PubMed

Int J Mol Sci. 2024 Nov 21;25(23):12504. doi: 10.3390/ijms252312504.ABSTRACTCertain molecules found on the surface or within the cargo of extracellular vesicles (EVs) are linked to osteoarthritis (OA) severity and progression. We aimed to identify plasma pathogenic EV subpopulations that can predict knee radiographic OA (rOA) progression. We analyzed the mass spectrometry-based proteomic data of plasma EVs and synovial fluid (SF) EVs from knee OA patients (n = 16, 50% female). The identified surface markers of interest were further evaluated in plasma EVs from an independent cohort of knee OA patients (n = 30, 47% female) using flow cytometry. A total of 199 peptides with significant correlation between plasma and SF EVs were identified. Of these, 41.7% were linked to immune system processes, 15.5% to inflammatory responses, and 16.7% to the complement system. Crucially, five previously identified knee rOA severity-indicating surface markers-FGA, FGB, FGG, TLN1, and AMBP-were confirmed on plasma EV subpopulations in an independent cohort. These markers' baseline frequencies on large plasma EVs predicted rOA progression with an AUC of 0.655-0.711. Notably, TLN1 was expressed in OA joint tissue, whereas FGA, FGB, FGG, and AMBP were predominantly liver derived. These surface markers define specific pathogenic EV subpopulations, offering potential OA prognostic biomarkers and novel therapeutic targets for disease modification.PMID:39684216 | DOI:10.3390/ijms252312504

Int J Mol Sci. 2024 Nov 21;25(23):12500. doi: 10.3390/ijms252312500.ABSTRACTThe effects of starvation and refeeding on the gut condition of juvenile largemouth bass (Micropterus salmoides) remain unclear. Therefore, our research aimed to explore these effects. Amylase and lipase activities were remarkably decreased in the starvation (ST) group, yet prominently increased in the refeeding (RE) group (p < 0.05). In addition to the malondialdehyde (MDA) level, catalase (CAT) and superoxide dismutase (SOD) activities were significantly upregulated in the ST group (p < 0.05) in marked contrast to those in the controls; however, the RE group showed no substantial variations in CAT and SOD activities or the MDA level (p > 0.05). During starvation, the expression of Nrf2-Keap1 pathway-associated genes was significantly upregulated (p < 0.05). The comparative levels of TNF-α, IL-1β, and IL-15 were highly increased, with the levels of TGF-β1 and IL-10 apparently downregulated in the ST group; in contrast, these levels were restored to their original values in the RE group (p < 0.05). In contrast to the controls, the ST group showed significantly lower height and width of the villi, muscle thickness, and crypt depth and a higher goblet cell number; however, these values were recovered to some extent in the RE group (p < 0.05). The dominant bacterial phyla in the intestines of both groups were Proteobacteria, Firmicutes, Bacteroidetes, Acidobacteria, and Actinobacteria, with marked inter-group differences in the genera Serratia and Lactobacillus. Metabolomics analysis showed that amino acid metabolism is disrupted during starvation and is restored after refeeding. In summary, this study expands our comprehension of the interaction between oxidative stress and antioxidant defenses among juvenile largemouth bass subjected to starvation and refeeding.PMID:39684211 | DOI:10.3390/ijms252312500

Int J Mol Sci. 2024 Nov 21;25(23):12487. doi: 10.3390/ijms252312487.ABSTRACTShort-chain fatty acids (SCFAs) are produced by the fermentation of undigested polysaccharides; they are a group of metabolites resulting from the activity of intestinal bacteria. The main SCFAs are acetic, butyric, propionic, valeric, and caproic acid, and their levels and proportions depend on various factors. The aim of this study was to investigate the relationship between the concentration of SCFAs and the occurrence of specific gastrointestinal symptoms in infants. This study was conducted using faecal samples obtained at 1, 3, 6, and 12 months of age. The SCFA content was measured using gas chromatography. At 1 month, an association was found between butyric acid and flatulence. At 3 months, an association was found between butyric acid and flatulence/gas and between 3,4-methylovaleric acid and mucus in the stool. At 6 months, an association was found between butyric and valeric acids and flatulence. By 12 months, the gastrointestinal symptoms had decreased significantly. This study confirms that there is an association between SCFA levels and the presence of bloating, gas, mucus in the stool, and constipation in the gastrointestinal tract. Higher levels of butyric and valeric acids may lead to an increase in troublesome symptoms, such as flatulence and gas, in the first few months of life but are not associated with the occurrence of intestinal colic. The level of 3,4-methylovaleric acid is associated with the presence of allergies, whereas a decrease in acetic acid and an increase in isovaleric acid may exacerbate defecation problems in infants.PMID:39684199 | DOI:10.3390/ijms252312487

Molecules. 2024 Dec 3;29(23):5703. doi: 10.3390/molecules29235703.ABSTRACTSelenium is an essential trace element for the human body. However, its intake is usually low. Therefore, the production and utilization of selenium-enriched food are currently a research hotspot. Despite the remarkable scientific interest in this topic, only a few of the numerous studies focus on commercially available products. This study examined the nutritional quality, physical and chemical properties, cooking characteristics, and eating quality of four commercially available hot-selling rice types, both selenium-enriched and non-selenium-enriched, and discovered that selenium-enriched rice outperforms ordinary rice in terms of both nutritional quality and taste. In addition, we employed the gas chromatography-ion mobility spectrometry (GC-IMS) technique to evaluate the volatile chemicals of rice. Some of the chemicals that made selenium-rich rice taste different from regular rice were pentanal, (E)-2-Hexen-1-ol, ethyl-3-methyl butanoate, 2-furan methanol acetate, ethyl heptanoate, ethyl hexanoate, methyl hexanoate, isopentyl pentanoate, and ethyl butyrate. We looked into the metabolite profiles of rice using LC-MS-based untargeted metabolomics to obtain a better idea of the different metabolites that are found in selenium-enriched rice compared to regular rice. We identified a total of 522 metabolites and screened 182, 227, and 100 differential metabolites in selenium-enriched (A) vs. non-selenium-enriched rice (B/C/D) groups, respectively. This study revealed that selenium primarily influenced the metabolism of D-amino acids, starch, sucrose, and linoleic acid in rice. This study systematically analyzed the quality differences between selenium-enriched and non-selenium-enriched rice available on the market. For consumers, it is essential to understand the quality of selenium-rich rice on the market to guide the purchase of rice.PMID:39683861 | DOI:10.3390/molecules29235703

Molecules. 2024 Nov 28;29(23):5647. doi: 10.3390/molecules29235647.ABSTRACTPost-fermented Pu-erh tea (PFPT) is a microbial fermented tea characterized by unique sensory attributes and multiple health benefits. Aspergillus niger is the dominant fungus involved in the fermentation process and plays a significant role in imparting the distinct characteristics of PFPT. To investigate the role of Aspergillus niger in the fermentation of Pu-erh tea, this study inoculated unsterilized sun-dried green tea with Aspergillus niger isolated from Pu-erh tea to enhance the fermentation process. Metabolites and microbial communities in sun-dried green tea (CK), fortified fermented tea (TF), and naturally fermented tea (NF) were analyzed using non-targeted metabolomics, 16S rDNA, and internal transcribed spacer sequencing. Non-targeted metabolomics revealed that Aspergillus niger significantly altered the metabolite profile of the tea samples, identifying a total of 200 different metabolites, with 95 showing significant increases and 105 significant decreases, predominantly enriched in metabolic pathways associated with amino acid biosynthesis and degradation. High-throughput sequencing revealed that although the relative abundance of the fungal community remained largely unchanged, the inoculation of Aspergillus niger significantly increased the abundance of Bacillales and Pseudomonas within the bacterial community, thereby influencing the dynamic balance of the microbial ecosystem. Collectively, the inoculation of Aspergillus niger altered the composition of the microbial community and metabolic activities, resulting in changes to the content of amino acid-dominated metabolites, thereby enhancing the flavor profile and overall quality of Pu-erh tea. These findings provide important insights for optimizing the production processes of Pu-erh tea and the application of microorganisms in other fermented foods.PMID:39683805 | DOI:10.3390/molecules29235647

Molecules. 2024 Nov 25;29(23):5556. doi: 10.3390/molecules29235556.ABSTRACTKudzu, scientifically known as Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (P. lobata), is a perennial vine belonging to the family Leguminosae. Puerarin, a unique constituent and primary active ingredient of this genus, exhibits a broad spectrum of pharmacological activities. This study started with several practical questions: Why is the root the main medicinal part? Why is it not peeled for medicinal purposes? Why is the harvest period usually from December to February? Although the puerarin biosynthesis pathway has been investigated, the stage at which the 8-C glycosylation reaction occurs remains controversial. In this study, metabolomics and transcriptomics analyses were performed on P. lobata organs and tissues, including leaves, young stems, mature stems, tuberous cortices, and cortex-excised tubers of roots. Two modules containing genes associated with puerarin biosynthesis were identified by WGCNA. The final selection of important candidate UDP-glucosyltransferases (UGTs) that may be involved in the puerarin biosynthesis pathway included two 8-C-GTs, three 7-O-GTs, and key transcription factors. On this basis, the regulatory network of puerarin biosynthesis was constructed and laid the foundation for the cultivation of high-quality medicinal kudzu with high puerarin content.PMID:39683717 | DOI:10.3390/molecules29235556

Nutrients. 2024 Dec 9;16(23):4242. doi: 10.3390/nu16234242.ABSTRACTBackground: Small vulnerable newborns (SVNs), including those born preterm, small for gestational age, or with low birth weight, are at higher risk of neonatal mortality and long-term health complications. Early exposure to maternal vaginal microbiota and breastfeeding plays a critical role in the development of the neonatal microbiota and immune system, especially in low-resource settings like Burkina Faso, where neonatal mortality rates remain high. Objectives: The DenBalo study aims to investigate the role of maternal and neonatal factors, such as vaginal and gut microbiota, immune development, and early nutrition, in shaping health outcomes in SVNs and healthy infants. Methods: This prospective cohort observational study will recruit 141 mother-infant pairs (70 SVNs and 71 healthy controls) from four health centers in Bobo-Dioulasso, Burkina Faso. The mother-infant pairs will be followed for six months with anthropometric measurements and biospecimen collections, including blood, breast milk, saliva, stool, vaginal swabs, and placental biopsies. Multi-omics approaches, encompassing metagenomics, metabolomics, proteomics, and immune profiling, will be used to assess vaginal and gut microbiota composition and functionality, immune cell maturation, and cytokine levels at critical developmental stages. Conclusions: This study will generate comprehensive data on how microbiota, metabolomic, and proteomic profiles, along with immune system development, differ between SVNs and healthy infants. These findings will guide targeted interventions to improve neonatal health outcomes and reduce mortality, particularly in vulnerable populations.PMID:39683635 | DOI:10.3390/nu16234242

Nutrients. 2024 Dec 4;16(23):4195. doi: 10.3390/nu16234195.ABSTRACTIn this review, we provide an evidence-based approach to determine the cellular and systemic actions of two structurally similar flavonoids, apigenin and chrysin. We have clearly evaluated and charted the overlapping and diverging properties of these two sister flavonoids. Based on two separate Omics-based approaches by our group and independent reports from others, the cholesterol-lowering properties have been revealed. In addition, the prevention of uric acid biosynthesis and enhancement of ketogenesis have also been quite evident in these two flavonoids. Along with these overlapping functions, apigenin and chrysin have also demonstrated unique properties that allow them to stand out from each other. Chrysin has demonstrated abilities like downregulating alanine metabolism and pyrimidine synthesis, which could be helpful in metabolic diseases like cancer. In contrast, apigenin has demonstrated anti-oxidant and anti-inflammatory properties by enhancing endogenous anti-inflammatory lipids and upregulating vasoprotective metabolites, which could be beneficial for cardiovascular, renal, and cerebrovascular complications. Further validation studies using in vivo and translational approaches could provide us with better clarity regarding the use of these agents therapeutically and to treat a combination or pool of metabolic diseases.PMID:39683588 | DOI:10.3390/nu16234195

Nutrients. 2024 Nov 30;16(23):4161. doi: 10.3390/nu16234161.ABSTRACTBackground: Fibromyalgia (FM) is a chronic disorder that causes damage to the neuro-muscular system and alterations in the intestinal microbiota and affects the psychological state of the patient. In our previous study, we showed that 22 women patients subjected to a specific very low-carbohydrate ketogenic therapy (VLCKD) showed an improvement in clinical scores as well as neurotransmission-related and psychological dysfunctions and intestinal dysbiosis. Furthermore, NMR metabolomic data showed that changes induced by VLCKD treatment were evident in all metabolic pathways related to fibromyalgia biomarkers. Methods: Based on this evidence, we extend our investigation into dietary interventions for fibromyalgia by evaluating the impact of transitioning from a VLCKD to a low-glycemic insulinemic (LOGI) diet over an additional 45-day period. Therefore, participants initially following a VLCKD were transitioned to the LOGI diet after 45 days to determine whether the improvements in FM symptoms and metabolic dysfunctions achieved through VLCKD could be sustained with LOGI. Results: Our findings suggested that while VLCKD serves as an effective initial intervention for correcting metabolic imbalances and alleviating FM symptoms, transitioning to a LOGI diet offers a practical and sustainable dietary strategy. This transition preserves clinical improvements and supports long-term adherence and quality of life, underscoring the importance of adaptable nutritional therapies in chronic disease management. Control patients who adhered only to the LOGI diet for 90 days showed only modest improvement in clinical and psychological conditions, but not elimination of fibromyalgia symptoms. Conclusions: In conclusion the LOGI diet is an excellent alternative to maintain the results obtained from the regime VLCKD.PMID:39683556 | DOI:10.3390/nu16234161

Nutrients. 2024 Nov 28;16(23):4096. doi: 10.3390/nu16234096.ABSTRACTObjectives: This study investigates the effectiveness of an herbal formulation, STRESSLESS (ST-65), which combines ashwagandha (Withania somnifera) and bacopa (Bacopa monnieri), on SH-SY5Y human neuroblastoma cells. Given the rising interest in natural compounds for neuroprotection and stress alleviation, we aimed to explore the cellular and molecular effects of this formulation. Methods: Utilizing a nuclear magnetic resonance (NMR) metabolomic approach and ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS), we identified key bioactive compounds in ST-65, including withanolides from ashwagandha and bacosides from bacopa. Results: Our findings indicate that ST-65 treatment significantly alters the metabolic profile of SH-SY5Y cells. Key changes included increased levels of metabolites linked to neuroprotection, energy metabolism, and antioxidant defense. Notable enhancements were observed in specific amino acids and neuroprotective compounds, suggesting activation of neuroprotective mechanisms and mitigation of stress-induced damage. Conclusions: The study reveals a complex phyto-chemical profile of ST-65 and underscores its potential as a natural active agent for addressing stress-related neurodegenerative conditions. These insights into neuronal mechanisms provide a foundation for further exploration of herbal formulations in neuroprotection.PMID:39683490 | DOI:10.3390/nu16234096

Commun Med (Lond). 2024 Dec 16;4(1):265. doi: 10.1038/s43856-024-00637-1.ABSTRACTBACKGROUND: Distal sensorimotor polyneuropathy (DSPN) is a common neurological disorder in elderly adults and people with obesity, prediabetes and diabetes and is associated with high morbidity and premature mortality. DSPN is a multifactorial disease and not fully understood yet.METHODS: Here, we developed the Interpretable Multimodal Machine Learning (IMML) framework for predicting DSPN prevalence and incidence based on sparse multimodal data. Exploiting IMMLs interpretability further empowered biomarker identification. We leveraged the population-based KORA F4/FF4 cohort including 1091 participants and their deep multimodal characterisation, i.e. clinical data, genomics, methylomics, transcriptomics, proteomics, inflammatory proteins and metabolomics.RESULTS: Clinical data alone is sufficient to stratify individuals with and without DSPN (AUROC = 0.752), whilst predicting DSPN incidence 6.5 ± 0.2 years later strongly benefits from clinical data complemented with two or more molecular modalities (improved ΔAUROC > 0.1, achieved AUROC of 0.714). Important and interpretable features of incident DSPN prediction include up-regulation of proinflammatory cytokines, down-regulation of SUMOylation pathway and essential fatty acids, thus yielding novel insights in the disease pathophysiology.CONCLUSIONS: These may become biomarkers for incident DSPN, guide prevention strategies and serve as proof of concept for the utility of IMML in studying complex diseases.PMID:39681608 | DOI:10.1038/s43856-024-00637-1

Zhonghua Xin Xue Guan Bing Za Zhi. 2024 Dec 24;52(12):1446-1451. doi: 10.3760/cma.j.cn112148-20240922-00561.ABSTRACT肥厚型心肌病是最常见的遗传性心脏病，是青少年和运动员心脏性猝死的主要病因。梗阻性肥厚型心肌病是肥厚型心肌病的重要类型，多项研究显示，与非梗阻性肥厚型心肌病患者及正常人群相比，梗阻性肥厚型心肌病患者机体及心肌细胞存在代谢改变，且与患者不良临床症状与临床结局密切相关。同时，应用代谢组学研究结果可对梗阻性肥厚型心肌病发病机制与通路进行探究。该文就梗阻性肥厚型心肌病能量代谢改变进行综述，总结与梗阻性肥厚型心肌病有关的发病机制及通路，归纳有效的治疗靶点或评估预后的科学指标。.PMID:39681452 | DOI:10.3760/cma.j.cn112148-20240922-00561

Am J Physiol Endocrinol Metab. 2024 Dec 16. doi: 10.1152/ajpendo.00248.2024. Online ahead of print.ABSTRACTDiabetic kidney disease (DKD) is a severe diabetic microvascular complication featured by chronic low-grade inflammation. Roux-en-Y gastric bypass (RYGB) surgery has gained importance as a safe and effective surgery to treat DKD. Bile acids are significantly changed after RYGB, which brings a series of metabolic benefits, but the relationship with the improvement of DKD is unclear. Therefore, this study performed RYGB surgery on db/db mice to observe the beneficial effects of the surgery on the kidneys, and performed bile acid targeted metabolomics analysis to explore bile acid changes. We found that RYGB significantly reduced albuminuria in db/db mice, improved renal function, reversed renal structural lesions, and attenuated podocyte injury, inflammation. Notably, bile acid metabolomic analysis revealed taurolithocholic acid (TLCA) as the most significantly altered bile acid after RYGB. Further in vitro and in vivo validation experiments revealed that TLCA supplementation improved renal function and reduced renal inflammatory damage in db/db mice. In addition, TLCA inhibited high glucose-induced inflammatory damage in MPC-5 cells, and its mechanism of action may be related to activating Takeda G protein-coupled receptor 5 (TGR5), inhibiting NF-κB phosphorylation, and thus inhibiting inflammatory response. In conclusion, RYGB may play a protective role in the kidneys of diabetic mice by activating the TLCA/TGR5 pathway.PMID:39681344 | DOI:10.1152/ajpendo.00248.2024

Respirology. 2024 Dec 16. doi: 10.1111/resp.14866. Online ahead of print.ABSTRACTBACKGROUND AND OBJECTIVE: Acute exacerbation (AE) is often the fatal complication of idiopathic pulmonary fibrosis (IPF). Emerging evidence indicates that metabolic reprogramming and dysregulation of lipid metabolism are distinctive characteristics of IPF. However, the lipid metabolic mechanisms that underlie the pathophysiology of AE-IPF remain elusive.METHODS: Serum samples for pilot study were collected from 34 Controls, 37 stable IPF (S-IPF) cases and 41 AE-IPF patients. UHPLC-MS/MS was utilized to investigate metabolic variations and identify lipid biomarkers in serum. ELISA, quantitative PCR and western blot were employed to validate the identified biomarkers.RESULTS: There were 32 lipid metabolites and 5 lipid metabolism pathways enriched in all IPF patients compared to Controls. In AE-IPF versus S-IPF, 19 lipid metabolites and 12 pathways were identified, with 5-hydroxyeicosatetraenoic Acid (5-HETE) significantly elevated in AE-IPF. Both in internal and external validation cohorts, the serum levels of 5-HETE were significantly elevated in AE-IPF patients compared to S-IPF subjects. Consequently, the indicators related to 5-HETE in lipid metabolic pathway were significantly changed in AE-IPF patients compared with S-IPF cases in the lung tissues. The serum level of 5-HETE was significantly correlated with the disease severity (CT score and PaO2/FiO2 ratio) and survival time. Importantly, the receiver operating characteristic (ROC) curve, Kaplan-Meier analysis and Multivariate Cox regression analysis demonstrated that 5-HETE represents a promising lipid biomarker for the diagnosis and prognosis of AE-IPF.CONCLUSION: Our study highlights lipid reprogramming as a novel therapeutic approach for IPF, and 5-HETE may be a potential biomarker of AE-IPF patients.PMID:39681341 | DOI:10.1111/resp.14866

Ann Pharm Fr. 2024 Dec 14:S0003-4509(24)00179-2. doi: 10.1016/j.pharma.2024.12.008. Online ahead of print.ABSTRACTIncreasingly, molecular chemistry and pharmacology are complementing classical studies in the field of archaeology. In this case, we present the results of the chemical study of pipe residues found in the context of an archaeological mission (AROMA mission: Archaeology of the Exercise of Royal and Magico-Religious Power) in the royal palaces of Abomey (Benin), dating from the 17th-19th century. The search for many products was carried out (mainly tobacco, cannabis) but surprisingly only highlighted the presence of caffeine residues. This result is discussed and compared with field notions and in particular with ethnological surveys where coffee was consumed in the old way, smoked in a pipe (peripheral part or shell, and not the bean itself or the leaves).PMID:39681307 | DOI:10.1016/j.pharma.2024.12.008

J Steroid Biochem Mol Biol. 2024 Dec 14:106663. doi: 10.1016/j.jsbmb.2024.106663. Online ahead of print.ABSTRACTBACKGROUND: This study investigates the protective effects and potential mechanisms of 1,25(OH)2D3 against high-altitude pulmonary edema (HAPE).METHODS: Hypoxia-induced rats were administered 1,25(OH)2D3 for 24, 48, and 72hours, and we observed lung tissue injury and pulmonary edema. Immunohistochemistry (IHC) and Western blot analyses were employed to analyze the expression of markers associated with ferroptosis and ferritinophagy in rat lungs. Metabolomics analysis was conducted to investigate changes in serum lipid metabolites. We validated the mechanism of action of 1,25(OH)2D3 in type II alveolar epithelial cells induced by hypoxia.RESULTS: Our results demonstrated that hypoxic exposure significantly altered sodium-water transport in the lungs, leading to edema formation. The degree of pulmonary edema was most pronounced at 48hours of hypoxi. Treatment with 1,25(OH)2D3 improved lung function and reduced the degree of pulmonary edema in hypoxic rats. Hypoxia-induced increases in 4-HNE and MDA levels in the lungs, along with iron accumulation, were observed. Hypoxia also resulted in elevated levels of NCOA4, LC3Ⅱ, and FTH1 proteins in the lungs. Furthermore, treatment with 1,25(OH)2D3 significantly inhibited ferroptosis and ferritinophagy in the lungs after hypoxia. The levels of lipid metabolites, such as L-Aspartic acid and L-Fucose, were significantly elevated in the serum of hypoxic rats. After 1,25(OH)2D3 treatment, these levels exhibited a significant reduction.CONCLUSION: In hypoxic type II alveolar epithelial cells, 1,25(OH)2D3 improved hypoxia-induced sodium-water transport, ferroptosis, and ferritinophagy, which were reversed by the autophagy agonist Rapamycin.By modulating ferroptosis and ferritinophagy, 1,25(OH)2D3 mitigated the deleterious effects of hypoxia on pulmonary function.PMID:39681240 | DOI:10.1016/j.jsbmb.2024.106663

J Ethnopharmacol. 2024 Dec 14:119246. doi: 10.1016/j.jep.2024.119246. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Buyang Huanwu Decoction (BYHWD) exerts its anti-cerebral ischemia effects through multiple pathways and targets, although its specific mechanisms remain unclear AIM OF THE STUDY: Ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) metabolomics and other methods were employed to investigate the role of BYHWD in inhibiting neuronal apoptosis following cerebral ischemia-reperfusion by modulating the RhoA/Rock2 pathway.METHODS: A rat model of exhaustion swimming combined with middle cerebral artery occlusion (ES+I/R) was established to evaluate the intervention effects of Buyang Huanwu Decoction on cerebral ischemia-reperfusion. This was assessed using neurological function scores, Qi deficiency and blood stasis syndrome scores, HE staining, Nissl staining and TT staining. Differential metabolites and metabolic pathways associated with cerebral ischemia-reperfusion were identified using UPLC-QTOF-MS metabolomics, with key differential metabolites validated through ELISA. Molecular docking techniques were employed to predict interactions between the key differential metabolite, hippuric acid, and its primary downstream pathways. Finally, the levels of neurocellular apoptosis, as well as key molecules in the RhoA/Rock2 signaling pathway and the mitochondrial apoptosis pathway, were measured.RESULTS: The results indicated that the primary differential metabolites associated with BYHWD's protective effects against ischemia-reperfusion injury were hippuric acid, lysophosphatidic acid, and lysophosphatidylethanolamine, with the main metabolic pathway being phenylalanine metabolism. Molecular docking studies demonstrated that malonic acid exhibited a strong affinity for proteins related to the RhoA/Rock2 signaling pathway and the mitochondrial apoptosis pathway.Furthermore, we found that BYHWD treatment significantly decreased the apoptosis rate of cells following cerebral ischemia-reperfusion and inhibited the expression of key molecules in both the RhoA/Rock2 signaling pathway and the mitochondrial apoptosis pathway in brain tissue.CONCLUSION: BYHWD ameliorated brain tissue injury after cerebral ischemia/reperfusion in rats with qi deficiency and blood stasis. The underlying mechanism may involve BYHWD's inhibition of the RhoA/Rock2 signaling pathway activation through modulation of the phenylalanine metabolism pathway, thereby reducing neuronal apoptosis mediated by the mitochondrial apoptosis pathway.PMID:39681201 | DOI:10.1016/j.jep.2024.119246

Anal Chem. 2024 Dec 16. doi: 10.1021/acs.analchem.4c03229. Online ahead of print.ABSTRACTApplications of advanced omics methodologies are increasingly popular in biomedicine. However, large-scale studies aiming at clinical translation are typically siloed to single technologies. Here, we present the first comprehensive large-scale population data combining 209 lipoprotein measures from a quantitative NMR spectroscopy platform and 809 lipid classes and species from a quantitative LC-MS/MS platform. These data with 1018 molecular measures were analyzed in two population cohorts totaling 7830 participants. The association and cluster analyses revealed excellent coherence between the methodologically independent data domains and confirmed their quantitative compatibility and suitability for large-scale studies. The analyses elucidated the detailed molecular characteristics of the heterogeneous circulatory macromolecular lipid transport system and the underlying structural and compositional relationships. Unsupervised neural network analysis─the so-called self-organizing maps (SOMs)─revealed that these deep molecular and metabolic data are inherently related to key physiological and clinical population characteristics. The data-driven population subgroups uncovered marked differences in the population distribution of multiple cardiometabolic risk factors. These include, e.g., multiple lipoprotein lipids, apolipoprotein B, ceramides, and oxidized lipids. All 79 structurally unique triglyceride species showed similar associations over the entire lipoprotein cascade and indicated systematically increased risk for carotid intima media thickening and other atherosclerosis risk factors, including obesity and inflammation. The metabolic attributes for 27 individual cholesteryl ester species, which formed six distinct clusters, were more intricate with associations both with higher─e.g., CE(16:1)─and lower─e.g., CE(20:4)─cardiometabolic risk. The molecular details provided by these combined data are unprecedented for molecular epidemiology and demonstrate a new potential avenue for population studies.PMID:39680883 | DOI:10.1021/acs.analchem.4c03229

Chem Rev. 2024 Dec 16. doi: 10.1021/acs.chemrev.3c00520. Online ahead of print.ABSTRACTThe octadecanoids are a broad class of lipids consisting of the oxygenated products of 18-carbon fatty acids. Originally referring to production of the phytohormone jasmonic acid, the octadecanoid pathway has been expanded to include products of all 18-carbon fatty acids. Octadecanoids are formed biosynthetically in mammals via cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) activity, as well as nonenzymatically by photo- and autoxidation mechanisms. While octadecanoids are well-known mediators in plants, their role in the regulation of mammalian biological processes has been generally neglected. However, there have been significant advancements in recognizing the importance of these compounds in mammals and their involvement in the mediation of inflammation, nociception, and cell proliferation, as well as in immuno- and tissue modulation, coagulation processes, hormone regulation, and skin barrier formation. More recently, the gut microbiome has been shown to be a significant source of octadecanoid biosynthesis, providing additional biosynthetic routes including hydratase activity (e.g., CLA-HY, FA-HY1, FA-HY2). In this review, we summarize the current field of octadecanoids, propose standardized nomenclature, provide details of octadecanoid preparation and measurement, summarize the phase-I metabolic pathway of octadecanoid formation in mammals, bacteria, and fungi, and describe their biological activity in relation to mammalian pathophysiology as well as their potential use as biomarkers of health and disease.PMID:39680864 | DOI:10.1021/acs.chemrev.3c00520

J Agric Food Chem. 2024 Dec 16. doi: 10.1021/acs.jafc.4c03818. Online ahead of print.ABSTRACTLactobacillus reuteri is a well-known probiotic with beneficial effects, such as anti-insulin resistance, anti-inflammatory, and improvement of the intestinal barrier. However, the underlying mechanisms remain unclear. Here, we found that gavage of L. reuteri improved the intestinal barrier and glucose homeostasis in HFD-fed mice. Analysis of lipid metabolomics reveals a significant increase in eicosatrienoic acid (ETA) levels in mouse feces after L. reuteri gavage. We found that ETA maintain intestinal barrier integrity and improve glucose homeostasis by promoting GLP-1 secretion. Mechanistically, by using CD36 inhibitor in vivo and CD36 knockdown STC-1 cells in vitro, we elucidate that ETA activates intestinal CD36-activated PLC/IP3R/Ca2+ signaling to promote GLP-1 secretion. In vivo administration of GLP-1R inhibitor and in vitro intestinal organoid experiments demonstrate that GLP-1 upregulates the PI3K/AKT/HIF-1α pathway by GLP-1R and increases intestinal tight junction protein expressions, which in turn enhance the intestinal barrier integrity, reduce serum LPS level, attenuate inflammation in white adipose tissue (WAT), and ultimately improve glucose homeostasis in HFD and db/db mice. Our study elucidates for the first time the mechanism by which L. reuteri and its enriched metabolite ETA inhibit WAT inflammation by ameliorating the intestinal barrier, ultimately improving glucose homeostasis, and provides a new treatment strategy for T2D.PMID:39680859 | DOI:10.1021/acs.jafc.4c03818