Search Results (822)

Gamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters with beneficial effects including sedative properties. However, despite various clinical trials, scientific evidence regarding the impact on sleep of orally ingested GABA, whether natural or synthesized through biological pathways, is not clear. GABALAGEN (GBL) is the product of fermented collagen by Lactobacillus brevis BJ20 (L. brevis BJ20) and Lactobacillus plantarum BJ21 (L. plantarum BJ21), enriched with GABA and characterized by low molecular weight. The aim of this study was to investigate the effect of GBL on sleep improvement via a receptor binding assay in a pentobarbital-induced sleep-related rat model. We utilized a pentobarbital-induced sleep-related rat model to conduct this research. The present study investigated the sedative effects of GBL through electroencephalography (EEG) analysis in the pentobarbital-induced sleep animal model. Exploration of the neural basis of these positive effects involved evaluating orexin in the brain via immunohistochemical methods and 5-HT in the serum using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we conducted a binding assay for 5-HT_2C receptors, as these are considered pivotal targets in the mechanism of action for sleep aids. Diazepam (DZP) was used as a positive control to compare the efficacy of GBL. Results: In the binding assay, GBL displayed binding affinity to the 5-HT_2C receptor (IC50 value, 5.911 µg/mL). Administration of a low dose of GBL (GBL_L; 100 mg/kg) increased non-rapid eye movement sleep time and decreased wake time based on EEG data in pentobarbital-induced rats. Administration of a high dose of GBL (GBL_H; 250 mg/kg) increased non-rapid eye movement sleep time. Additionally, GBL groups significantly increased concentration of the 5-HT level in the serum. GBL_H decreased orexin expression in the lateral hypothalamus. Conclusion: Overall, the sedative effect of GBL may be linked to the activation of serotonergic systems, as indicated by the heightened affinity of the 5-HT_2C receptor binding and elevated levels of 5-HT observed in the serum. This suggests that GBL holds promise as a novel compound for inducing sleep in natural products. Full article

Hydrokinetic tidal energy is one of the few marine renewable energy resources with sufficiently mature technology for commercial exploitation. However, several parameters affect its exploitability, such as the minimum speed threshold, ambient turbulence levels, or tidal asymmetry, to name but a few. These parameters are particularly important in regions with lower mean speeds than those in first-generation sites, such as the North Sea. The Gulf of California is one of those regions. In this paper, a Delft3D Flexible Mesh Suite (Delft3D FM) model in barotropic configuration is set up over the Gulf of California using a flexible mesh with resolution varying from O (500 m) in the deep regions to O (10 m) in the coastal regions. A simulation is run over the year of 2020, with a tidal forcing of 75 components. The model is validated at four tidal gauge locations and four Acoustic Doppler Current profiler (ADCP) locations. The speed, U, and tidal power density (TPD) indicators used for the validation were the annual means, the annual means for speeds above the 0.5 m s⁻¹ threshold, the annual means of the spring tide maxima, and the annual maxima. The contour maps of the annual means, that is, the annual means for speeds above the 0.5 m s⁻¹ threshold, allow us to identify tidal energy hot spots throughout the Gulf of California, particularly in the Great Island region (GIR). In this region, these hot spots have higher U and TPD values, in agreement with previous studies. The patterns of circulation around Tiburón Island and San Esteban Island on the East, and Ángel de la Guarda Island and San Lorenzo Island on the West, the four islands in the region with the highest tidal energy potential, are also discussed while recognizing that Tiburón Channel, between Tiburón Island and San Esteban Island, has proved to be the best siting location, based on the technical results obtained so far. The hot spots sites are further characterized by computing the tidal asymmetry in these small regions, showing the locations of the sites with smallest asymmetry, which would be the best for tidal energy exploitation. The hot spots around San Esteban Island are particularly important because they have the largest TPD in the GIR, with the model predicting a TPD on the order of 500–1000 W m⁻². Here, complementary field measurements obtained with two ADCPs, close to San Esteban Island, one at 15 m depth, SEs (shallow region), and the other at 60 m depth, SEd (deep region), produced TPDs of 1200 W m⁻² and 400 W m⁻², respectively. The analysis of the vertical profiles and the tidal asymmetry over the vertical shows the importance of developing 3D models in future investigations. Full article

The industry of off-highway vehicles is one of the fields of major application of nodular cast irons, which guarantee the manufacture of complex geometries and ensure good mechanical properties. The present investigation deals with the fatigue design of off-highway axles made of EN-GJS-500-7. Typically, off-highway axles are weakened by stress risers which must be assessed against fatigue. In this investigation, laboratory specimens have been extracted from an off-highway axle to take into account the manufacturing process effects. Different specimens’ geometries have been prepared, including plain, bluntly notched and sharply V-notched specimens, and constant amplitude, load-controlled axial fatigue tests were conducted using two nominal load ratios, namely push–pull and pulsating tension loading. As a result, both the notch and the mean stress effects on the fatigue behaviour of EN-GJS-500-7 have been experimentally investigated for the first time. A well-known local approach, which takes the strain energy density (SED) averaged over a properly defined structural volume as a fatigue damage parameter, has been applied both in the linear elastic and elastic plastic formulations. Since the SED correlated the geometrical notch effects of the specimens as well as the mean stress effects, a master curve based on the averaged SED has been defined for the first time, to the best of the authors’ knowledge, for the fatigue design of off-highway axles made of EN-GJS-500-7. Full article

Understanding the relationship between climate, snow cover, and vegetation Net Primary Productivity (NPP) in the Tibetan Plateau (TP) is crucial. However, the role of snow cover in influencing the NPP remains unclear. This study investigates the connection between the NPP and snow phenology (SP) across the TP from 2011 to 2020. Interannual trends were assessed using the Theil–Sen non-parametric regression approach combined with the Mann–Kendall test. Additionally, the pathways through which snow cover affects the NPP, considering various environmental factors, were analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). Approximately 10.72% of the TP showed a significant decrease in the NPP, accompanied by advancing trends in the Snow Onset Date (SOD) and Snow End Date (SED), as well as a gradual decrease in the Snow Cover Duration (SCD). The PLS-SEM results reveal that precipitation and soil temperature significantly influenced the NPP, with total effects of 0.309 and 0.206 in the SCD structural equation. Temperature had a relatively strong indirect effect on the NPP through its influence on the SOD and SCD, contributing 16% and 10% to the total effect, respectively. Neglecting the mediating effect of SP underestimates the environmental impact on the NPP. This study highlights how environmental factors influence the NPP through snow cover changes as the biomass increases, thereby enhancing our understanding of SP’s impact on the TP. Full article

The extract of the plant species Satureja hortensis L. (often used as traditional ethno-therapy and in food processing) was prepared using the ultrasonic extraction technique, and contains a large quantity of secondary metabolites, with scientific evidence for antioxidant, antimicrobial, sedative, antispastic and antidiarrheal activities. Process optimization was carried out using a mathematical–statistical method (response surface methodology—RSM), which models and examines the effects of three levels and three variables on the observed response. The investigated responses were the content of total phenolic components (TPC) and total flavonoids (TFC), as well as tests of antioxidant activity at the level of radicals. The independent variables were ethanol concentration (40–80%), temperature (40–80 °C) and the liquid–solid ratio (10–30 mL/g). Results from this study were entered into a second-degree polynomial with multiple non-linear regression. Analysis of variance (ANOVA) was applied to find the most favorable environment for assessing the model’s performance and effectiveness with an ethanol concentration of 20%, temperature of 80 °C and LSR of 21.4 mL/g. ANOVA assessed the model’s significance, and a second-order polynomial model described the relationships between variables and responses. Diagnostic plots confirmed the model’s adequacy and reliability. The estimated values were 4.11 mg chlorogenic acid equivalents per gram of dry weight (CEA/g), 2.18 mg of rutin equivalents per gram of dry weight (RE/g), and 0.030 mg/mL and 0.030 mg/mL for TPC, TFC, IC₅₀ and EC₅₀, respectively. High-Performance Liquid Chromatography with diode array detection (HPLC-DAD) examination revealed that the prominent substance in the tested extract is rosmarinic acid (46,172 µg/mL), followed by chlorogenic acid (1519 µg/mL). Full article

Plants of the genus Tribulus have been used in folk medicine for wound healing, alleviating liver, stomach, and rheumatism pains, and as cognitive enhancers, sedatives, antiseptics, tonics, and stimulants. The present work aimed to evaluate whether Tribulus terrestris (Tt) administered for 15 days attenuated cognitive deficits and exhibited anxiolytic and antidepressant profiles in scopolamine-induced amnesia in zebrafish. Animals were randomly divided into six groups (eight animals per group): (1)–(3) Tt treatment groups (1, 3 and 6 mg/L), (4) control, (5) scopolamine (SCOP, 0.7 mg/kg), and (6) galantamine (Gal, 1 mg/L). Exposure to SCOP (100 µM) resulted in anxiety in zebrafish, as assessed by the novel tank diving test (NTT) and novel approach test (NAT). When zebrafish were given SCOP and simultaneously given Tt (1, 3, and 6 mg/L once daily for 10 days), the deficits were averted. Molecular interactions of chemical compounds from the Tt fractions with the monoamine oxidase A (MAO-A) were investigated via molecular docking experiments. Using behavioral experiments, we showed that administration of Tt induces significant anxiolytic-antidepressant-like effects in SCOP-treated zebrafish. Our result indicated that flavonoids of Tt, namely kaempferol, quercetin, luteolin, apigetrin, and epigallocatechin, could act as promising phytopharmaceuticals for improving anxiety-related disorders. Full article

This study aimed to assess the effect of a combination of aerobic exercise training (ET) and Chlorella (CH) intake on arterial nitric oxide (NO) production and arterial stiffness in obese rats. Twenty-week-old obese male rats were randomly grouped into four (n = 6): OBESE-SED (sedentary control), OBESE-ET (treadmill 25 m/min, 1 h, 5 d/week), OBESE-CH (0.5% Chlorella powder in normal diet), and OBESE-ET+CH (combination of ET and CH intake) groups. The carotid–femoral pulse wave velocity (cfPWV), an index of arterial stiffness, was significantly lesser in the OBESE-ET, OBESE-CH, and OBESE-ET+CH groups than in the OBESE-SED group, and in the OBESE-ET+CH group significantly further enhanced these effects compared with the OBESE-ET and OBESE-CH groups. Additionally, arterial nitrate/nitrite (NOx) levels were significantly greater in the OBESE-ET, OBESE-CH, and OBESE-ET+CH groups than in the OBESE-SED group, and the OBESE-ET+CH group compared with the OBESE-ET and OBESE-CH groups. Furthermore, arterial NOx levels were positively correlated with arterial endothelial NO synthase phosphorylation levels (r = 0.489, p < 0.05) and negatively correlated with cfPWV (r = −0.568, p < 0.05). In conclusion, a combination of ET and CH intake may reduce arterial stiffness via an enhancement of the arterial NO signaling pathway in obese rats. Full article

This study evaluated the anaesthetic potential of clove basil (Ocimum gratissimum) essential oil (EO-OG) in the post-larvae (PLs) of M. rosenbergii. The PLs were individually transferred to aquariums (500 mL) containing 50, 100, 150, 200, or 300 μL L⁻¹ EO-OG. A sixth group of PLs was exposed to freshwater only, and a seventh group was exposed to the highest concentration of ethanol used to dilute EO-OG. Upon reaching the anaesthesia stage, the PLs were transferred to aquariums (500 mL) with freshwater only to evaluate the recovery time. The shortest sedation times were observed at 200 (15.98 s) and 300 μL L⁻¹ (25.85 s). The shortest anaesthesia time was observed at 200 μL L⁻¹ (22.52 s). The longest recovery time was observed at 100 μL L⁻¹ (1367.10 s); the shortest recovery time was observed at 150 μL L⁻¹ (630.10 s). No mortality or adverse effects were observed in any experimental group. The concentration of 150 μL L⁻¹ resulted in sedation (49.24 s), anaesthesia (80.10 s), and recovery (630.10 s) times within those suggested as adequate for freshwater prawn farming. This research demonstrated the sedative and anaesthetic properties of EO-OG and its potential application in prawn farming. This study recommends using 150 μL L⁻¹ of EO-OG in M. rosenbergii PLs. Full article

Common blue-tongued skinks (Tiliqua scincoides) are popular pet reptiles; however, there has been limited research to investigate sedatives for this species. The purpose of this study was to measure the physiologic effects of four combinations of alfaxalone, dexmedetomidine, and midazolam for minor procedures such as intubation and blood collection. Eleven common blue-tongued skinks (Tiliqua scincoides) were used for this prospective, randomized cross-over study. The subcutaneous combinations were used as follows: 20 mg/kg alfaxalone (A); 10 mg/kg alfaxalone and 1 mg/kg midazolam (AM); 0.1 mg/kg dexmedetomidine and 1 mg/kg midazolam (DM); and 5 mg/kg alfaxalone, 0.05 mg/kg dexmedetomidine, and 0.5 mg/kg midazolam (ADM). Heart rate, respiratory rate, palpebral reflex, righting reflex, escape reflex, toe pinch withdrawal reflex, tongue flicking, and the possibility of intubation were recorded at baseline and every 5 min for 60 min. Venous blood gases were measured at baseline, full sedation, and recovery. Heart and respiratory rates decreased significantly in all groups, but the reductions were most prominent in DM and ADM. Analgesic effects, as measured by the toe pinch withdrawal reflex, were only observed in DM and ADM. Intubation was possible in all four protocols; however, it was not possible in two DM skinks. Based on these trials, ADM and AM are recommended for minor procedures in blue-tongue skinks. Full article

Agarwood, a precious traditional medicinal herb and fragrant material, is known for its sedative and sleep-improving properties. This study explores the mechanisms underlying the aromatherapy effects of Chi-Nan agarwood and ordinary agarwood in improving sleep. Using a combination of gas chromatography–mass spectrometry (GC-MS), network pharmacology, and molecular docking techniques, we identified and c ompared the chemical compositions and potential molecular targets of both types of agarwood. The GC-MS analysis detected 87 volatile components across six types of agarwood aromatherapy, with 51 shared between Chi-Nan and ordinary agarwood, while each type also had 18 unique components. Ordinary agarwood was found to be richer in sesquiterpenes and small aromatic molecules, whereas Chi-Nan agarwood contained higher levels of chromones. These differences in chemical composition are likely responsible for the distinct sleep-improving effects observed between the two types of agarwood. Through network pharmacology, 100, 65, and 47 non-repetitive target genes related to sleep improvement were identified for components shared by both types of agarwood (CSBTs), components unique to common agarwood (CUCMs), and components unique to Chi-Nan agarwood (CUCNs), respectively. The constructed protein–protein interaction (PPI) networks revealed that key targets such as MAOA, MAOB, SLC6A4, and ESR1 are involved in the sleep-improving mechanisms of agarwood aromatherapy. Molecular docking further confirmed the strong binding affinities of major active components, such as 5-Isopropylidene-6-methyldeca-369-trien-2-one and 2-(2-Phenylethyl)chromone, with these core targets. The results suggest that agarwood aromatherapy enhances sleep quality through both hormonal and neurotransmitter pathways, with ordinary agarwood more deeply mediating hormonal regulation, while Chi-Nan agarwood predominantly influences neurotransmitter pathways, particularly those involving serotonin and GABA. This study provides valuable insights into the distinct therapeutic potentials of Chi-Nan and ordinary agarwood, highlighting their roles in sleep improvement and offering a foundation for future research in the clinical application of agarwood-based aromatherapy. Full article

Grounding, a therapeutic technique involving direct contact with the earth, has been proposed by various studies to potentially have beneficial effects on pressure, sleep quality, stress, inflammation, and mood. However, the scientific evidence supporting its sedative effects remains incomplete. This study examined the sedative effectiveness of an earthing mat on sleep quality and investigated the underlying neural mechanisms using electroencephalography (EEG) analysis in rodents, focusing on orexin and superoxide dismutase (SOD) levels in the brain. Rats were randomly assigned to four groups: the naïve normal group (Nor), the group exposed to an earthing mat for 7 days (A-7D), the group exposed to an earthing mat for 21 days (A-21D), and the group exposed to an electronic blanket for 21 days (EM). EEG results revealed that the A-21D group exhibited significantly reduced wake time and increased rapid eye movement (REM), non-rapid eye movement (NREM), and total sleep time compared to the Nor group (p < 0.05). Moreover, the A-21D group demonstrated a significant increase in NREM sleep (p < 0.001), REM sleep (p < 0.01), and total sleep time (p < 0.001), along with a decrease in wake time compared to the EM group (p < 0.001). The orexin level in the A-21D group was significantly lower compared to the Nor group (p < 0.01), while SOD1 expression was markedly elevated in the A-21D group compared to the Nor group (p < 0.001). These results suggest that the earthing mat may represent a promising new method for promoting sleep quality and could serve as an effective therapeutic technique. Full article

Pinelliae Rhizoma (PR), a highly esteemed traditional Chinese medicinal herb, is widely applied in clinical settings due to its diverse pharmacological effects, including antitussive, expectorant, antiemetic, sedative-hypnotic, and antitumor activities. Pinellia ternata exhibits morphological variation in its leaves, with types resembling peach, bamboo, and willow leaves. However, the chemical composition differences among the corresponding rhizomes of these leaf phenotypes remain unelucidated. This pioneering research employed Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) to conduct the in situ identification and spatial profiling of 35 PR metabolites in PR, comprising 12 alkaloids, 4 organic acids, 12 amino acids, 5 flavonoids, 1 sterol, and 1 anthraquinone. Our findings revealed distinct spatial distribution patterns of secondary metabolites within the rhizome tissues of varying leaf types. Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) effectively differentiated between rhizomes associated with different leaf morphologies. Furthermore, this study identified five potential differential biomarkers—methylophiopogonanone B, inosine, cytidine, adenine, and leucine/isoleucine—that elucidate the biochemical distinctions among leaf types. The precise tissue-specific localization of these secondary metabolites offers compelling insights into the specialized accumulation of bioactive compounds in medicinal plants, thereby enhancing our comprehension of PR’s therapeutic potential. Full article

(1) Background: Cervical screening and additional diagnostic procedures often lead to depression. This research aimed to develop a prediction model for depression in women who received an abnormal Papanicolaou screening test, prior to and following the diagnostic procedures. (2) Methods: The study included women who had a positive Papanicolaou screening test (N = 172) and attended the Clinical Center of Kragujevac in Serbia for additional diagnostic procedures (colposcopy/biopsy/endocervical curettage). Women filled out a sociodemographic survey and the Center for Epidemiologic Studies Depression questionnaire (CES-D scale) before and after diagnostic procedures. A prediction model was built with multilayer perceptron neural networks. (3) Results: A correlation-based filter method of feature selection indicated four variables that correlated with depression both prior to and following the diagnostic procedures—anxiety, depression, worry, and concern about health consequences. In addition, the use of sedatives and a history of both induced and spontaneous abortion correlated with pre-diagnostic depression. Important attributes for predicting post-diagnostic depression were scores for the domains ‘Tension/discomfort’ and ‘Embarrassment’ and depression in personal medical history. The accuracy of the pre-diagnostic procedures model was 70.6%, and the area under the receiver operating characteristic curve (AUROC) was 0.668. The model for post-diagnostic depression prediction showed an accuracy of 70.6%, and an AUROC = 0.836. (4) Conclusions: This study helps provide means to predict the occurrence of depression in women with an abnormal Papanicolaou screening result prior to and following diagnostic procedures, which can aid healthcare professionals in successfully providing timely psychological support to those women who are referred to further diagnostics. Full article

Barbituric acid is a heterocyclic compound with various pharmacological and biological applications. This review paper provides a comprehensive overview of barbituric acid’s synthesis, reactions, and bio-applications, highlighting its multifaceted role in various fields. Many heterocyclic derivatives were formed based on barbituric acid, for instance, pyrano-fused pyrimidine derivatives, spiro-oxindole derivatives, chrome-based barbituric acid derivatives, and many more via the atom economic method, Michael addition reaction, Knoevenagel condensation reaction, etc. In the context of bio-applications, this review examines the production of a wide range of bioactive drugs like anti-histamine, anti-leprotic, sedative–hypnotic, anti-inflammatory, anti-urease, antiviral, anti-AIDS, antimicrobial, antioxidant, anticonvulsant, anesthetic agent, antitumor, and anticancer drugs using efficient multicomponent reactions. By showcasing the versatility and potential of this compound, it aims to inspire further research and innovation in the field, leading to the development of novel barbituric acid derivatives with enhanced properties and diverse applications, with coverage of the literature relevant up to 2024. Full article

(1) Background: Insomnia is a neurological illness that poses a significant threat to both physical and mental health. It results in the activation of neuroglial cells, heightened neuroinflammation, oxidative stress, and disruptions in the Hypothalamic–Pituitary–Adrenal (HPA) axis. Ligusticum Chuanxiong (CX) and Finger citron (FC) are frequently utilized botanicals for addressing sleeplessness. Both herbs possess notable anti-inflammatory properties in their volatile oils. However, their effectiveness is hindered by the nasal mucosal irritation and instability they exhibit. (2) Methods: This study involved the preparation of a nanofiber composite system using carbon nanofiber (CNF) suspensions containing essential oils of Ligusticum chuanxiong–Finger citron (CXEO-FCEO-CNF). The effects and mechanisms of these essential oils in improving insomnia were investigated using an insomnia mouse model after encapsulation. (3) Results: The CXEO-FCEO-CNF had an average particle size of 103.19 ± 1.64 nm. The encapsulation rates of essential oils of Ligusticum chuanxiong (CXEO) and essential oils of Finger citron (FCEO) were 44.50% and 46.15%, respectively. This resulted in a considerable improvement in the stability of the essential oils over a period of 30 days. The essential oils effectively decreased the irritation of the nasal mucosa following encapsulation. Furthermore, CXEO-FCEO-CNF enhanced voluntary activity and sleep in mice with insomnia, notably boosted the activity of superoxide dismutase (SOD), reduced the concentration of lipoxidized malondialdehyde (MDA), decreased the levels of hormones associated with the HPA axis, and regulated the levels of neurotransmitters, resulting in a beneficial therapeutic outcome. CXEO-FCEO-CNF contains a total of 23 active ingredients, such as alpha-Asarone, (E)-methyl isoeugenol, and Senkyunolide. These ingredients primarily work by modulating the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling system to decrease oxidative stress and inflammatory reactions. (4) Conclusions: This study presented initial evidence that the combination of CXEO and FCEO in nanofiber formulations effectively reduces the nasal mucosal irritation and instability of essential oils. Furthermore, it demonstrated the potential anti-neuroinflammatory and therapeutic effects of these formulations in treating insomnia. Overall, this study provides a theoretical foundation for developing new essential oil formulations derived from herbs. Full article