Search Results (8,504)

Background/Objectives: Influenza is a major global health challenge, causing thousands of deaths annually. Antiviral drugs, particularly oseltamivir, a neuraminidase inhibitor, have become essential therapeutic options due to their oral bioavailability and efficacy. Previous studies suggest a potential association between oseltamivir use and the onset of diabetes mellitus. However, further investigation is needed to establish a definitive link. Methods: This retrospective cohort study utilized data from the Taiwan National Health Insurance Research Database (NHIRD), including 1,631,968 patients (815,984 oseltamivir users) between 1 January 2009 and 28 December 2018. All statistical analyses were performed using SAS 9.4M8 software (SAS Institute Inc., Cary, NC, USA). Results: Cox proportional hazards regression and multivariate analyses revealed a statistically significant association between oseltamivir use and overall diabetes risk (HR = 1.027, p = 0.0186). While no significant association was observed for Type 1 diabetes (HR = 1.021; p = 0.06795), oseltamivir users showed a higher incidence of Type 2 diabetes (HR = 1.024; p < 0.05). Oseltamivir was also linked to increased risks of comorbidities, including dyslipidemia (HR = 1.295, p < 0.0001), chronic liver disease (HR = 1.446, p < 0.0001), hypertension (HR = 1.586, p < 0.0001), and obesity (HR = 2.949, p < 0.0001). Conclusions: Oseltamivir is associated with an increased risk of Type 2 diabetes but not Type 1, and related comorbidities. Full article

Peptide-loaded poly(lactide-co-glycolide) (PLGA) nanocarriers represent a transformative approach to addressing the challenges of peptide-based therapies. These systems offer solutions to peptide instability, enzymatic degradation, and limited bioavailability by providing controlled release, targeted delivery, and improved stability. The versatility of PLGA nanocarriers extends across therapeutic domains, including cancer therapy, neurodegenerative diseases, vaccine development, and regenerative medicine. Innovations in polymer chemistry, surface functionalization, and advanced manufacturing techniques, such as microfluidics and electrospraying, have further enhanced the efficacy and scalability of these systems. This review highlights the key physicochemical properties, preparation strategies, and proven benefits of peptide-loaded PLGA systems, emphasizing their role in sustained drug release, immune activation, and tissue regeneration. Despite remarkable progress, challenges such as production scalability, cost, and regulatory hurdles remain. Full article

Intravenously transplanted mesenchymal stromal cells (MSCs) have been shown to interact with endothelial cells and to migrate to tissues. However, intracellular signals regulating MSC migration are still incompletely understood. Here, we analyzed the role of Rap1 GTPase in the migration of human bone marrow-derived MSCs in vitro and in short-term homing in mice in vivo. MSCs expressed both Rap1A and Rap1B mRNAs, which were downregulated after treatment with siRNA against Rap1A and/or B. In a flow chamber model with pre-established human umbilical vein endothelial cells (HUVECs), Rap1A/B downregulated MSCs interacted for longer distances before arrest, indicating adhesion defects. CXCL12-induced adhesion of MSCs on immobilized Vascular Cell Adhesion Molecule (VCAM)-1 was also decreased after the downregulation of Rap1A, Rap1B, or both, as was CXCL12-induced transwell migration. In a competitive murine short-term homing model with i.v. co-injection of Rap1A+B siRNA-treated and control MSCs that were labeled with PKH 26 and PKH 67 fluorescent dyes, the Rap1A+B siRNA-treated MSCs were detected at increased frequencies in blood, liver, and spleen compared to control MSCs. Thus, Rap1 GTPase modulates the adhesion and migration of MSCs in vitro and may increase the bio-availability of i.v.-transplanted MSCs in tissues in a murine model. Full article

In the context of rapid industrialization and agricultural modernization, the issue of heavy metal (HM) pollution has surfaced as a critical concern, posing a substantial threat to human health and having a profound impact on agricultural cultivation. Selenium (Se), a beneficial micronutrient for crop growth and development, exerts numerous beneficial effects, including facilitating photosynthesis, enhancing physiological attributes, improving nutritional quality, strengthening antioxidant systems, and modulating the expression of stress-responsive genes. Notably, Se plays a pivotal role in alleviating HM stress in crops and effectively mitigating the accumulation of HMs in edible plant parts. This study investigates the physiological and molecular mechanisms underlying Se’s capacity to alleviate HM stress in crops. Additionally, we discuss the application of Se-enriched fertilizers in agricultural practices, as well as the influence of environmental factors on their effectiveness. Our objective is to contribute to sustainable agricultural development and the production of safe, high-quality agricultural products, thereby providing valuable insights for the development of Se-functional industries and guiding agricultural practices in regions affected by HM pollution. Full article

Background: Magnolol (MG) and honokiol (HK) are bioactive compounds extracted from Magnolia obovata and Magnolia Officinalis trees with significant pharmacological properties, including antioxidant and antibacterial activity. However, their poor water solubility and low bioavailability limit the therapeutic potential. Methods: To address these limitations, this study aims to develop MG and HK formulations by co-electrospinning using custom-synthesized β-cyclodextrin–oligolactide (β-CDLA) derivatives. MALDI MS and NMR were employed for the structural assessment of the β-CDLA derivatives. This polymer-free electrospinning technique utilizes the high solubility of β-CDLA to incorporate MG and HK into fibrous webs. The morphology of the resulting fibers is established by SEM and further characterized using FTIR and NMR spectroscopy to confirm the successful incorporation of MG and HK. The antioxidant activity was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, while the antimicrobial activity was evaluated against several standard microorganisms (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans). Results: The MG and HK electrospun formulations were prepared using highly concentrated feed solutions in dimethylformamide (180% w/v). The resulting β-CDLA fibers, with diameters above 400 nm and an active compound content of 7% wt., exhibited enhanced long-term antioxidant activity and improved antimicrobial efficacy, including notable activity against Escherichia coli. Conclusions: This study demonstrates the potential of MG and HK-loaded β-CDLA fibrous formulations as delivery systems with prolonged antioxidant activity and notable antibacterial efficacy, providing a promising platform for biomedical applications. Full article

Viola, an edible wild plant, is valued for its distinctive flavor and health-promoting properties. This study examines the proximate composition, bioactive compounds, and in vitro biological activities of seven Viola leaves (Viola prionantha, Viola collina, Viola acuminata, Viola variegata, Viola tokubuchiana var. takedana, Viola mirabilis, and Viola philippica). Findings reveal that the leaves of the seven Viola species are rich in phenolic compounds (131.13 mg gallic acid equivalents (GAE)/100 g fresh weight (FW)–384.80 mg GAE/100 g FW), flavonoids (13.09 mg rutin equivalents (RE)/100 g FW–40.08 mg RE/100 g FW), fatty acids (palmitic acid, linoleic acid, oleic acid, and α-linolenic acid), and essential minerals, such as potassium, calcium, and magnesium. The leaf extracts demonstrated significant inhibitory effects on α-glucosidase (84.17%) and pancreatic lipase (77.54%) at a concentration of 1 g of extract per milliliter of solution. Additionally, the biological activity of Viola leaves, particularly their antioxidant capacity, is associated with their phenolic and flavonoid content, with caffeic acid contributing up to 35.2% of the total phenolic acids and isoquercitrin being one of the most bioavailable flavonoids. These results indicate that Viola offers potential notable health benefits, presenting a valuable addition to enhancing modern dietary patterns and overall health. Full article

Economic development increases and brings about issues such as the secure supply of food in a sustainable way. Phytases are enzymes catalyzing phytate hydrolysis to release phosphorus in an inorganic form. Animal feeds could be supplemented with bacterial phytases to increase their phosphorus and micronutrients bioavailability. To the best of our knowledge, this is the first report on the purification and characterization of an alkalophilic phytase from Cobetia marina. The purified newly isolated phytase from the halophilic Cobetia marina strain 439 appears to be appropriate for use as an additive in food and feed processing. Its molecular weight was determined to be 43 kDa by gel filtration and 40 kDa by SDS–polyacrylamide gel electrophoresis. The purified enzyme had maximum activity at pH 8.0 and 45 °C, while at 70 °C, it was 80% and about 50% at 80 °C for 40 min, showing its thermostability. Enzyme activity was retained at a broad pH range from 6.5 to 9.0. The half-life of the phytase of 15 min at pH 10 and 30 min at pH 4.0 was registered. The enzyme was proven to be with high substrate specificity. In addition, the purified phytase showed strong proteolytic tolerance against trypsin and pepsin. The pH profile, its thermostability, and proteolytic tolerance of the studied phytase as a halophilic bacterial product determine it as a unique candidate for application in agriculture, food, and feed industries. Full article

Sustainability is becoming increasingly important in the world we live in, because of the rapid global population growth and climate change (drought, extreme temperature fluctuations). People in developing countries need more sustainable protein sources instead of the traditional, less sustainable meat, fish, egg, and dairy products. Alternative sources (plant-based, such as grains (wheat, rice sorghum), seeds (chia, hemp), nuts (almond, walnut), pulses (beans, lentil, pea, lupins), and leaves (duckweed), as well as mycoproteins, microalgae, and insects) can compensate for the increased demand for animal protein. In this context, our attention has been specifically focused on duckweed—which is the third most important aquatic plant after the microalgae Chlorella and Spirulina—to explore its potential for use in a variety of areas, particularly in the food industry. Duckweed has special properties: It is one of the fastest-growing plants in the world (in freshwater), multiplying its mass in two days, so it can cover a water surface quickly even in filtered sunlight (doubling its biomass in 96 hours). During this time, it converts a lot of carbon dioxide into oxygen. It is sustainable, environmentally friendly (without any pesticides), and fast growing; can be grown in indoor vertical farms and aquaculture, so it does not require land; is easy to harvest; and has a good specific protein yield. Duckweed belongs to the family Araceae, subfamily Lemnoideae, and has five genera (Lemna, Spirodela, Wolffia, Wolffiella, Landolita) containing a total of approximately 36–38 recognised species. Duckweed is gaining attention in nutrition and food sciences due to its potential as a sustainable source of protein, vitamins, minerals, and other bioactive compounds. However, there are several gaps in research specifically focused on nutrition and the bioaccessibility of its components. While some studies have analysed the variability in the nutritional composition of different duckweed species, there is a need for comprehensive research on the variability in nutrient contents across species, growth conditions, harvesting times, and geographic locations. There has been limited research on the digestibility, bioaccessibility (the proportion of nutrients that are released from the food matrix during digestion), and bioavailability (the proportion that is absorbed and utilised by the body) of nutrients in duckweed. Furthermore, more studies are needed to understand how food processing (milling, fermentation, cooking, etc.), preparation methods, and digestive physiology affect the nutritional value and bioavailability of the essential bioactive components in duckweed and in food matrices supplemented with duckweed. This could help to optimise the use of duckweed in human diets (e.g., hamburgers or pastas supplemented with duckweed) or animal feed. More research is needed on how to effectively incorporate duckweed into diverse cuisines and dietary patterns. Studies focusing on recipe development, consumer acceptance, palatability, and odour are critical. Addressing these gaps could provide valuable insights into the nutritional potential of duckweed and support its promotion as a sustainable food source, thereby contributing to food security and improved nutrition. In summary, this article covers the general knowledge of duckweed, its important nutritional values, factors that may affect their biological value, and risk factors for the human diet, while looking for technological solutions (covering traditional and novel technologies) that can be used to increase the release of the useful, health-promoting components of duckweed and, thus, their bioavailability. This article, identifying gaps in recent research, could serve as a helpful basis for related research in the future. Duckweed species with good properties could be selected by these research studies and then included in the human diet after they have been tested for food safety. Full article

Background/Objectives: Charcot first described ALS in 1869, but the specific mechanisms that mediate the disease pathology are still not clear. Intense research efforts have provided insight into unique neuroanatomical regions, specific neuronal populations and genetic associations for ALS and other neurodegenerative diseases; however, the experimental results also suggest a convergence of these events to common toxic pathways. We propose that common toxic pathways can be therapeutically targeted, and this intervention will be effective in slowing progression and improving patient quality of life. Here, we focus on understanding the role of IL6 trans-signaling in ALS disease processes. Methods: We leveraged unique mouse models of IL6 trans-signaling that we developed that recapitulate the production of active sIL6R in a genotypic and quantitative fashion observed in humans. Given that the SOD1 transgenic mouse is one of the most highly studied and characterized models of ALS, we bred SOD1^G93A mice with IL6R trans-signaling mice to determine how enhanced trans-signaling influenced symptom onset and pathological processes, including neuromuscular junction (NMJ) denervation, glial activation and motoneuron (MN) survival. Results: The results indicate that in animals with enhanced trans-signaling, symptom onset and pathological processes were accelerated, suggesting a role in disease modification. Administration of an IL6R functional blocking antibody failed to alter accelerated symptom onset and disease progression. Conclusions: Future work to investigate the site-specific influence of enhanced IL6 trans-signaling and the tissue-specific bioavailability of potential therapeutics will be necessary to identify targets for precise therapeutic interventions that may limit disease progression in the 60% of ALS patients who inherit the common IL6R Asp³⁵⁸Ala variant. Full article

Background: Amphotericin B (AmB) is a commonly utilized antifungal agent, which is also recommended for the treatment of certain neglected tropical diseases, including leishmaniasis. However, its clinical application is constrained because of its poor oral bioavailability and adverse effects, prompting the investigation of alternative drug delivery systems. Polymeric nanoparticles (PNPs) have gained attention as a potential drug delivery vehicle, providing advantages such as sustained release and enhanced bioavailability, and could have potential as AmB carriers. However, concerns persist regarding nanomaterials’ toxicity, requiring more studies. Zebrafish (Danio rerio) embryos were used as a valuable model for toxicity testing, especially because of their genetic similarity to humans and standardized developmental assessments. Methods: In this study, we produced and characterized AmB loaded and non-loaded PNPs by nanoprecipitation, dynamic light scattering, transmission electron microscopy, atomic force microscopy and spectroscopy. Afterwards, we verified their toxicity through in vitro MTT assays in three cell lines (HEK293, HepG2, and J774 A1) and in vivo tests with zebrafish embryos. Results: In both trials, it was noted that nanoencapsulation of the drug led to increased toxicity when compared to non-encapsulated AmB, possibly indicating that they penetrated the embryo’s chorion. Nevertheless, it was demonstrated that the polymers used are safe and they are not the cause of toxicity, neither are the nanostructures per se. Conclusions: Therefore, it is believed that the objective of improving the bioavailability of AmB may have been achieved, and the observed toxicity was probably linked to AmB’s ability to destabilize cell membranes. Full article

Oleogels have been a revolutionary innovation in food science in terms of their health benefits and unique structural properties. They provide a healthier alternative to traditional solid or animal fats. They have improved oxidative stability and nutritional value to maintain the desirable sensory qualities of lipid-based foods. Moreover, oleogels offer an ideal carrier for poorly water-soluble bioactive compounds. The three-dimensional structure of oleogels can protect and deliver bioactive compounds in functional food products. Bioactive compounds also affect the crystalline behavior of oleogelators, the physical properties of oleogels, and storage stability. Generally, different incorporation techniques are applied to entrap bioactive compounds in the oleogel matrix depending on their characteristics. These approaches enhance the bioavailability, controlled release, stability of bioactive compounds, and the shelf life of oleogels. The multifunctionality of oleogels extends their applications beyond fat replacements, e.g., food preservation, nutraceutical delivery, and even novel innovations like 3D food printing. Despite their potential, challenges such as large-scale production, cost efficiency, and consumer acceptance remain areas for further exploration. This review emphasizes the understanding of the relationship between the structure of oleogels and their functional properties to optimize their design in different food applications. It also highlights the latest advancements in bioactive oleogels, focusing on how they incorporate bioactive compounds such as polyphenols, essential oils, and flavonoids into oleogels. The impact of these compounds on the gelation process, storage stability, and overall functionality of oleogels is also critically examined. Full article

Cannabidiol (CBD) is one of the major phytochemical constituents of cannabis, Cannabis sativa, widely recognized for its therapeutic potential. While cannabis has been utilized for medicinal purposes since ancient times, its psychoactive and addictive properties led to its prohibition in 1937, with only the medical use being reauthorized in 1998. Unlike tetrahydrocannabinol (THC), CBD lacks psychoactive and addictive properties, yet the name that suggests its association with cannabis has significantly contributed to its public visibility. CBD exhibits diverse pharmacological properties, most notably anti-inflammatory effects. Additionally, it interacts with key drug-metabolizing enzyme families, including cytochrome P450 (CYP) and uridine 5′-diphospho-glucuronosyltransferase (UGT), which mediate phase I and phase II metabolism, respectively. By binding to these enzymes, CBD can inhibit the metabolism of co-administered drugs, which can potentially enhance their toxicity or therapeutic effects. Mild to moderate adverse events associated with CBD use have been reported. Advances in chemical formulation techniques have recently enabled strategies to minimize these effects. This review provides an overview of CBD, covering its historical background, recent clinical trials, adverse event profiles, and interactions with molecular targets such as receptors, channels, and enzymes. We particularly emphasize the mechanisms underlying its anti-inflammatory effects and interaction with drugs relevant to organ transplantation. Finally, we explore recent progress in the chemical formulation of CBD in order to enhance its bioavailability, which will enable decreasing the dose to use and increase its safety and efficacy. Full article

Curcumin, a bioactive compound derived from the rhizome of Curcuma longa L., has garnered significant attention for its potent anticancer properties. Despite its promising therapeutic potential, its poor bioavailability, rapid metabolism, and low water solubility hinder curcumin’s clinical application. Nanotechnology offers a viable solution to these challenges by enabling the development of curcumin-based nanoparticles (CNPs) that enhance its bioavailability and therapeutic efficacy. This review provides a comprehensive overview of the recent advancements in the design and synthesis of CNPs for cancer therapy. We discuss various NP formulations, including polymeric, lipid-based, and inorganic nanoparticles, highlighting their role in improving curcumin’s pharmacokinetic and pharmacodynamic profiles. The mechanisms by which CNPs exert anticancer effects, such as inducing apoptosis, inhibiting cell proliferation, and modulating signaling pathways, are explored in details. Furthermore, we examine the preclinical and clinical studies that have demonstrated the efficacy of CNPs in treating different types of tumors, including breast, colorectal, and pancreatic cancers. Finally, the review addresses the current challenges and future perspectives in the clinical translation of CNPs, emphasizing the need for further research to optimize their design for targeted delivery and to enhance their therapeutic outcomes. By synthesizing the latest research, this review underscores the potential of CNPs as a promising avenue for advancing cancer therapy. Full article

Background/objectives: The aim of the study was to create a nanofiber insert incorporating Timolol (TIM) and Dorzolamide (DOR), targeting the management of glaucoma. This condition encompasses a variety of chronic, advancing ocular disorders typically associated with elevated intraocular pressure (IOP). Methods: The insert was made of Eudragite RL100 (EUD) polymer, a biocompatible material with high bioavailability, using the electrospinning method. The inserts were studied for morphology, drug–polymer interaction, physicochemical properties, and in vitro drug-release study. The pharmacokinetic properties of fibers were examined alongside consideration for irritation using a rabbit model and cell compatibility. Results: The results of the in vitro drug-release test showed retention and controlled release of both DOR/TIM over 80 h. Morphological examination demonstrated uniform nanofibers with mean diameters < 465 nm. The cell compatibility test showed a high percentage of cell survival, and none of the formulations irritated the rabbit’s eye. The Area Under the Curve (AUC0-72) for DOR and TIM in EDT formulations was approximately 3216.63 ± 63.25 µg·h/mL and 2598.89 ± 46.65 µg·h/mL, respectively, with Mean Residence Times (MRTs) of approximately 21.6 ± 0.19 h and 16.29 ± 6.44 h. Conclusions: Based on the results, the dual drug-loaded nanofiber preservative-free system can potentially be a suitable alternative to eye drops and can be used to reduce fluctuation and dose frequency. Full article

Vitamin D, essential for growth and health, is often deficient in Taiwan despite abundant sunlight. Plant-derived vitamin D₂ (ergocalciferol) is bioavailable, environmentally friendly, and cost-effective. This study evaluated the efficacy of enhancing Pleurotus citrinopileatus (PC) mushrooms’ vitamin D₂ content through pulsed ultraviolet (PUV) light and its impact on vitamin D status in humans. In a four-week randomized parallel trial, 36 healthy participants were assigned to three groups: a control group, a group consuming 10 g/day PUV-treated PC (PC-10 g), and a group consuming 100 g/day PUV-treated PC (PC-100 g). Blood samples collected pre- and post-intervention measured serum 25(OH)D₂, 25(OH)D₃, and biochemical parameters. After four weeks, serum 25(OH)D₂ levels significantly increased in the PC-10 g group (1.47 ± 1.42 ng/mL to 9.50 ± 7.10 ng/mL, p = 0.001) and in the PC-100 g group (1.94 ± 2.15 ng/mL to 21.82 ± 16.75 ng/mL, p = 0.002), showing a 10.2-fold rise. The PC-100 g group also experienced a 37.6% reduction in serum intact parathyroid hormone (I-PTH) levels (26.26 ± 9.84 pg/mL to 16.38 ± 5.53 pg/mL). No adverse effects were reported. PUV-treated PC mushrooms significantly increase serum 25(OH)D₂ levels and reduce I-PTH, particularly at higher doses. These findings underscore the potential of vitamin-D-enriched PC as a sustainable, fungi-derived food source for addressing vitamin D deficiency. Full article