Search Results (18,204)

Background and Objectives: Age-related macular degeneration (AMD) is an age-associated retinal disorder characterized by blood–retinal barrier (BRB) breakdown and pathological angiogenesis, leading to vascular leakage. The intravitreal administration of anti-VEGF agents remains the most effective treatment for neovascular AMD. However, repetitive intravitreal injections have risks, causing side effects such as cataracts, bleeding, retina damage, and, in severe cases, post-injection endophthalmitis. Hence, the development of innovative drug delivery systems is essential to minimize the risks and discomfort associated with intravitreal injections. Materials and Methods: We developed a microemulsion (ME)-based topical drug delivery system incorporating α-linolenic acid (ALA). In brief, pseudo-ternary phase diagrams were constructed by the water titration method using different combinations of surfactants and cosurfactants (S_mix-Cremophor RH 40: Span 80: Transcutol P in ratios of 1:1.05, 1:1:1, 1:1:1.5) containing ALA as the oil phase. Three blank microemulsions (ME1, ME2, and ME3) were prepared and characterized based on the optimized pseudo-ternary phase equilibrium with a S_mix ratio of 1:1:1. Results: ME3, with an average particle size of 38.59 nm, was selected as the optimized formulation for developing drug-loaded ME containing Fenofibrate, Axitinib, and Sirolimus. The drug-loaded ME showed particle size (46.94–56.39 nm) and in vitro release displayed sustained and longer time drug release for 240 h. The irritation and antiangiogenic activities were evaluated using the hen’s egg chorioallantoic membrane (HET-CAM) assay employing the optimized ME loaded with each drug. Among the three drug-loaded ME, the Sirolimus ME showed a reduction in blood vessel sprouting in the HET-CAM assay, indicating strong antiangiogenic activity. Treatment with the optimized blank ME and Sirolimus ME significantly (p < 0.05) reduced COX-2 protein expression in LPS-stimulated RAW 264.7 cells, suggesting their potential anti-inflammatory effects. Conclusions: Overall, we suggest that the α-linolenic acid-based Sirolimus microemulsion may serve as a promising topical therapeutic approach for managing AMD and offering a potential alternative to invasive intravitreal injections. Full article

This article examines the effects of climate change on the 32 million inhabitants of the Megalopolis of Central Mexico (MCM), which is threatened by chaotic urbanization, land-use changes, the deforestation of the Forest of Water by organized crime, unsustainable agriculture, and biodiversity loss. Expensive hydraulic management extracting water from deep aquifers, long pipes exploiting water from neighboring states, and sewage discharged outside the endorheic basin result in expensive pumping costs and air pollution. This mismanagement has increased water scarcity. The overexploitation of aquifers and the pollution by toxic industrial and domestic sewage mixed with rainfall has increased the ground subsidence, damaging urban infrastructure and flooding marginal neighborhoods with toxic sewage. A system approach, satellite data, and participative research methodology were used to explore potential water scarcity and weakened water security for 32 million inhabitants. An alternative nature-based approach involves recovering the Forest of Water (FW) with IWRM, including the management of Natural Protected Areas, the rainfall recharge of aquifers, and cleaning domestic sewage inside the valley where the MCM is found. This involves recovering groundwater, reducing the overexploitation of aquifers, and limiting floods. Citizen participation in treating domestic wastewater with eco-techniques, rainfall collection, and purification filters improves water availability, while the greening of urban areas limits the risk of climate disasters. The government is repairing the broken drinking water supply and drainage systems affected by multiple earthquakes. Adaptation to water scarcity and climate risks requires the recognition of unpaid female domestic activities and the role of indigenous people in protecting the Forest of Water with the involvement of three state authorities. A digital platform for water security, urban planning, citizen audits against water authority corruption, and aquifer recharge through nature-based solutions provided by the System of Natural Protected Areas, Biological and Hydrological Corridors [SAMBA] are improving livelihoods for the MCM’s inhabitants and marginal neighborhoods, with greater equity and safety. Full article

Oral cancer, the most common head and neck malignancy, has a high recurrence rate and poor prognosis largely owing to chemotherapy resistance. The adverse effects of conventional therapies have prompted investigations into safer and more effective alternative therapies. Chloroquine (CQ) and hydroxychloroquine (HCQ) have shown potential owing to their roles in autophagy modulation and immune regulation. This study clarifies the selective efficacy of hydroxychloroquine (HCQ) and chloroquine (CQ) in oral squamous cell carcinoma models, emphasizing distinct responses in gingival (Ca9-22) and tongue (SCC-9) carcinoma cells. Non-oncogenic oral epithelial cells (GMSM-K) and oral carcinoma cell lines from the tongue (SCC-9, Cal-27) and gingiva (Ca9-22) were used. Cell viability, cytotoxicity, and colony formation were assessed via MTT, LDH, and crystal violet assays. Flow cytometry was used to measure apoptosis, autophagy, oxidative stress, mitochondrial membrane potential, and DNA damage. The transcriptomic profiles of apoptosis and autophagy-related genes were assessed by qPCR arrays. Bioinformatics analysis allowed estimation of the main gene interaction networks. Pre-screening showed that GMSM-K and Cal-27 cells were non-responsive or exhibited non-specific toxicity at high doses; therefore, subsequent analyses focused on Ca9-22 (GC) and SCC-9 (TC). HCQ significantly reduced viability and colony formation in Ca9-22 cells while moderately affecting SCC-9 cells. Autophagy inhibition was accompanied by compensatory up-regulation of autophagy-related genes, consistent with feedback activation of TFEB and FOXO3a pathways. Gene expression profiling and flow-cytometry analyses revealed cell-type-specific differences in apoptosis, mitochondrial potential, and DNA damage, suggesting HCQ’s selective anti-tumor potential in gingival carcinoma. These findings highlight HCQ as a repurposed adjuvant therapy that modulates autophagy and apoptosis to enhance chemosensitivity in oral cancer. Full article

This study systematically explored the regulatory mechanisms of uterine function across four reproductive stages: sexual maturity sow (SMS), low-yield sow (LYS), high-yield sow (HYS), and culled sow (CS) in Large White (LW) pigs through integrated transcriptomic, proteomic, and metabolomic analyses. Twelve healthy LW sows were selected, and uterine tissues were collected for multi-omics detection. Combined with bioinformatics analysis, molecular regulatory networks were constructed. Results showed that transcriptomics identified 12 types of alternative splicing and 1243 novel genes, which were enriched in energy metabolism and signal transduction pathways. Proteomics revealed 430 differentially co-expressed proteins, indicating high protein synthesis activity in the SMS stage and extracellular inflammatory characteristics in the CS stage. Metabolomics detected numerous differential metabolites, among which XTP and DHA ethyl ester were associated with high fecundity and aging, respectively. Integrated multi-omics analysis identified hub genes such as PLA2G4A, which influence reproductive performance by regulating inflammatory and metabolic balance, and clarified stage-specific “gene–protein–metabolite” modules. This study provides a molecular map for understanding dynamic changes in uterine function in Large White pigs and offers a theoretical basis for optimizing reproductive lifespan and breeding strategies. Full article

Currently, an active debate is underway among the academic community, urban planners, and policymakers regarding optimal models of urban development, given that the majority of the population now resides in cities. One concept under discussion is the 15 min city, which posits that all urban residents should be able to reach key, frequently used services within a 15 min walk or cycle. Although the literature suggests numerous potential benefits, debate persists about whether such cities would be optimal from the standpoint of sustainable development objectives and residents’ quality of life. The ongoing discussion also concerns the extent to which existing cities are capable of aligning with this concept. This is directly linked to the actual spatial distribution of individual services within the city. The literature indicates a research gap arising from a shortage of robust case studies that would enable a credible assessment of the practical implementation of this idea across diverse cities, countries, and regions. This issue pertains to Poland as well as to other countries. A desirable future scenario would involve comprehensive mapping of all cities, with respect to both the spatial distribution of specific services and related domains such as the quality and coherence of linear infrastructure. This article presents an analysis of the spatial accessibility of basic urban services in the context of implementing the 15 min city concept, using the city of Koszalin (Poland) as a case study. This city was selected due to its representative character as a medium-sized urban centre, both in terms of population and area, as well as its subregional functions within Poland’s settlement structure. Koszalin also exhibits a typical spatial and functional layout characteristic of many Polish cities. In light of growing challenges related to urbanisation, climate change, and the need to promote sustainable mobility, this study focuses on evaluating access to services such as education, healthcare, retail, public transport, and green spaces. The use of Geographic Information System (GIS) tools enabled the identification of spatial variations in service accessibility across the city. The results indicate that only 11% of Koszalin’s area fully meets the assumptions of the 15 min city concept, providing pedestrians with convenient access to all key services. At the same time, 92% of the city’s area offers access to at least one essential service within a 15 min walk. Excluding forested areas not intended for development increases these values to 14% and 100%, respectively. This highlights the extent to which methodological choices in assessing pedestrian accessibility can shape analytical outcomes and the interpretations drawn from them. Moreover, given this article’s objective and the adopted analytical procedure, the assumed pedestrian walking speed is the key parameter. Accordingly, a sensitivity analysis was conducted, comparing the reference scenario (4 km/h) with alternative variants (3 and 5 km/h). This approach demonstrates the extent to which a change in a single parameter affects estimates of urban-area coverage by access to individual services reachable on foot within 15 min. The analysis reveals limited integration of urban functions at the local scale, highlighting areas in need of planning intervention. This article proposes directions for action to improve pedestrian accessibility within the city. Full article

Diphenylmethane, recently recognized as a candidate for liquid organic hydrogen carrier systems, is traditionally produced by alkylation of benzene with benzyl chloride using homogeneous catalysts. In the current context, the need for a transition toward processes that reduce environmental impact and move toward sustainability has become increasingly evident. In this work, the benzylation of benzene by benzyl chloride using metal–organic frameworks (MOFs) as catalysts is proposed, as alternative materials that combine the advantages of homogeneous and heterogeneous catalysis. Reaction experiments were carried out in an isothermal batch reactor with commercial Basolite C300 and Basolite F300 MOFs, based on Cu and Fe as active species, respectively. The results demonstrate catalytic activity using both proposed catalysts under the studied conditions, with the results of the Fe-based MOF being more favorable, given the greater standard reduction potential of Fe. Compared with their corresponding metal chlorides, the proposed MOFs improve the alkylation activity. Based on a two-step reaction mechanism, a pseudo first-order kinetic model has been developed for the reaction with MOFs as catalysts. The kinetic parameters were obtained by fitting the model to the experimental data, demonstrating good agreement and validating the proposed mechanistic pathway. Full article

Tenebrio molitor is a common stored grains pest. The conventional way for its management involves the use of synthetic fumigants. Despite their effectiveness, these can cause environmental damage. The use of essential oils has emerged as an alternative for its management. Therefore, the aim of this study was to assess Lantana camara essential oil (EO) and endo-borneol biological activities against T. molitor. Insecticidal activity and weight gain were evaluated through the impregnated paper method against larvae and adults, while repellency was conducted with a Y-tube olfactometer; L. camara EO showed higher mortality for T. molitor adults (LC₅₀ = 7.2 μL EO L⁻¹ air) than for larvae (LC₅₀ = 13.7 μL EO L⁻¹ air) after 30 d. Furthermore, L. camara EO was found to be repellent for T. molitor adults (RC₅₀ = 0.08 μL EO cm⁻²). Regarding the EO composition, endo-borneol was identified by GC-MS as a major compound with 14.24% abundance. Larvae exhibited higher susceptibility (LC₅₀ = 7.8 μL L⁻¹ air) to endo-borneol than adults (LC₅₀ = 46 μL L⁻¹ air) after 72 h. Notably, endo-borneol demonstrated significantly higher repellent activity (RC₅₀ = 0.03 μL cm⁻²) than L. camara EO (RC₅₀ = 0.08 μL EO cm⁻²). These findings suggest that endo-borneol has potential as a natural source alternative for T. molitor management. Full article

(1) Background: Research into incorporating plant powders into dairy products is growing because they significantly increase the nutritional value of the finished products, making them a more attractive option for consumers seeking healthier alternatives. The objective of this study is to develop a novel dairy product by incorporating camu-camu powder into fresh cow’s cheese. The material has been identified as a promising candidate due to its multiple health benefits and high antioxidant content, particularly vitamin C; (2) Methods: The stability of the product during storage was therefore evaluated by analysing its acidity, pH, dry matter content, water activity, syneresis and water holding capacity. The impact of camu-camu powder on the antioxidant activity of the cheese samples was determined using the DPPH method. A sensory evaluation was conducted to ascertain the potential functional properties and consumer acceptability of the subject; (3) Results: The bioactive compounds present in the powder have been shown to enhance the antioxidant capacity of fresh cheese, with the 2% sample demonstrating the most effective antioxidant performance. From a sensory perspective, the 1.5% sample received the highest ratings from tasters. The 1% sample is distinguished by its notable colour stability during storage. Physicochemical analysis shows that camu-camu powder is a sustainable ingredient that improves the quality and extends the shelf life of the finished product; (4) Conclusions: This information is indispensable for the evaluation of the safety and efficacy of camu-camu powder in dairy products. Moreover, it may serve as a point of departure for future studies involving the development of other food products with bioactive compounds using unconventional raw materials. Full article

The emergence of multidrug-resistant Shiga toxin-producing Escherichia coli (STEC) poses a major challenge to public health and necessitates the development of alternative antimicrobial strategies. This study aimed to isolate and characterize five lytic bacteriophages belonging to the genus Mosigvirus and evaluate their potential as biocontrol against MDR STEC strains and their biofilms. The five bacteriophages, designated vB_EcoM-pJBB (ΦB), vB_EcoM-pJBC (ΦC), vB_EcoM-pJBJ (ΦJ), vB_EcoM-pJBK (ΦK), and vB_EcoM-pJBL (ΦL), were isolated from sewage treatment plant samples using STEC ATCC 43895 as host. Biological characterization included host range determination against 19 MDR STEC strains, one-step growth analysis, environmental stability assays, bacteriolytic activity assessment, and antibiofilm efficacy testing. Whole-genome sequencing and phylogenetic analyses were performed to determine genomic features and taxonomic classification. The phages demonstrated varying infectious capacities, lysing between six and 12 strains, with ΦL exhibiting the broadest spectrum of activity. All phages showed MOI-independent antibiofilm activity, preventing biofilm formation by approximately 70% and disrupting pre-formed biofilms by up to 80.3%. Genomic analysis revealed the absence of lysogeny markers, virulence factors, and antimicrobial resistance genes, while identifying putative depolymerase genes associated with tail fiber proteins. Phylogenetic analysis confirmed the taxonomic position of these phages within the Mosigvirus genus in the Straboviridae family. Our findings indicate that the newly identified Mosigvirus phages are promising candidates for phage-based biocontrol applications. Full article

Background: The immunogenicity of polysaccharide conjugate vaccines is critically influenced by the choice of carrier protein, which promotes a T-cell-dependent immune response mechanism leading to strong antibody production. In this study, the cholera toxin B subunit (CTB), a non-toxic pentameric protein, was evaluated as a novel carrier protein for pneumococcal polysaccharide antigens. Methods: Recombinant CTB was produced in Escherichia coli and purified using scalable chromatographic methods. Pneumococcal polysaccharides from serotypes 7F, 22F, and 33F were chemically activated with CDAP and conjugated to CTB. Results: The resulting glycoconjugates were characterized by SEC-MALS, confirming successful conjugation, high molecular weights, consistent polysaccharide-to-protein ratios, and acceptable endotoxin levels. Immunogenicity was assessed in rabbits following immunization with alum-adjuvanted formulations. Results: Robust IgG responses were elicited by all CTB-based conjugates, with antibody levels found to be comparable to those induced by CRM197 conjugates, demonstrating the potential of CTB as a promising alternative for the next generation of conjugate vaccines. Full article

Sexually transmitted infections, notably herpes simplex virus, remain significant global health concerns. Localized delivery systems that provide sustained antiviral activity at mucosal surfaces offer an attractive alternative to systemic therapies. In this study, we developed electrohydrodynamically deposited coatings utilizing a covalent acyclovir–poly (lactic-co-glycolic acid) (ACV–PLGA) conjugate for potential antiviral functionalization of medical devices. The ACV–PLGA prodrug was synthesized via drug-initiated ring-opening polymerization, yielding a copolymer characterized by FTIR, NMR, GPC, and DSC, with controlled drug loading and biodegradable properties. Systematic optimization of electrospinning and electrospraying parameters enabled the fabrication of both particulate and nanofibrous coatings on silicone ring models. Morphological analysis by SEM demonstrated that polymer concentration, solvent composition, and applied voltage critically governed coating architecture, ranging from microparticle layers to uniform bead-free fibers. In vitro studies revealed morphology-dependent degradation profiles and sustained release of ACV over 56 days. This integrated approach combining covalent prodrug synthesis with tunable electrohydrodynamic deposition offers a promising strategy for long-acting local antiviral prophylaxis via functionalized medical surfaces. Full article

Background/Objectives: Traditional kombucha is produced by fermenting a sweetened infusion of Camellia sinensis leaves with a symbiotic consortium of bacteria and yeasts (SCOBY). The growing interest in this beverage has driven the exploration of alternative substrates, including a wide range of plant-based raw materials, such as leaves, fruits, flowers, and seeds. Consequently, numerous products are being investigated for their differential properties, not only organoleptic but also nutritional and bioactive. This review aims to summarize recent advances in alternative kombucha research, focusing on the substrates used, their physicochemical and biochemical characteristics, and the biological activities studied. Methods: A comprehensive literature search was conducted to select articles related to alternative kombuchas. A critical analysis of their current state was carried out through the Strengths, Weaknesses, Opportunities, and Threats (SWOT) methodology. Results: The SWOT analysis led to the identification of strengths, including promising in vitro results and growing consumer interest; weaknesses, including a lack of animal studies, clinical trials, and approved health claims, and an excessive focus on antioxidant activity and phenolic compounds; opportunities, including substrate diversity, innovation, and consumer education; and threats, including elaboration risks, misinformation, competitors, and potential consumer rejection. Conclusions: Despite the promising results achieved to date, it is essential that the scientific community and the food industry continue efforts to generate robust evidence, particularly through clinical validation, in order to draw reliable conclusions regarding the benefits of alternative kombuchas for human health. Full article

Intensive aquaculture practices heighten oxidative stress and infectious disease risk, necessitating sustainable alternatives to antibiotics. This study evaluated the integrative probiotic and postbiotic potential of Bacillus velezensis AAHM-BV2302 in red tilapia (Oreochromis spp.), focusing on growth, antioxidant defense, immune modulation, and resistance to Streptococcus agalactiae. Whole-genome sequencing confirmed its classification as B. velezensis (4.16 Mb, GC 45.9%, ANI 99.4% with NRRL B-41580). Fish were fed diets supplemented with probiotic cells (Cell), cell-free supernatant (Cfs), or their combination (Cell + Cfs) for 30 days, followed by 30 days without probiotic supplementation. Growth performance significantly improved in Cell and Cell + Cfs groups at both Day 30 and Day 60 (p < 0.05). Antioxidant enzymes (SOD, CAT, GSH) increased significantly across tissues at Day 30, while malondialdehyde (MDA) declined (p < 0.05), indicating enhanced redox homeostasis. Humoral immunity was elevated, with higher lysozyme, bactericidal activity, and total IgM persisting post-supplementation (p < 0.05). Expression of il1b, il6, and il8 was upregulated in immune-related and mucosal tissues, reflecting robust immune activation (p < 0.05). After S. agalactiae challenge, survival rates were 55% in Cfs, 60% in Cell, and 70% in Cell + Cfs, corresponding to relative percent survivals (RPS) of 43.8%, 50.0%, and 62.5%, respectively (p < 0.05). These results demonstrate that B. velezensis AAHM-BV2302 enhances growth, antioxidant capacity, and immune resilience through complementary probiotic–postbiotic mechanisms, supporting its application as a safe, multifunctional biotic for antibiotic-free tilapia aquaculture. Full article

Caffeoylquinic acids (CQAs), a class of phenolic acid metabolites widely distributed in plants, encompass 15 positional isomers from mono- to tetra-esters, with 5-O-caffeoylquinic acid (5-CQA) as the predominant form. The biosynthesis of 5-CQA from phenylalanine proceeds through five primary pathways, which are finely regulated by environmental, hormonal, and transcription factors from families such as MYB, WRKY, and bHLH. These regulators control 5-CQA synthesis by binding specifically to the promoter regions of key structural genes, including PAL, 4CL and HCT/HQT. Subsequently, 5-CQA serves as a central precursor for the biosynthesis of other CQAs. In terms of bioactivity, CQAs possess remarkable pharmacological activities, encompassing antioxidant, antimicrobial, anti-diabetic, anti-inflammatory and anti-tumor properties. For instance, anti-inflammatory effects are demonstrated by the ability of 5-CQA to reduce key pro-inflammatory cytokines (e.g., TNF-α and IL-1β) and downregulate the TLR4/NF-κB pathway. The synergistic action of 5-CQA with ultraviolet-A reduced succinate-coenzyme Q reductase activity by approximately 72%, highlighting its potential to disrupt bacterial metabolism and combat antibiotic resistance. Furthermore, 3,4,5-triCQA exhibits potent anti-influenza virus activity, potentially through a mechanism distinct from existing neuraminidase inhibitors. Beyond medicine, CQAs show promise in light industry. They serve as antibiotic alternatives in livestock feed to enhance gut health, extend food shelf life through their antioxidant activity, and function as active ingredients in UV-protective skincare formulations. CQAs also enhance plant stress tolerance to cold, arsenic, and pests by mechanisms such as scavenging reactive oxygen species and inhibiting pest mobility. While this review consolidates progress in the biosynthesis and bioactivity of CQAs specifically with caffeoyl substituents, future efforts should leverage modern biotechnological tools and interdisciplinary approaches to bridge critical knowledge gaps in their biosynthesis, transport, and clinical translation. Full article

Conventional plastics are widely utilised across industrial sectors and in consumer products. However, the growing use of plastics has led to plastic pollution, including the formation of nanoplastics (NPs), which are harmful to aquatic organisms. Bioplastics are emerging alternatives. They are renewable and/or biodegradable and are supposed to be more environmentally friendly. However, the toxicity and environmental fate of bioplastics are not yet fully understood. This study evaluated the toxicity and fate of commercially available plain or fluorescent polylactic acid (PLA) NPs (250 nm) on aquatic organisms. Confocal microscopy demonstrated the uptake of fluorescent PLA NPs by the test organisms, marine rotifers (Brachionus plicatilis), brine shrimps (Artemia salina) and zebrafish (Danio rerio) embryos. However, the results of the bioassays indicate that plain PLA NPs did not induce acute toxicity in either of the two zooplankton species and did not cause substantial mortality, malformations, or hatching delays in zebrafish embryos at the tested concentrations (up to 100 mg/L). However, brine shrimp showed a significant decrease in ingestion capability. The biochemical biomarkers, catalase activity induction, as an indicator of oxidative stress, and acetylcholinesterase inhibition, as a marker of neurotoxicity, showed no significant alterations compared to the control of both zooplankton species and that of zebrafish embryos. Overall, the findings suggest a pattern of no acute and low sublethal toxicity for the tested plain PLA NPs in the studied organisms. Nonetheless, further research is imperative to comprehensively assess the environmental fate of bioplastics found in various consumer products, as these may contain harmful chemical additives, as well as the effects of prolonged exposure and their impact on physiological parameters, ensuring informed decisions before their widespread commercialisation and presence in the environment. Full article