PubMed

J Agric Food Chem. 2024 Sep 1. doi: 10.1021/acs.jafc.4c04728. Online ahead of print.ABSTRACTFungal diseases could severely harm agricultural productions. To develop new antifungal agents, based on the Global Natural Products Social Molecular Networking, typical bromine isotope peak ratios, and ultraviolet absorptions, cultivation of the soft coral-derived endophytic fungi Aspergillus terreus EGF7-0-1 with NaBr led to the targeted isolation of 14 new brominated aromatic butenolides (1-14) and six known analogues (15-20). Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculations. Compounds 1-14 exhibited wildly antifungal activities (against Colletotrichum gloeosporioides, Pestalotiopsis microspora, Fusarium oxysporum f. sp. cubense, Botrytis cinerea, and Diaporthe phoenicicola). The bioassay results showed that compounds 1-14 exhibited excellent antifungal activities against C. gloeosporioides, with concentration for 50% of maximal effect (EC50) values from 2.72 to 130.41 nM. The mechanistic study suggests that compound 1 may disrupt nutrient signaling pathways by reducing the levels of metabolites, such as carbohydrates, lipids, and amino acids, leading to an increase in low-density granules and a decrease in high-density granules in the cytoplasm, accompanied by numerous vacuoles, thereby inhibiting the growth of C. gloeosporioides. Monobrominated γ-butenolide 1 may be expected to exploit a novel agriculturally antifungal leading drug. Meanwhile, compound M1 has conformed antifugual activities against C. gloeosporioides by papayas in vivo.PMID:39219104 | DOI:10.1021/acs.jafc.4c04728

J Food Sci. 2024 Sep 1. doi: 10.1111/1750-3841.17337. Online ahead of print.ABSTRACTMetabolite profiling is an analytical technique used to assess metabolites in complex biological samples. This technique allows for the identification of both targeted and untargeted metabolites. In this study, the effect of traditional (fermentation and malting) and novel processing (ultrasonication) on the metabolites of finger millet (FM) and Bambara groundnut (BGN) flour was investigated using gas chromatography-mass spectrometry. Various metabolite classes, including amino acids, alcohol, aldehyde, organic acid, ester, fatty acids, glycoside, and sugar, were identified in FM and BGN flours. The adopted processing techniques impacted metabolite composition, as evidenced by substantial variations in volatile compound levels and metabolite composition among the FM and BGN samples before and after traditional and novel processing. Important health-promoting compounds, such as oleic acid, linoelaidic acid, and linoleic acid, were identified at their highest levels in fermented FM and BGN flours. The results obtained from this study offer an important context for monitoring and regulating the metabolite composition of FM and BGN flours under traditional and novel processing. PRACTICAL APPLICATION: Fermentation, malting, and ultrasonication induced desirable changes in some health-promoting compounds of finger millet and Bambara groundnut flours. The food and pharmaceutical industries could benefit from these traditional- and novel-modified flours as they could be used as improved food sources with health benefits.PMID:39219001 | DOI:10.1111/1750-3841.17337

Sci Rep. 2024 Sep 2;14(1):20306. doi: 10.1038/s41598-024-70499-z.ABSTRACTHuanglongbing (HLB), associated with the psyllid-vectored phloem-limited bacterium, Candidatus Liberibacter asiaticus (CLas), is a disease threat to all citrus production worldwide. Currently, there are no sustainable curative or prophylactic treatments available. In this study, we utilized mass spectrometry (MS)-based metabolomics in combination with 3D molecular mapping to visualize complex chemistries within plant tissues to explore how these chemistries change in vivo in HLB-infected trees. We demonstrate how spatial information from molecular maps of branches and single leaves yields insight into the biology not accessible otherwise. In particular, we found evidence that flavonoid biosynthesis is disrupted in HLB-infected trees, and an increase in the polyamine, feruloylputrescine, is highly correlated with an increase in disease severity. Based on mechanistic details revealed by these molecular maps, followed by metabolic modeling, we formulated and tested the hypothesis that CLas infection either directly or indirectly converts the precursor compound, ferulic acid, to feruloylputrescine to suppress the antimicrobial effects of ferulic acid and biosynthetically downstream flavonoids. Using in vitro bioassays, we demonstrated that ferulic acid and bioflavonoids are indeed highly bactericidal to CLas, with the activity on par with a reference antibiotic, oxytetracycline, recently approved for HLB management. We propose these compounds should be evaluated as therapeutics alternatives to the antibiotics for HLB treatment. Overall, the utilized 3D metabolic mapping approach provides a promising methodological framework to identify pathogen-specific inhibitory compounds in planta for potential prophylactic or therapeutic applications.PMID:39218988 | DOI:10.1038/s41598-024-70499-z

BMC Med. 2024 Sep 2;22(1):353. doi: 10.1186/s12916-024-03577-8.ABSTRACTBACKGROUND: Higher cruciferous vegetable intake is associated with lower cardiovascular disease risk in observational studies. The pathways involved remain uncertain. We aimed to determine whether cruciferous vegetable intake (active) lowers 24-h brachial systolic blood pressure (SBP; primary outcome) compared to root and squash vegetables (control) in Australian adults with mildly elevated BP (SBP 120-160 mmHg inclusive).METHODS: In this randomized, controlled, crossover trial, participants completed two 2-week dietary interventions separated by a 2-week washout. Cruciferous vegetables were compared to root and squash vegetables (~ 300 g/day) consumed with lunch and dinner meals. Participants were blinded to which interventions were the active and control. Adherence was assessed using food diaries and biomarkers (S-methyl cysteine sulfoxide (SMCSO, active) and carotenoids (control)). Twenty-four-hour brachial ambulatory SBP and secondary outcomes were assessed pre- and post each intervention. Differences were tested using linear mixed effects regression.RESULTS: Eighteen participants were recruited (median (IQR) age: 68 (66-70); female: n = 16/18; mean ± SD clinic SBP: 135.9 ± 10.0 mmHg). For both interventions, 72% participants had 100% adherence (IQR: 96.4-100%). SMCSO and carotenoids were significantly different between interventions (mean difference active vs. control SMCSO: 22.93 mg/mL, 95%CI 15.62, 30.23, P < 0.0001; carotenoids: - 0.974 mg/mL, 95%CI - 1.525, - 0.423, P = 0.001). Twenty-four-hour brachial SBP was significantly reduced following the active vs. control (mean difference - 2.5 mmHg, 95%CI - 4.2, - 0.9, P = 0.002; active pre: 126.8 ± 12.6 mmHg, post: 124.4 ± 11.8 mmHg; control pre: 125.5 ± 12.1 mmHg, post: 124.8 ± 13.1 mmHg, n = 17), driven by daytime SBP (mean difference - 3.6 mmHg, 95%CI - 5.4, - 1.7, P < 0.001). Serum triglycerides were significantly lower following the active vs. control (mean difference - 0.2 mmol/L, 95%CI - 0.4, - 0.0, P = 0.047).CONCLUSIONS: Increased intake of cruciferous vegetables resulted in reduced SBP compared to root and squash vegetables. Future research is needed to determine whether targeted recommendations for increasing cruciferous vegetable intake benefits population health.TRIAL REGISTRATION: Clinical trial registry ACTRN12619001294145. https://www.anzctr.org.au.PMID:39218859 | DOI:10.1186/s12916-024-03577-8

Funct Integr Genomics. 2024 Sep 2;24(5):149. doi: 10.1007/s10142-024-01430-y.ABSTRACTProducing alternative staple foods like millet will be essential to feeding ten billion people by 2050. The increased demand for millet is driving researchers to improve its genetic variation. Millets include protein, dietary fiber, phenolic substances, and flavonoid components. Its climate resilience makes millet an appealing crop for agronomic sustainability. Integrative omics technologies could potentially identify and develop millets with desirable phenotypes that may have high agronomic value. Millets' salinity and drought tolerance have been enhanced using transcriptomics. In foxtail, finger, and pearl millet, proteomics has discovered salt-tolerant protein, phytohormone-focused protein, and drought tolerance. Metabolomics studies have revealed that certain metabolic pathways including those involving lignin, flavonoids, phenylpropanoid, and lysophospholipids are critical for many processes, including seed germination, photosynthesis, energy metabolism, and the synthesis of bioactive chemicals necessary for drought tolerance. Metabolomics integration with other omics revealed metabolome engineering and trait-specific metabolite creation. Integrated metabolomics and ionomics are still in the development stage, but they could potentially assist in comprehending the pathway of ionomers to control nutrient levels and biofortify millet. Epigenomic analysis has shown alterations in DNA methylation patterns and chromatin structure in foxtail and pearl millets in response to abiotic stress. Whole-genome sequencing utilizing next-generation sequencing is the most proficient method for finding stress-induced phytoconstituent genes. New genome sequencing enables novel biotechnological interventions including genome-wide association, mutation-based research, and other omics approaches. Millets can breed more effectively by employing next-generation sequencing and genotyping by sequencing, which may mitigate climate change. Millet marker-assisted breeding has advanced with high-throughput markers and combined genotyping technologies.PMID:39218822 | DOI:10.1007/s10142-024-01430-y

Anal Chim Acta. 2024 Oct 2;1324:343068. doi: 10.1016/j.aca.2024.343068. Epub 2024 Aug 6.ABSTRACTBACKGROUND: Live single-cell metabolomic studies encounter inherent difficulties attributed to the limited sample volume, minimal compound quantity, and insufficient sensitivity in the Mass Spectrometry (MS) method used to obtain single-cell data. However, understanding cellular heterogeneity, functional diversity, and metabolic processes within individual cells is essential. Exploring how individual cells respond to stimuli, including drugs, environmental changes, or signaling molecules, offers insights into biology, oncology, and drug discovery. Efficient release of cell contents (lysis) is vital for accurate metabolite detection at the single-cell level. Despite this, traditional approaches in live single cell metabolomics methods do not emphasize efficient lysis to prevent sample dilution. Instead, current live single cell metabolomics methods use direct infusion to introduce the cell into the mass spectrometry without prior chromatographic separation or a lysis step, which adversely affects sensitivity and metabolic coverage.RESULTS: To address this, we developed an integrated single-cell electrical lysis and nano spray (SCEL-nS) platform coupled to an Orbitrap MS capable of efficiently lysing a single cell after being sampled with specially manufactured micropipettes. Lysis efficiency was validated by comparing live cell stain fluorescent intensities of intact and electrically lysed cells through microscopy imaging. The SCEL-nS platform successfully induced the breakdown of a single cell, significantly reducing the live cell stain's fluorescent intensity indicating cell membrane breakdown. Additionally, SCEL-nS was validated by measuring single cells spiked with the anti-cancer drug tamoxifen by MS. SCEL-nS use resulted in statistically significant increase in the peak measured by the method compared to the traditional non-lysis method.SIGNIFICANCE: Overall, our results demonstrate that the newly incorporated SCEL-nS platform achieved higher sensitivities compared to traditional live single cell analysis methods.PMID:39218570 | DOI:10.1016/j.aca.2024.343068

Carbohydr Polym. 2024 Nov 15;344:122527. doi: 10.1016/j.carbpol.2024.122527. Epub 2024 Jul 22.ABSTRACTThe root of Millettia pulchra (YLS) has been traditionally used as a folk medicine for the treatment of depression and insomnia in the Zhuang nationality of China, and its polysaccharides have potential antidepressant effect. In this study, a novel homogeneous polysaccharide (YLP-1) was purified from the crude polysaccharides of YLS, and it is mainly composed of glucose, arabinose and mannose with molar ratio of 87.25%, 10.77%, and 1.98%, respectively. YLP-1 is a novel α-glucan with the backbone of 1,4-Glcp and branched at C6 of 1,4,6-Glcp to combine 1,4-Manp and 1,5-Araf. The microstructure of YLP-1 displayed a uniform ellipsoidal-like chain morphology and dispersed uniformly in solution. YLP-1 effectively ameliorated depression-like ethological behaviors and restored the decreased catecholamine levels in chronic variable stress (CVS)-induced depression rats. Additionally, it significantly improved the disturbance of gut microbiota induced by CVS stimuli, particularly affecting bacteria that produce short-chain fatty acids (SCFAs), such as bacteria species Lactobacillus spp.. In vitro fermentation study further confirmed that YLP-1 intake could promote SCFAs production by Lactobacillus spp. YLP-1 also mitigated the disruption of tryptophan metabolites in urine and serum. These findings provide evidences for the further development of YLP-1 as a macromolecular antidepressant drug.PMID:39218534 | DOI:10.1016/j.carbpol.2024.122527

Adv Food Nutr Res. 2024;112:385-433. doi: 10.1016/bs.afnr.2024.05.007. Epub 2024 Jun 15.ABSTRACTBACKGROUND: Precision nutrition, a personalized nutritional supplementation model, is widely acknowledged for its significant impact on human health. Nevertheless, challenges persist in the advancement of precision nutrition, including consumer dietary behaviors, nutrient absorption, and utilization. Thus, the exploration of effective strategies to enhance the efficacy of precision nutrition and maximize its potential benefits in dietary interventions and disease management is imperative.SCOPE AND APPROACH: The primary objective of this comprehensive review is to synthesize and assess the latest technical approaches and future prospects for achieving precision nutrition, while also addressing the existing constraints in this field. The role of delivery systems is pivotal in the realization of precision nutrition goals. This paper outlines the potential applications of delivery systems in precision nutrition and highlights key considerations for their design and implementation. Additionally, the review offers insights into the evolving trends in delivery systems for precision nutrition, particularly in the realms of nutritional fortification, specialized diets, and disease prevention.KEY FINDINGS AND CONCLUSIONS: By leveraging computer data collection, omics, and metabolomics analyses, this review scrutinizes the lifestyles, dietary patterns, and health statuses of diverse organisms. Subsequently, tailored nutrient supplementation programs are devised based on individual organism profiles. The utilization of delivery systems enhances the bioavailability of functional compounds and enables targeted delivery to specific body regions, thereby catering to the distinct nutritional requirements and disease prevention needs of consumers, with a particular emphasis on special populations and dietary preferences.PMID:39218507 | DOI:10.1016/bs.afnr.2024.05.007

J Rheumatol. 2024 Sep 1:jrheum.2024-0361. doi: 10.3899/jrheum.2024-0361. Online ahead of print.ABSTRACTOBJECTIVE: To examine whether gut microbes were associated with post-surgery sustained knee pain in knee osteoarthritis (OA) patients by a gut microbiomics approach.METHODS: Total knee replacement (TKR) patients due to primary knee OA were recruited. Sustained knee pain status at least one year after TKR was defined by the Western Ontario and McMaster University Arthritis Index (WOMAC). Fasting plasma sample and fecal sample were collected. Metabolomic profiling was performed on fasting plasma. 16S rRNA sequencing was performed on fecal samples to determine microbial composition.RESULTS: Twenty TKR patients due to primary knee OA were included in the study with 10 experiencing sustained post-surgery pain and 10 without such pain. Age, sex, and BMI were matched. Linear discriminant analysis of microbiome data identified 13 bacterial taxa that were highly abundant in the pain group, and 5 that were highly abundant in the non-pain group (all P < 0.05). Plasma metabolomic profiling measured 622 metabolites. The correlation analysis indicated that the 18 taxa were significantly correlated with 231 metabolites (all P < 0.05). sPLS-DA analysis showed that 30 out of the 231 metabolites explained 29% of total variance and can be used to clearly separate sustained knee pain patients from non-pain patients. Pathway enrichment analysis showed that these significant metabolites were enriched in arachidonic acid metabolic pathway, bile acid biosynthesis, and linoleic acid metabolism.CONCLUSION: The gut microbes may play a significant role in sustained knee pain in knee OA patients after TKR potentially through their activation of inflammatory pathways, lipid metabolism, and central sensitization.PMID:39218454 | DOI:10.3899/jrheum.2024-0361

J Affect Disord. 2024 Aug 30:S0165-0327(24)01442-3. doi: 10.1016/j.jad.2024.08.208. Online ahead of print.ABSTRACTBACKGROUND: Persons with Major Depressive Disorder (MDD), notably treatment-resistant depression (TRD), are differentially affected by type 2 diabetes mellitus and associated morbidity. Ketamine is highly efficacious in the treatment of adults living with MDD, notably TRD. Herein, we sought to determine the effect of ketamine on metabolic parameters in animal stress paradigms and human studies.METHODS: We performed a comprehensive search on PubMed, OVID, and Scopus databases for primary research articles from inception to May 5, 2024. Study screening and data extraction were performed by two reviewers (S.W. and G.H.L.). Both preclinical and clinical studies were included in this review.RESULTS: Results from the preclinical studies indicate that in experimental diabetic conditions, ketamine does not disrupt glucose-insulin homeostasis. Within adults with MDD, ketamine is associated with GLUT3 transporter upregulation and differentially affects metabolomic signatures. In adults with TRD, ketamine induces increased brain glucose uptake in the prefrontal cortex. Available evidence suggests that ketamine does not adversely affect metabolic parameters.LIMITATIONS: There are a paucity of clinical studies evaluating the effects of ketamine on glucose-insulin homeostasis in adults with MDD.CONCLUSIONS: Our results indicate that ketamine is not associated with significant and/or persistent disruptions in metabolic parameters. Available evidence indicates that ketamine does not adversely affect glucose-insulin homeostasis. These results underscore ketamine's efficacy and safety as an antidepressant treatment that is not associated with metabolic disturbances commonly reported with current augmentation therapies.PMID:39218315 | DOI:10.1016/j.jad.2024.08.208

Chemosphere. 2024 Aug 30:143229. doi: 10.1016/j.chemosphere.2024.143229. Online ahead of print.ABSTRACTDi(2-ethylhexyl)phthalate (DEHP) is one of the most widely used plasticizers in plastic manufacturing. However, the toxicological effects of DEHP on dandelions remain poorly understood. This study comprehensively analyzed and explored the response mechanisms of dandelions to 1, 10, 50, and 100 mg L-1 DEHP influencing the morphophysiological growth, metabolomics, and molecular docking. DEHP reduced chlorophyll synthesis, inhibited plant growth, and induced oxidative-state-associated stress, which was manifested by the excessive production of reactive oxygen species, an increase in antioxidant enzyme activities, and enhanced synthesis of some osmoregulatory compounds, including proline and soluble protein. An analysis of the integrated biological response index showed that the toxicity was dose-dependent. Molecular docking demonstrated that DEHP could bind stably to three enzymes, and the binding energy was peroxidase (POD) > catalase (CAT) > superoxide dismutase (SOD). Metabolomics revealed that metabolite abundance and metabolic pathways were altered by DEHP, with 88 and 72 primary metabolites identified in shoots and roots, respectively. Amino acid, sugar, and organic acid metabolism were severely disturbed, with the most significant effects being on carbohydrate metabolism, valine, leucine, and isoleucine biosynthesis. Our study elucidated the influence of DEHP exposure on dandelions, providing new insights into the toxicity mechanisms and toxicological risk assessment.PMID:39218265 | DOI:10.1016/j.chemosphere.2024.143229

Sci Total Environ. 2024 Aug 30:175931. doi: 10.1016/j.scitotenv.2024.175931. Online ahead of print.ABSTRACTMonocrotaline (MCT) is a toxic pyrrolizidine alkaloid found in plants of the Crotalaria genus. As primary pollinators of Crotalaria plants, honeybees come into contact with this harmful substance. However, limited research has been conducted on the effects of MCT on Apis mellifera, particularly the risks of long-term exposure to sublethal concentrations. Through evaluating the proboscis extension reflex (PER) ability, analyzing the honeybee brain transcriptome, and analyzing the honeybee hemolymph metabolome, we discovered that sublethal concentrations of MCT impair the olfactory and memory capabilities of honeybees by affecting tryptophan (Trp) metabolism. Furthermore, MCT upregulates the expression of the corazonin receptor (CrzR) gene in the honeybee brain, which elevates reactive oxygen species (ROS) levels in the brain while reducing glucose levels in the hemolymph, consequently shortening the honeybees' lifespan. Our findings regarding the multifaceted impact of MCT on honeybees lay the foundation for exploring its toxicological pathways and management in honeybee populations.PMID:39218096 | DOI:10.1016/j.scitotenv.2024.175931

Biochem Biophys Res Commun. 2024 Aug 29;734:150621. doi: 10.1016/j.bbrc.2024.150621. Online ahead of print.ABSTRACTEpigenetic modifications and their alterations can cause variation in gene expression patterns which can ultimately affect a healthy individual. Until a few years ago, it was thought that the epigenome affects the transcriptome which can regulate the proteome and the metabolome. Recent studies have shown that the metabolome independently also plays a major role in regulating the epigenome bypassing the need for transcriptomic control. Alternatively, an imbalanced metabolome, stemming from transcriptome abnormalities, can further impact the transcriptome, creating a self-perpetuating cycle of interconnected occurrences. As a result, external factors such as nutrient intake and diet can have a direct impact on the metabolic pools and its reprogramming can change the levels and activity of epigenetic modifiers. Thus, the epigenetic landscape steers toward a diseased condition. In this review, we have discussed how different metabolites and dietary patterns can bring about changes in different arms of the epigenetic machinery such as methylation, acetylation as well as RNA mediated epigenetic mechanisms. We checked for limiting metabolites such as αKG, acetyl-CoA, ATP, NAD+, and FAD, whose abundance levels can lead to common diseases such as cancer, neurodegeneration etc. This gives a clearer picture of how an integrated approach including both epigenetics and metabolomics can be used for therapeutic purposes.PMID:39217811 | DOI:10.1016/j.bbrc.2024.150621

J Pharm Biomed Anal. 2024 Aug 22;251:116443. doi: 10.1016/j.jpba.2024.116443. Online ahead of print.ABSTRACTAccurate and objective estimation of the postmortem interval (PMI) is crucial in forensic practice. This study aimed to infer PMI through equations based on the relationship between PMI and metabolomics biomarkers.Rats were subjected to models representing various temperatures and causes of death, with blood collected at different intervals. Untargeted gas chromatographymass spectrometry metabolomics detection methods were developed, and candidate biomarkers were chosen as co-differentially expressed metabolites in four models. A targeted method was then developed for quantitatively determining candidate biomarkers. Animal tests and human cadaver samples with clearly documented causes of death and time were used to verify the reliability of the regression equation.Results: Unique differential metabolites for CO poisoning deaths included 2,3-butanediol, hypoxanthine, and dehydrated hexanol, while those for mechanical asphyxia deaths comprised propylamine, 1,3-propylene glycol, phosphoric acid, and sorbitol. Pyruvate, glycerol and isoleucine were identified as candidate biomarkers. Human case results demonstrated the method's potential (error rate < 20 %). The findings of this study may offer reference points for estimating PMI and causes of death in forensic practice.PMID:39217704 | DOI:10.1016/j.jpba.2024.116443

Phytomedicine. 2024 Aug 23;134:155968. doi: 10.1016/j.phymed.2024.155968. Online ahead of print.ABSTRACTBACKGROUND: The incidence of hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is increasing globally and more so in China. The characteristics of liver-mediated metabolites and related key enzymes are rarely reported in HTG-AP. Chaiqin chengqi decoction (CQCQD) has been shown to protect against AP including HTG-AP in both patients and rodent models, but the underlying mechanisms in HTG-AP remain unexplored.PURPOSE: To assess the characteristics of liver-mediated metabolism and the therapeutic mechanisms of CQCQD in HTG-AP.METHODS: Male human apolipoprotein C3 transgenic (hApoC3-Tg; leading to HTG) mice or wild-type littermates received 7 intraperitoneal injections of cerulein (100 μg/kg) to establish HTG-AP and CER-AP, respectively. In HTG-AP, some mice received CQCQD (5.5 g/kg) gavage at 1, 5 or 9 h after disease induction. AP severity and related liver injury were determined by serological and histological parameters; and underlying mechanisms were identified by lipidomics and molecular biology. Molecular docking was used to identify key interactions between CQCQD compounds and metabolic enzymes, and subsequently validated in vitro in hepatocytes.RESULTS: HTG-AP was associated with increased disease severity indices including augmented liver injury compared to CER-AP. CQCQD treatment reduced severity and liver injury of HTG-AP. Glycerophospholipid (GPL) metabolism was the most disturbed pathway in HTG-AP in comparison to HTG alone. In HTG-AP, the mRNA level of GPL enzymes involved in phosphocholine (PC) and phosphatidylethanolamine (PE) synthesis (Pcyt1a, Pcyt2, Pemt, and Lpcat) were markedly upregulated in the liver. Of the GPL metabolites, lysophosphatidylethanolamine LPE(16:0) in serum of HTG-AP was significantly elevated and positively correlated with the pancreas histopathology score (r = 0.65). In vitro, supernatant from Pcyt2-overexpressing hepatocytes co-incubated with LPE(16:0) or phospholipase A2 (a PC- and PE-hydrolyzing enzyme) alone induced pancreatic acinar cell death. CQCQD treatment downregulated PCYT1a and PCYT2 enzyme levels in the liver. Hesperidin and narirutin were identified top two CQCQD compounds with highest affinity docking to PCYT1a and PCYT2. Both hesperidin and narirutin reduced the level of some GPL metabolites in hepatocytes.CONCLUSION: Liver-mediated GPL metabolism is excessively activated in HTG-AP with serum LPE(16:0) level correlating with disease severity. CQCQD reduces HTG-AP severity partially via modulating key enzymes in GPL metabolism pathway.PMID:39217651 | DOI:10.1016/j.phymed.2024.155968

Water Res. 2024 Aug 30;266:122351. doi: 10.1016/j.watres.2024.122351. Online ahead of print.ABSTRACTIn this study, the transformation mechanisms of extracellular polymeric substances (EPS) during ultraviolet/peracetic acid (UV/PAA) disinfection were elucidated based on multiple molecular-level analyses. After UV/PAA disinfection, the contents of soluble EPS (S-EPS), loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS) were reduced by 70.47 %, 57.05 % and 47.46 %, respectively. Fluorescence excitation-emission matrix-parallel factor and Fourier transform ion cyclotron resonance mass spectrometry analyses showed that during UV/PAA disinfection, EPS was transformed from the state characterized by high aromaticity, low saturation and low oxidation to the one with reduced aromaticity, increased saturation and higher oxidation. Specifically, sulfur-containing molecules (CHOS, CHONS, etc.) in EPS were converted into highly saturated and oxidized species (such as CHO), with the aromaticity index (AImod) decreasing by up to 53.84 %. Molecular characteristics analyses further indicated that saturation degree, oxidation state of carbon and molecular weight exhibited the most significant changes in S-EPS, LB-EPS and TB-EPS, respectively. Additionally, mechanistic analysis revealed that oxygen addition reaction was the predominant reaction for S-EPS (+O) and TB-EPS (+3O) (accounting for 31.78 % and 36.47 %, respectively), while the dealkylation was the main reaction for LB-EPS (29.73 %). The results were consistent with functional groups sequential responses analyzed by Fourier transform infrared and two-dimensional correlation spectroscopy, and were further verified by density functional theory calculations. Most reactions were thermodynamically feasible, with reaction sites predominantly located at functional groups such as CO, CO, CN and aromatic rings. Moreover, metabolomics analysis suggested that changes in metabolites in raw secondary effluent during UV/PAA disinfection were strongly correlated with EPS transformation. Our study not only provides a strong basis for understanding EPS transformation during UV/PAA disinfection at molecular-level but also offers valuable insights for the application this promising disinfection process.PMID:39217641 | DOI:10.1016/j.watres.2024.122351

Eur J Med Res. 2024 Aug 31;29(1):446. doi: 10.1186/s40001-024-02014-z.ABSTRACTBACKGROUND: Aortic stenosis (AS) is a prevalent and serious valvular heart disease with a complex etiology involving genetic predispositions, lipid dysregulation, and inflammation. The specific roles of lipid and protein biomarkers in AS development are not fully elucidated. This study aimed to elucidate the causal relationships between lipidome, inflammatory proteins, and AS using Mendelian randomization (MR), identifying potential therapeutic targets.METHODS: Utilizing data from large-scale genome-wide association studies (GWAS) and genome-wide protein quantitative trait loci (pQTL) studies, we conducted MR analyses on 179 plasma lipidome and 91 inflammatory proteins to assess their causal associations with AS. Our approach included Inverse Variance Weighting (IVW), Wald ratio, and robust adjusted profile score (RAPS) analyses to refine these associations. MR-Egger regression was used to address directional horizontal pleiotropy.RESULTS: Our MR analysis showed that genetically predicted 50 lipids were associated with AS, including 38 as risk factors [(9 Sterol ester, 18 Phosphatidylcholine, 4 Phosphatidylethanolamine, 1 Phosphatidylinositol and 6 Triacylglycerol)] and 12 as protective. Sterol ester (27:1/17:1) emerged as the most significant risk factor with an odds ratio (OR) of 3.11. Additionally, two inflammatory proteins, fibroblast growth factor 19 (FGF19) (OR = 0.830, P = 0.015), and interleukin 6 (IL-6) (OR = 0.729, P = 1.79E-04) were significantly associated with reduced AS risk. However, a two-step MR analysis showed no significant mediated correlations between these proteins and the lipid-AS pathway.CONCLUSION: This study reveals complex lipid and protein interactions in AS, identifying potential molecular targets for therapy. These results go beyond traditional lipid profiling and significantly advance our genetic and molecular understanding of AS, highlighting potential pathways for intervention and prevention.PMID:39217396 | DOI:10.1186/s40001-024-02014-z

Metabolism. 2024 Aug 29:156015. doi: 10.1016/j.metabol.2024.156015. Online ahead of print.ABSTRACTThe prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, making it the leading etiology of chronic liver diseases and a prime cause of liver-related mortality. MASLD can progress into steatohepatitis (termed MASH), fibrosis, cirrhosis, and ultimately cancer. MASLD is associated with increased risks of hepatocellular carcinoma (HCC) and also extrahepatic malignancies, which can develop in both cirrhotic and non-cirrhotic patients, emphasizing the importance of identifying patients with MASLD at risk of developing MASLD-associated malignancies. However, the optimal screening, diagnostic, and risk stratification strategies for patients with MASLD at risk of cancer are still under debate. Individuals with MASH-associated cirrhosis are recommended to undergo surveillance for HCC (e.g. by ultrasound and biomarkers) every six months. No specific screening approaches for MASLD-related malignancies in non-cirrhotic cases are established to date. The rapidly developing omics technologies, including genetics, metabolomics, and proteomics, show great potential for discovering non-invasive markers to fulfill this unmet need. This review provides an overview on the incidence and mortality of MASLD-associated malignancies, current strategies for HCC screening, surveillance and diagnosis in patients with MASLD, and the evolving role of omics technologies in the discovery of non-invasive markers for the prediction and risk stratification of MASLD-associated HCC. SUMMARY.PMID:39216799 | DOI:10.1016/j.metabol.2024.156015

J Ethnopharmacol. 2024 Aug 29:118765. doi: 10.1016/j.jep.2024.118765. Online ahead of print.NO ABSTRACTPMID:39216774 | DOI:10.1016/j.jep.2024.118765

J Ethnopharmacol. 2024 Aug 29:118763. doi: 10.1016/j.jep.2024.118763. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: At present,the global form of hypertension is severe,and liver-yang-hyperactivity hypertension（GYSK hypertension）is the most common type of hypertension.Folium Polygoni Cuspidati（HZY）are mainly used in Yunnan,China,to treat dizziness,headache,and hypertension caused by GYSK,and the content of the active ingredients of HZY and its efficacy varies in different periods.However,the mechanism of action and the effect of harvesting period are not clear.AIM OF THE STUDY: The purpose of this research was to investigate the effect of HZY in April and September on GYSK hypertension.MATERIALS AND METHODS: The model of GYSK hypertension was established with aconite decoction and L-NAME,and the blood pressure,the symptoms of GYSK,the cardiac index and the pathological changes of aorta were observed,to study the effect of HZY in April and September on GYSK hypertension.The chemical composition of HZY was analysed by UPLC-QTOF-MS and its mechanism for the treatment of GYSK hypertension was predicted by network pharmacological studies and experimentally validated using serum metabolomics and western blot techniques.RESULTS: April HZY and September HZY can significantly improve the GYSK symptoms of rats,inhibit the RAAS system,improve oxidative stress and regulate blood lipids so as to play a blood pressure lowering efficacy and have a protective effect on the vascular endothelial cells.UPLC-QTOF-MS yielded 29 components of HZY,and network pharmacology predicted that its mechanism may be related to Lipid and atherosclerosis,PI3K/Akt signaling pathway,MAPK signaling pathway and TNF signaling pathway,etc.Western Blot validation showed that HZY activated PI3K,p-Akt protein expression and inhibited p-erk,p-p38 and TNF-α protein expression.Serum metabolomics suggested that April HZY exerts its efficacy mainly by regulating amino acid metabolism and September HZY mainly by regulating lipid metabolism.CONCLUSIONS: In GYSK hypertensive rats treated for three weeks,both April HZY and September HZY could have antihypertensive effects,but the mechanisms of action were different and similar,both could regulate metabolite disorders of sugars,lipids,aminoacids and peptides,and regulate blood pressure through the PI3K/Akt-eNOS and MAPK signalling pathways,with the difference that April HZY had stronger regulatory effects on the metabolism of amino acids.metabolism.PMID:39216773 | DOI:10.1016/j.jep.2024.118763