Search Results (2,673)

Background: Acute mountain sickness (AMS) is a prevalent and potentially life-threatening condition caused by rapid exposure to high-altitude hypoxia, affecting pulmonary and neurological functions. Tongqiao Jiuxin Oil (TQ), a traditional Chinese medicine formula composed of aromatic and resinous ingredients such as sandalwood, agarwood, frankincense, borneol, and musk, has been widely used in the treatment of cardiovascular and cerebrovascular disorders. Clinical observations suggest its potential efficacy against AMS, yet its pharmacological mechanisms remain poorly understood. Methods: The chemical profile of TQ was characterized using UHPLC-Q-Exactive Orbitrap HRMS. Network pharmacology was applied to predict the potential targets and pathways involved in AMS. A rat model of AMS was established by exposing animals to hypobaric hypoxia (~10% oxygen), simulating an altitude of approximately 5500 m. TQ was administered at varying doses. Physiological indices, oxidative stress markers (MDA, SOD, GSH), histopathological changes, and the expression of hypoxia- and apoptosis-related proteins (HIF-1α, VEGFA, EPO, Bax, Bcl-2, Caspase-3) in lung and brain tissues were assessed. Results: A total of 774 chemical constituents were identified from TQ. Network pharmacology predicted the involvement of multiple targets and pathways. TQ significantly improved arterial oxygenation and reduced histopathological damage in both lung and brain tissues. It enhanced antioxidant activity by elevating SOD and GSH levels and reducing MDA content. Mechanistically, TQ downregulated the expression of HIF-1α, VEGFA, EPO, and pro-apoptotic markers (Bax/Bcl-2 ratio, Caspase-3), while upregulated Bcl-2, the anti-apoptotic protein expression. Conclusions: TQ exerts protective effects against AMS-induced tissue injury by improving oxygen homeostasis, alleviating oxidative stress, and modulating hypoxia-related and apoptotic signaling pathways. This study provides pharmacological evidence supporting the potential of TQ as a promising candidate for AMS intervention, as well as the modern research method for multi-component traditional Chinese medicine. Full article

A comprehensive metabolic profiling of Catharanthus roseus (L.) G. Don was performed using tandem mass spectrometry, along with an evaluation of the biological activities of its various solvent extracts. Among these, the methanolic leaf extract exhibited mild radical scavenging activity, low to moderate antimicrobial activity, and limited cytotoxicity in both the brine shrimp lethality assay and MTT assay against HeLa and A549 cell lines. High-performance liquid chromatography–electrospray ionization–high-resolution tandem mass spectrometry (HPLC-ESI-HRMS/MS) analysis led to the annotation of 34 metabolites, primarily alkaloids. These included 23 indole alkaloids, two fatty acids, two pentacyclic triterpenoids, one amino acid, four porphyrin derivatives, one glyceride, and one chlorin derivative. Notably, two metabolites—2,3-dihydroxypropyl 9,12,15-octadecatrienoate and (10S)-hydroxypheophorbide A—were identified for the first time in C. roseus. Furthermore, Global Natural Products Social Molecular Networking (GNPS) analysis revealed 18 additional metabolites, including epoxypheophorbide A, 11,12-dehydroursolic acid lactone, and 20-isocatharanthine. These findings highlight the diverse secondary metabolite profile of C. roseus and support its potential as a source of bioactive compounds for therapeutic development. Full article

Background/Objectives: Senecio scandens Buch.-Ham. is a flavonoid-rich traditional medicinal plant with established immunomodulatory properties. However, the mechanisms underlying the immunoregulatory and intestinal protective effects of its flavonoid extract (Senecio scandens flavonoids—SSF) remain unclear. This study characterized SSF’s bioactive components and evaluated its efficacy against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. Methods: The constituents of SSF were identified using UHPLC/Q-Orbitrap/HRMS. Mice with CTX-induced immunosuppression were treated with SSF (80, 160, 320 mg/kg) for seven days. Immune parameters (organ indices, lymphocyte proliferation, cytokine, and immunoglobulin levels) and gut barrier integrity markers (ZO-1, Occludin, Claudin-1 protein expression; sIgA secretion; microbiota composition) were assessed. Network pharmacology combined with functional assays elucidated the underlying regulatory mechanisms. Results: Twenty flavonoids were identified in SSF, with six prototype compounds detectable in the blood. The SSF treatment significantly ameliorated CTX-induced weight loss and atrophy of the thymus and spleen. It enhanced splenic T- and B-lymphocyte proliferation by 43.6% and 29.7%, respectively; normalized the CD4⁺/CD8⁺ ratio (1.57-fold increase); and elevated levels of IL-2, IL-6, IL-10, TNF-α, IFN-γ, IgM, and IgG. Moreover, SSF reinforced the intestinal barrier by upregulating tight junction protein expression and sIgA levels while modulating the gut microbiota, enriching beneficial taxa (e.g., the Lachnospiraceae_NK4A136_group, Akkermansia) and suppressing pathogenic Alistipes. Mechanistically, SSF activated the TLR/MyD88/NF-κB pathway, with isoquercitrin identified as a pivotal bioactive constituent. Conclusions: SSF effectively mitigates CTX-induced immunosuppression and intestinal damage. These findings highlight SSF’s potential as a dual-functional natural agent for immunomodulation and intestinal protection. Subsequent research should validate isoquercitrin’s molecular targets and assess SSF’s clinical efficacy. Full article

During the course of genome mining initiatives, we identified a marine-derived Micromonospora, assigned here as strain WMMD956; the genome of WMMD956 appeared to contain a number of features associated with everninomicins, well-known antimicrobial orthosomycins. In addition, LCMS-based hierarchical clustering analysis and principal component analysis (hcapca) revealed that WMMD956 displayed an extreme degree of metabolomic and genomic novelty. Dereplication of high-resolution tandem mass spectrometry (HRMS/MS) and Global Natural Product Social molecular networking platform (GNPS) analysis of WMMD956 resulted in the identification of several analogs of the previously known everninomicin. Chemical structures were unambiguously confirmed by HR-ESI-MS, 1D and 2D NMR experiments, and the use of MS/MS data. The isolated metabolites, 1–3, were evaluated for their antibacterial activity against methicillin-resistant Staphalococcus aureus (MRSA). Full article

This study investigates the metabolic responses of the model diatom Phaeodactylum tricornutum under different growth conditions, comparing benthic (adherent) and planktonic states. Using a multiblock metabolomics approach combining LC-HRMS², NMR, and GC-MS techniques, we compared the metabolome of P. tricornutum cultivated on three laboratory substrates (glass, polystyrene, and polydimethylsiloxane) and under planktonic conditions. Our results revealed metabolic differences between adherent and planktonic cultures, particularly concerning the lipid and carbohydrate contents. Adherent cultures showed a metabolic profile with an increase in betaine lipids (DGTA/S), fatty acids (tetradecanoic and octadecenoic acids), and sugars (myo-inositol and ribose), suggesting modifications in membrane composition and lipid remodeling, which play a potential role in adhesion. In contrast, planktonic cultures displayed a higher content of cellobiose, specialized metabolites such as dihydroactinidiolide, quinic acid, catechol, and terpenes like phytol, confirming different membrane composition, energy storage capacity, osmoregulation, and stress adaptation. The adaptative strategies do not only concern adherent and planktonic states, but also different adherent culture conditions, with variations in lipid, amino acid, terpene, and carbohydrate contents depending on the physical properties of the support. Our results highlight the importance of metabolic adaptation in adhesion, which could explain the fouling process. Full article

Doxorubicin (DOX) is widely used for the treatment of several tumors, but considerable dose-dependent side effects on many normal tissues, including bones, have been reported. The aim of the present study was to follow for the first time the kinetics of DOX accumulation/clearance in the non-vascularized intervertebral disc (IVD), as well as to assess the drug’s biological action in the annulus fibrosus (AF) and nucleus pulposus (NP) IVD cells and tissues. DOX was administered intravenously to rabbits before the isolation of IVDs, in which DOX quantification was performed using a highly sensitive LC-HRMS/MS analytical method. The effect of the drug on IVD cells’ physiology was assessed in vitro, while IVD tissue quality post-DOX administration was studied in vivo through histological analysis. DOX delivery was found significantly lower in the IVD compared to the highly vascularized skin, declining from the outer AF to the inner NP. The low DOX concentrations reaching the IVDs had marginal effects on cells’ viability, intracellular redox status, and p38 MAPK activation, while they did not evoke cellular senescence. Most importantly, the drug did not negatively affect ECM integrity, as collagen and proteoglycan content remained stable in vitro and in vivo. Full article

Operations management personnel emphasize the maintenance of workforce empowerment on the shop floor. This is made possible by implementing effective operations and human resource management practices. However, organizations are adept at controlling the workforce empowerment domain within operational scenarios. In the current industry revolution scenario, industry personnel often face failure due to a laggard mindset in the face of industry revolutions. There are higher possibilities of failure because of standardized operations controlling the shop floor. Organizations utilize well-established human resource concepts, including McClelland’s acquired needs theory, Herzberg’s two-factor theory, and Maslow’s hierarchy of needs, in order to enhance the workforce’s performance on the shop floor. Current SME individuals require fast-paced approaches for tracking the performance and idleness of a workforce in order to control them more efficiently in both flexible and transformational stages. The present study focuses on investigating the parameters and factors that contribute to workforce empowerment in an industrial revolution scenario. The present research is used to develop a framework utilizing operations and human resource management approaches in order to identify and address the issues responsible for deteriorating workforce contributions. The framework includes HRM and operations management practices, including Herzberg’s two-factor theory, Maslow’s theory, and lean and smart approaches. The developed framework contains four phases for achieving desired outcomes on the shop floor. The developed framework is validated by implementing it in a real-life electric vehicle manufacturing organization, where the human resources and operations team were exhausted and looking to resolve employee-related issues instantly and establish a sustainable work environment. The current industry is transforming from Industry 3.0 to Industry 4.0, and seeks future-ready innovations in operations, control, and monitoring of shop floor setups. The operations management and human resource management practices teams reviewed the results over the next three months after the implementation of the developed framework. The results revealed an improvement in workforce empowerment within the existing work environment, as evidenced by reductions in the number of absentees, resignations, transfer requests, and medical issues, by 30.35%, 94.44%, 95.65%, and 93.33%, respectively. A few studies have been conducted on workforce empowerment by controlling shop floor scenarios through modifications in operations and human resource management strategies. The results of this study can be used to fulfil manufacturers’ needs within confined constraints and provide guidelines for efficiently controlling workforce performance on the shop floor. Constraints refer to barriers that have been decided, including production time, working time, asset availability, resource availability, and organizational policy. The study proposes a decision-making plan for enhancing shop floor performance by providing suitable guidelines and an action plan, taking into account both workforce and operational performance. Full article

Background: Crystalline glucosamine sulfate (cGS) claims to be a stabilized form of glucosamine sulfate with a defined crystalline structure intended to enhance chemical stability. It is proposed to offer pharmacokinetic advantages over regular glucosamine sulfate (rGS) which is stabilized with potassium or sodium chloride. However, comparative human bioavailability data are limited. Since both forms dissociate in gastric fluid into constituent ions, the impact of cGS formulation on absorption remains uncertain. This pilot study aimed to compare the bioavailability of cGS and rGS using a randomized, double-blind, crossover design. Methods: Ten healthy adults received a single 1500 mg oral dose of either cGS or rGS with a 7-day washout between interventions. Capillary blood samples were collected over 24 h. Glucosamine and its metabolite concentrations were quantified by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS), and pharmacokinetic parameters—including maximum concentration (C_max), time to reach C_max (T_max), and area under the curve (AUC)—were calculated. Results: Mean AUC_0–24, C_max, T_max, and T_½ values for glucosamine and glucosamine-6-sulfate (GlcN-6-S) were comparable between cGS and rGS. Although the AUC_0–24 for glucosamine was modestly higher with rGS (18,300 ng·h/mL) than with cGS (12,900 ng·h/mL), the difference was not statistically significant (p = 0.136). GlcN-6-S exposure was also similar between formulations (rGS: 50,700 ng·h/mL; cGS: 50,600 ng·h/mL), with a geometric mean ratio of 1.39, a delayed T_max (6–8 h) and longer half-life, consistent with its role as a downstream metabolite. N-acetylglucosamine levels remained stable, indicating potential homeostatic regulation. Conclusions: This pilot study found no significant pharmacokinetic advantage of cGS over rGS. These preliminary findings challenge claims of cGS’ pharmacokinetic superiority, although the small sample size limits definitive conclusions. Larger, adequately powered studies are needed to confirm these results. Full article

A new bicyclic polyketide, amesilide (1), along with the previously reported metabolites, chamisides A (2), B (3), and E (4), chaetoconvosins B (5) and C (6), and chaetochromins A (7) and B (8), were isolated from the marine fungus Amesia nigricolor MUT6601. The structures of the compounds were determined by extensive spectrometric (HRMS) and spectroscopic (1D and 2D NMR) analyses, as well as specific rotation. Absolute configurations of the stereogenic centers of amesilide (1) were determined by a comparison of its experimental circular dichroism (CD) spectrum with its time-dependent density functional theory (TD-DFT) electronic circular dichroism (ECD) spectra. Among them, chaetochromins A (7) and B (8) showed strong antibacterial activity against Staphylococcus aureus S25 (MBC values of 12.50 µM and MIC values of 6.25 µM) and a moderate cytotoxicity against monocytes (THP-1) and peripheral blood cells (PBMC) (IC₅₀ values of 33.65–40.01 µM). Full article

Apples are one of the most popular fruits in Germany, valued for their regional availability and health benefits. When deciding which apple to buy, several characteristics are important to consumers, including the taxonomic variety, organic cultivation and regional production. To verify that these characteristics are correctly declared, powerful analytical methods are required. In this study, ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-ToF-MS) is applied in combination with random forest to 193 apple samples for the analysis of various authentication issues. Accuracies of 93.3, 85.5, 85.6 and 90% were achieved for distinguishing between German and non-German, North and South German, organic and conventional apples and for six different taxonomic varieties. Since the classification models largely use different parts of the data, which is shown by variable selection, this method is very well suited to answer different authentication issues with one analytical approach. Full article

Mauritia flexuosa, commonly known as “canangucha,” holds significant nutritional and economic value in the Amazon region. While its pulp is widely utilized in local food products, the seed or kernel is largely underutilized. This study investigated the proximal and phytochemical composition of M. flexuosa, alongside its biological properties, specifically focusing on the hypoglycemic activity of an ethanolic extract from M. flexuosa seeds (MFSs). Proximal analysis revealed that MFSs are a notable source of crude fiber (28.4%) and a moderate source of protein (9.1%). Phytochemical screening indicated a high total polyphenol content (123.4 mg gallic acid equivalents/100 mg dry weight) and substantial antiradical capacity against the ABTS radical (IC₅₀ = 171.86 µg/mL). Notably, MFS ethanolic extracts exhibited significant in vitro antihyperglycemic activity via inhibiting α-amylase and α-glucosidase enzymes, demonstrating comparable inhibition to acarbose at higher concentrations. This hypoglycemic effect was further corroborated in an in vivo rat model with induced diabetes, where the administration of 100 mg/kg of MFS ethanolic extract significantly reduced blood glucose levels compared to the diabetic control group (p < 0.05). A moderate antihypertensive effect was observed at a concentration of 150 mg/kg, correlating with ACE inhibition. High-performance liquid chromatography–mass spectrometry (UHPLC-ESI-HRMS) analysis of the seed extract identified phenolic compounds including ellagic, p-coumaric, and chlorogenic acids, as well as flavonoids such as quercetin, myricetin, and epicatechin. This study provides the first evidence of the hypoglycemic activity of MFSs, offering valuable insights into their phytochemistry and potential therapeutic applications. Full article

Narcotics trafficking is a fundamental part of organized crime, posing significant and evolving challenges for forensic investigations. Addressing these challenges requires rapid, precise, and scientifically validated analytical methods for reliable identification of illicit substances. Over the past five years, forensic drug testing has advanced considerably, improving detection of traditional drugs—such as tetrahydrocannabinol, cocaine, heroin, amphetamine-type stimulants, and lysergic acid diethylamide—as well as emerging new psychoactive substances (NPS), including synthetic cannabinoids (e.g., 5F-MDMB-PICA), cathinones (e.g., α-PVP), potent opioids (e.g., carfentanil), designer psychedelics (e.g., 25I-NBOMe), benzodiazepines (e.g., flualprazolam), and dissociatives (e.g., 3-HO-PCP). Current technologies include colorimetric assays, ambient ionization mass spectrometry, and chromatographic methods coupled with various detectors, all enhancing accuracy and precision. Vibrational spectroscopy techniques, like Raman and Fourier transform infrared spectroscopy, have become essential for non-destructive identification. Additionally, new sensors with disposable electrodes and miniaturized transducers allow ultrasensitive on-site detection of drugs and metabolites. Advanced chemometric algorithms extract maximum information from complex data, enabling faster and more reliable identifications. An important emerging trend is the adoption of green analytical methods—including direct analysis, solvent-free extraction, miniaturized instruments, and eco-friendly chromatographic processes—that reduce environmental impact without sacrificing performance. This review provides a comprehensive overview of innovations over the last five years in forensic drug analysis based on the ScienceDirect database and highlights technological trends shaping the future of forensic toxicology. Full article

The sustainable production of plant bioactive compounds is increasingly important as natural habitats decline. This study investigates whether in vitro cell cultures of Eryngium planum, Lychnis flos-cuculi, and Kickxia elatine can serve as alternative sources of biologically active biomass with antimicrobial and anti-Acanthamoeba properties. Callus cultures were established under optimized and controlled conditions, and metabolomic profiling was completed using UPLC-HRMS/MS. In silico analysis, using a molecular docking approach, was applied to understand the interaction between target compounds and Acanthamoeba profilin and identify possible targets for antimicrobial properties. Untargeted metabolomic analysis confirmed the presence of valuable compounds in the callus cultures of the studied species. Biological activity was assessed through anti-Acanthamoeba and antimicrobial assays. Lychnis flos-cuculi and Kickxia elatine callus extracts showed significant inhibitory effects on Acanthamoeba trophozoites, with 87.5% and 80.1% inhibition at 10 mg/mL, respectively. In contrast, E. planum extract stimulated amoebic growth. The anti-Acanthamoeba activity correlated with the presence of ferulic acid and p-coumaric acid in L. flos-cuculi extract, and acteoside in K. elatine extract. Antibacterial testing revealed moderate activity of E. planum and K. elatine extracts against Staphylococcus spp., while Gram-negative bacteria and fungi were largely resistant. These findings highlight the potential of in vitro cultures—particularly those from L. flos-cuculi and K. elatine—as promising, sustainable sources of anti-Acanthamoeba and antimicrobial agents, warranting further investigation into their pharmacologically active constituents. Full article

Tuberaria lignosa (Sweet) Samp. (Cistaceae) is a herbaceous species native to southwestern Europe, traditionally used to treat wounds, ulcers, and inflammatory or infectious skin conditions. This study aimed to characterize the phytochemical profile of its aqueous leaf extract and evaluate its skin-related in vitro biological activities. The phenolic composition was determined using UHPLC-HRMS/MS, HPLC-DAD, and quantitative colorimetric assays. Antioxidant activity was assessed against synthetic free radicals, reactive oxygen and nitrogen species, transition metals, and pro-oxidant enzymes. Enzymatic inhibition of tyrosinase, hyaluronidase, collagenase, and elastase were evaluated using in vitro assays. Cytocompatibility was tested on human keratinocytes and NIH/3T3 fibroblasts using MTT and resazurin assays, respectively, while wound healing was evaluated on NIH/3T3 fibroblasts using the scratch assay. Antifungal activity was investigated against several Candida and dermatophyte species, while antibiofilm activity was tested against Epidermophyton floccosum. The extract was found to be rich in phenolic compounds, accounting for nearly 45% of its dry weight. These included flavonoids, phenolic acids, and proanthocyanidins, with ellagitannins (punicalagin) being the predominant group. The extract demonstrated potent antioxidant, anti-tyrosinase, anti-collagenase, anti-elastase, and antidermatophytic activities, including fungistatic, fungicidal, and antibiofilm effects. These findings highlight the potential of T. lignosa as a valuable and underexplored source of bioactive phenolic compounds with strong potential for the development of innovative approaches for skin care and therapy. Full article

Dietary advanced glycation end-products (dAGEs) contained in high-sugar/fat and ultra-processed foods of the “Western diet” (WD) pattern predispose to several diseases by altering protein function or increasing oxidative stress and inflammation via RAGE (receptor for advanced glycation end-products). Although elevated endogenous AGEs are associated with loss of muscle mass and functionality (i.e., muscle wasting; MW), the impact of dAGEs on MW has not been elucidated. Here, we show that the most common dAGEs or their precursor, methylglyoxal (MGO), induce C2C12 myotube atrophy as endogenous AGE-derived BSA. ROS production, mitochondrial dysfunction, mitophagy, ubiquitin–proteasome activation, and inhibition of myogenic potential are common atrophying mechanisms used by MGO and AGE-BSA. Although of different origins, ROS are mainly responsible for AGE-induced myotube atrophy. However, while AGE-BSA activates the RAGE-myogenin axis, reduces anabolic mTOR, and causes mitochondrial damage, MGO induces glycolytic stress and STAT3 activation without affecting RAGE expression. Among thirty selected natural compounds, Vaccinium macrocarpon (VM), Camellia sinensis, and chlorophyll showed a surprising ability in counteracting in vitro AGE formation. However, only the standardized VM, containing anti-glycative metabolites as revealed by UHPLC-HRMS analysis, abrogates AGE-induced myotube atrophy. Collectively, our data suggest that WD-linked dAGE consumption predisposes to MW, which might be restricted by VM food supplements. Full article