PubMed

Pestic Biochem Physiol. 2024 Nov;205:106136. doi: 10.1016/j.pestbp.2024.106136. Epub 2024 Sep 18.ABSTRACTSpodoptera frugiperda is an economic agricultural pest that has invaded many countries around the world and caused huge losses in grain production. Camptothecin (CPT) is one of the botanical compounds with insecticidal activity and has the potential for pest control. However, the effects of CPT on development and metabolism of S. frugiperda remain unknown. In this study, we have investigated the adverse effects of 1.0 and 5.0 mg/kg CPT exposures on the growth and development of S. frugiperda. Our results found that 1.0 and 5.0 mg/kg CPT treatments altered the parameters of the life cycle, including inducing larval mortality, altering the weight of larvae, pupae, and adults, the larval duration, and decreasing the pupation rate and emergence rate. In addition, comparative metabolomics analysis was performed in the larval midgut of S. frugiperda to explore the toxicity mechanism of CPT. A total of 261 and 348 differential metabolites were identified in the groups with 1.0 and 5.0 mg/kg CPT treatments, respectively. Further analysis found that pantothenate and CoA biosynthesis, sulfur relay system, selenocompound metabolism, and fatty acid biosynthesis pathways were significantly altered by 5.0 mg/kg CPT exposure. Our results provided new insight into the toxicological mechanisms of CPT against S. frugiperda and laid the foundation for the field application of CPT in pest control.PMID:39477589 | DOI:10.1016/j.pestbp.2024.106136

J Appl Toxicol. 2024 Oct 30. doi: 10.1002/jat.4715. Online ahead of print.ABSTRACTAs global regulations on synthetic cannabinoids tighten, illicit vendors increasingly turn to new structures of synthetic cannabinoids to evade legal scrutiny. MDA-19, a novel synthetic cannabinoid, exhibited significant agonistic effects on type 2 cannabinoid receptors in vivo and showed emerging trends of abuse in illicit markets. However, research on the toxicological effects of MDA-19 remains scarce. In this study, we examined the effects of MDA-19 on neurodevelopment, behavior, oxidative stress, and metabolomics by exposing zebrafish embryos to MDA-19 solutions with concentrations of 1, 10, and 20 mg/L over 5 days. Results revealed that exposure to 10 and 20 mg/L of MDA-19 accelerated hatching in zebrafish embryos but led to reduced body length without affecting mortality or malformation. Furthermore, exposure to all concentrations of MDA-19 resulted in diminished swimming ability and reduced activity time in zebrafish. Transgenic zebrafish (hb9-GFP) exposed to MDA-19 exhibited impaired development of spinal motor neurons. Notably, exposure to 20 mg/L MDA-19 increased the levels of reactive oxygen species (ROS) in zebrafish and elevated the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), while the levels of the lipid oxidation product malondialdehyde (MDA) remained unaffected. Nontargeted metabolomics analyses showed that MDA-19 interfered with multiple metabolic pathways affecting energy metabolism, such as alanine, aspartate, and glutamate metabolism; the citric acid cycle (TCA cycle), pantothenate, and coenzyme A biosynthesis; and purine metabolism. In conclusion, the present study provided the essential evidence for the neurotoxic effects of MDA-19, which was associated with impaired neurodevelopment, dysregulation of oxidative stress homeostasis, and altered energy metabolism.PMID:39477463 | DOI:10.1002/jat.4715

Anticancer Res. 2024 Nov;44(11):4729-4735. doi: 10.21873/anticanres.17299.ABSTRACTBACKGROUND/AIM: Large extracellular vesicles (lEV) offer a unique window into the metabolism of their cells of orign and dysregulation of lipid metabolism has been described in patients with small cell lung cancer (SCLC). Therefore, metabolomic profiling of patients' lEVs may offer insight into cancer metabolism as well as new potential biomarkers for monitoring disease progression.MATERIALS AND METHODS: lEVs were isolated by differential centrifugation from the peripheral blood of SCLC patients and healthy controls. Targeted mass spectrometry was used to analyze the lipid composition of lEVs. After identifying relevant metabolites, biomarker and pathway analysis were conducted.RESULTS: SCLC patients exhibited a distinct metabolic profile compared to healthy controls. The metabolites TG(16:0:_38:3), TG(18:3_35:2), TG(16:0_40:7), Cer(d18:1/26:0), and CE(16:0) are not only able to discriminate between patients and control samples, but are also served as prognostic markers for survival. Patients with high concentrations of these metabolites showed significantly shorter survival times. Pathway analysis revealed alterations in 'sphingolipid metabolism', 'sphingolipid signaling pathway' and 'necroptosis'.CONCLUSION: Metabolic profiling of lEVs in SCLC patients is feasible and reveals a distinct metabolic profile. High concentrations of identified lipids are associated with poor prognosis.PMID:39477327 | DOI:10.21873/anticanres.17299

Anticancer Res. 2024 Nov;44(11):4801-4811. doi: 10.21873/anticanres.17306.ABSTRACTBACKGROUND/AIM: Natural compounds such as propolis have gained wide popularity in the last decades. While its antibacterial, antiviral, and antifungal properties are well known, the anticancer properties of propolis are just beginning to be appreciated. Herein, we comparatively investigate the cytotoxic and radiosensitizing potential of four different ethanolic propolis extracts originating from three different countries (Germany, Ireland, South Africa) in human lung cancer cell models.MATERIALS AND METHODS: Liquid chromatography-mass spectrometry (LC-MS/MS) was applied to characterize the four different propolis extracts. Cytotoxicity and radiation survival were determined by 3D matrix-based clonogenic assays and autophagy was examined by western blotting.RESULTS: We found cytotoxicity in a propolis type-, time- and cell model- dependent manner. In the four ethanolic propolis extracts, Coumaric acid, Caffeic acid phenethyl ester, Pinocembrin and Chrysin presented the major compounds identified. Examining the induction of autophagy using the marker LC3B and autophagy inhibition with chloroquine suggested autophagy to be part of the survival mechanisms upon propolis treatment in a cell model-dependent manner. Combining propolis with X-ray irradiation showed the radiosensitizing potential of propolis in human lung cancer cell models, which clearly presented in a manner dependent on the incubation time of propolis and the cell model treated.CONCLUSION: Propolis treatment showed cytotoxic and radiosensitizing effects of propolis on human lung cancer cells. Since these effects differ greatly between the four propolis extracts studied and originating from different regions, further studies are urgently needed to differentiate propolis species and their anticancer properties in more detail.PMID:39477309 | DOI:10.21873/anticanres.17306

Sci Total Environ. 2024 Oct 28:177248. doi: 10.1016/j.scitotenv.2024.177248. Online ahead of print.ABSTRACTN-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), a widely utilized antioxidant in automobile tires and rubber goods, is frequently detected in aquatic ecosystems and poses a potential threat to aquatic organisms. However, research on the impact of 6PPD on aquatic plants is still scarce. Here, we investigated the bioaccumulation of 6PPD in Myriophyllum verticillatum (M. verticillatum) (watermilfoil), and its impacts on biochemical characteristics and metabolomics. 6PPD (10,100 mg/L) significantly inhibited the growth and photosynthetic pigment content of M. verticillatum. After 14 days of exposure to 100 μg/L 6PPD, accumulation levels of 6PPD and its metabolite 6PPDQ in M. verticillatum reached 0.52 mg/kg and 0.09 mg/kg, respectively. Moreover, 6PPD significantly induced the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) enzymes and glutathione (GSH), reducing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), thereby mitigating oxidative damage in M. verticillatum. Furthermore, metabolic pathway analysis revealed that 6PPD has remarkable effects on amino acid and sugar metabolism. This study provides data support for understanding the toxic effects of 6PPD on aquatic plants and evaluating its potential risks.PMID:39477116 | DOI:10.1016/j.scitotenv.2024.177248

J Dairy Sci. 2024 Oct 28:S0022-0302(24)01249-9. doi: 10.3168/jds.2024-25430. Online ahead of print.ABSTRACTExploring the toxicity and metabolic mechanisms of Aflatoxin B1 (AFB1) in ruminants can help to develop strategies to prevent or reduce the transfer of the toxin and its metabolites to milk and meat. This study aimed to explore the effects of 3 concentrations of dietary AFB1 (0, 50, and 500 μg/kg) on hepatic injury and metabolism in Saanen goats via histological examination, Western blot analysis, as well as integrated multi-omics techniques. Eighteen Saanen goats were assigned to 1 of 3 treatments and the AFB1 challenge lasted for 14 d. Results showed that the liver tissue was enlarged and the relative organ index of the liver was linearly increased with elevated AFB1 levels. The hepatocyte apoptosis rate was significantly increased after AFB1 exposure and the Western blotting results revealed that both the external apoptotic pathway and mitochondrial-mediated intrinsic apoptotic pathway might be involved in AFB1-induced hepatocyte apoptosis. There were 251, 269, 154 significant differentially expressed genes (DEGs) and 340, 596, 127 significant differential metabolites for the control (C; 0 μg/kg) and low-dose (L; 50 μg/kg), C and high-dose (H; 500 μg/kg), L and H comparisons. The DEGs annotated were mainly involved in the cell part, cell, single-organism process, cellular process, binding, and other functional categories. The identified metabolites primarily belonged to glycerophospholipids, prenol lipids, carboxylic acids and derivatives. Integrative analysis of transcriptomics and metabolomics revealed that glycerophospholipids metabolism and choline metabolism in cancer were the most affected pathways related to AFB1 exposure. The identified differential metabolites, DEGs, and pathways might have played a crucial role in the hepatic injury induced by AFB1 in goats.PMID:39477065 | DOI:10.3168/jds.2024-25430

Eur J Pharm Biopharm. 2024 Oct 28:114552. doi: 10.1016/j.ejpb.2024.114552. Online ahead of print.ABSTRACTThis research is based on the incorporation of the methanolic extract of the Usnea ghattensis into poly (caprolactone) (PCL) nanofibers (NFs) to investigate the capacity in reducing reactive oxygen species (ROS). PCL-NFs were fabricated by the electrospinning technique and are investigated as potential dressing material focused on the release of usnic acid (PCL-USNIC NFs), and its encapsulation efficiency and kinetic release were analyzed by high performance liquid chromatography (HPLC). This investigation was performed by analyzing the usnic acid concentration as a function of the distance from the mat center point. The kinetic release analysis is also developed with the usnea ghattensis extract (PCL-USNEA NFs), performing a metabolomic analysis of the released molecules as a function of time by nuclear magnetic resonance (NMR). Usnic acid was revealed as the most relevant compound together with other molecules, such as sucrose, mannitol, arabitol or glycerol that generate a positive matrix effect on the release of usnic acid. Finally, we analize the cytotoxicity and the neuroprotective effect of PCL-USNEA and PCL-USNIC NFs using a human neuroblastoma cell line model. Negligible toxicity was appreciated for both polymeric systems, showing high protective effects in presence of highly oxidative environment (e.g. in presence of H2O2).PMID:39477028 | DOI:10.1016/j.ejpb.2024.114552

J Mol Cell Cardiol. 2024 Oct 28:S0022-2828(24)00172-X. doi: 10.1016/j.yjmcc.2024.10.011. Online ahead of print.ABSTRACTBACKGROUND: Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia associated with severe cardiovascular complications. AF presents a growing global challenge, however, current treatment strategies for AF do not address the underlying pathophysiology. To advance diagnosis and treatment of AF, a deeper understanding of AF root causes is needed. Metabolomics is a fast approach to identify, quantify and analyze metabolites in a given sample, such as human serum or atrial tissue. In the past two decades, metabolomics have enabled research on metabolite biomarkers to predict AF, metabolic features of AF, and testing metabolic mechanisms of AF in animal models. Due to the field's rapid evolution, the methods of AF metabolomics studies have not always been optimal. Metabolomics research has lacked standardization and requires expertise to face methodological challenges.PURPOSE OF THE REVIEW: We summarize and meta-analyze metabolomics research on AF in human plasma and serum, atrial tissue, and animal models. We present the current progress on metabolic biomarkers candidates, metabolic features of clinical AF, and the translation of metabolomics findings from animal to human. We additionally discuss strengths and weaknesses of the metabolomics method and highlight opportunities for future AF metabolomics research.PMID:39476947 | DOI:10.1016/j.yjmcc.2024.10.011

J Chromatogr A. 2024 Oct 19;1737:465459. doi: 10.1016/j.chroma.2024.465459. Online ahead of print.ABSTRACTUnknown impurities, metabolites and harmful pollutants present in pharmaceutical products, biological and environmental samples, respectively are of high concern in terms of their detection and quantification. The targeted analysis aims to quantify known chemical entities, but it lacks the ability to identify unknown components present in a sample. Non-targeted analysis is an analytical approach that can be made applicable to various disciplines of science to effectively search for unknown chemical, biological, or environmental entities that can answer various baffling mysteries of research. It employs various high-end analytical techniques that can specifically screen out multiple unknown compounds from complex mixtures. Non-targeted analysis is also applicable for complex studies such as metabolomics to search unidentified metabolites of new chemical entities. This review critically discusses the current advancements in non-targeted analysis related to the analysis of pharmaceutical, biological, and environmental samples. Various steps like sample collection, handling, preparation, extraction, its analysis using advanced techniques like high-resolution mass spectrometry, liquid chromatography mass spectrometry, and lastly interpretation of the huge amounts of complex data obtained upon analysis of complex matrices have been discussed broadly in this article. Besides the advantages of non-targeted analysis over targeted analysis, limitations, bioinformatics tools, sources of error, and research gaps have been critically analyzed.PMID:39476774 | DOI:10.1016/j.chroma.2024.465459

J Hazard Mater. 2024 Oct 26;480:136326. doi: 10.1016/j.jhazmat.2024.136326. Online ahead of print.ABSTRACTAn investigation was conducted by researchers on how dibutyl phthalate (DBP) and polystyrene microplastics (PS-MP) influence the development of pneumonia using a mouse model. For a duration of five weeks, the mice were subjected to exposure of DBP (30 mg/kg/day) and PS-MP (0.1 mg/day). The findings indicated notable pathological alterations in airway tissues, increased oxidative stress levels, and intensified inflammation, thereby establishing a connection between plastic pollution and pneumonia. Further examination indicated the involvement of ferroptosis and oxidative stress in the progression of the disease. Administration of deferoxamine (DFO) (100 mg/kg) resulted in symptom relief and reduced pathological alterations, as validated by metabolomic investigations. Increased levels of reactive oxygen species (ROS) triggered a Th2-mediated eosinophilic inflammatory response, marked by elevated IL-4 and reduced IFN-γ via the NFκB pathway. Moreover, analyses of the gut microbiome and metabolomics demonstrated that PPD modifies microbial populations and pulmonary metabolism, linking its effects on pneumonia through the gut-lung axis. This research highlights the health hazards associated with plastic pollution and proposes a framework for tackling these issues.PMID:39476687 | DOI:10.1016/j.jhazmat.2024.136326

Ecotoxicol Environ Saf. 2024 Oct 29;287:117262. doi: 10.1016/j.ecoenv.2024.117262. Online ahead of print.ABSTRACTHigh selenium (Se) levels can induce toxicity, inhibit growth, and affect gene expression and metabolite content in plants. However, the molecular mechanism by which high Se stress affects soybean plants remains unclear. This study examined the responses of soybean leaves and roots to high Se stress using transcriptome and metabolome analyses. High Se stress significantly inhibited soybean root growth, reduced leaf area, and affected the antioxidant enzyme system in roots and leaves, resulting in the accumulation of malondialdehyde (MDA). High Se stress increased indoleacetic acid (IAA), abscisic acid (ABA), jasmonic acid (JA), and salicylic acid (SA) in the roots by 3.34-fold, 8.94-fold, 0.25-fold, and 5.65-fold, respectively. Similarly, high Se stress increased IAA, ABA, JA, and SA in the leaves by 1.96-fold, 10.54-fold, 2.03-fold, and 4.22-fold, respectively. In addition, high Se stress affected ion absorption and transport in soybean plants. Transcriptome results showed that there were 10,038 differentially expressed genes (DEGs) in soybean roots and 5811 DEGs in leaves, which affected the expression of antioxidant enzymes, ion transport and hormone-related genes. Metabolome results revealed that there were 277 differentially expressed metabolites (DEMs) in soybean leaves and 312 DEMs in roots. Soybean roots and leaves were significantly enriched in the "β-alanine metabolism" pathway under high Se stress, with differential expression of Aldehyde dehydrogenase (ALDH), Amine oxidase (AO), and other related genes, thereby relieving oxidative stress. This study improves our understanding of the molecular mechanisms underlying the responses of soybean plants to high Se stress and provides a basis for breeding Se-enriched soybean plants.PMID:39476650 | DOI:10.1016/j.ecoenv.2024.117262

Food Chem. 2024 Oct 26;464(Pt 2):141784. doi: 10.1016/j.foodchem.2024.141784. Online ahead of print.ABSTRACTA prolonged diet laden with purine-rich foods represents a significant contributor to renal fibrosis (RF). Eucommia ulmoides Oliver, a plant homologous to food and medicinal materials, has long been employed to recover kidney function. This investigation presents a strategy integrating chemistry, biochemistry, and metabolomics to evaluate bioactive components and efficiency mechanism of crude and salt-stir fried Eucommiae Cortex (EC) extracts against RF. Firstly, 155 chemical components were identified in the EC extracts and the contents of 19 and 27 compounds decreased and increased respectively after salt-stir frying. Secondly, various biochemical indicators displayed that salt-stir fried EC (SEC) extracts had the optimal anti-RF effects in adenine-induced RF model rats, which were associated with the attenuation of TGF-β signaling pathway. Finally, untargeted metabolomics analysis demonstrated that after treatments with EC and SEC extracts, 30 and 32 efficacy biomarkers were significantly restored in the RF + EC and RF + SEC groups respectively, involving five metabolic pathways.PMID:39476582 | DOI:10.1016/j.foodchem.2024.141784

Theriogenology. 2024 Oct 26;231:197-209. doi: 10.1016/j.theriogenology.2024.10.025. Online ahead of print.ABSTRACTPhospholipase A (PLA) in goat semen aggregates with egg yolk in semen diluent, leading to sperm death. The aim of this study is to address the issue of sperm death caused by the interaction between PLA and egg yolk, and to explore the protective effect and metabolic regulation mechanism of the combination of dexamethasone (DXMS) and azithromycin (AZM) on goat sperm under low temperature conditions. At a low temperature of 4 °C, different concentrations of DXMS were added to semen diluents containing 30 μg/mL AZM to detect the quality of goat sperm. The optimal concentration of DXMS was determined to be 20 μg/mL. On the 5th day of storage, antioxidant capacity, total cholesterol (TC) levels, energy metabolism, and metabolomics analysis were performed on the sperm of the 20 μg/mL DXMS group. The results showed that there was no aggregation caused by the interaction between PLA and egg yolk in the group containing 30 μg/mL AZM at 4 °C. 20 μg/mL DXMS significantly improved sperm motility, plasma membrane integrity, acrosome integrity, glutathione peroxidase (GPX) (P < 0.05), catalase (CAT) (P < 0.01), and superoxide dismutase (SOD) activity (P < 0.01). The content of reactive oxygen species (ROS) and Fe2+ significantly decreased (P < 0.01), while the content of ATP (P < 0.01) and TC (P < 0.05) significantly increased. Through metabolomics analysis, a total of 56 differential metabolites (P < 0.05) were screened, including 5a, 6-Anhydrotetracycline, Betamethasone, and 11-Dehydrocorticosterone, mainly enriched in 8 metabolic pathways (P < 0.05), including steroid hormone biosynthesis, glycerophospholipid metabolism, and choline metabolism in cancer. Among them, 5 metabolic pathways are related to lipid metabolism. The results indicate that AZM effectively inhibits the aggregation of PLA and yolk, and the combination of AZM and DXMS enhances the preservation quality of goat sperm during low-temperature preservation by regulating lipid metabolism.PMID:39476552 | DOI:10.1016/j.theriogenology.2024.10.025

Cancer Discov. 2024 Oct 31. doi: 10.1158/2159-8290.CD-24-0187. Online ahead of print.ABSTRACTCopper (Cu) is a cofactor of cytochrome c oxidase (CuCOX), indispensable for aerobic mitochondrial respiration. This study reveals that advanced clear cell renal cell carcinomas (ccRCCs) accumulate Cu, allocating it to CuCOX. Using a range of orthogonal approaches, including metabolomics, lipidomics, isotope-labeled glucose and glutamine flux analysis, and transcriptomics across tumor samples, cell lines, xenografts, and PDX models, combined with genetic and pharmacological interventions, we explored Cu's role in ccRCC. Elevated Cu levels stimulate CuCOX biogenesis, providing bioenergetic and biosynthetic benefits that promote tumor growth. This effect is complemented by glucose-dependent glutathione production, which facilitates detoxification and mitigates Cu-H2O2 toxicity. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics reveal increased oxidative metabolism, altered glutathione and Cu metabolism, and diminished HIF activity during ccRCC progression. Thus, Cu drives an integrated oncogenic remodeling of bioenergetics, biosynthesis, and redox homeostasis, fueling ccRCC growth, which can be targeted for new therapeutic approaches.PMID:39476412 | DOI:10.1158/2159-8290.CD-24-0187

Plant Biol (Stuttg). 2024 Oct 30. doi: 10.1111/plb.13727. Online ahead of print.ABSTRACTCold resistance in fruit trees has a direct impact on food production and scientific studies. 'Donghe No.1' is an excellent cold-tolerant peach variety. Metabolomic changes under freezing stress were examined to understand the mechanisms of cold adaptation. The UPLC-MS/MS system was used to identify differentially expressed metabolites (DEMs) in branches of 'Donghe No.1' under freezing stress for 12 h at -5°C, -20°C, -25°C, or -30°C. In total, 1096 metabolites and 196 DEMs were obtained at -5°C vs -20°C, -25°C, and - 30°C, while 179 DEMs and eight shared DEMs obtained at -5°C vs -20°C, -20°C vs -25°C, and -25°C vs -30°C. KEGG enrichment identified 196 DEMs associated with amino acid metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, phenylpropanoid biosynthesis, and flavonoid biosynthesis under freezing stress. A metabolic network in 1-year-old peach branches under freezing stress is proposed. Moreover, these results enhance understanding of metabolite responses and mechanisms to freezing stress in peach and will help in future breeding of freezing-tolerant varieties and investigating tolerance mechanisms.PMID:39476336 | DOI:10.1111/plb.13727

Hist Philos Life Sci. 2024 Oct 30;46(4):34. doi: 10.1007/s40656-024-00630-w.ABSTRACT'Obesity' has, for decades, been a subject of intense scientific and public interest, and remains a key target for postgenomic science. I examine the emergence of determinism in research into 'obesity' in the postgenomic field of metabolomics. I argue that determinism appears in metabolomics research in two ways: firstly, fragmentation and narrow construal of the environment is evident in metabolomics studies on weight loss interventions, resulting in particular features of the environment (notably, dietary intake) having outsized influence while the wider social environment is neglected. Secondly, studies aiming to characterize the metabolic signature of 'obesity' are guided by a commitment to a deterministic connection between 'obesity' and dysfunction, leading to a neglect or distortion of metabolic heterogeneity across individuals regardless of body size.PMID:39476192 | DOI:10.1007/s40656-024-00630-w

PLoS One. 2024 Oct 30;19(10):e0305697. doi: 10.1371/journal.pone.0305697. eCollection 2024.ABSTRACTThis study was designed as a randomized, placebo-controlled, double-blinded, cross-over trial performed to investigate the effects of a dietary supplement containing undenatured type II collagen (UCII®) and Boswellia Serrata on mobility, pain and joint metabolism in mild moderate osteoarthritis (OA) in dogs. A total of 60 dogs with mobility problems were evaluated and enrolled in the study. Seventeen of these dogs with mild/moderate OA were randomized to receive the product A (UCII® + Boswellia Serrata supplement-UCII®-BW) or product B (Placebo -PL), 1 chew per day for 8 weeks by oral route, and repeated in a crossover design after 4 weeks of washout period. All the subjects had veterinary evaluations during the trial and owners were requested to fill out a questionnaire on mobility impairment using the Liverpool Osteoarthritis in dogs scale (L.O.A.D.) at each time of the study. Objective tools were used to assess mobility, activity, and pain. Metabolomic analysis was performed on synovial fluid of most affected joint at the beginning and the end of the study. The results proved that UCII®+Boswellia serrata supplemented group over a period of eight weeks results in an improvement of mobility impairment, already at 4 weeks of administration, according to the owner´s evaluation. In contrast, its absence increased the risk of OA crisis and decreased the pain threshold on the most affected joint. Furthermore, the synovial fluid metabolic profile showed moderate differences between the beginning and the end of the supplementation period, with a particular influence associated to the time of UCII®-BW administration.PMID:39475935 | DOI:10.1371/journal.pone.0305697

Anal Chem. 2024 Oct 30. doi: 10.1021/acs.analchem.4c04187. Online ahead of print.ABSTRACTMany chiral carboxylic acids with α-amino, α-hydroxyl, and α-methyl groups are concurrently present in mammals establishing unique molecular phenotypes and multiple biological functions, especially host-microbiota symbiotic interactions. Their chirality-resolved simultaneous quantification is essential to reveal the biochemical details of physiology and pathophysiology, though challenging with their low abundances in some biological matrices and difficulty in enantiomer resolution. Here, we developed a method of the chirality-resolved metabolomics with sensitivity-enhanced quantitation via probe-promotion (Met-SeqPro) for analyzing these chiral carboxylic acids. We designed and synthesized a hydrazide-based novel chiral probe, (S)-benzoyl-proline-hydrazide (SBPH), to convert carboxylic acids into amide diastereomers to enhance their retention and chiral resolution on common C18 columns. Using the d5-SBPH-labeled enantiomers as internal standards, we then developed an optimized ultrahigh-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous quantification of 60 enantiomers of 30 chiral carboxylic acids in one run. This enantiomer-resolved method showed excellent sensitivity (LOD < 4 fmol-on-column), linearity (R2 > 0.992), precision (CV < 15%), accuracy (|RE| < 20%), and recovery (80-120%) in multiple biological matrices. With the method, we then quantified 60 chiral carboxylic acids in human urine, plasma, feces, and A549 cells to define their metabolomic phenotypes. This provides basic data for human phenomics and a promising tool for investigating the mammal-microbiome symbiotic interactions.PMID:39475527 | DOI:10.1021/acs.analchem.4c04187

J Proteome Res. 2024 Oct 30. doi: 10.1021/acs.jproteome.4c00654. Online ahead of print.ABSTRACTPharmacological targeting of metabolic pathways represents an appealing strategy to selectively kill cancer cells while promoting antitumor functions of stromal cells. In this study, we assessed the effectiveness of 13 metabolic drugs (MDs) in steering in vitro generated breast tumor-educated macrophages (TEMs) toward an antitumoral phenotype. For that, the production of vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNF-α), two important regulators of tumor progression, was evaluated. Notably, dichloroacetate (DCA), 6-aminonicotinamide (6-AN), and etomoxir decreased VEGF production and enhanced TNF-α release. Hence, we further clarified their impact on TEM metabolism using an untargeted NMR-based metabolomics approach. DCA downregulated glycolysis and enhanced the utilization of extracellular substrates like lactate while reconfiguring lipid metabolism. Several DCA-induced changes significantly correlated with heightened TNF-α production in response to pro-inflammatory stimulation. The inhibition of the pentose phosphate pathway by 6-AN was accompanied by enhanced glutaminolysis, which correlated with a decreased level of VEGF production. In etomoxir-treated TEM, inhibition of fatty acid oxidation was compensated through upregulation of glycolysis, catabolism of intracellular amino acids, and consumption of extracellular branched chain alpha-ketoacids (BCKA) and citrate. Overall, our results offer a comprehensive view of the metabolic signature of each MD in breast TEM and highlight putative correlations with phenotypic effects.PMID:39475502 | DOI:10.1021/acs.jproteome.4c00654

J Food Sci. 2024 Oct 30. doi: 10.1111/1750-3841.17458. Online ahead of print.ABSTRACTPlant-based meat analogs (PBMAs) are common ultra-processed foods (UPFs) included in the vegan/vegetarian diets as presumed healthy alternatives to meat and meat products. However, such health claims need to be supported by scientific evidence. To gain further insight into this topic, two commercial UPFs typically sold as meat analogs, namely, seitan (S) and tofu (T), were included in a cereal-based chow and provided to Wistar rats for 10 weeks. A group of animals had, simultaneously, an isocaloric and isoprotein experimental diet formulated with cooked beef (B). In all cases, experimental chows (∼4 kcal/g feed) had their basal protein concentration increased from 14% to 30% using proteins from S, T, or B. Upon slaughter, in vivo protein digestibility was assessed, and the entire gastrointestinal tract (digests and tissues) was analyzed for markers of oxidative stress and untargeted metabolomics. Metagenomics was also applied to assess the variation of microbiota composition as affected by dietary protein. Diets based on PBMAs showed lower protein digestibility than those containing meat and promoted an intense luminal glycoxidative stress and an inflammatory intestinal response. The fermentation of undigested oxidized proteins from T in the colon of Wistar rats likely led to formation of mutagenic metabolites such as p-cresol. The presence of these compounds in the animal models raises concerns about the potential effects of full replacement of meat by certain PBMAs in the diet. Therefore, future research might target on translational human studies to shed light on these findings.PMID:39475341 | DOI:10.1111/1750-3841.17458