PubMed

Biomed Pharmacother. 2024 Oct 13;180:117518. doi: 10.1016/j.biopha.2024.117518. Online ahead of print.ABSTRACTThe incidence of inflammatory bowel disease (IBD) is rising globally, increasing interest in food ingredients for its prevention and control. This study evaluated the effect of farnesol (FAR), a key component of pomelo flower volatile oil, on dextran sodium sulfate (DSS)-induced colitis in C57BL/6 mice. FAR significantly alleviated DSS-induced colitis and secondary liver injury, as shown by improved body weight, DAI, colon length, and pathology, as well as liver function and blood lipid indices. The mechanism involves FAR-mediated regulation of inflammatory cytokines, increased expression of tight junction protein genes, and decreased expression of lipid metabolism-related proteins. FAR also enhanced gut microbiota diversity, balancing harmful and probiotic bacteria. Fecal metabolome analysis indicated FAR's role in reversing metabolic disturbances related to inflammation and liver lipid metabolism. These findings support developing functional foods for IBD treatment using pomelo flower volatile oil.PMID:39405907 | DOI:10.1016/j.biopha.2024.117518

Biomed Pharmacother. 2024 Oct 13;180:117546. doi: 10.1016/j.biopha.2024.117546. Online ahead of print.ABSTRACTSelaginella tamariscina extracts (STS), total flavonoids of Selaginella tamariscina (TFST) and the main active component amentoflavone (AMT) have hypoglycaemic-mitigating effects, but their efficacy and mechanism of action in db/db mice are unknown. This study aimed to evaluate the hypoglycaemic effects of Selaginella tamariscina and its extracts in db/db diabetic mice and explore their mechanisms through gut microbiota modulation and metabolomics. Sixty male db/db mice were divided into model (db/db), STS (1.1 g/kg), TFST (140 mg/kg), AMT (60 mg/kg), mulberry twig alkaloid tablets (MTA, 24 mg/kg), and metformin (Met, 160 mg/kg) groups. Another 10 db/m mice served as controls. Treatments lasted 4 weeks. Blood glucose, body weight, diabetes symptoms, lipid levels, pathological changes, oxidative stress markers and liver damage levels were assessed. The gut microbiota composition was analyzed via 16S rDNA sequencing, and urinary metabolomics was conducted to understand metabolic changes. Selaginella tamariscina and its extracts significantly improved hyperglycaemia, insulin sensitivity, lipid metabolism, oxidative stress and liver injury in db/db mice, among which TFST was the most effective, with an effect comparable to that of Met and superior to that of MTA. TFST regulates gut microbiota disorders and metabolic profiles in db/db diabetic mice and modulates Alloprevotella levels, affecting butyric acid content and, thus, exerting a hypoglycaemic effect. These findings suggest that TFST modulates Alloprevotella, influencing butyric acid levels, which improves glycaemic control, enhances insulin sensitivity, and prevents oxidative stress and tissue damage. In conclusion, TFST has potential as a natural therapeutic agent for the control of T2DM.PMID:39405904 | DOI:10.1016/j.biopha.2024.117546

J Pharm Biomed Anal. 2024 Oct 3;252:116502. doi: 10.1016/j.jpba.2024.116502. Online ahead of print.ABSTRACTAsari radix et rhizoma is the sole plant from the Aristolochiaceae family officially sanctioned for medicinal in China, primarily employed for treating colds and headaches, and is widely utilized in clinical practice. Initially, the entire plant was specified for medicinal use, but since 2005, the authorized part has been restricted to the roots and rhizomes. The chemical constituents are directly linked to its efficacy and safety, yet a comparative analysis of the chemical profiles between the overground and underground parts has not been reported. This paper represents the first comparative study of the chemical constituents in the two parts, achieved through the synergistic application of solid phase micro extraction coupled with gas chromatography mass spectrometry (SPME-GC-MS) and liquid chromatography Orbitrap MS (LC-Orbitrap-MS). Using SPME-GC-MS, 51 constituents were identified from both parts, with 89 % being shared components, indicating a close similarity in their volatile compositions. Through LC-Orbitrap-MS, 308 constituents were identified, sharing 76 % commonality, revealing a more pronounced disparity in non-volatile components. Plant metabolomics screening pinpointed 8 volatile and 14 non-volatile components capable of distinguishing the two parts, with the latter being more stable and thus better suited as markers for differentiation. This research furnishes a scientific rationale for selecting distinct parts of Asari radix et rhizoma and for implementing monitoring strategies in clinical application.PMID:39405788 | DOI:10.1016/j.jpba.2024.116502

J Pharm Biomed Anal. 2024 Oct 10;252:116516. doi: 10.1016/j.jpba.2024.116516. Online ahead of print.ABSTRACTQiliqiangxin (QLQX) capsule consists of 11 herbs, namely Huang qi (astragalus membranaceus), Ren shen (ginseng), Fu zi (radix aconiti carmichaeli), Dan shen (salvia miltiorrhiza), Ting li zi (lepidium seed), Ze xie (rhizoma alismatis), Yu zhu (radix polygonati officinalis), Gui zhi (cassia twig), Hong hua (carthamus tinctorious), Xiang jia Pi (cortex periplocae), Chen Pi (pericarpium citri reticulatae), and it is a standardized commercial formula designed to address yang deficiency and to restore the balance of qi in the heart. QLQX is also known to invigorate the blood and promote the circulation of the blood and to promote the use of fluids to relieve water retention and edema, and can be used in cardiovascular diseases such as mild to moderate congestive heart failure resulting from coronary artery disease and hypertension. The further research on the effect of QLQX on cardiac function in mice after myocardial infarction was manipulated. QLQX was given to mice in myocardial infarction model by gavage with appropriate dosage and the samples were analyzed at the end of the animal experiments through the UHPLC-Q-Exactive LC-MS. The liquid mass spectrometry was used to collect and followed by further analysis of the corresponding metabolites and metabolic pathways using metabolomics analysis. As a result, 9 differential metabolites were identified, with 15 being up-regulated and 4 down-regulated following intervention with QLQX. Then the metabolic pathways by KEGG enrichment pathway bubble diagram was analyzed, and 4 metabolic pathways were obtained, and combined with the metabolites that had been screened and analyzed together, finally the two differential metabolites, 2,5-Dihydroxybenzenesulfonic Acid and o-Cresol sulfate were found. The Glycerophospholipid metabolism pathway was closely related to the remaining seven differential metabolites, and the pathway might be an important pathway related to the effects of QLQX on cardiac function in mice.PMID:39405786 | DOI:10.1016/j.jpba.2024.116516

J Pharm Biomed Anal. 2024 Oct 9;252:116512. doi: 10.1016/j.jpba.2024.116512. Online ahead of print.ABSTRACTSnake melon (Cucumis melo var. flexuosus, CM) is a gourd with health-promoting nutritional traits and unexplored phytochemicals. This study aims to comprehensively investigate the phytoconstituents in the fruits, leaves, roots, seeds, and stems of CM, using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. Consequently, 118 metabolites were identified, encompassing phenolic compounds, flavonoids, megastigmanes, lignans, cucurbitacins, and fatty acids. Multivariate data analysis revealed differences in the metabolite composition of CM organs and correlated these variations with the potential in-vitro anti-inflammatory properties assessed against RAW 264.7 macrophages through the down-regulation of cyclo-oxygenase-Ⅱ, nuclear factor-kappa B, and tumor necrosis factor-α. The results indicated that leaf and seed extracts showed the highest anti-inflammatory activity due to their enrichment in several flavonoids, phenolic glycosides, and a megastigmane. These findings emphasize the health benefits of CM organs as potential functional foods and functional food by-products, serving as a natural source for developing new anti-inflammatory agents.PMID:39405783 | DOI:10.1016/j.jpba.2024.116512

Drug Resist Updat. 2024 Oct 10;77:101159. doi: 10.1016/j.drup.2024.101159. Online ahead of print.ABSTRACTAlthough immune checkpoint inhibitors (ICIs) have revolutionized immuno-oncology with effective clinical responses, only 30 to 40 % of patients respond to ICIs, highlighting the need for reliable biomarkers to predict and enhance therapeutic outcomes. This study investigated how amino acid, glycolysis, and bile acid metabolism affect ICI efficacy in non-small cell lung cancer (NSCLC) patients. Through targeted metabolomic profiling and machine learning analysis, we identified amino acid metabolism as a key factor, with histidine (His) linked to favorable outcomes and homocysteine (HCys), phenylalanine (Phe), and sarcosine (Sar) linked to poor outcomes. Importantly, the His/HCys+Phe+Sar ratio emerges as a robust biomarker. Furthermore, we emphasize the role of glycolysis-related metabolites, particularly lactate. Elevated lactate levels post-immunotherapy treatment correlate with poorer outcomes, underscoring lactate as a potential indicator of treatment efficacy. Moreover, specific bile acids, glycochenodeoxycholic acid (GCDCA) and taurolithocholic acid (TLCA), are associated with better survival and therapeutic response. Particularly, TLCA enhances T cell activation and anti-tumor immunity, suggesting its utility as a predictive biomarker and therapeutic agent. We also suggest a connection between gut microbiota and TLCA levels, with the Eubacterium genus modulating this relationship. Therefore, modulating specific metabolic pathways-particularly amino acid, glycolysis, and bile acid metabolism-could predict and enhance the efficacy of ICI therapy in NSCLC patients, with potential implications for personalized treatment strategies in immuno-oncology. ONE SENTENCE SUMMARY: Our study identifies metabolic biomarkers and pathways that could predict and enhance the outcomes of immune checkpoint inhibitor therapy in NSCLC patients.PMID:39405736 | DOI:10.1016/j.drup.2024.101159

J Hazard Mater. 2024 Oct 9;480:136120. doi: 10.1016/j.jhazmat.2024.136120. Online ahead of print.ABSTRACTAlthough animal studies have evaluated lead (Pb) toxicity, they are limited to soluble forms, such as Pb-acetate, which do not reflect the range found in the exposome. Recent studies on Pb speciation of residential soils in urban areas revealed that the initial Pb sources are not persistent and are extensively repartitioned into adsorbed forms of Pb rather than insoluble phosphates. We investigated the inhalation and neurological toxicity of dusts generated from a surficial soil sample collected from a residential site with an exposomic mixture of various Pb species, both adsorbed phases (Fe and Mn oxide, humate bound Pb) and mineral phases (Pb hydroxycarbonate, pyromorphite, galena). Mice inhaled East Chicago dust (ECD) generated from a composite soil sample for 4 h/day, 7 days/week, for 4 weeks. Mice were necropsied immediately, 1, 14 and 30 days post exposure to evaluate both toxicity and recovery. Exposure to ECD caused changes in memory and spatial learning in the Morris Water Maze test. RNAseq analysis of the hippocampus region revealed multiple differentially expressed genes and impacts on pathways involved in ion channel complexes, and neuron-to-neuron synapse. Metabolomics analysis of plasma highlighted significant alterations in metabolic processes immediately after exposure that resolved after 14 days of rest.PMID:39405708 | DOI:10.1016/j.jhazmat.2024.136120

J Hazard Mater. 2024 Oct 9;480:136086. doi: 10.1016/j.jhazmat.2024.136086. Online ahead of print.ABSTRACTHeavy metals (HMs) present in the natural aquatic environment can form a ternary aggregate of "EPS-DOM-HMs" with the prevalent microalgae extracellular polymers substances (EPS) and macromolecular dissolved organic matters (DOMs), which show special molecular structure and biological interaction. This study reveals the formation of "EPS-TA-HMs" and the mechanism of their physiological and metabolic effects on Raphidocelis subcapitata. Results indicate that TA-Cr(III) can bind to EPS to form ternary aggregates with substances coexisting large and small hydrodynamic diameters and that the interactions are dominated by hydrophobic interactions of the protein binding to the pyrrole ring of the polyphenol and hydrogen bonding interactions formed by OC-(N R O). The protein structure of EPS has the largest proportion of proline, glycine, aspartic acid, and tryptophan. These interactions promoted the secretion of EPS components and reduced the growth inhibition of Raphidocelis subcapitata by 45.9 % compared with Cr(III) exposure. TEM analysis combined with EDS analysis indicated that Cr(III) was taken intracellularly and TA-Cr(III) was not. In addition, metabolomics analyses revealed that microalgae initiate adaptive mechanisms via the activation of a two-component system (i.e., maintenance of high metabolic activity). This study underscored the morphology of HMs in real aquatic environments and the mechanisms of metabolic effects on aquatic organisms.PMID:39405697 | DOI:10.1016/j.jhazmat.2024.136086

Transl Oncol. 2024 Oct 13;50:102152. doi: 10.1016/j.tranon.2024.102152. Online ahead of print.ABSTRACTBACKGROUND: Plasma-derived Extracellular Vesicles (EVs) have been suggested as novel biomarkers in melanoma, due to their ability to reflect the cell of origin and ease of collection. This study aimed to identify novel EV biomarkers that can discriminate between disease stages. This was achieved by characterising the plasma-derived EVs of patients with melanoma, and comparing their proteomic and metabolomic profile to those from healthy controls.METHODS: EVs were isolated from the plasma of 36 patients with melanoma and 13 healthy controls using Size Exclusion Chromatography. Proteomic and Metabolomic Analyses were performed, and machine learning algorithms were used to identify potential proteins and metabolites to differentiate the plasma-derived EVs from melanoma patients of different disease stages.RESULTS: The concentration and size of the EV population isolated was similar between groups. Proteins (APOC4, PRG4, PLG, TNC, VWF and SERPIND1) and metabolites (lyso PC a C18:2, PC ae C44:3) previously associated with melanoma pathogenesis were identified as relevant in differentiating between disease stages.CONCLUSION: The results further support the continued investigation of circulating plasma-derived EVs as biomarkers in melanoma. Furthermore, the potential of combined proteo-metabolomic signatures for differentiation between disease stages may provide valuable insights into early detection, prognosis, and personalised treatment strategies.PMID:39405606 | DOI:10.1016/j.tranon.2024.102152

Ticks Tick Borne Dis. 2024 Oct 13;15(6):102404. doi: 10.1016/j.ttbdis.2024.102404. Online ahead of print.ABSTRACTThe control and prevention of ticks and tick-borne diseases rely on chemical insecticides and repellents. Plant-derived compounds potentially represent new and safer repellents. Cinnamaldehyde, a component of cinnamon oil, exhibits antibacterial, anti-inflammatory, acaricidal, and repellent activity against ticks. Here we studied the molecular mechanism of the repellent effect of cinnamaldehyde on Haemaphysalis longicornis. A 2 % cinnamaldehyde treatment resulted in >90 % nymph repellency within 6 h. Nymphs were exposed to cinnamaldehyde for 30 min, and subsequent transcriptome and metabolome analyses revealed the involvement of H. longicornis Acetylcholinesterases (HL-AchEs) in the response process. HL-AchEs was transcribed in all tick developmental stages and tissues. Following cinnamaldehyde treatment, the transcript and specific activity of the enzyme of AchE were significantly altered. Following RNAi, electroantennography (EAG) tests demonstrated a significant decrease in response to various repellents as well as a significant decrease in repellency. Our findings have revealed that HL-AchEs mediates cinnamaldehyde-induced tick repellency, and the results provide insights into the mechanism of plant-derived tick repellents.PMID:39405601 | DOI:10.1016/j.ttbdis.2024.102404

J Med Chem. 2024 Oct 15. doi: 10.1021/acs.jmedchem.4c01926. Online ahead of print.ABSTRACTPregnane X receptor (PXR) is a ligand-activated transcription factor that binds diverse compounds and upregulates drug metabolism machinery in response. PXR activation is detrimental to drug efficacy and safety because it reduces active drug concentrations and increases reactive metabolites, leading to toxicity and/or drug-drug interactions. Thus, effort must be expended in drug development pipelines to assess PXR activation by lead candidates and chemically modify agonists to reduce PXR liabilities while maintaining on-target potencies. Coadministration of drugs with PXR antagonists could prevent PXR-mediated metabolism events, but such compounds are rare and may themselves be converted to agonists by metabolic enzymes or PXR mutations. Here, we report the design, synthesis, optimization, and biological validation of proteolysis targeting chimeras that induce PXR degradation through E3 ubiquitin ligase recruitment. PXR degradation blocks agonist-induced gene expression and enhances anticancer effects of the chemotherapy paclitaxel, a known PXR agonist and substrate of downstream metabolic enzymes.PMID:39405362 | DOI:10.1021/acs.jmedchem.4c01926

PLoS Genet. 2024 Oct 15;20(10):e1011432. doi: 10.1371/journal.pgen.1011432. Online ahead of print.ABSTRACTSeveral protein ensembles facilitate crossover recombination and the associated assembly of synaptonemal complex (SC) during meiosis. In yeast, meiosis-specific factors including the DNA helicase Mer3, the "ZZS" complex consisting of Zip4, Zip2, and Spo16, the RING-domain protein Zip3, and the MutSγ heterodimer collaborate with crossover-promoting activity of the SC component, Zip1, to generate crossover-designated recombination intermediates. These ensembles also promote SC formation - the organized assembly of Zip1 with other structural proteins between aligned chromosome axes. We used proximity labeling to investigate spatial relationships between meiotic recombination and SC proteins in S. cerevisiae. We find that recombination initiation and SC factors are dispensable for proximity labeling of Zip3 by ZZS components, but proteins associated with early steps in recombination are required for Zip3 proximity labeling by MutSγ, suggesting that MutSγ joins Zip3 only after a recombination intermediate has been generated. We also find that zip1 separation-of-function mutants that are crossover deficient but still assemble SC fail to generate protein ensembles where Zip3 can engage ZZS and/or MutSγ. The SC structural protein Ecm11 is proximity labeled by ZZS proteins in a Zip4-dependent and Zip1-independent manner, but labeling of Ecm11 by Zip3 and MutSγ requires, at least in part, Zip1. Finally, mass spectrometry analysis of biotinylated proteins in eleven proximity labeling strains uncovered shared proximity targets of SC and crossover-associated proteins, some of which have not previously been implicated in meiotic recombination or SC formation, highlighting the potential of proximity labeling as a discovery tool.PMID:39405359 | DOI:10.1371/journal.pgen.1011432

JCI Insight. 2024 Oct 15:e181172. doi: 10.1172/jci.insight.181172. Online ahead of print.ABSTRACTLeft ventricular hypertrophy (LVH) and dyslipidemia are strong, independent predictors for cardiovascular disease, but their relationship is less well-studied. A longitudinal lipidomic profiling of left ventricular mass (LVM) and LVH is still lacking. Using LC-MS, we repeatedly measured 1,542 lipids from 1,755 unique American Indians attending two exams (mean~5-year apart). Cross-sectional associations of individual lipid species with LVM index (LVMI) were examined by generalized estimating equation (GEE), followed by replication in an independent bi-racial cohort (65% white, 35% black). Baseline plasma lipids associated with LVH risk beyond traditional risk factors were identified by Cox frailty model in American Indians. Longitudinal associations between changes in lipids and changes in LVMI were examined by GEE, adjusting for baseline lipids, baseline LVMI, and covariates. Multiple lipid species (e.g., glycerophospholipids, sphingomyelins, acylcarnitines) were significantly associated with LVMI or the risk of LVH in American Indians. Some lipids were confirmed in black and white individuals. Moreover, some LVH-related lipids were inversely associated with risk of coronary heart disease (CHD). Longitudinal changes in several lipid species (e.g., glycerophospholipids, sphingomyelins, cholesterol esters) were significantly associated with changes in LVMI. These findings provide insights into the role of lipid metabolism in LV remodeling and the risk of LVH or CHD.PMID:39405119 | DOI:10.1172/jci.insight.181172

Food Funct. 2024 Oct 15. doi: 10.1039/d4fo03657c. Online ahead of print.ABSTRACTEpidemiological and animal studies have indicated that calcium and boron are essential for bone development and metabolism. However, limited information is available regarding the effects of boron supplementation on bone development and metabolism in newly weaned infants with either calcium deficiency or calcium sufficiency. This study assessed the effects of dietary boron supplementation (0 and 3 mg kg-1) on bone development and metabolism, in a newly weaned mouse model, under both calcium deficiency and sufficiency feeding conditions. The results show that mice fed a calcium sufficient diet exhibited lower fat percentage and final body weight than those fed a calcium deficient diet. Boron supplementation reduced the serum high-density lipoprotein cholesterol level and up-regulated the mRNA levels of FABP3, PPAR-γ, and CaMK in the intestinal mucosa. Importantly, boron supplementation increased the tibial weight in mice on a calcium-sufficient diet and enhanced the tibial volume in those on a calcium-deficient diet. Metabolomic analysis highlighted calcium and boron's impact on metabolites like carboxylic acids and derivatives, fatty acyls, steroids and steroid derivatives, benzene and substituted derivatives, organonitrogen compounds, organooxygen compounds, and phenols, and were related to lipid metabolism and the neural signaling pathway. Transcriptomic analysis corroborated the role of calcium and boron in modulating bone metabolism via the JAK-STAT, calcium signaling, lipid metabolism, and inflammatory pathways. Multi-omics analysis indicated a strong correlation between calcium signaling pathways, lipid metabolism signaling, and dietary calcium and boron contents. This research provides insights into these complex mechanisms, potentially paving the way for novel interventions against calcium and boron deficiencies and bone metabolism abnormalities in clinical settings.PMID:39405052 | DOI:10.1039/d4fo03657c

Crit Rev Microbiol. 2024 Oct 15:1-24. doi: 10.1080/1040841X.2024.2412007. Online ahead of print.ABSTRACTListeria monocytogenes, a resilient bacterium in diverse food conditions, such as refrigeration, reduced water activity and low pH, poses a significant threat to the food industry and public health. In recent years, it has been documented an increase in the antibiotic resistance of zoonotic pathogens, including L. monocytogenes. This review provides new insight into the molecular mechanisms involved in both intrinsic and acquired antibiotic resistance of L. monocytogenes with an emphasis on the effect of different environmental and food-related factors. It also explores the relationship of these resistance mechanisms with virulence factors. An analysis of literature data (2009-2021) was conducted to investigate statistically and graphically potential associations between specific antibiotic resistance patterns in the pathogen and food categories using an unbiased variance analysis. The results evidenced that food type had an influence on the antibiotic resistance profiles of L. monocytogenes, with meat and vegetables being the food categories exhibiting the most prevalent profiles. The frequent detection of resistance to ampicillin, penicillin, and tetracycline (non-intrinsic resistances) indicates that specific processing conditions along the food chain may induce them. Many questions remain about the impact of food chain factors (e.g. thermal treatments, cold chain, preservatives, etc.) and food type (low pH, reduced water activity, etc.) on the antibiotic resistance patterns of the pathogen, particularly concerning food-related sources, the resistance mechanisms involved (e.g. cross-protection, horizontal gene transfer, etc.), and the evolutionary processes of antibiotic-resistant microbial populations. Metagenomics, in addition to other -omics technologies (metabolomics and transcriptomics), allows a better understanding of the processes involved in the acquisition of resistance.PMID:39404832 | DOI:10.1080/1040841X.2024.2412007

ISME J. 2024 Oct 15:wrae187. doi: 10.1093/ismejo/wrae187. Online ahead of print.ABSTRACTSalmonella enterica serovar Typhimurium is a pervasive enteric pathogen and ongoing global threat to public health. Ecological studies in the Salmonella impacted gut remain underrepresented in the literature, discounting microbiome mediated interactions that may inform Salmonella physiology during colonization and infection. To understand the microbial ecology of Salmonella remodeling of the gut microbiome, we performed multi-omics on fecal microbial communities from untreated and Salmonella-infected mice. Reconstructed genomes recruited metatranscriptomic and metabolomic data providing a strain-resolved view of the expressed metabolisms of the microbiome during Salmonella infection. These data informed possible Salmonella interactions with members of the gut microbiome that were previously uncharacterized. Salmonella-induced inflammation significantly reduced the diversity of genomes that recruited transcripts in the gut microbiome, yet increased transcript mapping was observed for 7 members, among which Luxibacter and Ligilactobacillus transcript read recruitment was most prevalent. Metatranscriptomic insights from Salmonella and other persistent taxa in the inflamed microbiome further expounded the necessity for oxidative tolerance mechanisms to endure the host inflammatory responses to infection. In the inflamed gut lactate was a key metabolite, with microbiota production and consumption reported amongst members with detected transcript recruitment. We also showed that organic sulfur sources could be converted by gut microbiota to yield inorganic sulfur pools that become oxidized in the inflamed gut, resulting in thiosulfate and tetrathionate that supports Salmonella respiration. This research advances physiological microbiome insights beyond prior amplicon-based approaches, with the transcriptionally active organismal and metabolic pathways outlined here offering intriguing intervention targets in the Salmonella-infected intestine.PMID:39404095 | DOI:10.1093/ismejo/wrae187

Actas Esp Psiquiatr. 2024 Oct;52(5):641-652. doi: 10.62641/aep.v52i5.1723.ABSTRACTBACKGROUND: The pathogenesis of Alzheimer's disease (AD) is complex. Recent research suggests that AD patients have early disorders in brain cholesterol metabolism. Cholesterol and its derivatives accumulate in neurons, leading to p-Tau overproduction and synaptic dysfunction, initiating AD progression. Calycosin-7-O-β-D-glucoside (CG), a distinctive constituent of Astragali Radix, holds a representative position. Many clinical trials have demonstrated that CG can attenuate cerebral ischemia/reperfusion injury and preserve the structural integrity of the blood-brain barrier. However, whether CG alleviates tau-mediated neurodegeneration by increasing cholesterol efflux after lipid accumulation remains unexplored.METHODS: Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and multivariate data analysis were employed to investigate metabolic changes in HT22 cells induced by sodium palmitate following 24 hours of CG treatment. The potential therapeutic mechanisms of CG on AD were further examined through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.RESULTS: Metabolomic analysis characterized 24 potential biomarkers, revealing that CG could ameliorate cholesterol metabolic pathways. The results of cell experiments revealed that CG can increase the expression of enzyme cholesterol 24-hydroxylase (CYP46A1) (p < 0.05) and the level of 24 hydroxycholesterol (24-OHC) (p < 0.05), reduce the expression of p-Tau (Thr231)/Tau (p < 0.01), inhibit the formation of lipid droplets.CONCLUSION: CG may inhibit the accumulation of cholesterol and its derivatives in neurons by affecting the CYP46A1-CE-Tau axis, offering a potential therapeutic strategy for AD.PMID:39403908 | DOI:10.62641/aep.v52i5.1723

Front Endocrinol (Lausanne). 2024 Sep 30;15:1415474. doi: 10.3389/fendo.2024.1415474. eCollection 2024.ABSTRACTBACKGROUND: Pancreatitis is a serious and complex inflammatory disease that imposes a severe effect on quality of life. Links between plasma lipidome and pancreatitis have been reported, some of which have not yet been clearly elucidated.METHODS: Therefore, our study aimed to investigate the causal relationships between plasma lipidome and four types of pancreatitis by conducting a bidirectional, two-sample Mendelian randomization (MR) analysis. We obtained genetic variants associated with 179 lipid species from a Genome-wide association analysis of plasma lipidome. The aggregated statistical data of acute pancreatitis (AP), alcohol-induced acute pancreatitis (AAP), chronic pancreatitis (CP), and alcohol-induced chronic pancreatitis (ACP) from the FinnGen consortium were exploited as the outcome. The inverse variance weighted (IVW) technique as the main method was used for MR analysis and sensitivity analyses were used to evaluate heterogeneity and pleiotropy.RESULTS: After FDR correction, SE (27:1/20:4) (OR = 0.938, 95%CI = 0.906-0.972, P = 4.38 × 10-4, PFDR = 0.039) was identified to be significantly associated with AP risk. Eight lipid species were identified to be significantly associated with CP risk: SE (27:1/20:4) (OR = 0.911, 95%CI = 0.869-0.954, P = 8.89 × 10-5, PFDR = 0.016), LPC (20:4) (OR = 0.892, 95%CI = 0.843-0.945, P = 9.74 × 10-5, PFDR = 0.009), PC (16:0_22:5) (OR = 0.880, 95%CI = 0.818-0.947, P = 6.29 × 10-4, PFDR = 0.028), PC (17:0_20:4) (OR = 0.893, 95%CI = 0.842-0.948, P = 1.76 × 10-4, PFDR = 0.010), PC (18:0_20:4) (OR = 0.920, 95%CI = 0.874-0.969, P = 1.70 × 10-3, PFDR = 0.038), PC (O-16:0/20:4) (OR = 0.871, 95%CI = 0.804-0.943, P = 6.95 × 10-4, PFDR = 0.025), PC (O-16:1/20:4) (OR = 0.890, 95%CI = 0.832-0.953, P = 7.85 × 10-4, PFDR = 0.023), and PE (O-18:1/20:4) (OR = 0.866, 95%CI = 0.791-0.947, P = 1.61 × 10-3, PFDR = 0.041). Furthermore, genetically predicted increased LPC (20:4) (OR = 0.862, 95%CI = 0.796-0.934, P = 3.00 × 10-4, PFDR = 0.027) and SM (34:2;O2) (OR = 0.753, 95%CI = 0.659-0.860, P = 2.97 × 10-5, PFDR = 0.005) levels were associated with decreased risk of ACP.CONCLUSIONS: Our findings provide evidence of causal associations between the specific types of lipidome and pancreatitis, offering new insights into future clinical research.PMID:39403583 | PMC:PMC11471641 | DOI:10.3389/fendo.2024.1415474

Heliyon. 2024 Sep 28;10(19):e38551. doi: 10.1016/j.heliyon.2024.e38551. eCollection 2024 Oct 15.ABSTRACTGlucose is a major energy substrate for cellular life activities, and its metabolic pathways include glycolysis, the pentose phosphate pathway, the hexosamine biosynthesis pathway, and the polyol pathway. Here, we review the glucose uptake pathways, metabolic characteristics, glucose transport, glucose metabolism-related enzymes, and biological importance in mammalian oocyte maturation, early embryo development, and embryonic stem cell proliferation and differentiation. Moreover, the interrelationships among glucose metabolism, female reproduction-related diseases and assisted reproductive technologies are focused. In addition, we review a number of analytical methodologies with the intention to integrate a multi-tiered strategy that encompasses cutting-edge metabolomics, artificial intelligence, epigenetics, and morphological assessments, setting the stage for a pivotal approach to cultivating high-caliber embryos in the future.PMID:39403464 | PMC:PMC11471579 | DOI:10.1016/j.heliyon.2024.e38551

Food Chem X. 2024 Sep 28;24:101864. doi: 10.1016/j.fochx.2024.101864. eCollection 2024 Dec 30.ABSTRACTChinese baijiu is highly regarded for its unique flavor, and a variety of crops can be utilized as raw materials in its production. Waxy crops are essential ingredients in the brewing of high-quality baijiu; however, there is currently no comprehensive identification of volatile organic compounds (VOCs) and non-volatile compounds (N-VOCs) in waxy wheat baijiu (WWB). This study aims to investigate the dynamic changes of VOCs and N-VOCs in WWB during several important time periods from new to aged. A total of 25 amino acids underwent changes in the samples, with numerous physiologically active beneficial amino acids showing significant accumulation after aging. Additionally, 517 VOCs changed after aging, predominantly comprising esters and terpenoids, with 72 major VOCs being identified. A total of 718 metabolites were identified in the metabolome, primarily comprising alterations in lipids, amino acids, phenolic acids, organic acids, and alkaloids. These metabolites significantly influenced the levels of amino acids and VOCs. Our study is the first to provide a comprehensive examination of these aspects of WWB, highlighting its unique advantages over other crops. We believe that this research will establish a theoretical foundation for the application of waxy wheat in the baijiu industry, improve baijiu quality, and promote the development of functional baijius.PMID:39403296 | PMC:PMC11471596 | DOI:10.1016/j.fochx.2024.101864