Search Results (298,120)

Background and Objectives: Polydeoxyribonucleotides (PDRN), composed of DNA fragments derived from salmon DNA, is widely recognized for its regenerative properties. It has been extensively used in medical applications, such as dermatology and wound healing, due to its ability to enhance cellular metabolic activity, stimulate angiogenesis, and promote tissue regeneration. In the field of dentistry, PDRN has shown potential in promoting periodontal healing and bone regeneration. This study aims to investigate the effects of PDRN on the morphology, survival, and osteogenic differentiation of gingiva-derived stem cell spheroids, with a focus on its potential applications in tissue engineering and regenerative dentistry. Materials and Methods: Gingiva-derived mesenchymal stem cells were cultured and formed into spheroids using microwells. The cells were treated with varying concentrations of PDRN (0, 25, 50, 75, and 100 μg/mL) and cultivated in osteogenic media. Cell morphology was observed over seven days using an inverted microscope, and viability was assessed with Live/Dead Kit assays and Cell Counting Kit-8. Osteogenic differentiation was evaluated by measuring alkaline phosphatase activity and calcium deposition. The expression levels of osteogenic markers RUNX2 and COL1A1 were quantified using real-time polymerase chain reaction. RNA sequencing was performed to assess the gene expression profiles related to osteogenesis. Results: The results demonstrated that PDRN treatment had no significant effect on spheroid diameter or cellular viability during the observation period. However, a PDRN concentration of 75 μg/mL significantly enhanced calcium deposition by Day 14, suggesting increased mineralization. RUNX2 and COL1A1 mRNA expression levels varied with PDRN concentration, with the highest RUNX2 expression observed at 25 μg/mL and the highest COL1A1 expression at 75 μg/mL. RNA sequencing further confirmed the upregulation of genes involved in osteogenic differentiation, with enhanced expression of RUNX2 and COL1A1 in PDRN-treated gingiva-derived stem cell spheroids. Conclusions: In summary, PDRN did not significantly affect the viability or morphology of gingiva-derived stem cell spheroids but influenced their osteogenic differentiation and mineralization in a concentration-dependent manner. These findings suggest that PDRN may play a role in promoting osteogenic processes in tissue engineering and regenerative dentistry applications, with specific effects observed at different concentrations. Full article

As a component of circulating lipoproteins, APOE binds to cell surface receptors mediating lipoprotein metabolism and cholesterol transport. A growing body of evidence, including the identification of a broad variety of cellular proteins interacting with APOE, suggests additional independent functions. Investigating cellular localization and protein–protein interactions in cultured human hepatocytes, we aimed to contribute to the elucidation of hitherto unnoted cellular functions of APOE. We observed a strong accumulation of APOE in MAMs, equally evident for the two major isoforms APOE3 and APOE4. Using mass spectrometry proteome analyses, novel and previously noted APOE interactors were identified, including the mitochondrial proteins TOMM40, LONP1 and VDAC1. All three interactors were present in MAM fractions, which we think initially facilitates interactions with APOE. LONP1 is a protease with chaperone activity, which migrated to MAMs in response to ER stress, displaying a reinforced interaction with APOE. We therefore hypothesize that APOE may help in the unfolded protein response (UPR) by acting as a co-chaperone in cooperation with LONP1 at the interface of mitochondria and ER membranes. The interaction of APOE with the integral proteins TOMM40 and VDAC1 may point to the formation of bridging complexes connecting mitochondria with other organelles. Full article

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a major complication of rheumatoid arthritis (RA), but effective treatment remains an unmet need in its management. Our aim was to evaluate the therapeutic efficacy of abatacept for RA-ILD. Methods: This observational retrospective study included patients with RA-ILD treated with abatacept between 2012 and 2021. Indices of RA disease activity and interstitial lung disease (Disease Activity Score in 28 joints using C-reactive Protein [DAS28-CRP], Simplified Disease Activity Index [SDAI], Clinical Disease Activity Index [CDAI], serum Krebs von den Lungen-6 levels, % forced vital capacity [%FVC], and semi-quantified chest high-resolution computed tomography scores) were evaluated before and 1 year after the start of abatacept administration. Results: Overall, 38 patients were included. DAS28-CRP, SDAI, and CDAI were significantly improved (all with p < 0.0001). Total ground-glass opacity scores were decreased in both patients with usual interstitial pneumonia (UIP)-like patterns and with non-UIP-like patterns (p = 0.008 and <0.002, respectively). Total fibrosis scores were also decreased in the UIP-like pattern group (p < 0.042). The %FVC remained stable. Conclusions: Abatacept significantly improves RA disease activity and reduces pulmonary inflammation in patients with RA-ILD. Full article

Atherosclerosis is initiated by injury or damage to the vascular endothelial cell monolayer. Therefore, the early repair of the damaged vascular endothelium by a proliferation of neighbouring endothelial cells is important to prevent atherosclerosis and thrombotic events. Arthrospira platensis (AP) has been used as a dietary supplement, mainly due to its high content of vitamins, minerals, amino acids, and pigments such as chlorophylls, carotenoids, and phycocyanin, ingredients with antioxidant, anti-inflammatory, and anti-thrombotic properties. Therefore, in this prospective, placebo-controlled, data-driven, sample-size-estimated in vitro study, we tested whether an aqueous extract of AP at different concentrations (50, 100, and 200 µg/mL) had an effect on the different cellular parameters of human umbilical vein endothelial cells. Therefore, cell impedance measurement and cell proliferation were measured to investigate the monolayer formation. In addition, cell viability, integrity, and metabolism were analysed to evaluate singular cellular functions, especially the antithrombotic state. Furthermore, cell–cell and cell–substrate interactions were observed. The highest proliferation was achieved after the addition of 100 µg/mL. This was consistently confirmed by two independent optical experiments in cell cultures 48 h and 85 h after seeding and additionally by an indirect test. At this concentration, the activation or dysfunction of HUVECs was completely prevented, as confirmed by prostacyclin and interleukin-6 levels. In conclusion, in this study, AP induced a significant increase in HUVEC proliferation without inducing an inflammatory response but altered the hemostasiological balance in favour of prostacyclin over thromboxane, thereby creating an antithrombotic state. Thus, APE could be applied in the future as an accelerator of endothelial cell proliferation after, e.g., stent placement or atherosclerosis. Full article

Background: One defining feature of various aggressive cancers, including glioblastoma multiforme (GBM), is glycolysis upregulation, making its inhibition a promising therapeutic approach. One promising compound is 2-deoxy-d-glucose (2-DG), a d-glucose analog with high clinical potential due to its ability to inhibit glycolysis. Upon uptake, 2-DG is phosphorylated by hexokinase to 2-DG-6-phosphate, which inhibits hexokinase and downstream glycolytic enzymes. Unfortunately, therapeutic use of 2-DG is limited by poor pharmacokinetics, suppressing its efficacy. Methods: To address these issues, we synthesized novel halogenated 2-DG analogs (2-FG, 2,2-diFG, 2-CG, and 2-BG) and evaluated their glycolytic inhibition in GBM cells. Our in vitro and computational studies suggest that these derivatives modulate hexokinase activity differently. Results: Fluorinated compounds show the most potent cytotoxic effects, indicated by the lowest IC₅₀ values. These effects were more pronounced in hypoxic conditions. ¹⁹F NMR experiments and molecular docking confirmed that fluorinated derivatives bind hexokinase comparably to glucose. Enzymatic assays demonstrated that all halogenated derivatives are more effective HKII inhibitors than 2-DG, particularly through their 6-phosphates. By modifying the C-2 position with halogens, these compounds may overcome the poor pharmacokinetics of 2-DG. The modifications seem to enhance the stability and uptake of the compounds, making them effective at lower doses and over prolonged periods. Conclusions: This research has the potential to reshape the treatment landscape for GBM and possibly other cancers by offering a more targeted, effective, and metabolically focused therapeutic approach. The application of halogenated 2-DG analogs represents a promising advancement in cancer metabolism-targeted therapies, with the potential to overcome current treatment limitations. Full article

Background/Objectives: Digital health applications (DHAs) promise to improve disease self-management, but adherence remains suboptimal. We aimed to explore self-monitoring practices of rheumatic and musculoskeletal diseases (RMD) patients. A web-survey was conducted over 7 months including RMD patients to study their self-monitoring practices and the potential of DHAs. Methods: Health, sociodemographic, and technology adherence indicators were retrieved for comparison. Regression analyses and unsupervised profiling were performed to investigate multiple patient profiles. Results: From 228 responses gathered, most reported willingness to use DHAs to monitor their condition (78% agreement), although the majority rarely/never tracked symptoms (64%), often due to stable condition or no perceived value (62%). Of those tracking regularly, 52% used non-digital means. Participants with regular self-monitoring practices were more open to use a self-monitoring app (OR = 0.8 [0.6, 0.9]; p = 0.008) and be embedded in multidisciplinary care (OR = 1.4 [1.1, 1.6]; p < 0.001), but showed worse health status (g = 0.4; p = 0.006). Cluster analyses revealed three distinct groups of reasons for not tracking regularly (χ2 = 174.4; p < 0.001), two characterised by perceived low disease activity. Conclusions: Effective use of DHAs remains limited and non-digital means prevail in symptom monitoring. Findings suggest that better patient engagement strategies and passive monitoring should be adopted in early development stages of DHAs for better long-term disease self-care. Full article

In northwest China, changes in cultivation patterns and the scarcity of preferred hosts have forced Helicoverpa armigera to feed on the marginal host walnut (Juglans regia). However, the mechanisms allowing this adaptation remain poorly understood. Here, we investigated the behavioral, physiological, and molecular mechanisms underlying the local adaptation of this pest to walnut fruits. The green husk and shell generally contained higher levels of phytochemicals than the kernel. Bioassays revealed that the phytochemical-rich green husk and shell were less preferred, reduced larval fitness and growth, and elevated the activity of detoxification enzymes compared to the nutrient-rich kernel, which were further supported by a larger number of upregulated detoxification genes in insects fed green husks or shells based on transcriptome sequencing. Together, these data suggest that P450 genes (LOC110371778) may be crucial to H. armigera adaptation to the phytochemicals of walnuts. Our findings provide significant insight into the adaptation of H. armigera to walnut, an alternative host of lower quality. Meanwhile, our study provides a theoretical basis for managing resistance to H. armigera larvae in walnut trees and is instrumental in developing comprehensive integrated pest management strategies for this pest in walnut orchards and other agricultural systems. Full article

Introduction: Overactive bladder (OAB) is a syndrome of the lower urinary tract characterized by urinary urgency, frequency, and nocturia, with or without urgency urinary incontinence. OAB significantly impacts all aspects of life—social, psychological, physical, professional, domestic, and sexual—for both women and men. The aim of this study was to investigate sexual dysfunction in both women and men with OAB treated with intravesical onabotulinumtoxinA (Botox) injections using the Sexual Quality of Life questionnaire in two versions: female (SQoL-F) and male (SQoL-M). Methods: Forty sexually active patients (thirty women and ten men) with idiopathic OAB were recruited. Patients completed the SQoL-F or SQoL-M questionnaire before treatment, and again at 3 and 6 months after treatment with intravesical onabotulinumtoxinA injections. Results: All 40 patients completed the study (30 women and 10 men). There were no statistically significant differences in SQoL results before the procedure or at 3- and 6-months post-treatment. Conclusions: OAB treatment with onabotulinumtoxinA did not significantly affect the quality of sexual life in either women or men. Further research is needed using questionnaires specifically designed to assess the sexual life of patients with OAB, especially in men. Full article

Photodynamic therapy (PDT) is a medical treatment that utilizes photosensitizing agents, along with light, to produce reactive oxygen species that can kill nearby cells. When the photosensitizer is exposed to a specific wavelength of light, it becomes activated and generates reactive oxygen that can destroy cancer cells, bacteria, and other pathogenic micro-organisms. PDT is commonly used in dermatology for treating actinic keratosis, basal cell carcinoma, and other skin conditions. It is also being explored for applications in oncology, such as treating esophageal and lung cancers, as well as in ophthalmology for age-related macular degeneration. In this study, we provide a comprehensive review of PDT, covering its fundamental principles and mechanisms, as well as the critical components for its function. We examine key aspects of PDT, including its current clinical applications and potential future developments. Additionally, we discuss the advantages and disadvantages of PDT, addressing the various challenges associated with its implementation and optimization. This review aims to offer a thorough understanding of PDT, highlighting its transformative potential in medical treatments while acknowledging the areas requiring further research and development. Full article

Ageratum conyzoides L. is native to Tropical America, and it has naturalized in many other tropical, subtropical, and temperate countries in South America, Central and Southern Africa, South and East Asia, Eastern Austria, and Europe. The population of the species has increased dramatically as an invasive alien species, and it causes significant problems in agriculture and natural ecosystems. The life history traits of Ageratum conyzoides, such as its short life cycle, early reproductive maturity, prolific seed production, and high adaptive ability to various environmental conditions, may contribute to its naturalization and increasing population. Possible evidence of the molecules involved in the defense of Ageratum conyzoides against its natural enemies, such as herbivore insects and fungal pathogens, and the allelochemicals involved in its competitive ability against neighboring plant species has been accumulated in the literature. The volatiles, essential oils, extracts, residues, and/or rhizosphere soil of Ageratum conyzoides show insecticidal, fungicidal, nematocidal, and allelopathic activity. The pyrrolizidine alkaloids lycopsamine and echinatine, found in the species, are highly toxic and show insecticidal activity. Benzopyran derivatives precocenes I and II show inhibitory activity against insect juvenile hormone biosynthesis and trichothecene mycotoxin biosynthesis. A mixture of volatiles emitted from Ageratum conyzoides, such as β-caryophyllene, β-bisabolene, and β-farnesene, may work as herbivore-induced plant volatiles, which are involved in the indirect defense function against herbivore insects. Flavonoids, such as nobiletin, eupalestin, 5′-methoxynobiletin, 5,6,7,3′,4′,5′-hexamethoxyflavone, and 5,6,8,3,4′,5′-hexamethoxyflavone, show inhibitory activity against the spore germination of pathogenic fungi. The benzoic acid and cinnamic acid derivatives found in the species, such as protocatechuic acid, gallic acid, p-coumaric acid, p-hydroxybenzoic acid, and ferulic acid, may act as allelopathic agents, causing the germination and growth inhibition of competitive plant species. These molecules produced by Ageratum conyzoides may act as defense molecules against its natural enemies and as allelochemicals against neighboring plant species, and they may contribute to the naturalization of the increasing population of Ageratum conyzoides in new habitats as an invasive plant species. This article presents the first review focusing on the defense function and allelopathy of Ageratum conyzoides. Full article

Wild boar (Sus scrofa) populations are increasing worldwide, leading to health, economic and conservation issues. Assessing genetic structure and diversity can aid in the effective monitoring and management of wild boar populations. Processes related to sexual selection and behavioral differences between sexes support the importance of considering sex in measuring genetic diversity. In this study, we investigated the genetic diversity of wild boar in southwestern Spain by comparing multilocus heterozygosity (MLH) in males and females. We collected tissue samples from 142 culled individuals and 146 fetuses during routine hunting activities and used 16 microsatellite markers to quantify MLH. Paternity analyses were conducted to infer the genotypes of reproductive males. Our results indicated that the sampled individuals constituted a unique polygynandrous population without clear genetic structure. We found that males tended to exhibit lower MLH than females, with reproductive males showing significantly lower MLH than females. We discuss the selection and demographic processes that might explain our results. We highlight the importance of sex-balanced culling for population control, as well as the use of sex-balanced samples for monitoring genetic diversities. Full article

Climate change is one of the trending terms in the world nowadays due to its profound impact on human health and activity. Extreme drought events and desertification are some of the results of climate change. This study utilized the power of AI tools by using the long short-term memory (LSTM) model to predict the drought index for Anbar Province, Iraq. The data from the standardized precipitation evapotranspiration index (SPEI) for 118 years have been used for the current study. The proposed model employed seven different optimizers to enhance the prediction performance. Based on different performance indicators, the results show that the RMSprop and Adamax optimizers achieved the highest accuracy (90.93% and 90.61%, respectively). Additionally, the models forecasted the next 40 years of the SPEI for the study area, where all the models showed an upward trend in the SPEI. In contrast, the best models expected no increase in the severity of drought. This research highlights the vital role of machine learning models and remote sensing in drought forecasting and the significance of these applications by providing accurate climate data for better water resources management, especially in arid regions like that of Anbar province. Full article

The current research is focused on the discovery and optimization of an effective cosmetic carrier of alpha-bisabolol as a first step in the development of a cosmetic product with cleansing and antimicrobial action for facial skin hygiene. A micellar solution of Poloxamer 407 was selected as a cosmetic base because of the good washing ability, easy application, and high tolerability of this polymeric surfactant. The solubilization capacity of a 5% micellar solution with respect to α-bisabolol was investigated by applying varying solubilization techniques and increasing concentrations of the oily active substance. The test samples were subjected to an accelerated physical stability test, viscosimetry, dynamic light scattering (DLS), electrophoretic light scattering (ELS), foamability test, and antimicrobial screening. Over the course of this research, the advantage of the film-hydration method over direct solubilization was demonstrated by the narrower size distribution and smaller hydrodynamic size of the micellar nano-carriers (ranging from 29.02 to 116.5 nm) and the respective higher physical stability of the dispersions. The optimized composition was found to be suitable for application on large skin areas in terms of viscosity in the temperature range from 20 °C to 40 °C (3.4–2.3 mPa.s). Preservation of the washing capacity of the micellar solution in the presence of solubilized α-bisabolol was established. The active composition demonstrated inhibitory activity against Staphylococcus aureus and Escherichia coli and fungicidal activity against Candida albicans. This study concludes that the optimal concentration of α-bisabolol to be solubilized in a 5% Poloxamer 407 micellar solution by the film-hydration technique is 1%, considering the desirable physical endurance and antimicrobial activity. Full article

In this work, a new methodology is proposed for the online and non-invasive extraction of partial discharge (PD) pulses from raw measurement data obtained using a simplified setup. This method enables the creation of sub-windows with optimized size, each containing a single candidate PD pulse. The proposed approach integrates mathematical morphological filtering (MMF) with kurtosis, a first-order Savitzky-Golay smoothing filter, the Otsu method for thresholding, and a specific technique to associate each sub-window with the phase angle of the applied voltage waveform, enabling the construction of phase-resolved PD (PRPD) patterns. The methodology was validated against a commercial PD detection device adhering to the IEC (International Electrotechnical Commission) standard. Experimental results demonstrated that the proposed method, utilizing an off-the-shelf 8-bit resolution data acquisition system and a low-cost high-frequency current transformer (HFCT) sensor, effectively diagnoses and characterizes PD activity in high-voltage equipment, such as surge arresters and instrument transformers, even in noisy environments. It was able to characterize PD activity using only a few cycles of the applied voltage waveform and identify low amplitude PD pulses with low signal-to-noise ratio signals. Other contribution of this work is the diagnosis and fault signature obtained from a real surge arrester (SA) with a nominal voltage of 192 kV, corroborated by destructive disassembly and internal inspection of the tested equipment. This work provides a cost-effective and accurate tool for real-time PD monitoring, which can be embedded in hardware for continuous evaluation of electrical equipment integrity. Full article

In this study, we propose a method for assessing the temporal and spatial distribution of Carcharhinus melanopterus in shallow waters using unmanned aerial vehicles (UAVs). Aerial surveys were conducted in Tien Og Bay (Koh Tao, Thailand) thrice daily (morning, afternoon, evening) along a 360 m transect at a 30 m altitude. Environmental factors, including cloudiness, sea conditions, wind, tide, and anthropogenic disturbance, were recorded for each time slot. We developed a Python/AppleScript application to facilitate individual counting, correlating sightings with GPS data and measuring pixel-based length. Abundance varied significantly across time slots (p < 0.001), with a strong morning preference, and was influenced by tide (p = 0.040), favoring low tide. Additionally, abundance related to anthropogenic disturbance (p = 0.048), being higher when anthropogenic activity was absent. Spatial distribution analysis indicated time-related, sector-based abundance differences (p < 0.001). Pixel-based length was converted to Total Length, identifying juveniles. They exhibited a strong sector preference (p < 0.001) irrespective of the time of day. Juvenile abundance remained relatively stable throughout the day, constituting 94.1% of afternoon observations. Between 2020 and 2022, an underwater video survey was conducted to determine the sex ratio of the individuals. Only females and juveniles were sighted in the bay. Full article