Liquid Chromatography-tandem Mass Spectrometry Research Articles

To Explore the Mechanism of Maiwei Dihuang Decoction in the Treatment of Non-small Cell Lung Cancer based on Network Pharmacology Combined with LC-MS.

To explore the mechanism of Maiwei Dihuang decoction in the treatment of non-small cell lung cancer (NSCLC) by using network pharmacology and LC-MS technology. The effective components in Maiwei Dihuang decoction were detected by liquid chromatography- mass spectrometry (LC-MS). Use the SuperPred database to collect the relevant targets of the active ingredients of Mai Wei Di Tang, and then collect the relevant targets of nonsmall cell lung cancer from GeneCards, DisgenNET and OMIM databases. On this basis, PPI network construction, GO enrichment analysis and KEGG pathway annotation analysis were carried out for target sites. Finally, AutoDock Vina is used for molecular docking. We further screened 16 effective Chinese herbal compounds through LC-MS combined with ADME level. On this basis, we obtained 77 core targets through protein interaction network analysis. Through GO, KEGG analysis and molecular docking results, we finally screened out the potential targets of Maiwei Dihuang Decoction for NSCLC: TP53, STAT3, MAPK3. Maiwei Dihuang decoction may play a role in the treatment of NSCLC by coregulating TP53/STAT3/MAPK3 signal pathway.

An Investigation of Pharmacokinetic Interaction of Vericiguat with Apigenin based on a Newly Developed Ultra-performance Liquid Chromatography-tandem Mass Spectrometry Assay.

Vericiguat, as a new stimulator of soluble guanylate cyclase (s- GC), was recently approved as a first-in-class treatment for reducing risks in patients with ejection fraction less than 45 percent and heart failure (HF) in the USA. The main aim of the present experiment was to establish an acceptable, sensitive assay based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for quantitatively analyzing the plasma concentration levels of vericiguat in rats, and to further evaluate the effect of apigenin on the metabolism of vericiguat in vivo. In sample processes, acetonitrile was finally chosen for quickly precipitating protein. The levels of vericiguat in plasma were analyzed by a Xevo TQ-S triple quadrupole tandem mass spectrometry (Milford, MA, USA) in a positive ion mode. The scope of the calibration standard for vericiguat ranged from 0.5 to 1000 ng/mL, where a great linearity was acceptable. The lower limit of quantification (also called LLOQ) of vericiguat presented the sensitivity of this assay was evaluated as low as 0.5 ng/mL. Additionally, selectivity, accuracy and precision, extraction recovery, matrix effect, and stability were all verified. Subsequently, this approach also supported to assess the plasmatic concentrations of vericiguat from an interaction survey on herb-- drug, in which oral administration of apigenin (20 mg/kg) obviously increased the plasmatic levels of vericiguat and altered the pharmacokinetics of vericiguat in rats. These results would help us to further understand the pharmacokinetic properties of vericiguat when co-administration with apigenin, and to avoid unexpected clinical risks in the future.

Caspase-3 interactins with calpain and cathepsin L: implications for protein stability and quality in fish fillets during postmortem storage

The degradation of structural proteins during fish postmortem storage is a critical factor affecting meat quality, leading to economic losses in the seafood industry. The complex interplay between caspase-3 and structural protein stability during fish postmortem storage remains largely unexplored. By treating grass carp fillets with a caspase-3 inhibitor, we establish a model for inhibiting apoptosis, delineating the role of caspase-3 in protein degradation. The effect of caspase-3 on grass carp proteins following postmortem storage and its cascade interaction with calpain and cathepsin L was further investigated. The result demonstrated that the destabilisation of the mitochondrial membrane during apoptosis led to modifications in the B-cell lymphoma (Bcl) family proteins, subsequently triggered the activation of caspase-9/caspase-3. Additionally, caspase-3 reduced the expression of the calpastatin and lysosomal membrane protein 1 (LAMP-1) gene, resulting in increased calpain and cathepsin L activity. SDS-PAGE and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis indicated that caspase-3 inhibitor treatment reduced actin fractures and preserved critical structural proteins. This investigation unveils the molecular mechanisms through which caspase-3 affects protein degradation in fish fillets during storage, providing valuable insights into the postmortem degradation processes.

Camptothecin and its Analogs: High-Yielding Ophiorrhiza Species from Sri Lanka for Sustainable Anticancer Compound Production

Introduction: Camptothecin (CPT) is pivotal in cancer treatment, derived from various CPT-producing plant species, and is a fundamental component in synthesizing valuable cancer drugs like Irnotican and Topotecan. Sourcing from nature poses conservation issues, fostering interest in the herbaceous Ophiorrhiza plant as a more sustainable alternative. Ophiorrhiza species in Sri Lanka lack comprehensive study, warranting exploration for echo-friendly anticancer compound production. Objectives: This study examines CPT and analog content in Ophiorrhiza mungos, O. pectinata, and O. rugosa across diverse Sri Lankan regions. Methods: The study employs Thin Layer Chromatography (TLC), High-Performance Liquid Chromatography-DAD (HPLC-DAD), and Liquid Chromatography-Mass Spectrometry (LC-MS) to quantify and confirm CPT and its analogs. Results: Significant variations in the content of CPT and its analogs were observed among plant parts and regions. O. mungos from Deraniyagala and Bibile regions notably exhibited elevated CPT levels in fruits and roots. O. rugosa var. Angustifolia and O. pectinata also exhibited a considerable content of CPT in their roots, though it was significantly lower (p < 0.005) than O. mungos. Conclusion: The study validates analytical methods for specificity, linearity, precision, accuracy, and sensitivity per ICH guidelines. The results indicate that Ophiorrhiza species, especially O. mungos and O. rugosa var. Angustifolia holds the potential to be a sustainable source of CPT. Optimizing cultivation practices offers an eco-friendly solution for anticancer compound production, alleviating species threats and conserving biodiversity.

SrHPO4-coated Mg alloy implant attenuates postoperative pain by suppressing osteoclast-induced sensory innervation in osteoporotic fractures

Osteoporotic fractures have become a common public health problem and are usually accompanied by chronic pain. Mg and Mg-based alloys are considered the next-generation orthopedic implants for their excellent osteogenic inductivity, biocompatibility, and biodegradability. However, Mg-based alloy can initiate aberrant activation of osteoclasts and modulate sensory innervation into bone callus resulting in postoperative pain at the sequential stage of osteoporotic fracture healing. Its mechanism is going to be investigated. Strontium hydrogen phosphate (SrHPO4) coating to delay the Mg-based alloy degradation, can reduce the osteoclast formation and inhibit the growth of sensory nerves into bone callus, dorsal root ganglion hyperexcitability, and pain hypersensitivity at the early stage. Liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis of bone marrow-derived macrophages (BMMs) treated with SrHPO4-coated Mg alloy extracts shows the potential effect of increased metabolite levels of AICAR (an activator of the AMPK pathway). We demonstrate a possible modulated secretion of AICAR and osteoclast differentiation from BMMs, which inhibits sensory innervation and postoperative pain through the AMPK/mTORc1/S6K pathway. Importantly, supplementing with AICAR in Mg-activated osteoclasts attenuates postoperative pain. These results suggest that Mg-induced postoperative pain is related to the osteoclastogenesis and sensory innervation at the early stage in the osteoporotic fractures and the SrHPO4 coating on Mg-based alloys can reduce the pain by upregulating AICAR secretion from BMMs or preosteoclasts.

TRIM35 triggers cardiac remodeling by regulating SLC7A5-mediated amino acid transport and mTORC1 activation in fibroblasts

BackgroundCardiac maladaptive remodeling is one of the leading causes of heart failure with highly complicated pathogeneses. The E3 ligase tripartite motif containing 35 (TRIM35) has been identified as a crucial regulator governing cellular growth, immune responses, and metabolism. Nonetheless, the role of TRIM35 in fibroblasts in cardiac remodeling remains elusive.MethodsHeart tissues from human donors were used to verify tissue-specific expression of TRIM35. Fibroblast-specific Trim35 gene knockout mice (Trim35cKO) were used to investigate the function of TRIM35 in fibroblasts. Cardiac function, morphology, and molecular changes in the heart tissues were analyzed after transverse aortic constriction (TAC) surgery. The mechanisms by which TRIM35 regulates fibroblast phenotypes were elucidated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and RNA sequencing (RNA-Seq). These findings were further validated through the use of adenoviral and adeno-associated viral transfection systems, as well as the mTORC1 inhibitor Rapamycin.ResultsTRIM35 expression is primarily up-regulated in cardiac fibroblasts in both murine and human fibrotic hearts, and responds to TGF-β1 stimulation. Specific deletion of TRIM35 in cardiac fibroblasts significantly improves cardiac fibrosis and hypertrophy. Consistently, the overexpression of TRIM35 promotes fibroblast proliferation, migration, and differentiation. Through paracrine signaling, it induces hypertrophic growth of cardiomyocytes. Mechanistically, we found that TRIM35 interacts with, ubiquitinates, and up-regulates the amino acid transporter SLC7A5, which enhances amino acid transport and activates the mTORC1 signaling pathway. Furthermore, overexpression of SLC7A5 significantly reverses the reduced cardiac fibrosis and hypertrophy caused by conditional knockout of TRIM35.ConclusionOur findings demonstrate a novel role of fibroblast-TRIM35 in cardiac remodeling and uncover the mechanism underlying SLC7A5-mediated amino acid transport and mTORC1 activation. These results provide a potential novel therapeutic target for treating cardiac remodeling.

Purine nucleoside phosphorylase as a target for the treatment of interstitial cystitis/bladder pain syndrome with and without Hunner lesions

Chronic visceral pain disorders, such as interstitial cystitis/bladder pain syndrome (IC/BPS), are difficult to treat, and therapies are limited in number and efficacy. Emerging evidence suggests that alterations in the enzyme purine nucleoside phosphorylase (PNPase) may participate in oxidative injury and cellular damage. PNPase is important for the metabolism of ‘tissue-protective’ purine metabolites to ‘tissue-damaging’ purines that generate free radicals. The aim of this study is to test whether patients living with IC/BPS without or with Hunner lesions and irrespective of any therapies exhibit purine dysregulation with higher levels of tissue-damaging purine metabolites as measured by liquid chromatography-tandem mass spectrometry. Our results demonstrate that levels of urotoxic purine metabolites (hypoxanthine and xanthine) in IC/BPS patients with and without Hunner lesions are elevated compared to healthy controls. These findings suggest there may be pathophysiologic commonalities between patient subtypes. Furthermore, the accumulation of uroprotective purines and depletion of urodamaging purines by PNPase inhibition may be therapeutically effective in both groups of patients.

Chemical Profiling, In Silico Pharmacokinetics Analysis and Molecular Docking Study of Phytocompounds of Homeopathy Medicine Echinacea angustifolia Q against Suppurative Bacterial Proteins

Background Computer-aided drug design is the emerging field for identification of drug action on its target organs. The pharmacokinetic study helps find out drug ADMET (absorption, distribution, metabolism, excretion, and toxicity) and drug likeness properties. PyRx software helps with molecular docking of the bioactive compounds on their target organ within a short period of time. In homeopathy, Echinacea angustifolia is one of the most commonly used drugs for microbial infective skin lesions used in internal administration as well as an external application. Objective This study was aimed at identifying the compounds present in Echinacea angustifolia Q through liquid chromatography mass spectrometry (LC-MS), ADMET, and drug likeness properties, followed by molecular docking by PyRx software to recognize the interaction between drug compounds against 12 target microbial proteins of commonly infective suppurative bacteria. Materials and Methods An analysis of the phytoconstituents of Echinacea angustifolia Q was performed using the Agilent 1290 Infinity LC system coupled to the Agilent 6545 Accurate Mass Quadrupole Time-of-Flight (QTOF) with Agilent Jet Stream Thermal Gradient Technology. In silico ADMET and drug likeness properties were assessed by free online tools, followed by a detailed docking study by PyRx software. The drug compounds with the lower glide docking score are considered to have the best binding affinity. Result The five compounds of Echinacea angustifolia Q satisfy all properties of ADMET and drug likeness. The three compounds of Echinacea angustifolia Q have low glide score of >-7.0 kcal/mol against the three microbial target proteins of Salmonella enterica, Proteus mirabilis, and Staphylococcus aureus. Conclusion Echinacea angustifolia Q has fulfilled the ADMET and drug-likeness properties for internal administration as well as external application for various suppurative bacterial infective disorders, which were confirmed through molecular docking. Therefore, Echinacea angustifolia Q may function as a potential therapeutic agent for the treatment of illnesses associated with antimicrobial resistance.

DNA Adductomics: A Narrative Review of Its Development, Applications, and Future

DNA adductomics is the global study of all DNA adducts and was first proposed in 2006 by the Matsuda group. Its development has been greatly credited to the advances in mass spectrometric techniques, particularly tandem and multiple-stage mass spectrometry. In fact, liquid chromatography-mass spectrometry (LC-MS)-based methods are virtually the sole technique with practicality for DNA adductomic studies to date. At present, DNA adductomics is primarily used as a tool to search for DNA adducts, known and unknown, providing evidence for exposure to exogenous genotoxins and/or for the molecular mechanisms of their genotoxicity. Some DNA adducts discovered in this way have the potential to predict cancer risks and/or to be associated with adverse health outcomes. DNA adductomics has been successfully used to identify and determine exogenous carcinogens that may contribute to the etiology of certain cancers, including bacterial genotoxins and an N-nitrosamine. Also using the DNA adductomic approach, multiple DNA adducts have been observed to show age dependence and may serve as aging biomarkers. These achievements highlight the capability and power of DNA adductomics in the studies of medicine, biological science, and environmental science. Nonetheless, DNA adductomics is still in its infancy, and great advances are expected in the future.

Intraperitoneally Administered Vancomycin Results in Suboptimal Serum and Peritoneal Effluent Drug Levels in Patients with PD-related Peritonitis

Background Intraperitoneal vancomycin is commonly used to treat peritoneal dialysis (PD)-related peritonitis. Therapeutic drug level monitoring helps optimize the use of vancomycin in CKD patients. We studied whether sufficient serum levels were achieved in patients with PD-related peritonitis treated with the commonly used dose of vancomycin in patients with end stage renal disease. Materials and Methods All consecutive patients with PD-related peritonitis during 19 months were studied. Patients received IP Vancomycin 15 mg/kg Q96H and amikacin 2 mg/kg while awaiting culture reports. Vancomycin concentration in serum and dialysate was determined by a validated liquid chromatography-tandem mass spectrometry assay at 1, 12, 24, and 96 h. The primary outcome was the drug levels in serum and peritoneal fluid, and the secondary outcome was peritonitis treatment failure. Results A total of 45 episodes of PD-related peritonitis were treated, of which 41 fulfilled the inclusion criteria and were included in the PK analysis. Recommended serum vancomycin trough level of >15 mg/L was achieved in only two cases. Twenty-one episodes required catheter removal. Conclusion In patients with PD-related peritonitis, intermittent intraperitoneal administration of 15 mg/kg of vancomycin every 96 h does not achieve the recommended serum and dialysate levels of vancomycin. There is an urgent need for pharmacokinetic studies on commonly used IP antibiotics in the PD population to facilitate correct dose recommendations.

Licochalcone D from Glycyrrhiza uralensis Improves High-Glucose-Induced Insulin Resistance in Hepatocytes

This study investigated the therapeutic potential of licochalcone D (LicoD), which is derived from Glycyrrhiza uralensis, for improving glucose metabolism in AML12 hepatocytes with high-glucose-induced insulin resistance (IR). Ultra-high-performance liquid chromatography–mass spectrometry revealed that the LicoD content of G. uralensis was 8.61 µg/100 mg in the ethanol extract (GUE) and 0.85 µg/100 mg in the hot water extract. GUE and LicoD enhanced glucose consumption and uptake, as well as Glut2 mRNA expression, in high-glucose-induced IR AML12 cells. These effects were associated with the activation of the insulin receptor substrate/phosphatidylinositol-3 kinase signaling pathway, increased protein kinase B α phosphorylation, and suppression of gluconeogenesis-related genes, such as Pepck and G6pase. Furthermore, GUE and LicoD promoted glycogen synthesis by downregulating glycogen phosphorylase. Furthermore, LicoD and GUE mitigated the downregulated expression of mitochondrial oxidative phosphorylation proteins in IR hepatocytes by activating the PPARα/PGC1α pathway and increasing the mitochondrial DNA content. These findings demonstrate the potential of LicoD and GUE as therapeutic options for alleviating IR-induced metabolic disorders by improving glucose metabolism and mitochondrial function.

Positive Intervention of Distinct Peptides in Clostridioides difficile Infection in a Mouse Model

Clostridioides difficile infection (CDI) is a common healthcare-associated infection and the leading cause of gastroenteritis-related deaths worldwide. To investigate the effects of peptide composition of different protein products on CDI, we analyzed and compared the peptide sequences and compositions from Engraulis japonicus and Glycine max using Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). An animal model of CDI was also established to investigate the potential therapeutic effects of these peptides in vivo. The peptide compositions of E. japonicus and G. max differed, with only 11% of the peptide sequences being identical. Oral administration of the tested peptides could reduce intestinal inflammation, repair the intestinal barrier, increase the proportion of beneficial bacteria, and reduce the proportion of harmful bacteria, providing a therapeutic effect against CDI. However, the peptides may differ considerably in some aspects. E. japonicus peptides were superior to G. max peptides in promoting colon epithelial cell proliferation and repairing tight intestinal cell junctions. Interestingly, the two sources of peptides have different effects on the cecal microbiome. E. japonicus peptides can effectively restore the diversity and richness of intestinal microbiota, while G. max peptides have poor regulatory effects on the intestinal microbiota structure. Overall, E. japonicus peptides showed better results than G. max peptides in treating CDI. This study supports the potential treatment of CDI with natural peptides and promotes the development of specialty foods for CDI enteritis. Clostridioides difficile infection (CDI) is a common healthcare-associated infection and the leading cause of gastroenteritis-related deaths worldwide. To investigate the effects of peptide composition of different protein products on CDI, we analyzed and compared the peptide sequences and compositions from Engraulis japonicus and Glycine max using Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). An animal model of CDI was also established to investigate the potential therapeutic effects of these peptides in vivo. The peptide compositions of E. japonicus and G. max differed, with only 11% of the peptide sequences being identical. Oral administration of the tested peptides could reduce intestinal inflammation, repair the intestinal barrier, increase the proportion of beneficial bacteria, and reduce the proportion of harmful bacteria, providing a therapeutic effect against CDI. However, the peptides may differ considerably in some aspects. E. japonicus peptides were superior to G. max peptides in promoting colon epithelial cell proliferation and repairing tight intestinal cell junctions. Interestingly, the two sources of peptides have different effects on the cecal microbiome. E. japonicus peptides can effectively restore the diversity and richness of intestinal microbiota, while G. max peptides have poor regulatory effects on the intestinal microbiota structure.

Circulating Estrogen Metabolites and Risk of Breast Cancer among Postmenopausal Women in the Nurses' Health Study.

Estradiol and estrone are well-established risk factors for postmenopausal breast cancer (BC). Experimental evidence suggests that specific estrogen metabolites, produced via irreversible hydroxylation of estrone and estradiol at the 2- or 16-position may independently influence carcinogenesis. We performed a nested case-control study of BC (328 BC cases; 639 controls) among postmenopausal women within the Nurses' Health Study (NHS)to examine the role of estrogens and estrogen metabolites (jointly referred to as EM). Plasma concentrations of each EM (unconjugated+conjugated forms) were measured by liquid chromatography-tandem mass spectrometry. Multivariable conditional logistic regression, adjusting for BC risk factors, estimated relative risks (RR) and 95% confidence intervals (CI) of BC across quintiles of individual EM, EM pathways, and pathway ratios. Associations by estrogen/progesterone receptor (ER/PR) status were analyzed by unconditional logistic regression. Estradiol and estrone were strongly associated with increased BC risk [estradiol: RRQ5v.Q1 (95% CI)=2.64 (1.64-4.26), estrone: 2.78 (1.74-4.45); both p-trends<0.001]. The 2-hydroxylation pathway was strongly associated with risk [RRQ5v.Q1=3.09 (1.81-5.27), p-trend<0.001], and remained so after adjusting for unconjugated estradiol [RRQ5v.Q1=2.23 (1.25-3.96), p-trend=0.01]. While the 16-hydroxylation pathway was modestly associated with risk [RRQ5v.Q1=1.62 (1.03-2.54), p-trend=0.01], the association was attenuated after unconjugated estradiol adjustment [RRQ5v.Q1=1.24 (0.77-1.99), p-trend=0.19]. Similar positive associations with the 2-pathway and 16-pathway were observed for ER+/PR+ and ER-/PR- tumors. In this cohort of postmenopausal women, 2-hydroxylation of estrone and estradiol was associated with increased BC risk, independent of unconjugated estradiol. These results highlight the need to revisit the role of estrogen metabolism in BC etiology and prevention.

Influence of Pesticide Application Method, Timing, and Rate on Contamination of Nectar with Systemic and Nonsystemic Pesticides.

Exposure to pesticides is one potential factor contributing to the recent loss of pollinators and pollinator diversity. Few studies have specifically focused on the relationship between pesticide management during ornamental plant production and contamination of nectar. We evaluated contamination of nectar in Salvia 'Indigo Spires' (Salvia longispicata M. Martens & Galeotti × S. farinacea Benth.) associated with applications of the systemic insecticide thiamethoxam, and the nonsystemic fungicides boscalid and pyraclostrobin. Applications were made at the labeled rates for the commercially available products, and we compared the influence of application method (drench vs. spray), timing (relative to flowering), and rate (low vs. high) for each pesticide. Nectar was sampled using 50-µL microcapillary tubes and analyzed by liquid chromatography-tandem mass spectrometry. The results indicate that concentrations from the spray application resulted in the least contamination of nectar with the systemic thiamethoxam, with lower concentrations occurring when thiamethoxam was applied before blooming at the lowest rate. Concentrations of thiamethoxam and its metabolite clothianidin were detected in nectar in all treatments (regardless of the method, timing, or rate of application), and ranged from 3.6 ± 0.5 ng/mL (spray-applied before blooming, low rate) to 1720.0 ± 80.9 ng/mL (drench-applied after blooming, high rate). Residues of clothianidin in nectar ranged from below quantification limits (spray-applied before blooming, low rate) to 81.2 ± 4.6 ng/mL (drench-applied after blooming, high rate). Drench applications resulted in the highest levels of nectar contamination with thiamethoxam, and exceeded published median lethal concentrations (LC50s/median lethal doses for native bees and/or honeybees in all cases). Spray treatments resulted in nectar concentrations exceeding published LC50s for some bee species. In comparison, all nonsystemic treatments resulted in concentrations much lower than the published no-observable-effect doses and sublethal toxicity values, indicating low risks of toxicity. Environ Toxicol Chem 2024;001:1-12. © 2024 SETAC.

Exposure of Cattle Breeding Herds to Naturally Co-Contaminated Zearalenone and Deoxynivalenol: The Relevance of a Urinary Mycotoxin Monitoring System for Herd Health and Food Safety

The widespread presence of Fusarium mycotoxins in animal feed is a global issue, not only for the health of livestock but also for ensure the safety of food as an end product. High concentrations of zearalenone (ZEN) and deoxynivalenol (DON) have been detected in the diets of Japanese Black (JB) and Holstein Friesian (HF) breeding herds. Consequently, we monitored serum biochemical parameters over a long time in both herds, focusing on anti-Müllerian hormone (AMH) levels and acute-phase inflammation. Additionally, urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) and progesterone levels were measured in the HF herd. The JB herd, a ZEN-dominant model with low DON contamination, demonstrated ZEN levels that exceeded the Japanese limit in the purchased total mixed rations (TMR). Conversely, the HF herd, which primary consumes DON-dominant feed with low ZEN contamination, had high DON levels in the dent corn silage. Specifically, the JB herd’s TMR contained 1.79 mg/kg ZEN and 0.58 mg/kg DON, whereas the HF herd’s silage had 15.3 mg/kg DON (dried sample) and 0.1 mg/kg ZEN. Enzyme-linked immunoassay were used to measure urinary ZEN-DON levels following confirmation through liquid chromatography-tandem mass spectrometry. Urinary ZEN-DON levels measured were significantly correlated (p &lt; 0.05, r &gt; 0.6) in both herds. In the HF herd, AMH levels increased (p = 0.01) and serum amyloid A (SAA) levels decreased (p = 0.02) when contaminated and at the end of the monitoring period. Additionally, urinary ZEN and DON levels were significantly correlated with SAA levels (ZEN: p = 0.00, r = 0.46; DON: p = 0.03, r = 0.33), with an increase in ZEN and DON levels resulting in higher SAA levels. The JB herd showed no significant differences. Additionally, in the HF herd, 8-OHdG/Cre levels increased significantly during major contamination periods (p &lt; 0.05). Clinical data from the HF herd indicated an increase in mastitis cases and treatment rates during periods of major contamination. Abortion rates in the HF herd decreased from 22.9% (before monitoring) to 8.9% (during the high contamination period) and finally to 1% (at the end of the monitoring period), with corresponding increases in progesterone levels. ZEN-DON contamination adversely affects breeding cattle’s productivity, reproductive performance, and health. Therefore, monitoring urinary ZEN-DON is valuable for detecting contaminants and ensuring the safety of food products.

Metabolomics and quantitative analysis to determine differences in the geographical origins and species of Chinese dragon’s blood

ObjectiveThe aim of this study was to comprehensively analyze the differences in Chinese dragon’s blood (CDB), specifically Dracaena cochinchinensis and Dracaena cambodiana, from different geographical origins.MethodsMetabolomic analysis of CDB was performed by liquid chromatography-tandem mass spectrometry (LC–MS/MS). A reliable ultrahigh-performance liquid chromatography method with a photodiode array detector (UHPLC-PDA) was developed and applied for the quantitative analysis of 12 phenolic compounds in 51 batches of samples.ResultsA total of 1394 metabolites were detected, of which 467 were identified as differentially accumulated metabolites. Multivariate analysis revealed that both origin and species had an effect on the composition of CDB, with greater variation between species. 19 phenolic compounds were selected as quality markers to distinguish D. cochinchinensis (Hdsp) from D. cambodiana (Hdca), and oppositin and spinoflavanone a were identified as quality markers to discriminate D. cochinchinensis samples from Hainan (Hdsp) and Guangxi Provinces (Gdc). Quantitative analysis indicated that four phenolic compounds, including loureirin D, 4H-1-benzopyran-4-one,2,3-dihydro-3,5,7-trihydroxy-3-[(4-methoxyphenyl)methyl]-,(R)-, loureirin B, and pterostilbene, showed significant differences between Gdc and Hdsp. Additionally, five phenolic compounds, namely resveratrol, loureirin D, pinostilbene, 4H-1-benzopyran-4-one,2,3-dihydro-3,5,7-trihydroxy-3-[(4-methoxyphenyl)methyl]-, (R)-, and loureirin B, exhibited significant differences between Hdsp and Hdca.ConclusionThere are significant differences in the quality of CDB from different geographical origins and species, which lays the foundation for the in-depth development and utilization of different sources of CDB.

The benthic and epiphytic marine dinoflagellates of Aotearoa New Zealand and Rangitāhua Kermadec Islands, an updated checklist from 2018 to 2024

ABSTRACT A checklist collating records of New Zealand’s benthic and epiphytic dinoflagellate species was published on-line in 2018 [(Rhodes L, Smith KF. 2019. A checklist of the benthic and epiphytic marine dinoflagellates of New Zealand, including Rangitāhua/Kermadec Islands. N Z J Mar Freshw Res. 53:258–277. doi:10.1080/00288330.2018.1492425]. Over the last six years, seventeen species from nine genera (three newly reported genera) have been documented, including sand-dwelling species. Isolation and identification of species using traditional microscopic techniques combined with analysis of DNA sequencing data has been supplemented by high-throughput sequencing techniques (i.e. metabarcoding). Toxin data, based on liquid chromatography mass spectrometry (LC-MS/MS), and toxicity of isolates are included where applicable. Forty-two benthic and epiphytic dinoflagellate genera, including genera having benthic life stages, have now been recorded in Aotearoa New Zealand coastal waters including Rangitāhua Kermadec Islands (new record genera in bold): Adenoides , Alexandrium, Amphidinium, Archaeperidinium, Azadinium, Biecheleria, Blastodinium, Bysmatrum, Cachonina, Coolia, Crypthecodinium, Cryptoperidiniopsis, Dinophysis, Durinskia, Ensiculifera, Fukuyoa, Fragilidium, Gambierdiscus, Gonyaulax, Gymnodinium, Gyrodinium, Heterocapsa, Karenia, Karlodinium, Kryptoperidinium, Lepidodinium, Ostreopsis, Pelagodinium, Pentapharsodinium, Pfiesteria, Polarella, Prorocentrum, Protodinium, Protoperidinium, Pseudadenoides , Pseudopfiesteria, Scrippsiella, Symbiodinium, Thecadinium , Togula, Vulcanodinium and Woloszynskia.

Analysis of the gut microbiota and fecal metabolites in people living with HIV.

The gut microbiome has a pivotal function in human immunodeficiency virus (HIV). However, the associated alterations in the gut microbiome-host interaction are unknown. Herein, we aimed to investigate the gut microbiota and fecal metabolites in people living with HIV (PLWH). We collected stool samples from 70 PLWH and 34 healthy controls (HCs) and carried out 16S rRNA gene sequencing and analyzed the metabolites using liquid chromatography-mass spectrometry. Firmicutes, Proteobacteria, Actinobacteriota, and Bacteroidota were the most abundant phyla in both groups. Among genera, the level of Escherichia-Shigella was upregulated significantly in the PLWH group, whereas in the HC group, Bacteroides spp. were upregulated. Prediction of microbial function indicated significant reductions in alanine, aspartate, glutamate, and histidine metabolism. Furthermore, a comparison of the fecal metabolites between the HC and PLWH groups identified 38 differentially abundant metabolites in four differentially enriched human metabolic pathways. According to Spearman correlation analysis, there are close relationships between four differentially abundant microbiota members and five differentially abundant fecal metabolites, which might influence particular human metabolic pathways. Our findings provide a basis for further experimental investigation of the contribution of the gut microbiota and its associated metabolites to HIV/AIDS, providing a novel perspective for the further study of HIV/AIDS.IMPORTANCEGrowing evidence demonstrates that the gut microbiota is associated with HIV. This study investigated changes in the gut microbiota and fecal metabolites in PLWH. We identified 38 differentially abundant metabolites in four differentially enriched human metabolic pathways. Moreover, close relationships were noted between the four differentially abundant microbiota members and five differentially abundant fecal metabolites, which might influence particular human metabolic pathways. Thus, to benefit PLWH, potential pathobionts could be reduced (e.g., g_Enterococcus); probiotics could be increased (e.g., g_Faecalibacterium and g_Agathobacter); or certain metabolites (e.g., N-acetyl-L-phenylalanine and trehalose) could be reduced by changes in diet or the use of nutritional supplements. Our results provide insights into the interaction between the gut microbiota and the host, identifying possible targets that might be beneficial for PLWH.

Plasma concentrations of multiple oxysterols and risk of colorectal adenomas.

Oxysterols are metabolites of cholesterol that regulate homeostasis of cholesterol, fatty acids, and glucose. These metabolites are generated throughout the body, either enzymatically or from oxidative stress, and are detectable in peripheral circulation. We previously reported that circulating 27-hydroxycholesterol (27-OHC), an endogenous selective estrogen receptor modulator, may be a risk factor for colorectal adenomas. Here, in addition to 27-OHC, we report on four other circulating oxysterols: 25-hydroxycholesterol (25-OHC), 24(S)-hydroxycholesterol (24(S)-OHC), 7ɑ-hydroxycholesterol (7ɑ-OHC), and 4β-hydroxycholesterol (4β-OHC). Oxysterol concentrations were measured using liquid chromatography-mass spectrometry from fasting plasma collected at baseline from 1,246 participants of the Vitamin D/Calcium Polyp Prevention Study, a multicenter adenoma chemoprevention trial. To evaluate multiple oxysterols simultaneously, we used both log-linear regression and Bayesian kernel machine regression (BKMR) models developed for analyses of complex mixtures adjusted for potential confounding factors. Higher circulating 7ɑ-OHC was associated with higher adenoma risk (BKMR-based multivariable-adjusted risk ratios, RR, for the 75th vs. 25th percentile, 1.22; 95% credible interval, CI, 1.04-1.42). In contrast, higher circulating 4β-OHC was associated with lower risk of these polyps (RR, 0.84; 95% CI, 0.71-0.99). The positive association with advanced adenoma risk that we previously reported for circulating 27-OHC persisted when controlling for other oxysterols (RR, 1.26; 95% CI, 0.98-1.62), including among those with advanced adenomas at baseline (RR, 1.75; 95% CI, 1.01-3.06).

Analysis of riociguat and desmethyl riociguat by UPLC-MS/MS and its interaction with quercetin

Riociguat, an orally soluble guanylate cyclase (sGC)-promoting drug, is mainly used in the clinical treatment of pulmonary hypertension (PH). In this study, a novel ultra-performance liquid chromatography-tandem mass spectrometry method was developed to quantify the concentrations of riociguat and its metabolite (M1) in plasma. The precision, stability, accuracy, matrix effect, and recovery of the methodology were satisfactory. Quercetin, a well-recognized compound, functions as a novel anticancer agent with the potential to alleviate symptoms of PH. Therefore, the potential interaction between quercetin and riociguat was investigated in this study. The levels of riociguat and M1 in rat plasma were measured using the method developed in this study to evaluate the interactions between riociguat and quercetin in rats. The results revealed that quercetin significantly inhibited riociguat and M1 metabolism with increased systemic exposure.