Search Results (1,267)

Poly(lactic-co-glycolic acid) (PLGA) sustained-release systems for intra-articular (IA) delivery aim to extend joint residence time and reduce the reinjection frequency of conventional IA therapies. This review synthesizes current understanding of PLGA degradation, the acidic microenvironment inside degrading microspheres, and release behavior in joints, and surveys clinical experience with extended-release corticosteroid depots alongside emerging platforms for nonsteroidal and biologic agents. To situate PLGA within the broader IA field, we briefly summarize selected non-PLGA sustained-release approaches—such as multivesicular liposomes, hyaluronic acid conjugates, and hybrid matrices—to contextualize comparative performance and safety. For proteins and peptides, central barriers include acidification inside degrading microspheres, aggregation during fabrication and storage, and incomplete or delayed release, as illustrated by glucagon-like peptide-1 analog formulations. Mitigation strategies span pH buffering, excipient-based stabilization, and gentler manufacturing that improve encapsulation efficiency and preserve bioactivity. Translation hinges on manufacturing scale-up and quality systems that maintain critical particle attributes and enable informative in vitro–in vivo interpretation. Clinically, prolonged symptom relief after single dosing has been demonstrated for corticosteroid depots (e.g., ~50% pain reduction over 12 weeks with a single PLGA–triamcinolone injection), whereas repeat-dose safety and indication expansion beyond the knee remain active needs best addressed through multicenter trials incorporating imaging and patient-reported outcomes. Consistent real-world performance will depend on controlling batch-to-batch variability and implementing pharmacovigilance approaches suited to long dosing intervals, enabling broader clinical adoption. Full article

Hypoxis hemerocallidea (Hypoxidaece) is thoroughly researched and well documented for its plethora of anecdotal and scientifically backed pharmacological potentials. Its anecdotal uses and pharmacological activities are attributed to its extract’s inherent bioactive compounds like hypoxoside, rooperol, and β-sitosterol. This study aimed at conducting a targeted and holistic phytochemical profiling of variations in Hypoxis hemerocallidea (H. hemerocallidea) and related species. The chemotaxonomic classifications of H. hemerocallidea and seven other related species were also carried out to avert the possibility of over harvesting H. hemerocallidea and the encouragement of species inter-change. The plant extracts were analysed with reverse phase ultra-pure liquid chromatography quadrupole time-of-flight mass spectrometry and gas chromatography, as well as high-performance thin-layer chromatography. The generated chromatographic data were made compatible for chemometric computation using Principal Component Analysis (PCA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) models. The results obtained unveil orcinol glycoside, curculigoside C, hypoxoside, dehydroxyhypoxoside, bisdehydroxy hypoxoside, hemerocalloside, galpinoside, cholchicoside, geraniol glycoside, β-sitosterol, oleic acid, and 2-hydroxyethyl linoleate as target phytochemicals that define the profiles of the Hypoxis species. In addition, three distinct chemotypes defined by hemerocalloside, galpinoside, and colchicoside, respectively, were observed, as well as holistic variations in all secondary metabolites. Due to similarities in the phytochemical constituents of selected species, species inter-change seems imminent if further research confirms the findings of this study. Full article

Background: Growing evidence highlights the beneficial effects of flavonoids, including anthocyanins, as key components in reducing cardiovascular risk, and emphasizes that incorporating anthocyanin-rich fruits into the daily diet significantly impacts public health. Methods: The effect of bioactive polyphenols from raspberry fruit (RBF) on molecular pathways in inflammation was studied in activated RAW 264.7 macrophages and their protective potential against endothelial dysfunction was analyzed using TNF-α-induced human umbilical vein endothelial cells (HUVECs). Results: The results have shown that RBF extract, along with its anthocyanin and polyphenol fractions, has a significant anti-inflammatory effect in macrophage cell culture by inhibiting the LPS-induced expression of pro-inflammatory genes, including IL-6, IL-1β, TNF-α, and NF-κB. Moreover, RBF and both fractions have demonstrated a protective effect on endothelial function by decreasing the expression of several inflammation-related genes and adhesion molecules, such as IL-6, IL-1β, VCAM-1, ICAM-1, and SELE, in TNF-α-induced HUVECs. Conclusions: The consumption of RBF and/or polyphenol-rich extracts may help prevent the onset of early atherosclerosis. This is attributed to their ability to improve inflammation status and enhance vascular endothelial function. Given the strong anti-inflammatory properties of RBF, incorporating them into a daily diet could significantly reduce the risk of non-communicable diseases related to inflammation. Full article

Chronickidney disease (CKD) poses a major global public health challenge, driven by a complex pathogenesis involving multiple interconnected processes—including metabolic disturbances, chronic inflammation, oxidative stress, endoplasmic reticulum stress, and ferroptosis—which collectively contribute to progressive and often irreversible loss of renal function. Although current standard therapies can ameliorate CKD progression, a substantial number of patients still advance to end-stage renal disease, highlighting the urgent need for innovative treatment strategies. Natural products have shown great promise in the prevention and management of CKD, largely attributable to their multi-target and multi-pathway synergistic effects. This review systematically outlines the core pathogenic mechanisms underlying CKD and elucidates the molecular mechanisms through which bioactive natural compounds exert renoprotective effects. Despite robust preclinical evidence, the clinical translation of these compounds remains hindered by limitations such as poor bioavailability and a lack of large-scale clinical trials. Moving forward, research should prioritize clinical translation of these compounds, aiming to provide novel therapeutic perspectives for CKD management. Full article

Coconut oil is highly regarded for its nutritional and functional attributes, making it an attractive candidate for diverse food and health applications. This study evaluates the fatty acid profile, antioxidant and antimicrobial activities, oxidative stability, and sensory properties of selected coconut oils (Coco24, Health, Kospa, Smetol, and Vita) from the Slovak republic market. Acid values (0.09 ± 0.060–0.42 ± 0.060 mg KOH/g) and peroxide values (0.51 ± 0.058–1.20 ± 0.010 mmol O₂/kg) were within recommended safety limits. Oxidative stability varied significantly (p ˂ 0.05), with Smetol showing the highest induction time (124.5 ± 0.98 h) and Coco24 the lowest (25.8 ± 0.22 h). DPPH antioxidant activity was highest in health (469.2 ± 2.01 mg TEAC/kg) and Coco24 (369.3 ± 1.99 mg TEAC/kg) (TEAC—Trolox equivalent antioxidant capacity). Coco24, Health, and Kospa exhibited the most potent antimicrobial activity against Staphylococcus aureus (2.01 ± 0.001 mm, 1.37 ± 0.021 mm, 1.15 ± 0.010 mm, respectively), Candida glabrata (1.17 ± 0.015 mm, 1.17 ± 0.015 mm, 0.45 ± 0.025 mm, respectively), Candida tropicalis (2.12 ± 0.017 mm, 2.13 ± 0.017 mm, 1.52 ± 0.006 mm, respectively), and Bacillus subtilis (1.29 ± 0.055 mm, 1.35 ± 0.006 mm, 0.31 ± 0.020 mm, respectively). FAME analysis revealed that saturated fatty acids dominated, especially in Smetol (97.6 ± 0.067%), while Coco24 had the highest levels of unsaturated fatty acids. Vita and Kospa received the highest panel ratings for smell, taste, and overall acceptability, indicating superior sensory appeal, whereas Smetol scored the lowest. Correlation analysis showed strong positive relationships between MUFA and PUFA (r = 0.986) and taste and acceptability (r = 0.993), as well as between antioxidant activity and Candida albicans inhibition (r = 0.859). Oxidative stability was negatively correlated with PUFA (r = –0.924). PCA grouped oils high in MUFA/PUFA (Kospa, Vita) with superior sensory scores, while PC2 reflected microbial safety. These differences suggest that Coco24, Health, Vita, and Kospa offer enhanced functional and sensory benefits, whereas Smetol is better suited for applications that prioritize oxidative stability. Full article

Background: Fragile X Syndrome (FXS) is the most common monogenic cause of autism spectrum disorders, and is characterized by the excessive immature excitatory synapses in cortical neurons, leading to excitatory/inhibitory imbalance and core autistic behaviors. This synaptic pathology has been attributed to dysregulated levels of synaptic proteins, including CYFIP2: a key regulator of synaptic structure and plasticity. However, the mechanism underlying the increased CYFIP2 protein level in FXS neurons remains unclear. Neurons abundantly secrete extracellular vesicles (EVs) enriched with bioactive cargos (proteins and miRNAs). Objectives: the goal of this research is to identify whether EV-dependent secretion plays important roles in regulating the intracellular CYFIP2 protein level in WT and FXS neurons. Methods and Results: our proteomic analysis reveals that CYFIP2 protein is packaged in EVs released by mouse cortical neurons. Pharmacological and genetic blockades of neuronal EV release significantly elevated intracellular CYFIP2 levels by 78 ± 14% and 168 ± 39%, respectively. Glutamate-evoked EV release significantly reduced the CYFIP2 level by 24 ± 2%. Neurons from Fmr1 KO mice, an FXS model, secreted significantly less EVs (46 ± 5%) than the wild type, and showed significantly elevated CYFIP2 (by 155 ± 31%). Evoking EV release in FXS neurons significantly lowered the intracellular CYFIP2 (by 53 ± 6%). Conclusions: these findings identify an EV-secretion-dependent mechanism that controls neuronal CYFIP2 level, implicating EV-mediated export in the regulation of synaptic protein homeostasis, synaptic remodeling, and FXS-associated synaptic deficits. Full article

The growing worldwide demand for essential oils (EOs) brings new opportunities for Azorean Cryptomeria japonica aerial parts waste valorization. Therefore, the phytochemical and bioactivity investigation of EOs from different Azorean C. japonica tissues, such as twigs (Az–CJT), remains imperative to add more value to C. japonica’s EO industry, alongside the contribution to the local sustainable circular bioeconomy. This study provides, for the first time, GC–MS analysis and brine shrimp toxicity of the EO hydrodistilled from Az–CJT and aims to compare these parameters with those determined for a commercial Azorean C. japonica (branches and foliage) EO obtained through steam distillation. The main Az–CJT EO components were α-eudesmol (19.53%), phyllocladene (14.80%), elemol (12.43%), nezukol (11.34%), and γ-eudesmol (5.32%), while α-pinene (28.62%), sabinene (24.30%), phyllocladene (5.10%), β-myrcene (5.09%), and limonene (4.93%) dominated in the commercial EO. Thus, Az–CJT EO exhibited the highest sesquiterpenoids (43.52%), diterpenes (20.85%), and diterpenoids (13.21%) content, while the commercial EO was dominated by monoterpenes (74.61%). The Az–CJT EO displayed significantly higher toxicity than the commercial EO, with mortality rates of 87.7% and 16.9%, respectively, at 100 µg/mL. This result is likely related to the substantially higher terpenoid content of Az–CJT EO (61.20% vs. 9.44%), largely attributed to the sesquiterpenoid fraction. Due to its distinct chemical profile, Az–CJT EO may have differential commercial applications, warranting further investigation into its bioactive value and safe use. In conclusion, this study adds knowledge on the potentialities of C. japonica aerial parts’ EOs from the Azorean region. Full article

This study investigated the phytochemical composition, antioxidant properties, and sensory characteristics of cold-pressed juices prepared from red beet (Beta vulgaris L.) and tarragon (Artemisia dracunculus L.) microgreens, which remain largely unexplored as raw materials for beverage production. Targeted analyses using spectrophotometric methods and UHPLC-Q-ToF-MS identified betalains as major pigments in beet juice and estragole together with quercetin glycosides in tarragon juice, highlighting their contrasting phytochemical profiles. Beet juice exhibited higher total phenolic 73.48 ± 2.11 mg GAE/100 mL and flavonoid contents 47.26 ± 1.44 mg QE/100 mL, along with betalains 32.85 ± 1.09 mg/100 mL, while tarragon juice contained more chlorophylls 18.73 ± 0.92 mg/100 mL. Antioxidant assays confirmed superior ABTS 132.84 mg TE/100 mL and FRAP 118.42 mg TE/100 mL activities in beet juice, with values strongly correlated to phenolic concentration. Sensory evaluation with trained panelists and a consumer group n = 74 indicated moderate acceptance, with tarragon juice rated slightly higher for taste and overall acceptability despite the stronger visual appeal of beet juice. These findings provide evidence that both beet and tarragon microgreens can serve as complementary sources of bioactive compounds and colorants, supporting their application in the development of cold-pressed functional beverages with distinct nutritional and sensory attributes. Full article

Ganoderma lucidum (Lingzhi), a traditional medicinal mushroom, is renowned for its immunomodulatory, anti-inflammatory, and antioxidant properties, primarily attributed to its bioactive components such as polysaccharides and triterpenoids. This review focuses on the mechanisms by which Ganoderma lucidum modulates immune responses, particularly in the context of gut–liver–brain axis disorders. Polysaccharides enhance immune function by activating macrophages, natural killer cells, and T cells, thereby promoting phagocytosis and cytokine production. Triterpenoids contribute through anti-inflammatory and antioxidant activities, inhibiting inflammatory mediators and protecting tissues from damage. Ganoderma lucidum also influences immune regulation via key signaling pathways, including NF-κB and MAPK, and supports immune tolerance, potentially reducing the risk of autoimmune diseases. Additionally, it modulates gut microbiota, which further impacts systemic immunity. Importantly, polysaccharides and triterpenoids demonstrate promising clinical application prospects in metabolic diseases, inflammatory conditions, neurodegenerative disorders, and cancer immunotherapy, attributed to their multi-target immunomodulatory activities and prebiotic properties. Despite promising applications in treating metabolic, inflammatory, and neurodegenerative diseases, further research is needed to fully elucidate the molecular mechanisms and potential of Ganoderma lucidum in precision medicine. This comprehensive analysis underscores the value of Ganoderma lucidum as a multifaceted immunomodulatory agent. Full article

With growing consumer demand for functional dairy products, developing yogurts enriched with natural bioactive ingredients has become a research focus. Millet, a traditional cereal rich in polyphenols and dietary fiber, remains understudied in fermented dairy applications. This study evaluated the physicochemical properties, sensory quality, and functional activities of yogurt co-fermented with millet. Millet liquid, pre-treated through gelatinization and α-amylase liquefaction, was co-fermented with milk at addition ratios of 40% and 60% (w/w). The results indicated that millet liquid increased Lactobacillus delbrueckii subsp. Bulgaricus viability (8.55–8.58 log CFU/g vs. 8.26 log CFU/g in the control), improved viscosity (up to 1.0–1.6-fold higher than the control), enhanced texture properties (51–65-fold increase in springiness, 4.3–4.6-fold higher chewiness), and reduced syneresis (18.6–49.2% lower than the control). Sensory evaluation revealed superior flavor and sweetness in millet-enriched yogurt, achieving significantly higher scores than plain yogurt (p < 0.05). Functionally, the 60% millet yogurt showed 77.8% and 84.3% higher DPPH and ABTS radical scavenging capacities, respectively. Additionally, it suppressed DSS-induced inflammatory cytokine secretion in Caco-2 cells (27.2–69.7% inhibition of TNF-α, IL-6, and IL-1β). The improved antioxidant and anti-inflammatory activities may be attributed to polyphenol release from millet. This work highlights the potential of millet–milk co-fermentation for developing yogurts with enhanced texture, sensory appeal, and bioactive properties. Full article

Moringa oleifera, renowned for its medicinal potency, was investigated to discern the impact of varying storage temperatures (4 °C, 25 °C, 40 °C) and light conditions (dark and light) on the quality attributes of its leaf powder during a 12-month storage period. The study encompassed comprehensive analyses of phytochemical levels, nutritional properties, microbial contamination, and colour changes in response to these diverse storage environments. The lightness L* colour value changed significantly (40 to 60) from baseline tests when stored at 40 °C in transparent packaging. Results highlighted distinct variations in phytochemical composition and nutritional content based on the interplay between temperature and light conditions. Lower temperatures, particularly 4 °C, in both dark and light environments, demonstrated superior preservation of bioactive compounds, with mean values for quercetin-3-rutinoside of 3.34 µg/g and 3.19 µg/g, respectively; both are significantly higher compared to other treatments (p < 0.05). This trend was also observed for rutin, chlorogenic acid, and quercetin. Conversely, higher temperatures (25 °C, 40 °C) coupled with light exposure hastened degradation, notably impacting phytochemical stability. Microbial proliferation was evident in elevated temperatures, indicating potential safety risks. Further observations unveiled significant colour changes within the leaf powder, notably influenced by storage temperatures and light exposure. Lower temperatures exhibited diminished colour alterations compared to higher temperatures, underscoring their impact on product quality. This study underscores the critical role of controlled storage conditions, especially cooler temperatures and reduced light exposure, in maintaining the potency and quality of M. oleifera leaf powder. Recommendations advocate for stringent temperature control (preferably 4 °C) and light shielding during storage to uphold phytochemical stability and mitigate microbial proliferation. While this study provides valuable insights into temperature-mediated alterations, future research avenues should delve deeper into elucidating the underlying mechanisms of colour changes and long-term temperature effects on phytochemical and nutritional integrity. Full article

Background/Objectives: This study aimed to develop an advanced oral delivery platform for Salvia officinalis (S. officinalis) extract by co-encapsulating it with inulin and pectin in alginate-based microbeads, formulated via ionic gelation. Methods: The microbeads were comprehensively characterized, including the assessment of morphology, particle size, encapsulation efficiency, swelling behavior, in vitro dissolution, and enzymatic stability, and Caco-2 cell-based assays for cytocompatibility, permeability, and transepithelial electrical resistance. Antioxidant capacity and anti-inflammatory effects were also evaluated. Results: The resulting microbeads (~275 µm) achieved > 90% encapsulation efficiency and exhibited pronounced swelling (~90%). The release of S. officinalis constituents displayed pH sensitivity, with sustained release in simulated intestinal fluid, alongside significant enhancement of enzymatic stability. Encapsulation led to markedly improved permeability of bioactive compounds across Caco-2 monolayers, attributable to reversible modulation of tight junctions. Encapsulated extract retained potent antioxidant activity and significantly reduced pro-inflammatory cytokines. The formulation, across various concentrations, further promoted the growth and viability of Lactobacillus strains. Conclusions: Collectively, these findings demonstrate that alginate–inulin–pectin microbeads provide a multifunctional system for stabilizing S. officinalis extract, enabling controlled release, enhanced intestinal absorption, and maintained bioefficacy. Importantly, the formulation also promoted Lactobacillus viability, indicating a prebiotic effect and offering considerable potential for improved oral therapeutic applications. Full article

Various therapeutic approaches have been explored to speed up wound healing, with angiogenesis being a crucial factor in this process and skin repair. This study shows that a polysaccharide extracted from the red alga Osmundea pinnatifida (PSOP) can promote angiogenesis and accelerate healing. The structural properties of PSOP were investigated using various techniques, including scanning electron microscopy, X-ray diffraction, Fourier–transform infrared spectroscopy, ultraviolet–-visible spectroscopy, and high-performance liquid chromatography coupled with a refractive index detector. Additionally, the in vitro antioxidant activity of PSOP was evaluated using the reducing power assay, total antioxidant capacity measurement, and DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging tests. The PSOP extract exhibited significant pro-angiogenic effects in the avian chorioallantoic membrane model. Furthermore, the efficacy of PSOP-based hydrogels for wound healing was assessed in vivo using an excision wound model in Wistar rats. The results indicated accelerated wound healing, increased collagen deposition, and enhanced tissue regeneration. Computational studies suggest that the observed wound healing and pro-angiogenic effects may be attributed to the affinity of the PSOP units for cyclooxygenase-2 and vascular endothelial growth factor. These findings support the potential use of PSOP as a bioactive agent in wound care. Full article

This study reports the development and characterization of novel active edible films based on apple pectin and honey (80:20, w/w), incorporating raw propolis powder at 0.1%, 0.2%, and 0.3% (w/w, relative to honey) as a natural source of bioactive compounds for sustainable packaging of soluble coffee and matcha powders. The study aims to provide sustainable and functional packaging solutions capable of maintaining the stability and quality of these powdered beverages. The effects of honey and propolis incorporation on the physicochemical, mechanical, optical, and microbiological properties of the films were systematically evaluated. Propolis addition resulted in decreased tensile strength, elastic modulus, and elongation at break, but did not significantly alter the thermal stability of the films, as evidenced by differential scanning calorimetry and thermogravimetric analysis. Increasing propolis concentrations led to higher total phenolic content and significantly improved antioxidant activity, with the 0.3% formulation exhibiting the most pronounced effect. Application tests demonstrated that the honey–propolis-enriched pectin films effectively preserved the sensory attributes and physicochemical quality of soluble coffee and matcha powders. Overall, these results highlight the potential of pectin–honey–propolis films as bioactive carriers and functional materials for active packaging of powdered beverages. Full article

Corneal regeneration has gained growing interest in recent years, largely due to the limitations of conventional treatments and the persistent shortage of donor tissue. Among the emerging strategies, extracellular vehicles (EVs), especially those derived from mesenchymal stromal cells (MSCs), have shown great promise as a cell-free therapeutic approach. These nanoscale vesicles contribute to corneal healing by modulating inflammation, supporting epithelial and stromal regeneration, and promoting nerve repair. Their therapeutic potential is largely attributed to the diverse and bioactive proteomic cargo they carry, including growth factors, cytokines, and proteins involved in extracellular matrix remodeling. This review presents a comprehensive examination of the proteomic landscape of EVs in the context of corneal regenerative medicine. We explore the biological functions of EVs in corneal epithelial repair, stromal remodeling, and neurodegeneration. In addition, we discuss advanced proteomic profiling techniques such as mass spectrometry (MS) and liquid chromatography–mass spectrometry (LC-MS/MS), which have been used to identify and characterize the protein contents of EVs. This review also compares the proteomic profiles of EVs derived from various MSC sources, including adipose tissue, bone marrow, and umbilical cord, and considers how environmental cues, such as hypoxia and inflammation, influence their protein composition. By consolidating current findings, this article aims to provide valuable insights for advancing the next generation of cell-free therapies for corneal repair and regeneration. Full article