enhanced probiotic viability, antidiabetic potential, and desirable physical properties. This work highlights the potential of camel milk and date synergies in combating some NCDs in vitro, suggesting potential for functional food application. Full article
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41 pages, 2975 KiB  
Review
Algal Metabolites as Novel Therapeutics Against Methicillin-Resistant Staphylococcus aureus (MRSA): A Review
by Ibraheem Borie M. Ibraheem, Reem Mohammed Alharbi, Neveen Abdel-Raouf, Nouf Mohammad Al-Enazi, Khawla Ibrahim Alsamhary and Hager Mohammed Ali
Pharmaceutics 2025, 17(8), 989; https://doi.org/10.3390/pharmaceutics17080989 (registering DOI) - 30 Jul 2025
Viewed by 107
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA), a multidrug-resistant pathogen, poses a significant threat to global healthcare. This review evaluates the potential of marine algal metabolites as novel antibacterial agents against MRSA. We explore the clinical importance of S. aureus, the emergence of MRSA as [...] Read more.
Methicillin-resistant Staphylococcus aureus (MRSA), a multidrug-resistant pathogen, poses a significant threat to global healthcare. This review evaluates the potential of marine algal metabolites as novel antibacterial agents against MRSA. We explore the clinical importance of S. aureus, the emergence of MRSA as a “superbug”, and its resistance mechanisms, including target modification, drug inactivation, efflux pumps, biofilm formation, and quorum sensing. The limitations of conventional antibiotics (e.g., β-lactams, vancomycin, macrolides) are discussed, alongside the promise of algal-derived compounds such as fatty acids, pigments, polysaccharides, terpenoids, and phenolic compounds. These metabolites exhibit potent anti-MRSA activity by disrupting cell division (via FtsZ inhibition), destabilizing membranes, and inhibiting protein synthesis and metabolic pathways, effectively countering multiple resistance mechanisms. Leveraging advances in algal biotechnology, this review highlights the untapped potential of marine algae to drive innovative, sustainable therapeutic strategies against antibiotic resistance. Full article
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15 pages, 1375 KiB  
Article
Photodegradation of Turmeric Oleoresin Under Fluorescent Light and White LED: Impacts on the Chemical Stability, Bioactivity, and Photosensitizing Property of Curcuminoids
by Heejeong Kim, Juyeon Oh and Jungil Hong
Molecules 2025, 30(15), 3187; https://doi.org/10.3390/molecules30153187 - 30 Jul 2025
Viewed by 109
Abstract
Turmeric oleoresin (TO), a natural pigment derived from Curcuma longa rhizomes, is valued for its health benefits, which are primarily attributed to its rich curcuminoid content (curcumin, demethoxycurcumin, and bisdemethoxycurcumin). Despite these benefits, curcuminoids are known to be light-sensitive and possess photosensitizing properties. [...] Read more.
Turmeric oleoresin (TO), a natural pigment derived from Curcuma longa rhizomes, is valued for its health benefits, which are primarily attributed to its rich curcuminoid content (curcumin, demethoxycurcumin, and bisdemethoxycurcumin). Despite these benefits, curcuminoids are known to be light-sensitive and possess photosensitizing properties. This study investigated the impact of common light sources, fluorescent light and white LED (both at 10 W/m2), on the chemical stability, antioxidant activity, cytotoxicity, and photosensitizing properties of TO. Exposure to both light sources significantly reduced TO’s color and fluorescence intensity, with white LED causing greater instability. HPLC analysis confirmed a decrease in individual curcuminoid levels, with curcumin degrading most rapidly under both conditions. The DPPH radical scavenging activity of irradiated TO decreased compared to fresh or dark-stored turmeric, whereas its ABTS radical scavenging activity increased upon light exposure. Photosensitizing potency, measured by formazan decolorization and lipid peroxide formation, declined as TO decomposed under light. Conversely, the cytotoxicity of TO against B16F10 melanoma cells was significantly enhanced under light exposure, though this effect was diminished significantly after 24 h of pre-irradiation. These findings underscore the instability of turmeric pigment under common lighting conditions, which should be a crucial consideration when processing, storing, and distributing turmeric-containing products. Full article
(This article belongs to the Special Issue Photochemistry in Asia)
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15 pages, 4667 KiB  
Article
Longitudinal High-Resolution Imaging of Retinal Sequelae of a Choroidal Nevus
by Kaitlyn A. Sapoznik, Stephen A. Burns, Todd D. Peabody, Lucie Sawides, Brittany R. Walker and Thomas J. Gast
Diagnostics 2025, 15(15), 1904; https://doi.org/10.3390/diagnostics15151904 - 29 Jul 2025
Viewed by 193
Abstract
Background: Choroidal nevi are common, benign tumors. These tumors rarely cause adverse retinal sequalae, but when they do, they can lead to disruption of the outer retina and vision loss. In this paper, we used high-resolution retinal imaging modalities, optical coherence tomography [...] Read more.
Background: Choroidal nevi are common, benign tumors. These tumors rarely cause adverse retinal sequalae, but when they do, they can lead to disruption of the outer retina and vision loss. In this paper, we used high-resolution retinal imaging modalities, optical coherence tomography (OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO), to longitudinally monitor retinal sequelae of a submacular choroidal nevus. Methods: A 31-year-old female with a high-risk choroidal nevus resulting in subretinal fluid (SRF) and a 30-year-old control subject were longitudinally imaged with AOSLO and OCT in this study over 18 and 22 months. Regions of interest (ROI) including the macular region (where SRF was present) and the site of laser photocoagulation were imaged repeatedly over time. The depth of SRF in a discrete ROI was quantified with OCT and AOSLO images were assessed for visualization of photoreceptors and retinal pigmented epithelium (RPE). Cell-like structures that infiltrated the site of laser photocoagulation were measured and their count was assessed over time. In the control subject, images were assessed for RPE visualization and the presence and stability of cell-like structures. Results: We demonstrate that AOSLO can be used to assess cellular-level changes at small ROIs in the retina over time. We show the response of the retina to SRF and laser photocoagulation. We demonstrate that the RPE can be visualized when SRF is present, which does not appear to depend on the height of retinal elevation. We also demonstrate that cell-like structures, presumably immune cells, are present within and adjacent to areas of SRF on both OCT and AOSLO, and that similar cell-like structures infiltrate areas of retinal laser photocoagulation. Conclusions: Our study demonstrates that dynamic, cellular-level retinal responses to SRF and laser photocoagulation can be monitored over time with AOSLO in living humans. Many retinal conditions exhibit similar retinal findings and laser photocoagulation is also indicated in numerous retinal conditions. AOSLO imaging may provide future opportunities to better understand the clinical implications of such responses in vivo. Full article
(This article belongs to the Special Issue High-Resolution Retinal Imaging: Hot Topics and Recent Developments)
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27 pages, 4786 KiB  
Article
Whole RNA-Seq Analysis Reveals Longitudinal Proteostasis Network Responses to Photoreceptor Outer Segment Trafficking and Degradation in RPE Cells
by Rebecca D. Miller, Isaac Mondon, Charles Ellis, Anna-Marie Muir, Stephanie Turner, Eloise Keeling, Htoo A. Wai, David S. Chatelet, David A. Johnson, David A. Tumbarello, Andrew J. Lotery, Diana Baralle and J. Arjuna Ratnayaka
Cells 2025, 14(15), 1166; https://doi.org/10.3390/cells14151166 - 29 Jul 2025
Viewed by 311
Abstract
RNA-seq analysis of the highly differentiated human retinal pigment epithelial (RPE) cell-line ARPE-19, cultured on transwells for ≥4 months, yielded 44,909 genes showing 83.35% alignment with the human reference genome. These included mRNA transcripts of RPE-specific genes and those involved in retinopathies. Monolayers [...] Read more.
RNA-seq analysis of the highly differentiated human retinal pigment epithelial (RPE) cell-line ARPE-19, cultured on transwells for ≥4 months, yielded 44,909 genes showing 83.35% alignment with the human reference genome. These included mRNA transcripts of RPE-specific genes and those involved in retinopathies. Monolayers were fed photoreceptor outer segments (POS), designed to be synchronously internalised, mimicking homeostatic RPE activity. Cells were subsequently fixed at 4, 6, 24 and 48 h when POS were previously shown to maximally co-localise with Rab5, Rab7, LAMP/lysosomes and LC3b/autophagic compartments. A comprehensive analysis of differentially expressed genes involved in proteolysis revealed a pattern of gene orchestration consistent with POS breakdown in the autophagy-lysosomal pathway. At 4 h, these included elevated upstream signalling events promoting early stages of cargo transport and endosome maturation compared to RPE without POS exposure. This transcriptional landscape altered from 6 h, transitioning to promoting cargo degradation in autolysosomes by 24–48 h. Longitudinal scrutiny of mRNA transcripts revealed nuanced differences even within linked gene networks. POS exposure also initiated transcriptional upregulation in ubiquitin proteasome and chaperone-mediated systems within 4–6 h, providing evidence of cross-talk with other proteolytic processes. These findings show detailed evidence of transcriptome-level responses to cargo trafficking and processing in RPE cells. Full article
(This article belongs to the Special Issue Retinal Pigment Epithelium in Degenerative Retinal Diseases)
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14 pages, 1517 KiB  
Review
HSV-1 Infection in Retinal Pigment Epithelial Cells: A Possible Contribution to Age-Related Macular Degeneration
by Victoria Belen Ayala-Peña
Viruses 2025, 17(8), 1056; https://doi.org/10.3390/v17081056 - 29 Jul 2025
Viewed by 269
Abstract
Herpes simplex virus type 1 (HSV-1) is associated with eye infections. Specifically, the acute consequences of eye infections have been extensively studied. This review gathers information on possible collateral damage caused by HSV-1 in the retina, such as age-related macular degeneration (AMD), a [...] Read more.
Herpes simplex virus type 1 (HSV-1) is associated with eye infections. Specifically, the acute consequences of eye infections have been extensively studied. This review gathers information on possible collateral damage caused by HSV-1 in the retina, such as age-related macular degeneration (AMD), a neurodegenerative disease. The synthesis and accumulation of Amyloid-β peptide (Aβ) is a key hallmark in these types of pathologies. AMD is a disease of multifactorial origin, and viral infections play an important role in its development. It is known that once this virus has entered the eye, it can infect adjacent cells, thus having the ability to infect almost any cell type with great tropism. In the retina, retinal pigment epithelial (RPE) cells are primarily involved in AMD. This work reviews publications that show that RPE can produce Aβ, and once they are infected by HSV-1, the release is promoted. Also, all the information available in the literature that explains how these events may be interconnected has been compiled. This information is valuable when planning new treatments for multifactorial neurodegenerative diseases. Full article
(This article belongs to the Special Issue Viruses and Eye Diseases)
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17 pages, 13173 KiB  
Article
High-Resolution Imaging and Interpretation of Three-Dimensional RPE Sheet Structure
by Kevin J. Donaldson, Micah A. Chrenek, Jeffrey H. Boatright and John M. Nickerson
Biomolecules 2025, 15(8), 1084; https://doi.org/10.3390/biom15081084 - 26 Jul 2025
Viewed by 201
Abstract
The retinal pigment epithelium (RPE), a monolayer of pigmented cells, is critical for visual function through its interaction with the neural retina. In healthy eyes, RPE cells exhibit a uniform hexagonal arrangement, but under stress or disease, such as age-related macular degeneration (AMD), [...] Read more.
The retinal pigment epithelium (RPE), a monolayer of pigmented cells, is critical for visual function through its interaction with the neural retina. In healthy eyes, RPE cells exhibit a uniform hexagonal arrangement, but under stress or disease, such as age-related macular degeneration (AMD), dysmorphic traits like cell enlargement and apparent multinucleation emerge. Multinucleation has been hypothesized to result from cellular fusion, a compensatory mechanism to maintain cell-to-cell contact and barrier function, as well as conserve resources in unhealthy tissue. However, traditional two-dimensional (2D) imaging using apical border markers alone may misrepresent multinucleation due to the lack of lateral markers. We present high-resolution confocal images enabling three-dimensional (3D) visualization of apical (ZO-1) and lateral (α-catenin) markers alongside nuclei. In two RPE damage models, we find that seemingly multinucleated cells are often single cells with displaced neighboring nuclei and lateral membranes. This emphasizes the need for 3D analyses to avoid misidentifying multinucleation and underlying fusion mechanisms. Lastly, images from the NaIO3 oxidative damage model reveal variability in RPE damage, with elongated, dysmorphic cells showing increased ZsGreen reporter protein expression driven by EMT-linked CAG promoter activity, while more regular RPE cells displayed somewhat reduced green signal more typical of epithelial phenotypes. Full article
(This article belongs to the Section Molecular Biophysics: Structure, Dynamics, and Function)
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26 pages, 3023 KiB  
Article
Multi-Parameter Analysis of Photosynthetic and Molecular Responses in Chlorella vulgaris Exposed to Silver Nanoparticles and Ions
by Bruno Komazec, Sandra Vitko, Biljana Balen, Mario Cindrić, Renata Biba and Petra Peharec Štefanić
Toxics 2025, 13(8), 627; https://doi.org/10.3390/toxics13080627 - 26 Jul 2025
Viewed by 381
Abstract
Due to widespread use of silver nanoparticles (AgNPs), the assessment of their potential harm to microalgal photosynthesis is crucial, as microalgae, together with cyanobacteria, contribute to approximately 50% of global oxygen production. This study investigated photosynthetic pigments, photosynthetic rate, chlorophyll a fluorescence, and [...] Read more.
Due to widespread use of silver nanoparticles (AgNPs), the assessment of their potential harm to microalgal photosynthesis is crucial, as microalgae, together with cyanobacteria, contribute to approximately 50% of global oxygen production. This study investigated photosynthetic pigments, photosynthetic rate, chlorophyll a fluorescence, and the expression of photosynthesis-related genes and proteins in green alga Chlorella vulgaris after 72 h exposure to citrate- and cetyltrimethylammonium bromide (CTAB)-stabilized AgNPs, as well as silver ions (AgNO3), at concentrations allowing 75% cell survival (EC25). All treatments impaired photosynthetic performance. The most pronounced decreases in chlorophyll fluorescence parameters and photosynthetic rate, alongside elevated energy dissipation, were observed after exposure to AgNP-CTAB and AgNO3. AgNP-citrate had milder effects and induced compensatory responses, reflected in an increased performance index and upregulation of photosynthesis-related proteins. AgNP-CTAB induced the strongest downregulation of gene and protein expression, likely due to its higher EC25 concentration and cationic surface promoting interaction with photosynthetic structures. Although AgNO3 caused fewer molecular changes, it significantly disrupted photosynthetic function, suggesting a direct effect of Ag+ ions on photosynthesis-related proteins. Overall, the results highlight the role of AgNPs’ surface coatings and dosage in determining their phytotoxicity, with photosystem disruption and oxidative stress emerging as key mechanisms of action. Full article
(This article belongs to the Special Issue Toxic Pollutants and Ecological Risk in Aquatic Environments)
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18 pages, 2600 KiB  
Article
Nintedanib Induces Mesenchymal-to-Epithelial Transition and Reduces Subretinal Fibrosis Through Metabolic Reprogramming
by David Hughes, Jüergen Prestle, Nina Zippel, Sarah McFetridge, Manon Szczepan, Heike Neubauer, Heping Xu and Mei Chen
Int. J. Mol. Sci. 2025, 26(15), 7131; https://doi.org/10.3390/ijms26157131 - 24 Jul 2025
Viewed by 297
Abstract
This study aimed to investigate the tyrosine kinase inhibitor Nintedanib and its potential role in reversing epithelial–mesenchymal transition (EMT) induced by transforming growth factor beta 2 (TGF-β2) in retinal pigment epithelial (RPE) cells, along with its therapeutic potential using a mouse model of [...] Read more.
This study aimed to investigate the tyrosine kinase inhibitor Nintedanib and its potential role in reversing epithelial–mesenchymal transition (EMT) induced by transforming growth factor beta 2 (TGF-β2) in retinal pigment epithelial (RPE) cells, along with its therapeutic potential using a mouse model of subretinal fibrosis. We hypothesized that the blockade of angiogenesis promoting and fibrosis inducing signaling using the receptor tyrosine kinase inhibitor Nintedanib (OfevTM) can prevent or reverse EMT both in vitro and in our in vivo model of subretinal fibrosis. Primary human retinal pigment epithelial cells (phRPE) and adult retinal pigment epithelial cell line (ARPE-19) cells were treated with TGF-β210 ng/mL for two days followed by four days of Nintedanib (1 µM) incubation. Epithelial and mesenchymal phenotypes were assessed by morphological examination, quantitative real-time polymerase chain reaction(qPCR) (ZO-1, Acta2, FN, and Vim), and immunocytochemistry (ZO-1, vimentin, fibronectin, and αSMA). Metabolites were measured using luciferase-based assays. Extracellular acidification and oxygen consumption rates were measured using the Seahorse XF system. Metabolic-related genes (GLUT1, HK2, PFKFB3, CS, LDHA, LDHB) were evaluated by qPCR. A model of subretinal fibrosis using the two-stage laser-induced method in C57BL/6J mice assessed Nintedanib’s therapeutic potential. Fibro-vascular lesions were examined 10 days later via fluorescence angiography and immunohistochemistry. Both primary and ARPE-19 RPE stimulated with TGF-β2 upregulated expression of fibronectin, αSMA, and vimentin, and downregulation of ZO-1, consistent with morphological changes (i.e., elongation). Glucose consumption, lactate production, and glycolytic reserve were significantly increased in TGF-β2-treated cells, with upregulation of glycolysis-related genes (GLUT1, HK2, PFKFB3, CS). Nintedanib treatment reversed TGF-β2-induced EMT signatures, down-regulated glycolytic-related genes, and normalized glycolysis. Nintedanib intravitreal injection significantly reduced collagen-1+ fibrotic lesion size and Isolectin B4+ neovascularization and reduced vascular leakage in the two-stage laser-induced model of subretinal fibrosis. Nintedanib can induce Mesenchymal-to-Epithelial Transition (MET) in RPE cells and reduce subretinal fibrosis through metabolic reprogramming. Nintedanib can therefore potentially be repurposed to treat retinal fibrosis. Full article
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26 pages, 1899 KiB  
Review
Extracellular Matrix (ECM) Aging in the Retina: The Role of Matrix Metalloproteinases (MMPs) in Bruch’s Membrane Pathology and Age-Related Macular Degeneration (AMD)
by Ali A. Hussain and Yunhee Lee
Biomolecules 2025, 15(8), 1059; https://doi.org/10.3390/biom15081059 - 22 Jul 2025
Viewed by 329
Abstract
The extracellular matrix (ECM) is a collagen-based scaffold that provides structural support and regulates nutrient transport and cell signaling. ECM homeostasis depends on a dynamic balance between synthesis and degradation, the latter being primarily mediated by matrix metalloproteinases (MMPs). These enzymes are secreted [...] Read more.
The extracellular matrix (ECM) is a collagen-based scaffold that provides structural support and regulates nutrient transport and cell signaling. ECM homeostasis depends on a dynamic balance between synthesis and degradation, the latter being primarily mediated by matrix metalloproteinases (MMPs). These enzymes are secreted as pro-forms and require activation to degrade ECM components. Their activity is modulated by tissue inhibitors of metalloproteinases (TIMPs). Aging disrupts this balance, leading to the accumulation of oxidized, cross-linked, and denatured matrix proteins, thereby impairing ECM function. Bruch’s membrane, a penta-laminated ECM structure in the eye, plays a critical role in supporting photoreceptor and retinal pigment epithelium (RPE) health. Its age-related thickening and decreased permeability are associated with impaired nutrient delivery and waste removal, contributing to the pathogenesis of age-related macular degeneration (AMD). In AMD, MMP dysfunction is characterized by the reduced activation and sequestration of MMPs, which further limits matrix turnover. This narrative review explores the structural and functional changes in Bruch’s membrane with aging, the role of MMPs in ECM degradation, and the relevance of these processes to AMD pathophysiology, highlighting emerging regulatory mechanisms and potential therapeutic targets. Full article
(This article belongs to the Special Issue Role of Matrix Metalloproteinase in Health and Disease)
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27 pages, 4223 KiB  
Article
Prolyl Hydroxylase Inhibitor-Mediated HIF Activation Drives Transcriptional Reprogramming in Retinal Pigment Epithelium: Relevance to Chronic Kidney Disease
by Tamás Gáll, Dávid Pethő, Annamária Nagy, Szilárd Póliska, György Balla and József Balla
Cells 2025, 14(14), 1121; https://doi.org/10.3390/cells14141121 - 21 Jul 2025
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Abstract
Chronic kidney disease (CKD)-associated anemia is a global health concern and is linked to vascular and ocular complications. Hypoxia-inducible factor (HIF) stabilizers, or HIF prolyl hydroxylase inhibitors (PHIs), are promising candidates for the treatment of CKD-associated anemia. Since hypoxia and angiogenesis are involved [...] Read more.
Chronic kidney disease (CKD)-associated anemia is a global health concern and is linked to vascular and ocular complications. Hypoxia-inducible factor (HIF) stabilizers, or HIF prolyl hydroxylase inhibitors (PHIs), are promising candidates for the treatment of CKD-associated anemia. Since hypoxia and angiogenesis are involved in eye diseases, this study examined the effects of HIF-PHIs on metabolism and gene expression in retinal pigment epithelium (RPE) cells. Results revealed that PHIs differentially induced angiogenic (VEGFA, ANG) and glycolytic (PDK1, GLUT1) gene expression, with Roxadustat causing the strongest transcriptional changes. However, Roxadustat-induced angiogenic signals did not promote endothelial tube formation. Moreover, it did not induce oxidative stress, inflammation, or significant antioxidant gene responses in ARPE-19 cells. Roxadustat also reduced the inflammatory cytokine response to tumor necrosis factor-α, including IL-6, IL-8, and MCP-1, and did not exacerbate VEGF expression under high-glucose conditions. Overall, Roxadustat triggered complex gene expression changes without promoting inflammation or oxidative stress in RPE cells. Despite these findings, ophthalmologic monitoring is advised during PHI treatment in CKD patients receiving HIF-PHIs. Full article
(This article belongs to the Section Cellular Immunology)
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