Search Results (44,637)

In vitro cartilage explant culture has been used to assess nutraceuticals on cartilage responses to inflammatory stimuli. However, applying extracts of nutraceuticals directly to cartilage explants does not account for effects of digestion and hepatic biotransformation, or selective exclusion of product metabolites from joint fluid by the synovial membrane. The current study produced a simulated biological extract of a common nutraceutical (glucosamine; G_sim) by exposing it to a simulated upper gastrointestinal tract digestion, hepatic biotransformation by liver microsomes, and purification to a molecular weight cut-off of 50 kDa. This extract was then used to condition cartilage explants cultured for 120 h in the presence or absence of an inflammatory stimulus (lipopolysaccharide). Media samples were analyzed for prostaglandin E₂ (PGE₂), glycosaminoglycan (GAG), and nitric oxide (NO). Tissue was digested and analyzed for GAG content and stained for viability. Conditioning of explants with G_sim significantly reduced media GAG in stimulated and unstimulated explants and reduced nitric oxide production in unstimulated explants. These data provide evidence for the value of glucosamine in protecting cartilage from deterioration following an inflammatory challenge, and the model improves applicability of these in vitro data to the in vivo setting. Full article

This study introduces an efficient and sustainable catalytic system utilizing cobalt ferrite nanoparticles (CoFe₂O₄-NPs) for the synthesis of valuable 6-amino-2-oxo-4-phenyl (or 4-chlorophenyl)-1,2,3,4-tetrahydropyrimidine-5-carbonitrile derivatives. Recognizing the limitations of traditional methods for the Biginelli reaction, we thoroughly characterized CoFe₂O₄-NPs, alongside individual iron oxide nanoparticles (Fe₂O₃-NPs) and cobalt oxide nanoparticles (CoO-NPs), using FTIR, XRD, TEM, SEM, XPS, TGA, and BET analysis. These characterizations revealed the unique structural, morphological, and physicochemical properties of CoFe₂O₄-NPs, including an optimized porous structure and significant bimetallic synergy between Fe and Co ions. Catalytic studies demonstrated that CoFe₂O₄-NPs significantly outperformed individual Fe₂O₃-NPs and CoO-NPs under mild conditions. While the latter only catalyzed the Knoevenagel condensation, CoFe₂O₄-NPs uniquely facilitated the complete Biginelli reaction. This superior performance is attributed to the synergistic electronic environment within CoFe₂O₄-NPs, which enhances reactant activation, intermediate stabilization, and proton transfer during the multi-step reaction. This work highlights the potential of CoFe₂O₄-NPs as highly efficient and selective nanocatalysts for synthesizing biologically relevant 1,2,3,4-tetrahydropyrimidines, offering a greener synthetic route in organic chemistry. Full article

Background/Objectives: Chronological age (CA) is commonly used in clinical decision-making, yet it may not accurately reflect biological aging. Recent advances in artificial intelligence (AI) allow estimation of electrocardiogram (ECG)-derived heart age, which may serve as a non-invasive biomarker for physiological aging. This study aimed to develop and validate a deep learning model to predict ECG-heart age in individuals with no structural heart disease. Methods: We trained a convolutional neural network (DenseNet-121) using 12-lead ECGs from 292,484 individuals (mean age: 51.4 ± 13.8 years; 42.3% male) without significant cardiac disease. Exclusion criteria included missing age data, age <18 or >90 years, and structural abnormalities. CA was used as the target variable. Model performance was evaluated using the coefficient of determination (R²), Pearson correlation coefficient (PCC), mean absolute error (MAE), and root mean square error (RMSE). External validation was conducted using 1191 independent ECGs. Results: The model demonstrated strong predictive performance (R² = 0.783, PCC = 0.885, MAE = 5.023 years, RMSE = 6.389 years). ECG-heart age tended to be overestimated in younger adults (≤30 years) and underestimated in older adults (≥70 years). External validation showed consistent performance (R² = 0.703, PCC = 0.846, MAE = 5.582 years, RMSE = 7.316 years). Conclusions: The proposed AI-based model accurately estimates ECG-heart age in individuals with structurally normal hearts. ECG-derived heart age may serve as a reliable biomarker of biological aging and support future risk stratification strategies. Full article

The growing demand for food and the environmental impact of conventional agriculture have prompted the search for sustainable alternatives. Phycocyanin (PC) and total phenolic compounds (TPC) extracted from Spirulina platensis have shown potential for the biological control of phytopathogens. The extraction method directly influences the yield and stability of these compounds. This study aimed to establish an efficient extraction protocol for PC and TPC and to evaluate their antimicrobial efficacy in vitro against Colletotrichum orchidearum, Fusarium nirenbergiae, and Alternaria sp. isolated from hydroponically grown lettuce. The phytopathogens were identified based on phylogenetic analyses using sequences from the ITS, EF1-α, GAPDH, and RPB2 gene regions. This is the first report of C. orchidearum in hydroponic lettuce culture in Brazil, expanding its known host range. Extracts were obtained using hydroalcoholic solvents and phosphate buffer (PB), combined with ultrasound-assisted extraction (bath and probe). The extracts were tested for in vitro antifungal activity. Data were analyzed by ANOVA (p < 0.05), followed by Tukey’s test. The combination of the PB and ultrasound probe resulted in the highest PC (95.6 mg·g⁻¹ biomass) and TPC (21.9 mg GAE·g⁻¹) yields, using 10% (w/v) biomass. After UV sterilization, the extract retained its PC and TPC content. The extract inhibited C. orchidearum by up to 53.52% after three days and F. nirenbergiae by 54.17% on the first day. However, it promoted the growth of Alternaria sp. These findings indicate that S. platensis extracts are a promising alternative for the biological control of C. orchidearum and F. nirenbergiae in hydroponic systems. Full article

Black gay and bisexual older men face numerous barriers across the life course that can contribute to negative health and well-being as they age. Drawing on strengths-based social determinants discussed in the health literature and literature on intersectionality, justice, and critical consciousness, this study examines qualitative data from seventeen Black gay and bisexual older men about sources and strategies of resilience and thriving amidst intersecting systems of power and oppression that shape health inequities. The findings revealed an evolution of positive support networks across their life courses, including biological family and families of choice such as “houses” and support groups. Early and ongoing negative experiences relating to intersecting positionalities (e.g., race, gender, sexual orientation) also provided sources of strength and resilience. Participants identified three strategies for building resilience and thriving: naming external ignorance, acknowledging common struggles, and reconciling contradictions. These strategies reflected various levels of critical consciousness that helped them navigate complex and intersecting systems of power that they encountered as Black gay men across the life course. Overall, the findings underscore the importance of considering intersecting systems of power and critical consciousness when examining resilience and social determinants of health and contribute new insights on a vastly understudied population. Full article

Essential oils (EOs) constitute intricate mixtures of volatile phytochemicals that have garnered significant attention due to their multifaceted biological effects. Notably, the presence of bioactive constituents capable of inhibiting tyrosinase enzyme activity and scavenging reactive oxygen species (ROS) underpins their potential utility in skin-related applications, particularly through the modulation of melanin biosynthesis and protection of skin-relevant cells from oxidative damage—a primary contributor to hyperpigmentation disorders. Zingiber officinale Rosc. (ginger) and Humulus lupulus L. (hop) are medicinal plants widely recognized for their diverse pharmacological properties. To the best of our knowledge, this study provides the first report on the synergistic interactions between essential oils derived from these species (referred to as EOZ and EOH) offering novel insights into their combined bioactivity. The purpose of this study was to evaluate essential oils extracted from ginger rhizomes and hop strobiles with respect to the following: (1) chemical composition, determined by gas chromatography–mass spectrometry (GC-MS); (2) tyrosinase inhibitory activity; (3) capacity to inhibit linoleic acid peroxidation; (4) ABTS^•+ radical scavenging potential. Furthermore, the study utilizes both the combination index (CI) and dose reduction index (DRI) as quantitative parameters to evaluate the nature of interactions and the dose-sparing efficacy of essential oil (EO) combinations. GC–MS analysis identified EOZ as a zingiberene-rich chemotype, containing abundant sesquiterpene hydrocarbons such as α-zingiberene, β-bisabolene, and α-curcumene, while EOH exhibited a caryophyllene diol/cubenol-type profile, dominated by oxygenated sesquiterpenes including β-caryophyllene-9,10-diol and 1-epi-cubenol. In vitro tests demonstrated that both oils, individually and in combination, showed notable anti-tyrosinase, radical scavenging, and lipid peroxidation inhibitory effects. These results support their multifunctional bioactivity profiles with possible relevance to skin care formulations, warranting further investigation. Full article

Background: Local anesthesia is essential for most dental procedures, but its parenteral administration is often painful. Topical anesthetics are commonly used to minimize local anesthesia pain; however, commercial formulations fail to fully prevent the discomfort of local anesthetic injection. Methods: We developed and characterized a novel lidocaine and epinephrine co-loaded liquid crystalline precursor system (LCPS) for topical anesthesia. The formulation was structurally characterized using polarized light microscopy (PLM) and small-angle X-ray scattering (SAXS). Rheological behavior was assessed through continuous and oscillatory rheological analyses. Texture profile analysis, in vitro mucoadhesive force evaluation, in vitro drug release and permeation studies, and an in vivo toxicity assay using the chicken chorioallantoic membrane (CAM) model were also conducted. Results: PLM and SAXS confirmed the transition of the LCPS from a microemulsion to a lamellar liquid crystalline structure upon contact with artificial saliva. This transition enhanced formulation consistency by over 100 times and tripled mucoadhesion strength. The LCPS also provided controlled drug release, reducing permeation flow by 93% compared to the commercial formulation. Importantly, the CAM assay indicated that the LCPS exhibited similar toxicity to the commercial product. Conclusions: The developed LCPS demonstrated promising physicochemical and biological properties for topical anesthesia, including enhanced mucoadhesion, controlled drug delivery, and acceptable biocompatibility. These findings support its potential for in vivo application and future clinical use to reduce pain during dental anesthesia procedures. Full article

Protein enzymes are highly efficient catalysts that exhibit adaptability and selectivity under diverse biological conditions. In some organisms, such as bacteria, structurally similar enzymes, for instance, shikimate kinase (SK) and adenylate kinase (AK), coexist and act on chemically related ligands. This raises the question of whether these enzymes can accommodate and potentially react with each other’s ligands. In this study, we investigate the stability of non-cognate ligand binding in SK and explore whether external electric fields (EFs) can modulate this interaction, leading to cross-reactivity in SK. Using molecular dynamics simulations, we assess the structural integrity of SK and the binding behavior of ATP and AMP under EF-off and EF-on cases. Our results show that EFs enhance protein structure stability, stabilize non-cognate ligands in the binding pocket, and reduce local energetic frustration near the R116 residue located in the binding site. In addition to this, dimensionality reduction analyses reveal that EFs induce more coherent protein motions and reduce the number of metastable states. Together, these findings suggest that external EFs can reshape enzyme–ligand interactions and may serve as a tool to modulate enzymatic specificity and functional promiscuity. Thus, we provide computational evidence that supports the concept of using an EF as a tunable parameter in enzyme engineering and synthetic biology. However, further experimental investigation would be valuable to assess the reliability of our computational predictions. Full article

Macrophages are undoubtedly one of the most widely studied cells of the immune system, among other reasons, because they are involved in a wide variety of biological processes. Deregulation of their activity is observed in a number of different disorders, including autoimmune diseases. At the same time, mammalian target of rapamycin (mTOR) is attracting increasing research attention because the pathways dependent on this kinase are activated by a variety of signals, including cytokines and proinflammatory mediators, mediate essential processes for cell survival and metabolism, and can be regulated epigenetically via microRNAs. Therefore, our narrative review aimed to summarize and discuss recent advances in the knowledge of the activation of mTOR signaling in macrophages, with a special focus on autoimmune disorders and the possibility of mTOR control by microRNAs. The summarized research observations allowed us to conclude that the effects of activity and/or inhibition of individual mTOR complexes in macrophages are largely context dependent, and therefore, these broad immunological contexts and other specific conditions should always be taken into account when attempting to modulate these pathways for therapeutic purposes. Full article

Background and Clinical Significance: Hemophilia A presents a considerable challenge in cardiac surgery due to the elevated risk of perioperative bleeding, particularly during procedures involving cardiopulmonary bypass. Standard management typically involves standard half-life (SHL) factor VIII (FVIII) concentrates, which require frequent dosing. Extended half-life (EHL) FVIII products offer theoretical advantages, including prolonged action and reduced infusion frequency, but their use in cardiac surgery remains largely undocumented. Case Presentation: We report the case of a 73-year-old male with mild Hemophilia A who underwent successful aortic valve replacement using a 25 mm Carpentier-Edwards Magna Ease biological prosthesis. The patient was managed perioperatively with an anti-hemorrhagic protocol based on EHL recombinant FVIII. The surgery and postoperative course were uneventful, with no bleeding complications or need for transfusion. Conclusions: This case illustrates the potential role of EHL FVIII in safely managing hemophilic patients undergoing major cardiac surgery. Given the lack of existing reports in the literature, further studies are warranted to evaluate the efficacy and safety of EHL FVIII in this setting and to potentially optimize perioperative care protocols for this patient population. Full article

Serial block-face scanning electron microscopy (SBEM) is a powerful technique for three-dimensional ultrastructural analysis of biological samples, though its application to in vitro cultured human cells remains underutilized. In this study, we present an optimized SBEM sample preparation protocol using human dermal fibroblasts and induced pluripotent stem cells (iPSCs). The method includes key modifications to the original protocol, such as using only glutaraldehyde for fixation and substituting the toxic cacodylate buffer with a less hazardous phosphate buffer. These adaptations result in excellent preservation of cellular ultrastructure, with high contrast and clarity, as validated by transmission electron microscopy (TEM). The loss of natural cell morphology resulted from fixation during passage, when cells formed a precipitate, rather than from fixation directly within the culture medium. The protocol is time-efficient, safe, and broadly applicable to both stem cells and differentiated cells cultured under 2D conditions, providing a valuable tool for ultrastructural analysis in diverse biomedical research settings. Full article

Alkyd resins are among the most common coatings used for exterior wood joinery. In Romania, solvent-borne alkyd coatings are widely used to finish wood. The study aims to compare the performance after 7 years of outdoor exposure of two types of alkyd coatings, a semi-transparent brown stain with micronized pigments (Alk1) and an opaque white enamel (Alk2), applied directly on wood or wood pre-treated with three types of resins: acryl-polyurethane (R1), epoxy (R2), and alkyd-polyurethane (R3). Fir (Abies alba) wood served as the substrate. Cracking, coating adhesion, and biological degradation were periodically assessed through visual inspection and microscopy. Additionally, a cross-cut test was performed, and the loss of coating on the directly exposed upper faces was measured using ImageJ. The results indicated that resin pretreatments somewhat reduced cracking but negatively affected coating adhesion after long-term exposure. All samples pretreated with resins and coated with Alk1 lost more than 50% (up to 78%) of the original finishing film by the end of the test. In comparison, coated control samples lost less than 50%. The Alk2 coating exhibited a film loss between 2% and 12%, compared to an average loss of 9% for the coated control. Overall, samples pretreated with alkyd-polyurethane resin (R3) and coated with alkyd enamel (Alk2) demonstrated the best performance in terms of cracking, adhesion, and discoloration. Full article

The large number of underutilized tree residues in Japan is a matter of concern, and their appropriate application needs to be promoted. Trees are very diverse, and there are differences in the volatile essential oil compounds and biological activities among different tree species. However, the effects of these tree species’ characteristics on human sensitivity and mental and physical functionality remain underexplored. This study investigated the effects of essential oils from multiple tree species on subjective and physiological responses. The essential oils from nine tree species were tested, subjective scent assessments were conducted, and their effect on autonomic nervous activity was measured. The volatile profiles of the oils were analyzed using gas chromatography–mass spectrometry. Our findings revealed clear differences in the composition of volatile essential oils among species, which influenced the scent evaluation and individual preferences. We suggest that scent preferences have the potential to influence physiological responses. The findings indicate that volatile essential oils could play a potential role in making use of tree resources effectively, and they may also be beneficial for maintaining human health. Full article

The small-spotted catshark and the smooth-hound are cartilaginous, carnivorous fish with similar depth ranges in their habitats. These two species are among the most abundant elasmobranchs in the Adriatic Sea and are frequently caught by local fishermen using longline fishing. Despite their ecological similarities, little is known about the physiological differences in their digestive processes. The study of enzymatic digestion in these ecologically relevant species helps to fill the knowledge gap in the understanding of nutrient processing in cartilaginous fish. Therefore, the aim of this study was to determine, measure and compare the enzymatic activity of alkaline phosphatase, acid phosphatase, non-specific esterase and aminopeptidase. Fish were caught in the central part of the Adriatic Sea between 2021 and 2023. A total of 60 adult individuals were analyzed, with samples taken from six parts of the digestive tract. Histochemical analysis of 1440 slides revealed clear differences in enzyme activity between the two species. In the small-spotted catshark, cellular protein degradation was most pronounced in esophagus, posterior stomach and rectum, whereas in the smooth-hound, it was concentrated in posterior stomach and spiral intestine. Cellular digestion of lipids in the small-spotted catshark appears to occur primarily in the stomach. The results of this study provide new insights into the distribution of cellular digestive enzymes in cartilaginous fish and emphasize the importance of studying the entire digestive tract as an integrated system rather than focusing on individual parts. This study fills an important knowledge gap and contributes to a deeper understanding of digestive physiology, which in turn has implications for species conservation and biological variability. Full article

Corn is one of the most consumed cereals in the Mexican diet. In this country, there are multiple varieties that exhibit nutraceutical potential due to their content of different metabolites with biological activity, such as blue corn. Another variety that has received little study is the red pigmented corn variety Chilac from Puebla, Mexico, which is being studied for its nutraceutical potential. A differential extraction using the Soxhlet method was carried out to evaluate the phenolic content, total flavonoid content, and monomeric anthocyanins, and free radical scavenging test was performed using the DPPH reagent. A proximate analysis was also conducted to identify the main macronutrients. The results of the proximate analysis were comparable to those of other traditional corn varieties, with carbohydrates being the macronutrient present in the highest amount at 77.9%. Regarding phenolic content and the presence of anthocyanins, the best extractions were obtained using alcoholic solvents; for example, ethanol for phenols, yielding 1368.420 ± 104.094 mg of gallic acid equivalents (GAE)/kg plant. In contrast, the flavonoid content was higher in the aqueous extract, with 833.984 ± 65.218 mg QE/Kg. In the case of the DPPH assay, the best result was obtained with ethyl acetate (73.81 ± 5.31%). These findings provide a foundation for expanding the use of corn varieties with nutraceutical potential, opening the possibility of studies focused on deeper characterization. Full article