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Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Smoke-water (SW) and Karrikinolide1 (KAR1) release dormancy and improve seed germination in many plant species. Therefore, we tested SW (1:2500 v/v) and KAR1 (10−7 M) to break the morphological dormancy of celery cultivar (Apium graveolens L.). In the first trial, seeds were subjected to a 21-day incubation period at 20 °C with SW and KAR1 applied as single treatments. KAR1 showed significantly improved germination (30.7%) as compared to SW (17.2%) and a water control (14.7%). In seed soaking experiments, SW, KAR1, and gibberellic acid (GA3) treatments showed higher germination percentages than the water control after 3 and 6 h of soaking. However, prolonged soaking (12 h) reduced germination percentages for all treatments, indicating a detrimental effect. Analysis of KAR1 content dynamics in 7-day- and 21-day-old celery seeds indicated its prolonged effects on germination and dormancy alleviation. Phytohormones, including auxins in 7-day-old and cytokinins in 7-day- and 21-day-old celery seedlings, along with their precursors and metabolites, were analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) after treatment with KAR1 and SW. The analysis of auxin levels in 7-day-old seeds revealed a negative correlation between seed germination and auxin (indole-3-acetic acid, IAA) content. Notably, it was found that KAR1-treated seeds significantly reduced IAA levels in all treatments. SW and KAR1 did not significantly affect cytokinin levels during celery germination except for N6-Isopentenyladenine. Hence, further research is needed to understand their precise role in celery seed germination. This work will improve our understanding of the role of bioactive compounds from plant-derived smoke and how they regulate hormonal responses and improve germination efficiency in celery. [ABSTRACT FROM AUTHOR]

Context Type 2 diabetes (T2D) is the major contributor to chronic kidney disease and end-stage kidney disease (ESKD). The influence of trimethylamine N-oxide (TMAO) on kidney outcomes in T2D remains unclear. Objective To examine the association between fasting serum TMAO levels and adverse kidney outcomes in patients with T2D. Methods Between October 2016 and June 2020, patients with T2D were recruited and monitored every 3 months until December 2021. Serum TMAO levels were assessed using liquid chromatography-mass spectrometry. The primary kidney outcomes were doubling of serum creatinine levels or progression to ESKD necessitating dialysis; the secondary kidney outcome was a rapid 30% decline in estimated glomerular filtration rate within 2 years. All-cause mortality was also evaluated. Results Among the 440 enrolled patients with T2D, those in the highest serum TMAO tertile (≥0.88 μM) were older, had a longer diabetes duration, elevated blood urea nitrogen, and lower estimated glomerular filtration rate. Over a median follow-up period of 4 years, 26 patients (5.9%) had a doubling of serum creatinine level or progression to ESKD. After propensity score weighting, the patients in the highest serum TMAO tertile had a 6.45-fold increase in the risk of doubling of serum creatinine levels or progression to ESKD and 5.86-fold elevated risk of rapid decline in kidney function compared with those in the lowest tertile. Additionally, the stepwise increase in serum TMAO was associated with all-cause mortality. Conclusion Patients with T2D with elevated circulating TMAO levels are at higher risk of doubling serum creatinine, progressing to ESKD, and mortality. TMAO is a potential biomarker for kidney function progression and mortality in patients with T2D. [ABSTRACT FROM AUTHOR]

Pollution by active ingredients is one of the most significant and widespread forms of pollution on Earth. Medicines can have a negative impact on ecosystems, and contamination can have unpredictable consequences. An urgent and unexplored task is to study the Lake Baikal ecosystem and its organisms for the presence of trace concentrations of active pharmaceutical ingredients. Our study aimed to conduct a qualitative analysis of active pharmaceutical ingredients, and quantitative analysis of ibuprofen in endemic amphipods of Lake Baikal, using methods of high-performance liquid chromatography and mass spectrometry (HPLC-MS). Acetylsalicylic acid (aspirin), ibuprofen, acetaminophen, azithromycin, dimetridazole, metronidazole, amikacin, spiramycin, and some tetracycline antibiotics were detected in the studied littoral amphipods. We also detected different annual loads of active pharmaceutical ingredients on amphipods. Using the multiple reaction monitoring (MRM) mode mentioned in GOST International Technical Standards, we detected molecules, fragmented as amikacin, chlortetracycline, doxycycline, oxytetracycline, dimetridazole, metronidazole and spiramycin. Thus, we first revealed that invertebrates of Lake Baikal can uptake pharmaceutical contaminants in the environment. [ABSTRACT FROM AUTHOR]

Emerging contaminants (ECs) are substances that have no defined environmental quality standards or regulations, and have the potential to pose major adverse impacts on the environment and human health. The detection of contaminants in the natural environment is the key step for establishing precise environmental risk assessment approach for ECs. However, ECs come from different origins with various physicochemical properties, making their detection a complicated process. Moreover, their presence in the aquatic environment at trace concentration range (ng/L-µg/L), requires an accurate detection at low concentration levels. This study aims to develop an efficient analytical method for simultaneous determination of 5 different ECs in aqueous solution based on solid phase extraction technique (SPE) followed by liquid chromatography-mass spectrometry (LC–MS/MS). High recovery rates (72% to 114%) were achieved for all targeted compounds. Ciprofloxacin (CIP), diuron (DIU), terbutryn (TER) and diclofenac (DIC) had a limit of detection (LOD) of 5 µg/L and a limit of quantification (LOQ) of 10 ng/L, while LOD and LOQ for EE2 were 25 µg/L and 50 ng/L, respectively. These results confirm that the optimized method can be applied for extraction and analysis of ECs from different classes in the aquatic environment. [ABSTRACT FROM AUTHOR]

Uterine leiomyoma or fibroids are prevalent noncancerous tumors of the uterine muscle layer, yet their origin and development remain poorly understood. We analyzed RNA expression profiles of 15 epigenetic mediators in uterine fibroids compared to myometrium using publicly available RNA sequencing (RNA-seq) data. To validate our findings, we performed RT-qPCR on a separate cohort of uterine fibroids targeting these modifiers confirming our RNA-seq data. We then examined protein profiles of key N6-methyladenosine (m6A) modifiers in fibroids and their matched myometrium, showing no significant differences in concordance with our RNA expression profiles. To determine RNA modification abundance, mRNA and small RNA from fibroids and matched myometrium were analyzed by ultra-high performance liquid chromatography-mass spectrometry identifying prevalent m6A and 11 other known modifiers. However, no aberrant expression in fibroids was detected. We then mined a previously published dataset and identified differential expression of m6A modifiers that were specific to fibroid genetic subtype. Our analysis also identified m6A consensus motifs on genes previously identified to be dysregulated in uterine fibroids. Overall, using state-of-the-art mass spectrometry, RNA expression, and protein profiles, we characterized and identified differentially expressed m6A modifiers in relation to driver mutations. Despite the use of several different approaches, we identified limited differential expression of RNA modifiers and associated modifications in uterine fibroids. However, considering the highly heterogenous genomic and cellular nature of fibroids, and the possible contribution of single molecule m6A modifications to fibroid pathology, there is a need for greater in-depth characterization of m6A marks and modifiers in a larger and diverse patient cohort. [ABSTRACT FROM AUTHOR]

Objective: To explore the rapid antidepressant potential and the underlying mechanism of Chaihu Shugan San (CSS) in female mice. Methods: Liquid chromatography mass spectrometry (LC-MS)/MS was used to determine the content of main components in CSS to determine its stability. Female C57BL/6J mice were randomly divided into 4 groups, including control (saline), vehicle (saline), CSS (4 g/kg) and ketamine (30 mg/kg) groups. Mice were subjected to irregular stress stimulation for 4 weeks to establish the chronic mild stress (CMS) model, then received a single administration of drugs. Two hours later, the behavioral tests were performed, including open field test, tail suspension test (TST), forced swimming test (FST), novelty suppression feeding test (NSF), and sucrose preference test (SPT). Western blot analysis was used to detect the expression levels of N-methyl-D-aspartate receptor (NMDA) subtypes [N-methyl-D-aspartate receptor 1 (NR1), NR2A, NR2B], synaptic proteins [synapsin1 and post synaptic density protein 95 (PSD95)], and brain-derived neurotrophic factor (BDNF). Moreover, the rapid antidepressant effect of CSS was tested by pharmacological technologies and optogenetic interventions that activated glutamate receptors, NMDA. Results: Compared with the vehicle group, a single administration of CSS (4 g/kg) reversed all behavioral defects in TST, FST, SPT and NSF caused by CMS (P<0.05 or P<0.01). CSS also significantly decreased the expressions of NMDA subtypes (NR1, NR2A, NR2B) at 2 h in hippocampus of mice (all P<0.01). In addition, similar to ketamine, CSS increased levels of synaptic proteins and BDNF (P<0.05 or P<0.01). Furthermore, the rapid antidepressant effects of CSS were blocked by transient activation of NMDA receptors in the hippocampus (all P<0.01). Conclusion: Rapid antidepressant effects of CSS by improving behavioral deficits in female CMS mice depended on rapid suppression of NMDA receptors and activation of synaptic proteins. [ABSTRACT FROM AUTHOR]

Objective: To identify whether Banxia Xiexin Decoction (BXD) alleviates cerebral glucose metabolism disorder by intestinal microbiota regulation in APP/PS1 mice. Methods: Forty-five 3-month-old male APP/PS1 mice were divided into 3 groups using a random number table (n=15 per group), including a model group (MG), a liraglutide group (LG) and a BXD group (BG). Fifteen 3-month-old male C57BL/6J wild-type mice were used as the control group (CG). Mice in the BG were administered BXD granules by gavage at a dose of 6 g/(kg•d) for 3 months, while mice in the LG were injected intraperitoneally once daily with Liraglutide Injection (25 nmol/kg) for 3 months. Firstly, liquid chromatography with tandem-mass spectrometry was used to analyze the active components of BXD granules and the medicated serum of BXD. Then, the cognitive deficits, Aβ pathological change and synaptic plasticity markers, including synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), were measured in APP/PS1 mice. Brain glucose uptake was detected by micropositron emission tomography. Intestinal microbial constituents were detected by 16S rRNA sequencing. The levels of intestinal glucagon-like peptide 1 (GLP-1) and cerebral GLP-1 receptor (GLP-1R), as well as the phosphoinositide-3-kinase/protein kinase B/glycogen synthase kinase-3β (PI3K/Akt/GSK3β) insulin signaling pathway were determined by immunohistochemical (IHC) staining and Western blot analysis, respectively. Results: BXD ameliorated cognitive deficits and Aβ pathological features (P<0.01). The expressions of SYP and PSD95 in the BG were higher than those in the MG (P<0.01). Brain glucose uptake in the BG was higher than that in the MG (P<0.01). The intestinal microbial composition in the BG was partially reversed. The levels of intestinal GLP-1 in the BG were higher than those in the MG (P<0.01). Compared with the MG, the expression levels of hippocampal GLP-1R, Akt, PI3K and p-PI3K in the BG were significantly increased (P<0.01), while the levels of GSK3β were reduced (P<0.01). Conclusion: BXD exhibited protective effects against Alzheimer's disease by regulating the gut microbiota/GLP-1/GLP-1R, enhancing PI3K/Akt/GSK3β insulin signaling pathway, and improving brain glucose metabolism. [ABSTRACT FROM AUTHOR]

To further promote the pretreatment technique, the immunoaffinity column (IAC), immunoaffinity magnetic (IAM) and multi-component immunoaffinity magnetic (multi-IAM) for mycotoxins were developed and evaluated systematically. Anti-mycotoxin-McAbs had immobilized on the CNBr-Sepharose 4B, carboxyl magnetic bead and protein G magnetic bead to prepare the IAC/IAM/multi-IAM, respectively. The capture efficiencies of mycotoxins (100 ng) reached 92.8% for IAC and exceeded 94.0% for IAM/multi-IAM. The multi-IAM showed more beneficial features in multiple targets, pretreatment time and recycling time than IAC/IAM, which could simultaneously pretreat AFB1/DON/ZEN in 15 min with three recycling times. The recoveries of IAC/IAM/multi-IAM coupled with ELISA ranged from 85.2 to 105.1%, with RSD between 4.0 and 13.2%. Moreover, the mycotoxin-positive authentic samples were detected from 1.1 to 749.6 ng/g by ELISA, and 1.2 to 762.7 ng/g by LC-MS/MS, with correlated R2 exceeding 0.9955. The proposed IAC/IAM/multi-IAM owned the desired performance, such as specificity, accuracy, simpleness, efficiency, cost-effectiveness, simultaneity and environmentally friendly. This study can provide the theoretical basis for three immunoaffinity pretreatment techniques systematically, which may guide their application under different requirements and scenarios. [ABSTRACT FROM AUTHOR]

Antibiotic misuse has led to the development and spread of multidrug-resistant (MDR) microorganisms. This study evaluated the antibacterial activity of n-hexane, ethyl acetate, and aqueous extracts of the marine sponge Amphimidon chloros. The antibacterial activity of n-hexane, ethyl acetate, and aqueous extracts was evaluated using broth microdilution and disc diffusion. The chemical composition of the extracts was analysed using Liquid Chromatography-Mass spectrometry (LC-MS). The antibacterial potency of the extracts was in the following order: aqueous > n-hexane > ethyl acetate extracts. The most significant inhibitory activity of the aqueous extract was against Shigella flexneri, with an inhibition zone of 20.6 mm. Klebsiella pneumonia, Pseudomonas aeruginosa, and Listeria monocytogenes were utterly resistant to ampicillin and chloramphenicol; however, the aqueous extract efficiently inhibited these bacteria. The extract MIC ranged from 0.0195-2.5 mg/mL. With maximal inhibition against Staphylococcus aureus (0.0195 mg/mL), Bacillus cereus (0.0390 mg/mL), Shigella flexneri (0.0390 mg/mL), and Salmonella enterica (0.0781 mg/mL). While L. monocytogenes (0.3125 mg/mL) and S. aureus (0.625 mg/mL) were the only Gram-positive bacteria inhibited, the ethyl acetate extract was equally effective (MIC of 0.3125 mg/mL) against Gram-negative bacteria, including K. pneumonia, S. typhi, S. enterica, Enterobacter aerogenes, and E. coli. The n-hexane extract inhibited S. aureus, S. flexneri, and S. enterica with a MIC value of 0.1562/mL. The most prevalent phytochemicals in the aqueous and n-hexane extracts from the LC-MS study were nakinadine and kermaphidine. The study revealed that the aqueous extract of A. chloros possesses both Gram-positive and Gram-negative antibacterial activity. [ABSTRACT FROM AUTHOR]

Over the past decade, there has been a global focus on herbal medicines derived from plants. Mas Banana bracts have great potential to be transformed into natural medicine and nutraceuticals to improve the global health, in addition to being a local food supply. This study explores the phytochemical content, antioxidant, and anticancer activity of Mas Banana bracts grown in Lampung, Indonesia. Mas Banana bracts were fractionated with ethyl acetate. Using LC-MS/MS QTOF (Liquid Chromatography-Mass Spectrometry/Tandem Mass Spectrometry Quadrupole Time-of-Flight), the phytochemical composition of the ethyl acetate fraction of mas banana bracts was investigated. The analysis revealed the presence of Afzelechin and Moracenin D. The antioxidant potential was assessed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, yielding a value of 810.79 mg/100 g. The anticancer activity tested against the HeLa cell line using standard procedures was seen from the cells viability percentage that reached 51.28%. The ethyl acetate fraction of Mas Banana bracts exhibited significant antioxidant and anticancer activities with greater activity against the HeLa cell line. The results show that the ethyl acetate fraction of Mas Banana bracts possesses anticancer and antioxidant properties and it can be used as a natural food preservative and as an anticancer agent for the treatment of cancer. [ABSTRACT FROM AUTHOR]

Wine quality and safety is affected by the food contact materials (FCMs) used. These materials are expected to protect the beverage from any chemical, physical, or biological hazard and preserve its composition stable throughout its shelf-life. However, the migration of chemical substances from FCMs is a known phenomenon and requires monitoring. This review distinguishes the migrating chemical substances to those of (i) industrial origin with potential safety effects and those of (ii) natural occurrence, principally in cork (ex. tannins) with organoleptic quality effects. The review focuses on the migration of industrial chemical contaminants. Migration testing has been applied only for cork stoppers and tops, while other materials like polyethylene terephthalate (PET) bottles with aluminum cups, paperboard cartons, stainless steel vats, and oak casks have been examined for the presence of chemical migrating substances only by wine analysis without migration testing. The dominant analytical techniques applied are gas and liquid chromatography coupled to mass spectrometry (MS) for the determination of organic compounds and Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES) and ICP-MS for elemental analysis. Targeted approaches are mostly applied, while limited non-target methodologies are reported. The identified migrating substances include authorized substances like phthalate plasticizers, monomers (bisphenol A), antioxidants (Irganox 1010), known but non-authorized substances (butylparaben), break-down products, oxidation products (nonylphenol), polyurethane adhesive by-products, oligomers, ink photoinitiators, and inorganic elements. A preliminary investigation of microplastics' migration has also been reported. It is proposed that further research on the development of comprehensive workflows of target, suspect, and non-target analysis is required to shed more light on the chemical world of migration for the implementation of an efficient risk assessment and management of wine contact materials. [ABSTRACT FROM AUTHOR]

The etiology of lung cancer in never‐smokers remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Here, we aimed to enhance our understanding of lung cancer pathogenesis among never‐smokers using untargeted metabolomics. This nested case‐control study included 395 never‐smoking women who developed lung cancer and 395 matched never‐smoking cancer‐free women from the prospective Shanghai Women's Health Study with 15,353 metabolic features quantified in pre‐diagnostic plasma using liquid chromatography high‐resolution mass spectrometry. Recognizing that metabolites often correlate and seldom act independently in biological processes, we utilized a weighted correlation network analysis to agnostically construct 28 network modules of correlated metabolites. Using conditional logistic regression models, we assessed the associations for both metabolic network modules and individual metabolic features with lung cancer, accounting for multiple testing using a false discovery rate (FDR) < 0.20. We identified a network module of 121 features inversely associated with all lung cancer (p =.001, FDR = 0.028) and lung adenocarcinoma (p =.002, FDR = 0.056), where lyso‐glycerophospholipids played a key role driving these associations. Another module of 440 features was inversely associated with lung adenocarcinoma (p =.014, FDR = 0.196). Individual metabolites within these network modules were enriched in biological pathways linked to oxidative stress, and energy metabolism. These pathways have been implicated in previous metabolomics studies involving populations exposed to known lung cancer risk factors such as traffic‐related air pollution and polycyclic aromatic hydrocarbons. Our results suggest that untargeted plasma metabolomics could provide novel insights into the etiology and risk factors of lung cancer among never‐smokers. [ABSTRACT FROM AUTHOR]

Some olive cultivars grown in southeastern Italy are characterized by the production of olives with a reduced level of bitterness. They are known as sweet olive cultivars and fruits are usually consumed directly or cooked without any debittering process, offering either health benefits to consumers, thanks to the high content of antioxidants, or an economic benefit to farmers for their higher price with respect to both table and oil olives. This study evaluates and compares the organoleptic, pomological, chemical, and physical parameters of seven sweet olive cultivars at different ripening degrees in the Puglia region over 8 weeks of maturity stage for two consecutive seasons (2022 and 2023). The organoleptic evaluation was performed by a restricted panel of usual consumers/experts of sweet olives. The results showed a higher preference for the olive cultivars locally named Triggiano Dolce, Cerasella, and Mele. Significant differences in weight, length, and width of the fruits were observed based on both cultivar and year. The phenolic composition of olive cultivars was significantly affected by both cultivar and harvest year, with Cazzinicchio and Cellina di Nardò having the highest total polyphenols. The analysis of water fraction extracted from olive samples by liquid chromatography coupled with mass spectrometry led to the identification of eleven compounds belonging to the secoiroids, phenylpropanoids, phenylethanolids, and flavonoids classes. The comparison of these compounds among the studied cultivars highlighted significant differences. [ABSTRACT FROM AUTHOR]

Copyright of Food Research & Development is the property of Food Research & Development Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article presents a case study of a 60-year-old woman with chronic obstructive pulmonary disease and other health issues who presented with confusion, coma, and brainstem areflexia. It states that despite initial concerns of brain death, further investigation revealed no acute brain injury or clear cause for her symptoms, highlighting diagnostic challenges and the potential for false positive drug screenings.

Objective: This study aims to conduct a comprehensive investigation of the serum amino acid profiles of individuals with type 2 diabetes (T2D) and its related complications. Methods: Patients with T2D were enrolled in this study. Sixteen kinds of common amino acids in the fasting circulating were assessed through liquid chromatography-mass spectrometry (LC-MS). Subsequently, correlation, regression analyses, and receiver operating characteristic (ROC) curves were conducted to assess the associations between amino acids and clinical indicators. Results: Thirteen different kinds of amino acids were identified in diabetic patients, as compared with normal controls. The Glutamine/Glutamate (Gln/Glu) ratio was negatively correlated with BMI, HbA1c, serum uric acid, and the triglyceride-glucose (TyG) index, while it was positively correlated with HDL-C. Logistic regression analyses indicated that Gln/Glu was a consistent protective factor for both T2D (OR = 0.65, 95% CI 0.50-0.86) and obesity (OR = 0.79, 95% CI 0.66-0.96). The ROC curves demonstrated that Gln/Glu, proline, valine, and leucine provided effective predictions for diabetes risk, with Gln/Glu exhibiting the highest AUC [0.767 (0.6780.856)]. In patients with T2D, Gln was the only amino acid that displayed a negative correlation with HbA1c (r = -0.228, p = 0.017). Furthermore, HOMA-β exhibited a negative correlation with Glu (r = -0.301, p = 0.003) but a positive correlation with Gln/Glu (r = 0.245, p = 0.017). Notably, logistic regression analyses revealed an inverse correlation of Gln/Glu with the risk of diabetic kidney disease (OR = 0.74,95% CI 0.55-0.98) and a positive association with the risk of diabetic retinopathy (OR = 1.53, 95% CI 1.08-2.15). Conclusion: The Gln/Glu ratio exhibited a significant association with diabetes, common metabolic parameters, and diabetic complications. These findings shed light on the pivotal role of Gln metabolism in T2D and its associated complications. [ABSTRACT FROM AUTHOR]

Background: Gut microbiota has significant impact on the cardio-metabolism and inflammation, and is implicated in the pathogenesis and progression of atherosclerosis. However, the long-term prospective association between trimethylamine N-oxide (TMAO) level and major adverse clinical events (MACEs) in patients with coronary artery disease (CAD) with or without diabetes mellitus (DM) habitus remains to be investigated. Methods: This prospective, single-center cohort study enrolled 2090 hospitalized CAD patients confirmed by angiography at Beijing Hospital from 2017-2020. TMAO levels were performed using liquid chromatography-tandem mass spectrometry. The composite outcome of MACEs was identified by clinic visits or interviews annually. Multivariate Cox regression analysis, Kaplan-Meier analysis, and restricted cubic splines were mainly used to explore the relationship between TMAO levels and MACEs based on diabetes mellitus (DM) habitus. Results: During the median follow-up period of 54 (41, 68) months, 266 (12.7%) developed MACEs. Higher TMAO levels, using the tertile cut-off value of 318.28 ng/mL, were significantly found to be positive dose-independent for developing MACEs, especially in patients with DM (HR 1.744, 95%CI 1.084-2.808, p = 0.022). Conclusions: Higher levels of TMAO are significantly associated with long-term MACEs among CAD patients with DM. The combination of TMAO in patients with CAD and DM is beneficial for risk stratification and prognosis. [ABSTRACT FROM AUTHOR]

Per‐ and poly‐fluoroalkyl substances (PFAS), which are long‐lasting environmental contaminants that are released into the environment during the e‐waste disassembly process, pose a threat to human health. Human milk is a complex and dynamic mixture of endogenous and exogenous substances, including steroid hormones and PFAS. Therefore, in this study, we aimed to investigate the association between PFAS and steroid hormones in human milk from women living close to an e‐waste disassembly area. In 2021, we collected milk samples from 150 mothers within 4 weeks of delivery and analyzed them via liquid chromatography‐tandem mass spectrometry to determine the levels of 21 perfluorinated compounds and five steroid hormones (estrone, estriol, testosterone, progesterone, and androstenedione [A‐dione]). We also performed multiple linear regression analysis to clarify the association between maternal PFAS exposure and steroid hormone concentrations. Our results indicated that PFOA and PFOS were positively associated with estrone (β, 0.23; 95% CI, 0.08–0.39) and A‐dione (β, 0.186; 95% CI, 0.016–0.357) concentrations in human milk, respectively. Further, the average estimated daily intake of PFOA and PFOS were 36.5 ng/kg bw/day (range, 0.52–291.7 ng/kg bw/day) and 5.21 ng/kg bw/day (range, 0.26–32.3 ng/kg bw/day), respectively. Of concern, the PFAS intake of breastfeeding infants in the study area was higher than the recommended threshold. These findings suggested that prenatal exposure to PFAS from the e‐waste disassembly process can influence steroid hormones levels in human milk. Increased efforts to mitigate mother and infant exposure to environmental pollutants are also required. Plain Language Summary: We recruited 150 mothers who provided human milk samples within 4 weeks of delivery. Using liquid chromatography‐tandem mass spectrometry, we measured concentrations of 21 perfluorinated compounds and five steroid hormones (estrone, estriol, testosterone, progesterone, and androstenedione [A‐dione]) in the human milk samples. Multiple linear regression analysis was performed to examine the association between maternal PFAS exposure and steroid hormone concentrations. Our findings revealed significant positive associations between specific PFAS compounds (PFOA and PFOS) and certain steroid hormone concentrations in human milk. Notably, PFOA showed positive associations with estrone concentrations, PFOS was associated with A‐dione levels. These results suggest that prenatal exposure to PFAS from e‐waste disassembly areas can impact the levels of steroid hormones in human milk. Key Points: Per‐ and poly‐fluoroalkyl substances and steroid hormones concentrations in human milk measured in an e‐waste disassembly areaPFOA was positively associated with DHEA and estrone concentrations in human milkPFOS was positively associated with A‐dione in human milk [ABSTRACT FROM AUTHOR]

Bile, a crucial fluid produced continuously by the liver, plays an essential role in digestion within the small intestine. Beyond its primary function in lipid digestion, bile also acts as a pathway for the elimination of various endogenous and exogenous substances. There have been limited studies focusing on interspecies differences. This study offers a comprehensive analysis of bile acid (BA) composition and its correlation with gene expression patterns across six different species, including mammals and poultry, through combining Liquid Chromatography-Mass Spectrometry (LC-MS) and transcriptome sequencing. The BA profiles revealed distinct metabolite clusters: D-glucuronic acid (GLCA) and glycochenodeoxycholic acid (GCDCA) were predominant in mammals, while taurolithocholic acid (TLCA) and T-alpha-MCA were prevalent in poultry, highlighting species-specific BA compositions. Differentially abundant metabolites, particularly GDCA, glycohyodeoxycholic acid (GHDCA) and taurodeoxycholic acid (TDCA) showed significant variations across species, with pigs showing the highest BA content. Transcriptome analysis of the liver and small intestine tissues of 56 cDNA libraries across the six species revealed distinct mRNA expression patterns. These patterns clustered samples into broad categories based on tissue type and phylogenetic relationships. Furthermore, the correlation between gene expression and BA content was examined, identifying the top 20 genes with significant associations. These genes potentially serve as biomarkers for BA regulation. [ABSTRACT FROM AUTHOR]

Currently, the clinical cure rate for primary liver cancer remains low. Effective screening and early diagnosis of hepatocellular carcinoma (HCC) remain clinical challenges. Exosomes are intimately associated with tumor development and their contents have the potential to serve as highly sensitive tumor-specific markers. A comprehensive untargeted metabolomics study was conducted using exosome samples extracted from the serum of 48 subjects (36 HCC patients and 12 healthy controls) via a commercial kit. An ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) strategy was used to identify the metabolic compounds. A total of 18 differential metabolites were identified using the non-targeted metabolomics approach of UPLC-QTOF-MS/MS. Pathway analysis revealed significant alterations in the arachidonic acid metabolism, linoleic acid metabolism, and unsaturated fatty acid metabolism pathways. ROC analysis indicated that three metabolites with AUC values exceeding 0.900 were selected as potential biomarkers: caprylic acid and linoleic acid were upregulated in the HCC group, whereas pentadecanoic acid was downregulated. Linoleic acid, caprylic acid, and pentadecanoic acid are potential biomarkers for diagnosing HCC. The significant alterations in these three metabolic pathways offer new insights into the mechanisms underlying HCC formation and progression. [ABSTRACT FROM AUTHOR]

Metabolic perturbation has been associated with depression. An untargeted metabolomics approach using liquid chromatography-high resolution mass spectrometry was employed to detect and measure the rat serum metabolic changes following chronic social isolation (CSIS), an animal model of depression, and effective antidepressant fluoxetine (Flx) treatment. Univariate and multivariate statistics were used for metabolic data analysis and differentially expressed metabolites (DEMs) determination. Potential markers and predictive metabolites of CSIS-induced depressive-like behavior and Flx efficacy in CSIS were evaluated by the receiver operating characteristic (ROC) curve, and machine learning (ML) algorithms, such as support vector machine with linear kernel (SVM–LK) and random forest (RF). Upregulated choline following CSIS may represent a potential marker of depressive-like behavior. Succinate, stachydrine, guanidinoacetate, kynurenic acid, and 7-methylguanine were revealed as potential markers of effective Flx treatment in CSIS rats. RF yielded better accuracy than SVM–LK (98.50% vs. 85.70%, respectively) in predicting Flx efficacy in CSIS vs. CSIS, however, it performed almost identically in classifying CSIS vs. control (75.83% and 75%, respectively). Obtained DEMs combined with ROC curve and ML algorithms provide a research strategy for assessing potential markers or predictive metabolites for the designation or classification of stress-induced depressive phenotype and mode of drug action. [ABSTRACT FROM AUTHOR]

BACKGROUND: The leaves of guabirobeira contain important phenolic and flavonoid compounds, known for their antioxidant, anti‐inflammatory, antibacterial, and antinociceptive activities. The purpose of this work was to obtain extracts from guabirobeira leaves through aqueous infusion and pressurized liquid extraction with water, ethanol, and a combination of water–ethanol (ratio 1:1, v/v; PLE‐W:E). Subsequently, we used liquid chromatography coupled with mass spectrometry to identify the chemical compounds, and to study the antioxidant activity in rat brain cells; thiobarbituric acid reactive substances (TBARS) and reactive oxygen species (ROS) antibacterial activity against Gram‐negative and Gram‐positive bacteria were also seen. RESULTS: According to the findings, all four extracts contained a significant amount of phytochemical compounds. Among them, the PLE‐W:E extract showed a higher concentration of flavonoids, demonstrating significant antioxidant activity in in vitro assays of TBARS and ROS in rat brain cells. It also exhibited antibacterial activity against both Gram‐positive and Gram‐negative bacteria. CONCLUSION: Guabirobeira leaf extracts hold promise as a potential source of bioactive compounds. These extracts can be applied across various sectors, including cosmetics and skincare products, pharmaceuticals, food and beverages, natural preservatives, and functional materials. By exploring these potential applications, valuable contributions can be made to the field of sustainable chemistry and pharmacy, furthering the utilization of guabirobeira leaf extracts in diverse industries. This approach also aligns with the promotion of environmentally friendly and sustainable practices. © 2024 Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]

Targeted mass spectrometry (MS) holds promise for precise protein and protein‐representative peptide identification and quantification, enhancing disease diagnosis. However, its clinical application is hindered by complex data analysis and expert review requirements. It is hypothesized that machine learning (ML) models can automate data analysis to accelerate the clinical application of MS. The approach involves an ML‐driven pipeline that extracts statistical and morphological features from an MS target region and feeds these features into ML algorithms to generate and assess predictive models. The findings demonstrate ML prediction models exhibit superior performance when trained on extracted features versus raw spectra intensity data and that random forest models exhibit robust classification performance in both internal and external validation datasets. These models remain effective across varying training dataset sizes and positive sample rates and are enhanced by a nested active learning approach. This approach can thus revolutionize clinical MS applications. [ABSTRACT FROM AUTHOR]

Background/objectives: Prolonged fasting triggers a stress response within the human body. Our objective was to investigate the impact of prolonged fasting, in conjunction with stress, on kynurenine pathway metabolites. Subjects/methods: Healthy males were divided into fasting group (zero-calorie-restriction) for 6 days (FAST, n = 14), and control group (CON, n = 10). Blood and saliva samples were collected at baseline, Day 2, Day 4, Day 6 during fasting period, and 1 week after resuming regular diet. Plasma levels of kynurenine pathway metabolites were measured using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Plasma and salivary samples were analyzed for stress markers. Results: A pronounced activation of the kynurenine pathway in individuals on FAST trial was revealed. Concentrations of picolinic acid (PIC), kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK) were significantly increased, with peak levels observed on Day 6 (P < 0.0001). Conversely, concentrations of tryptophan (TRP) and quinolinic acid (QUIN) decreased (P < 0.0001), while kynurenine (KYN) and nicotinamide (NAM) levels remained stable. Cortisol and noradrenaline concentrations remained unchanged. However, adrenaline levels significantly increased on Day 4 within FAST compared to CON (P = 0.005). Notably, all deviations in kynurenine pathway metabolite levels returned to baseline values upon resuming regular diet following the 6-day fasting regimen, even when weight and BMI parameters were not restored. Conclusions: Extended fasting over 6 days induces the kynurenine pathway and has minimal effects on stress markers. Restoration of metabolite concentrations upon regular feeding implies rapid adaptation of the kynurenine pathway synthetic enzymes to maintain homeostasis when faced with perturbations. [ABSTRACT FROM AUTHOR]

Background: Catheter ablation in patients with atrial fibrillation is associated with a transient increase in thromboembolic risk and adequate anticoagulation is highly important. When patients are anticoagulated with apixaban, monitoring of plasma concentrations of the drug is not routinely performed. This study aimed to assess the influence of clinical patient characteristics, concomitant drug treatment and self-reported adherence on apixaban concentrations, and to describe the intra- and inter-individual variability in apixaban concentrations in this group of patients. Method Apixaban concentrations from 141 patients were measured in plasma one week before ablation and two, six and ten weeks after ablation, employing ultra-high performance liquid chromatography coupled with tandem mass spectrometry. In samples not obtained at trough, apixaban concentrations were adjusted to trough levels. Self-reported adherence was registered by means of the 8-item Morisky Medication Adherence Scale before and after ablation. Results: There were statistically significant, positive correlations between apixaban concentrations and increased age, female sex, lower glomerular filtration rate, higher CHA2DS2-VASc score, use of cytochrome P450 3A4 and/or p-glycoprotein inhibitors, and use of amiodarone. Self-reported adherence was generally high. The mean intra-individual and inter-individual coefficients of variation were 29% and 49%, respectively. Conclusion: In patients undergoing catheter ablation for atrial fibrillation, age, sex, renal function, interacting drugs and cerebrovascular risk profile were all associated with altered plasma apixaban concentration. In this group of patients with a generally high self-reported adherence, intra-individual variability was modest, but the inter-individual variability was substantial, and similar to those previously reported in other patient apixaban-treated populations. If a therapeutic concentration range is established, there might be a need for a more flexible approach to apixaban dosing, guided by therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

Multimodal analgesia is defined as using several drugs or techniques simultaneously to target different pain pathways or receptors to avoid pain propagation. This study evaluated the pharmacokinetic profile and comparative bioavailability of etoricoxib 90 mg and tramadol 50 mg dosing alone (reference drugs) or in a novel fixed‐dose combination (test drug) under fasting conditions in Mexican healthy volunteers. This was a randomized, open‐label, 3‐way, crossover, single‐dose, prospective, and longitudinal study with a 14‐day washout period. Eligible subjects were healthy Mexican adult volunteers. The drugs were dosing orally, according to the randomization sequence, after 10 hours of fasting and 4 hours before breakfast with 250 mL of water at room temperature. Serial blood samples were collected before and after dosing, both drugs were quantified using high‐performance liquid chromatography coupled with tandem mass spectrometry. Forty‐two subjects were enrolled and 38 completed the study (28 men and 14 women, mean age 25.2 years, mean weight 66.6 kg). Test products were considered to have comparative bioavailability if confidence intervals of natural log‐transformed for (maximum plasma drug concentration (Cmax), (area under the plasma drug concentration‐time curve form 0 up to last sampling time (AUC0‐t), and (area under the plasma drug concentration‐time curve from 0 up to infinity (AUC0‐∞) data were within the range of 80%‐125%. Non‐serious adverse events were observed. The results demonstrate that the pharmacokinetic profile and bioavailability of the etoricoxib/tramadol fixed‐dose combination are comparable to those of the reference products. [ABSTRACT FROM AUTHOR]

Background: Haemaphysalis flava is a notorious parasite for humans and animals worldwide. The organs of H. flava are bathed in hemolymph, which is a freely circulating fluid. Nutrients, immune factors, and waste can be transported to any part of the body via hemolymph. The main soluble components in hemolymph are proteins. However, knowledge of the H. flava proteome is limited. Methods: The hemolymph was collected from fully engorged H. flava ticks by leg amputation. Hemolymph proteins were examined by both blue native polyacrylamide gel electrophoresis (BN-PAGE) and sodium dodecyl sulfate PAGE (SDS-PAGE). Proteins extracted from the gels were further identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Two bands (380 and 520 kDa) were separated from tick hemolymph by BN-PAGE and were further separated into four bands (105, 120, 130, and 360 kDa) by SDS-PAGE. LC-MS/MS revealed that seven tick proteins and 13 host proteins were present in the four bands. These tick proteins mainly belonged to the vitellogenin (Vg) family and the α-macroglobulin family members. In silico structural analysis showed that these Vg family members all had common conserved domains, including the N-terminus lipid binding domain (LPD-N), the C-terminus von Willebrand type D domain (vWD), and the domain of unknown function (DUF). Additionally, two of the Vg family proteins were determined to belong to the carrier protein (CP) by analyzing the unique N-terminal amino acid sequences and the cleaving sites. Conclusion: These findings suggest that the Vg family proteins and α-macroglobulin are the primary constituents of the hemolymph in the form of protein complexes. Our results provide a valuable resource for further functional investigations of H. flava hemolymph effectors and may be useful in tick management. [ABSTRACT FROM AUTHOR]

Objective: Carotid atherosclerosis is a chronic progressive vascular disease that can be complicated by stroke in severe cases. Prompt diagnosis and treatment of high‐risk patients are quite difficult due to the lack of reliable clinical biomarkers. This study aimed to explore potential plaque metabolic markers of stroke‐prone risk and relevant targets for pharmacological intervention. Method: Carotid intima and plaque sample tissues were obtained from 20 patients with cerebrovascular symptoms of carotid origin. An untargeted metabolomics approach based on liquid chromatography–tandem mass spectrometry was utilized to characterize the metabolic profiles of the tissues. Multivariate and univariate analysis tools were used. Results: A total of 154 metabolites were significantly altered in carotid plaque when compared with thickened intima. Of these, 62 metabolites were upregulated, whereas 92 metabolites were downregulated. Support vector machines identified the 15 most important metabolites, such as N‐(cyclopropylmethyl)‐N′‐phenylurea, 9(S)‐HOTrE, ACar 12:2, quinoxaline‐2,3‐dithiol, and l‐thyroxine, as biomarkers for high‐risk plaques. Metabolic pathway analysis showed that abnormal purine and nucleotide metabolism, amino acid metabolism, glutathione metabolism, and vitamin metabolism may contribute to the occurrence and progression of carotid atherosclerotic plaque. Conclusions: Our study identifies the biomarkers and related metabolic mechanisms of carotid plaque, which is stroke‐prone, and provides insights and ideas for the precise prevention and targeted intervention of the disease. [ABSTRACT FROM AUTHOR]

Rationale: Huahong tablet, a commonly used clinical Chinese patent medicine, shows good efficacy in treating pelvic inflammation and other gynaecological infectious diseases. However, the specific composition of Huahong tablets, which are complex herbal formulations, remains unclear. Therefore, this study aims to identify the active compounds and targets of Huahong tablets and investigate their mechanism of action in pelvic inflammatory diseases. Methods: We utilised ultrahigh‐performance liquid chromatography Q‐Exactive‐Orbitrap mass spectrometry and the relevant literature to identify the chemical components of Huahong tablets. The GNPS database was employed to further analyse and speculate on the components. Potential molecular targets of the active ingredients were predicted using the SwissTargetPrediction website. Protein–protein interaction analysis was conducted using the STRING database, with visualisation in Cytoscape 3.9.1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database. Additionally, a traditional Chinese medicine–ingredient–target–pathway network was constructed using Cytoscape 3.10.1. Molecular docking validation was carried out to investigate the interaction between core target and specific active ingredient. Results: A total of 66 chemical components were identified, and 41 compounds were selected as potential active components based on the literature and the TCMSP database. Moreover, 38 core targets were identified as key targets in the treatment of pelvic inflammatory diseases with Huahong tablets. GO and KEGG enrichment analysis revealed 986 different biological functions and 167 signalling pathways. Conclusion: The active ingredients in Huahong tablets exert therapeutic effects on pelvic inflammatory diseases by acting on multiple targets and utilising different pathways. Molecular docking confirmed the high affinity between the specific active ingredients and disease targets. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Drug exposure and response is determined by pharmacokinetic (PK) and pharmacodynamic (PD) profiles. Interindividual differences in abundance of drug metabolizing enzymes (DMEs) and drug target proteins underpin PK and PD variability and impact treatment efficacy and tolerability. Extracellular vesicles (EVs) carry protein cargo inherited from originating cells and may be useful for defining differences in key proteins related to hepatic drug metabolism and the treatment of metabolic‐associated fatty liver disease (MAFLD). We sought to quantify these proteins in liver‐derived EVs and establish the profile relative to paired tissue.EVs were recovered from human liver tissue samples (LT‐EV, n = 11). Targeted liquid chromatography with tandem mass spectrometry (LC–MS/MS) assays were employed for absolute quantification of proteins in EV isolates and matched liver tissue.DMEs and MAFLD drug targets were readily detected and quantified in LT‐EVs. Twelve of 15 DMEs exhibited moderate to strong correlation (Spearman ⍴ = 0.618–0.973) between tissue and EVs. Correlation in protein abundance was influenced by the extent of extra‐hepatic expression of the target.This study provides evidence that key proteins related to PK and PD profiles can be measured in liver‐derived EVs and abundance of liver‐enriched DMEs are robustly correlated between paired tissue and EVs. The robust detection of protein markers related to drug PD profile in MAFLD opens the possibility to track within‐subject changes in MAFLD and lays the foundation for future development of a liver‐derived EV liquid biopsy to assess markers of drug exposure and response in vivo. [ABSTRACT FROM AUTHOR]

Ciprofol is a novel short-acting intravenous anaesthetic developed in China that is mainly metabolized by cytochrome P450 2B6 (CYP2B6) and uridine diphosphate glucuronosyltransferase 1A9 (UGT1A9). Currently, insufficient evidence is available to support drug‒drug interactions between ciprofol and CYP2B6 inactivators. Here, we established a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to assess the concentration of ciprofol and investigated the effects of psoralen and clopidogrel on the metabolism of ciprofol in liver microsomes and rats. In rat and human liver microsomes, the median inhibitory concentration (IC50) values of psoralen were 63.31 μmol·L-1 and 34.05 μmol·L-1, respectively, showing mild inhibitory effects on ciprofol metabolism, whereas the IC50 values of clopidogrel were 6.380 μmol·L-1 and 2.565 μmol·L-1, respectively, with moderate inhibitory effects. SD rats were randomly divided into three groups: psoralen (27 mg·kg-1), clopidogrel (7.5 mg·kg-1), and the same volume of 0.5% carboxy methyl cellulose. After 7 days, all rats were injected with 2.4 mg·kg-1 ciprofol. Compared with the control group, the AUC and MRT values of ciprofol in the psoralen and clopidogrel groups were significantly greater, whereas the CL values were significantly lower. In addition, the durations of loss of righting reflex (LORR) in the psoralen and clopidogrel groups were 16.1% and 23.0% longer than that in the control group, respectively. In conclusion, psoralen and clopidogrel inhibit ciprofol metabolism to different degrees and prolong the duration of LORR in rats. [ABSTRACT FROM AUTHOR]

Objective Animal Studied Procedures Results Conclusions The application of canine amniotic membrane (cAM) for corneal reconstruction is widely used in the veterinary field. However, the information on biological properties and alternative forms of cAM for corneal wound healing is limited. This study aimed to investigate the proteomic profiles and corneal wound healing properties of cAM, cAM extract (cAME), and lyophilized cAM extract (cAMX).A total number of 14 cAMs were sterilely harvested from healthy full‐term puppies and randomly divided into three different forms: cAM (n = 14), cAME (n = 14), and cAMX (n = 14).Each form of cAMs was subjected to proteomic analysis using label‐free liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS), followed by bioinformatic analysis. The proteins were classified into properties by comparing them with the literature search on human amniotic membrane (hAM) properties and the effect on corneal wound healing when given topically.The analyses identified 8136 proteins in cAM, 8211 proteins in cAME, and 7093 proteins in cAMX. A total number of 100 proteins were matched with proteins in hAM properties and were classified into anti‐inflammatory, anti‐fibrotic, anti‐microbial, anti‐angiogenic, promotion of epithelialization, analgesic, and support cell adhesion and growth properties. Furthermore, proteins with corneal wound healing effects were identified in cAME and cAMX.cAM and its extracts contain numerous proteins, including proteins related to corneal wound healing properties. Additionally, cAME and cAMX showed proteins involved in corneal wound healing and their potential benefits for topical use in ophthalmology. [ABSTRACT FROM AUTHOR]

Charcot–Marie–Tooth disease type 1E (CMT1E) is an inherited autosomal dominant peripheral neuropathy caused by mutations in the peripheral myelin protein 22 (PMP22) gene. The identical leucine‐to‐proline (L16P) amino acid substitution in PMP22 is carried by the Trembler J (TrJ) mouse and is found in CMT1E patients presenting with early‐onset disease. Peripheral nerves of patients diagnosed with CMT1E display a complex and varied histopathology, including Schwann cell hyperproliferation, abnormally thin myelin, axonal degeneration, and subaxonal morphological changes. Here, we have taken an unbiased data‐independent analysis (DIA) mass spectrometry (MS) approach to quantify proteins from nerves of 3‐week‐old, age and genetic strain‐matched wild‐type (Wt) and heterozygous TrJ mice. Nerve proteins were dissolved in lysis buffer and digested into peptide fragments, and protein groups were quantified by liquid chromatography‐mass spectrometry (LC–MS). A linear model determined statistically significant differences between the study groups, and proteins with an adjusted p‐value of less than 0.05 were deemed significant. This untargeted proteomics approach identified 3759 quality‐controlled protein groups, of which 884 demonstrated differential expression between the two genotypes. Gene ontology (GO) terms related to myelin and myelin maintenance confirm published data while revealing a previously undetected prominent decrease in peripheral myelin protein 2. The dataset corroborates the described pathophysiology of TrJ nerves, including elevated activity in the proteasome‐lysosomal pathways, alterations in protein trafficking, and an increase in three macrophage‐associated proteins. Previously unrecognized perturbations in RNA processing pathways and GO terms were also discovered. Proteomic abnormalities that overlap with other human neurological disorders besides CMT include Lafora Disease and Amyotrophic Lateral Sclerosis. Overall, this study confirms and extends current knowledge on the cellular pathophysiology in TrJ neuropathic nerves and provides novel insights for future examinations. Recognition of shared pathomechanisms across discrete neurological disorders offers opportunities for innovative disease‐modifying therapeutics that could be effective for distinct neuropathies. [ABSTRACT FROM AUTHOR]

Assessment of Wilson disease is complicated, with neither ceruloplasmin, nor serum or urine copper, being reliable. Two new indices, accurate non-ceruloplasmin copper (ANCC) and relative ANCC were developed and applied to a cohort of 71 patients, as part of a Wilson Disease Registry Study.Elemental copper-protein speciation was developed for holo-ceruloplasmin quantitation using strong anion exchange chromatography coupled to triple quadrupole inductively coupled plasma mass spectrometry. The serum proteins were separated using gradient elution and measured at m/z 63 (63Cu+) and 48 (32S16O+) using oxygen reaction mode and Cu-EDTA as calibration standard. The ANCC was calculated by subtraction of the ceruloplasmin bound copper from the total serum copper and the RelANCC was the percentage of total copper present as the ANCC.The accuracy of the holo-ceruloplasmin measurement was established using two certified reference materials, giving a mean recovery of 94.2 %. Regression analysis between the sum of the copper containing species and total copper concentration in the patient samples was acceptable (slope=0.964, intercept=0, r=0.987) and a difference plot, gave a mean difference for copper of 0.38 μmol/L. Intra-day precision for holo-ceruloplasmin at serum copper concentrations of 0.48 and 3.20 μmol/L were 5.2 and 5.6 % CV and the intermediate precision at concentrations of 0.80 and 5.99 μmol/L were 6.4 and 6.4 % CV, respectively. The limit of detection (LOD) and lower limit of quantification (LLOQ) for holo-ceruloplasmin were 0.08 and 0.27 μmol/L as copper, respectively.ANCC and Relative ANCC are important new diagnostic and monitoring biomarker indices for Wilson disease (WD). [ABSTRACT FROM AUTHOR]

Phthalates used in the industry penetrate the environment and negatively affect humans and animals. Hair samples seem to be the best matrix for studies on long-term exposure to phthalates, but till now they were used only in investigations on humans. Moreover, the knowledge of the wild terrestrial animal exposure to phthalates is extremely limited. This study aimed to establish of concentration levels of selected phthalate metabolites (i.e. monomethyl phthalate—MMP, monoethyl phthalate—MEP, mono-isobutyl phthalate—MiBP, monobutyl phthalate—MBP, monobenzyl phthalate—MBzP, mono-cyclohexyl phthalate—MCHP, mono(2-ethylhexyl) phthalate—MEHP and mono-n-octyl phthalate—MOP) in wild boar hair samples using liquid chromatography with mass spectrometry (LC–MS) analysis. MEHP was noted in 90.7% of samples with mean 66.17 ± 58.69 pg/mg (median 49.35 pg/mg), MMP in 59.3% with mean 145.1 ± 310.6 pg/mg (median 64.45 pg/mg), MiBP in 37.0% with mean 56.96 ± 119.4 pg/mg (median < limit of detection—LOD), MBP in 35.2% with mean 19.97 ± 34.38 pg/mg (median < LOD) and MBzP in 1.9% with concentration below limit of quantification. MEP, MCHP, and MOP have not been found in wild boar hair samples during this study. The results have shown that wild boars are exposed to phthalates and hair samples may be used as a matrix during studies on levels of phthalate metabolites in wild animals. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Dried blood volumetric absorptive microsamples (VAMS) may facilitate home‐based sampling to enhance therapeutic drug monitoring after transplantation. This study aimed to clinically validate a liquid chromatography–tandem mass spectrometry assay using 2 VAMS devices with different sampling locations (Tasso‐M20 for the upper arm and Mitra for the finger). Patient preferences were also evaluated.Clinical validation was performed for tacrolimus and mycophenolic acid by comparison of paired VAMS and venipuncture samples using Passing–Bablok regression and Bland–Altman analysis. Conversion of mycophenolic acid VAMS to serum concentrations was evaluated using haematocrit‐dependent formulas and fixed correction factors defined a priori. Patients' perspectives, including useability, acceptability and feasibility, were also investigated using established questionnaires.Paired samples (n = 50) were collected from 25 kidney transplant recipients. Differences for tacrolimus whole‐blood concentration were within ±20% for 86 and 88% of samples from the upper arm and fingerstick, respectively. Using correction factors of 1.3 for the upper‐arm and 1.47 for finger‐prick samples, 84 and 76% of the paired samples, respectively, were within ±20% for mycophenolic acid serum concentration. Patient experience surveys demonstrated limited pain and acceptable useability of the upper‐arm device.Tacrolimus and mycophenolic acid can be measured using 2 common VAMS devices with similar analytical performance. Patients are supportive of home‐based monitoring with a preference for the Tasso‐M20 device. [ABSTRACT FROM AUTHOR]

Background Results Conclusion Peanut peptides can chelate iron but their chelation mechanism remains unclear. The purpose of this study is to separate peanut ferrous‐chelating peptides and explore the chelation mechanism of peanut peptides with iron.Peanut peptide component F‐122, which had a higher chelation rate, was separated using ultrafiltration, gel filtration chromatography, and ion exchange chromatography, achieving a ferrous chelation rate of 90.7%. Six peptide segments were screened and their amino acid sequences were identified by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Spectral analysis confirmed that the chelation between peanut peptides and ferrous ions occurred and a new substance was formed. Molecular docking simulation indicated that the amino acids in peanut peptides involved in the chelating reaction were glutamic acid, arginine, glycine, threonine, phenylalanine, and lysine. The binding sites included the main chain oxygen atom, side chain oxygen atom, and carboxyl oxygen atom of amino acid.The isolated peanut peptide had a higher ferrous‐chelation rate. The chelating mechanism of peanut peptide with ferrous ion was elucidated. This study provides a theoretical basis for the development of new peptide‐ferrous preparations. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Lepionurus sylvestris Blume has a long history of folklore medicinal usage against various ailments. However, studies on these plants were neglected particularly their pharmacological potential. Methods: The crude extract was identified using LC-MS analysis. In vitro assays were carried out to determine the properties of antioxidant, anti-microbial, and anti-cancer. Further, network pharmacology was proposed to evaluate the potential targets of the compounds against breast cancer and type II diabetes. Molecular docking and molecular dynamic simulation were used to determine the potential compounds for the drug formulation of diabetes. Results: Various bioactive compounds were identfied using LC-MS and Galiposin, Fujikinetin, Boeravinone B, 4-Deoxybryaquinone, and Norbaeocystin were described for the first time from the plant. Determination of antioxidant potential showed that the IC50 value of ABTS, DPPH, and phosphomolybdate was 24.33 µg/ml, 37.81 µg/ml, 60.35 µg/ml, and reducing power assays 1.185. The antibacterial activity against Streptococcus pyogenes, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli was determined, and the minimum inhibition concentration (MIC) was found to be 5.3 mg/ml, 3.47 mg/ml, 3.33 mg/ml, and 2.7 mg/ml respectively, revealing the extracts as effective antibacterial agents. The IC50 values for the plant extract were determined to be 26 µg/ml, 30.52 µg/ml, and 24.39 µg/ml for HeLa, MCF-7, and K-562 cells, respectively, and the increasing concentration of the plant extract increased LDH release. Furthermore, the in silico network pharmacology, molecular docking which had the highest docking score for GAPDH and HIF-1 target proteins of -9.3 kcal/mol, and − 11.3 kcal/mol binding affinities, and molecular dynamic simulation analysis revealed the bioactive compound Boeravinone B present in the plant was significant for the treatment of various ailments. Conclusion: Based on our findings, plant extracts could be a promising option for developing new drug formulations. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance and/or insulin secretion dysfunction are crucial causes of type 2 diabetes mellitus (T2DM). Although some studies have suggested potential roles for vitamins D and K in glucose metabolism and insulin sensitivity, there is limited and inconclusive research on their levels in T2DM patients and their relationship with blood glucose levels and insulin resistance. Additionally, there is a lack of large-scale clinical trials and comprehensive studies investigating the combined effects of vitamins D and K on T2DM. Methods: A total of 195 participants with newly diagnosed T2DM were included in the research group, while 180 volunteers undergoing physical examinations in our hospital served as the control group. Fasting plasma glucose (FPG) was estimated using the glucose-oxidase technique, and fasting serum insulin (FINS) was evaluated by radioimmunoassay. FPG and FINS were used to calculate the homeostasis model assessment-insulin resistance (HOMA-IR). Serum vitamin D levels were measured using 25-hydroxyvitamin D, and vitamin K levels were evaluated using phylloquinone (VK1) and menaquinone (VK2) via ultra-high performance liquid chromatography and tandem mass spectrometry. Receiver operating characteristic (ROC) analysis was performed to assess the predictive value of these vitamins for T2DM. Results: Circulating levels of 25-hydroxyvitamin D (25.95 ± 10.42 ng/mL), VK1 (1.24 ± 0.89 ng/mL), and VK2 (0.2 ± 0.21 ng/mL) in T2DM patients were significantly lower than in the control group (37.46 ± 13.95 ng/mL for 25- hydroxyvitamin D, 1.99 ± 1.39 ng/mL for VK1, and 0.33 ± 0.22 ng/mL for VK2; p<0.001 for all comparisons). ROC analysis indicated that 25-hydroxyvitamin D, VK1, and VK2 could predict the occurrence of T2DM, with AUC values of 0.75, 0.69, and 0.71, respectively. In T2DM patients, 25-hydroxyvitamin D levels were positively correlated with VK1 (r=0.43, p<0.001) and VK2 (r=0.40, p<0.001) levels. FPG and HOMA-IR in T2DM patients were negatively correlated with circulating levels of 25-hydroxyvitamin D (r=-0.57, p<0.001), VK1 (r=-0.44, p<0.001), and VK2 (r=-0.36, p<0.001).Conclusion: Circulating levels of vitamins D and K are lower in T2DM patients and show significant correlations with blood glucose levels and insulin resistance. These findings suggest that measurements of 25-hydroxyvitamin D, VK1, and VK2 could have predictive value for T2DM, highlighting the potential roles of these vitamins in T2DM management. [ABSTRACT FROM AUTHOR]

Background: Bile acids (BAs), products of gut microbiota metabolism, have long been implicated in atherosclerotic disease pathogenesis. Characterizing the serum bile acid profile and exploring its potential role in carotid atherosclerosis (CAS) development are crucial tasks. Methods: In this study, we recruited 73 patients with CAS as the disease group and 77 healthy individuals as the control group. We systematically measured the serum concentrations of 15 bile acids using ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression were applied to analyze the impact of bile acids on the disease and select the key BAs. The possible molecular mechanism was elucidated by network pharmacology. Results: (1) The BA profile of patients with CAS significantly differed. (2) Multifactorial logistic regression analysis identified elevated levels of GCDCA (OR: 1.01, P < 0.001), DCA (OR: 1.01, P = 0.005), and TDCA (OR: 1.05, P = 0.002) as independent risk factors for CAS development. Conversely, GCA (OR: 0.99, P = 0.020), LCA (OR: 0.83, P = 0.002), and GUDCA (OR: 0.99, P = 0.003) were associated with protective effects against the disease. GCA, DCA, LCA, and TDCA were identified as the four key BAs. (3) TNF, FXR, GPBAR1, ESR1 and ACE were predicted to be targets of BAs against AS. These four BAs potentially impact AS progression by triggering signaling pathways, including cAMP, PPAR, and PI3K-AKT pathways, via their targets. Conclusion: This study offers valuable insights into potential therapeutic strategies for atherosclerosis that target bile acids. [ABSTRACT FROM AUTHOR]

The early and accurate identification of predictive biomarkers for antiviral treatment efficacy remains a significant clinical challenge, particularly in the management of chronic hepatitis B (CHB). This study aimed to assess whether the plasma metabolome could reliably predict the success of antiviral therapy in CHB patients. We conducted a retrospective analysis on 56 treatment-naive CHB patients at the First Affiliated Hospital of Zhejiang University from December 2013 to March 2016. Patients who underwent a 48-week treatment regimen of entecavir (ETV) and interferon-alpha (IFN-α) were randomly assigned to either a discovery cohort (n=29) or a validation cohort (n=27). Based on the outcome of the treatment, patients were classified as HBeAg seroconversion group (High responders, Hrp) or the non-remission group (Low responder, Lrp). Our methodology involved an untargeted analysis of the amine/phenol and carboxylic acid submetabolomes in the CHB patients under treatment, utilizing chemical isotope labeling (CIL) techniques with liquid chromatography-mass spectrometry (LC-MS). Several metabolites were identified as having significant diagnostic potential for distinguishing Hrp from Lrp, with areas under the receiver operating characteristic curve (AUC) exceeding those typical clinical indicators. Notably, four metabolites, namely 2-methyl-3-ketovaleric acid, 2-ketohexanoic acid, 6-oxo-1,4,5,6-tetrahydronicotinic acid, and α-ketoisovaleric acid, demonstrated exceptionally high sensitivity and specificity in both cohorts, nearing 100%. In contrast, the clinical indicators, including HBcAb, log(HBsAg), and HBeAb, demonstrated lower and inconsistent sensitivity and specificity between the discovery and validation cohorts. Using HBcAb as a marker, the sensitivity was 87.5% with 76.9% specificity in the discovery cohort; however, the sensitivity dropped to 46.7% with 91.7% specificity in the validation cohort. Using log(HBsAg), the sensitivity was 84.6% with 69.2% specificity in the discovery cohort, compared to 85.7% sensitivity and 83.3% specificity in the validation cohort. For HBeAb, the separation of Hrp and Lrp had a sensitivity of 87.5% with 69.2% specificity in the discovery cohort, while the validation cohort showed 86.7% sensitivity and 91.7% specificity. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is the most common malignancy of the head and neck. Zeng-Sheng-Ping, composed of Sophora tonkinensis Gagnep., Bistorta officinalis Delarbre, Sonchus arvensis L., Prunella vulgaris L., Dioscorea bulbifera L., and Dictamnus dasycarpus Turcz., was regarded as an anti-cancer drug with significant clinical efficacy, but was discontinued due to liver toxicity. Our research group developed a modified Zeng-Sheng-Ping (ZSP-M) based on original Zeng-Sheng-Ping that exhibited high efficiency and low toxicity in preliminary investigations, although its pharmacodynamic mechanism is still unclear. Here, we aimed to elucidate the pharmacodynamic material basis of ZSP-M and investigate its chemopreventive effect on OSCC by modulating tumor associated macrophages (TAMs). Methods: Components of ZSP-M were characterized using ultra-performance liquid chromatography-mass spectrometry. Chemopreventive effect induced by ZSP-M against experimental oral cancer was investigated using the 4-nitroquinoline N-oxide precancerous lesion mouse model. RNA sequencing analysis was used to gain a global transcriptional view of the effect of ZSP-M treatment. A cell co-culture model was used to study the targeted effect of ZSP-M on TAMs and the biological properties of OSCC cells and to detect changes in TAM phenotypes. The binding of ZSP-M active compounds to TNF alpha induced protein 6 (TNFAIP6) protein was analyzed by molecular docking and dynamic simulation. Results: Forty main components of ZSP-M were identified, the most abundant of which were flavonoids. ZSP-M inhibited the degree of epithelial dysplasia in precancerous lesions by inhibiting the expression of the TNFAIP6 and CD163 proteins in the precancerous lesions of the tongue. ZSP-M inhibited proliferation, colony formation, migration and invasion of SCC7 cells by targeting TAMs. ZSP-M reduced the expression of CD163+ cells, inhibited the expression of TNFAIP6 protein, Arg1 mRNA and Il10 mRNA in TAMs, and reduced IL-10 cytokine release in the co-culture environment. This effect was maintained after the addition of recombinant TNFAIP6 protein. Computer simulations showed that trifolirhizin and maackiain are well-connected to TNFAIP6. Conclusions: ZSP-M counteracts the immunosuppressive action of TAMs by specific targeting of TNFAIP6, thereby exerting chemopreventive activity of OSCC. [ABSTRACT FROM AUTHOR]

Practical Application Food adulteration involving the illegal addition of dyes to foodstuffs has become an alarming issue in recent years. This study developed and validated a high‐performance liquid chromatography (HPLC)–DAD (diode array detector) method for the simultaneous determination of nine azo dyes (Butter Yellow, Sudan Orange G, Para Red, Sudan I, Sudan II, Sudan III, Sudan IV, Sudan Red 7B, and Scarlet 808). Moreover, a qualitative analysis method using liquid chromatography–tandem mass spectrometry was developed to more accurately identify peaks detected in HPLC–DAD. The calibration curve represented good linearity (r2 ≥ 0.9998) over the measured concentration range of 0.5–25 mg/kg. limit of detection and limit of quantification were 0.01–0.04 and 0.04–0.12 mg/kg, respectively. Accuracy and precision were 96.0–102.6 and 0.16–2.01 (relative standard deviation%), respectively. Additionally, the measurement uncertainty and HorRat value were estimated. Several Curcuma longa L. distributed in Korea were collected and monitored for azo dye contaminants.The proposed HPLC–DAD method represents a significant advancement in the field, offering a reliable means of quantifying azo dyes and identifying their presence even at trace levels in adulterated turmeric. This not only contributes to ensuring the safety and integrity of turmeric products but also establishes precedent for robust analytical techniques in addressing food safety challenges. [ABSTRACT FROM AUTHOR]

Pulmonary Mycobacterium avium-intracellulare complex (MAC) disease is a typical non-tuberculous mycobacterial infection. The incidence of pulmonary MAC is increasing worldwide. This study aimed to clarify the pharmacokinetic parameters of anti-pulmonary MAC disease drugs in silkworms. The pharmacokinetic parameters investigated included maximum concentration, area under the concentration–time curve, total clearance, and volume of distribution at steady-state. In addition, protein-binding rates, fat body transferability, and drug-drug interactions were examined. Antibiotic concentrations were measured using a validated high-performance liquid chromatography-mass spectrometry method. Among the antibiotics investigated, amikacin was not eliminated from silkworms during the 48-h observation period. In contrast, dose-proportional pharmacokinetics were observed in silkworms for all antibiotics tested, except for amikacin. Protein-binding rates in hemolymph for clarithromycin, azithromycin, rifampicin, ethambutol, and amikacin were 39.6 ± 3.0%, 39.5 ± 4.3%, 76.3 ± 3.2%, 20.9 ± 4.2%, and 73.1 ± 4.7%, respectively (mean ± standard deviation). The distribution of antibiotics in the fat bodies of silkworms was related to drug lipophilicity. No drug-drug interactions were observed in the silkworms. The pharmacokinetics of these drugs in silkworms differed significantly from those in humans. Therefore, while it is challenging to predict the pharmacokinetics of these drugs in humans based on silkworm data, the silkworm infection model has facilitated a comprehensive assessment of the relationship between antibiotic exposure and efficacy. [ABSTRACT FROM AUTHOR]

Poultry meat-production is increasing worldwide; leading to the selection of chickens for meat-production that show a fast growth. A label-free quantitative proteomic-approach and Western-blot were applied to investigate the dynamics of muscle protein under rapid growth conditions in two common fast-growing broiler genetic-lines (Ross 508 and AZ Extra Heavy Red-chicken). Muscle exudate from chicken Pectoralis major was used as substrate to unveil the proteome of these genetic-lines. Six-hundred forty-five proteins were identified in total from all samples, and after statistical-analysis 172 proteins were found to be differentially-expressed, clearly distinguishing the two chicken genetic-lines. Several of these differentially-expressed proteins were involved with the proteasome and glycolysis/gluconeogenesis-pathways. Changes in meat-quality traits were also observed, which were reflected in the proteomic-profile. Proteins involved in the ubiquitin–proteasome system were associated with the bigger muscle mass of Ross 508, while phosphoglucomutase 1 was associated with a possible higher capability of AZ Extra Heavy Red-chickens to cope with stressors. This pilot proteomic-approach applied on muscle exudate samples provided key evidence about the pathways and processes underlying these two chicken genetic-lines and their meat-quality parameters. We also identified potential biomarkers that could determine the peculiar production potentials (e.g. breast-growth) of these broilers-lines, which arise from differences in their genetic-backgrounds. [ABSTRACT FROM AUTHOR]

Background: Bletilla striata (Thunb.) Reichb.f. (B. striata) is a traditional Chinese medicinal herb. B. striata polysaccharides (BSP), stilbenes and 2-isobutyl malic acid glucosoxy-benzyl ester compounds are the main active ingredients in B. striata. However, there is limited report on the changes of medicinal components and their biosynthesis regulation mechanisms in the tubers of B. striata at different stages. Method: The tubers of B. striata were collected during the flowering period, fruiting period, and harvest period to determine the total polysaccharide content using the phenol sulfuric acid method. The changes in secondary metabolites in the tubers at these stages were analyzed by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS), and transcriptomics was conducted for further exploration of their biosynthetic pathways. Result: The BSP content gradually increases from the flowering period to the fruiting period as the tubers develop, reaching its peak, but subsequently decreases at harvest time, which may be associated with the germination of B. striata buds in later stage. A total of 294 compounds were identified in this study. Among them, a majority of the compounds, such as 2-isobutyl malate gluconoxy-benzyl ester, exhibited high content during the fruit stage, while stilbenes like coelonin, 3'-O-methylbatatasin III, and blestriarene A accumulated during the harvesting period. The transcriptome data also revealed a substantial number of differentially expressed genes at various stages, providing a partial explanation for the complex changes in metabolites. We observed a correspondence between the expression pattern of GDP-Man biosynthesis-related enzyme genes and cumulative changes in BSP. And identified a positive correlation between 9 transcription factors and genes associated with polysaccharide biosynthesis, while 5 transcription factors were positively correlated with accumulation of 2-isobutyl malate gluconoxy-benzyl ester compounds and 5 transcription factors exhibited negative correlated with stilbene accumulation. Conclusion: It is imperative to determine the appropriate harvesting period based on the specific requirements of different active ingredients and the accumulation patterns of their metabolites. Considering the involvement of multiple transcription factors in the biosynthesis and accumulation of its active ingredients, a comprehensive investigation into the specific regulatory mechanisms that facilitate high-quality cultivation of B. striata is imperative. [ABSTRACT FROM AUTHOR]

Haemaphysalis longicornis is a common Ixodida tick species found in temperate areas of Asian countries. An anti-tick assay was conducted on adult female H. longicornis ticks. Plant extract solutions were prepared at concentrations of 50, 25, and 10 mg/mL. Tick survival and mortality were assessed by counting the number of dead and live ticks at 24 h, 48 h, 72 h, and 96 h posttreatment. Out of 11 plant extracts screened, Artemisia judaica extract exhibited the highest potency with 100% mortality (5/5) at 48 h when applied at high and moderate concentrations (50 and 25 mg/mL). Similar results were observed at 96 h for the 10 mg/mL group compared to the untreated ticks. Cleome droserifolia extract demonstrated partial activity with 60% (3/5) and 20% (1/5) mortality at 96 h posttreatment at concentrations of 50 and 25 mg/mL, respectively. Forsskaolea tenacissima extract showed a weak effect with 100% tick mortality (5/5) only at the highest treatment concentration after 96 h. To confirm the activity of A. judaica, trial 2 was conducted. A. judaica demonstrated potency within 48 h in high dose and 72 h in moderate dose, with 100% mortality (15/15) at 96 h posttreatment compared to untreated ticks. The median lethal time 50 (LT50) values were 30.37 h for the high and 55.08 h for the moderate doses. Liquid chromatography‒mass spectrometry was performed on the most potent candidate (A. judaica) to identify its phytochemical components. The results revealed the presence of 9 compounds identified through manual annotation and 74 compounds from the Global Natural Products Social library. These compounds included terpenoids, steroids, phenylpropanoids, flavonoid glycosides, flavonoids, and benzenoids. Camphor was identified as the major component via both approaches. These findings suggest the potential use of A. judaica extract in the future development of acaricidal therapeutics. [ABSTRACT FROM AUTHOR]

Patients with diabetes face a 2‐4‐fold greater cardiovascular risk compared to those without diabetes. Both metformin and acetylsalicylic acid (aspirin) treatment have demonstrated a significant reduction in this risk. This single‐center, open‐label, sequence randomized, 2 × 2 crossover, single‐dose clinical trial evaluated the pharmacokinetics profile and comparative bioavailability of a novel oral fixed‐dose combination (FDC) of metformin/acetylsalicylic acid (500/100 mg tablet) versus the reference mono‐drugs administered concomitantly, metformin 500 mg tablet and acetylsalicylic acid 100 mg tablet, in 22 healthy Mexican adult volunteers under fasting conditions. Blood samples were collected predose and at specified intervals across a 24‐hour period following administration and were analyzed for metformin and salicylic acid using high‐performance liquid chromatography coupled with tandem mass spectrometry. Test products were considered to have comparative bioavailability if confidence intervals of natural log‐transformed (maximum plasma drug concentration (Cmax), (area under the plasma drug concentration‐time curve form 0 up to last sampling time (AUC0‐t), and (area under the plasma drug concentration‐time cruve from 0 up to infinity (AUC0∞) data were within the range of 80%‐125%. The results obtained from the present clinical study demonstrate the comparative bioavailability of the FDC when compared with the coadministration of reference mono‐drugs. There were no adverse events or adverse reactions reported throughout the study. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to determine the typical clearance and volume of distribution values of tamsulosin in patients with benign prostatic hyperplasia (BPH), and to identify factors with a measurable impact on the drug's elimination. Methods: This open-label, single-arm population pharmacokinetic study involved 65 adult men with BPH who had been on tamsulosin therapy for at least seven days. The steady-state serum concentrations of tamsulosin were measured using liquid chromatography-tandem quadrupole mass spectrometry. Population pharmacokinetic parameters, their variability, and influencing factors were estimated based on a two-compartment pharmacokinetic model using NONMEM software. Results: The estimated tamsulosin clearance in BPH patients was 0.719 L/h, and the steady-state volume of distribution was 32 L. Neither renal nor liver function parameters had a statistically significant effect on tamsulosin clearance. However, a positive correlation was observed between hemoglobin levels and tamsulosin clearance in the BPH patient cohort. Conclusion: Our investigation reveals significant associations between tamsulosin pharmacokinetics and specific characteristics of patients with lower urinary tract symptoms (LUTS) due to BPH. The study highlights that tamsulosin clearance is associated with hemoglobin levels in patients with LUTS/BPH. This study underscores the importance of considering patient-specific factors when managing BPH treatment with tamsulosin, emphasizing associations rather than causative relationships. [ABSTRACT FROM AUTHOR]