PubMed

J Fungi (Basel). 2024 Jul 30;10(8):533. doi: 10.3390/jof10080533.ABSTRACTAgaricus bisporus is one of the most popular mushroom species in the world; however, mushrooms are highly susceptible to browning due to the absence of a protective cuticle layer and high respiration rate. The molecular mechanism underlying the process of mushroom browning needs to be explored. Here, we analyzed the transcriptomic and metabolomic data from A. bisporus at ambient temperature. Specifically, a total of 263 significantly changed metabolites and 4492 differentially expressed genes were identified. Lipid metabolites associated with cell membrane degradation were predominantly up-regulated during ambient storage. Transcriptomic data further revealed the alterations of the expression of membrane lipid metabolism-related enzymes. Additionally, energy metabolic processes and products such as glycolysis and linoleic acid changed significantly during ambient storage, indicating their potential roles in the quality deterioration of A. bisporus. These findings provide new insights into the underlying lipid metabolic mechanisms of A. bisporus during postharvest ambient storage and will provide values for mushroom preservation techniques.PMID:39194859 | DOI:10.3390/jof10080533

J Fungi (Basel). 2024 Jul 27;10(8):524. doi: 10.3390/jof10080524.ABSTRACTIn traditional Chinese medicine, Ganoderma is a kind of edible and medicinal mushroom, which is widely used because of its significant pharmacological activity. There are many species within the Ganoderma genus, each with different material bases and applications. However, detailed studies on these species are still lacking. In this study, we investigated the metabolites of G. leacontextum (B), G. lucidum (C), G. tsugae (S) from Changbai Mountain, and G. tsugae (M) from Mongolia using metabolomics. The PCA results indicated minimal differences between M and S, whereas B and S exhibited significant variations. A total of 708 differential metabolites were identified in this study, with steroids, triterpenoids, phenols, and quinones being the major metabolites. Specifically, triterpenoids and steroids were higher in C. Meanwhile, phenolic compounds were more abundant in B. Additionally, quinones were more abundant in M and S. We validated some of the main compounds, and the results showed that paracetamol was most abundant in B, making paracetamol a potential marker for identifying B. Additionally, vitamin K3 was found to be more abundant in M and S, which can serve as a marker for their identification. This study provides new insights and a theoretical basis for the development and utilization of the genus Ganoderma.PMID:39194850 | DOI:10.3390/jof10080524

J Clin Endocrinol Metab. 2024 Aug 28:dgae593. doi: 10.1210/clinem/dgae593. Online ahead of print.ABSTRACTOBJECTIVE: To study whether inflammation is associated with and helps predict mortality risk in patients with type 2 diabetes. To explore the intertwined link between inflammation and tryptophan metabolism on death risk.DESIGN: Two prospective cohorts: the aggregate Gargano Mortality Study (1,731 individuals; 872 all-cause deaths) as discovery sample, the Foggia Mortality Study (490 individuals; 256 deaths) as validation sample. Twenty-seven inflammatory markers were measured. Causal mediation analysis and in vitro studies were carried out to explore the link between inflammatory markers and the kynurenine-to-tryptophan ratio (KTR) in shaping mortality risk.RESULTS: Using multivariable stepwise Cox regression analysis, IL-4, IL-6, IL-8, IL-13, RANTES and IP-10, were independently associated with death. An inflammation score (I-score) comprising these six molecules is strongly associated with death in both the discovery and the validation cohorts HR (95%CI) = 2.13 (1.91-2.37) and 2.20 (1.79-2.72), respectively. The I-score improved discrimination and reclassification measures (all P<0.01) of two mortality prediction models based on clinical variables. The causal mediation analysis showed that 28% of the KTR effect on mortality was mediated by IP-10. Studies in cultured endothelial cells showed that 5-Methoxy-tryptophan, an anti-inflammatory metabolite derived from tryptophan, reduces the expression of IP-10, thus providing a functional basis for the observed causal mediation.CONCLUSIONS: Adding the I-score to clinical prediction models may help identify individuals who are at greater risk of death. Deeply addressing the intertwined relationship between low-grade inflammation and imbalanced tryptophan metabolism in shaping mortality risk may help discover new therapies targeting patients characterized by these abnormalities.PMID:39193712 | DOI:10.1210/clinem/dgae593

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2024 Aug 7;59(8):872-878. doi: 10.3760/cma.j.cn115330-20240131-00073.ABSTRACT慢性鼻窦炎（CRS）是一种常见的慢性炎性疾病，由于其存在高度异质性，早期准确的临床诊断和治疗对控制CRS的病情至关重要。多种组学技术可以全面系统地分析CRS患者DNA、RNA、蛋白质的差异表达及生物学功能，有利于深入研究CRS内在机制，为实现CRS的精准诊疗提供了可能。本文分别概述基因组学、表观基因组学、转录组学、蛋白质组学和代谢组学等各类组学方法在CRS中的研究进展，对既往研究数据进行归纳整合和分析，阐明多组学技术在推动CRS精准诊疗中的重要作用，并为CRS的精准诊疗提供新的方向。.PMID:39193600 | DOI:10.3760/cma.j.cn115330-20240131-00073

Front Cell Infect Microbiol. 2024 Aug 13;14:1426340. doi: 10.3389/fcimb.2024.1426340. eCollection 2024.ABSTRACTINTRODUCTION: With the continuous growth of bullfrog supply, it has become an important aquaculture species. Due to the lack of actionable industry standards and regulation, the misuse of anti-disease drugs and abnormal liver lipid metabolism in bullfrogs have become a major obstacle to the development of bullfrog aquaculture industry. Glutathione is a natural tripeptide that can be synthesized intracellularly, and its physiological functions mainly include the treatment of liver diseases, antioxidant, detoxification, anti-tumor, enhancement of immunity, and delaying aging.METHODS: In this study, the therapeutic effect of glutathione on bullfrogs with abnormal liver lipid metabolism was revealed from hepatic lipid metabolism and serum metabolomics analysis. The survival rate, liver histomorphology, serum antioxidant enzyme activity, liver lipase activity and serum metabolomics, liver metabolomics were studied and analyzed by feeding the bullfrogs with abnormal lipid metabolism with glutathione for 20 days in the NC, FI and GSH groups.RESULTS: The results of the study showed that glutathione was able to repair the liver and improve the survival rate of bullfrogs with abnormal lipid metabolism; the activity of serum SOD enzymes was significantly increased; the activities of ACP and AKP were significantly decreased; the activities of HDL-C and T-CHO were significantly increased; and the activities of LDL-C, TBA, and TG were significantly decreased in the liver; the contents of metabolites, such as PC, PS, and PE were significantly up-regulated, and the levels of up-regulated Autophagy - other, Necroptosis and ErbB signaling pathway, and down-regulated Sphingolipid metabolism, D-Amino acid metabolism metabolic pathway, to some extent The metabolic pathways of Sphingolipid metabolism and D-Amino acid metabolism were down-regulated to alleviate the disorders of glycerophospholipid and amino acid metabolism to a certain extent, thus alleviating the abnormalities of liver lipid metabolism.DISCUSSION: The results showed that glutathione could effectively treat the liver lipid metabolism disorder of bullfrogs, promote the growth and development of bullfrogs, repair the liver function, reduce the inflammation, and promote the healthy and green development of bullfrog industry.PMID:39193504 | PMC:PMC11347949 | DOI:10.3389/fcimb.2024.1426340

Front Microbiol. 2024 Aug 13;15:1450306. doi: 10.3389/fmicb.2024.1450306. eCollection 2024.ABSTRACTThe gut microbiota plays a crucial role in host health and metabolism. This study explores the differences in gut microbiota and metabolites between domestic pigs (DP) and wild boars (WB) in urban environments. We analyzed gut microbial composition, metabolic profiles, virome composition, antibiotic resistance genes (ARGs), and human pathogenic bacteria (HPB) in both DP and WB. Our results revealed that DP exhibited a higher Firmicutes/Bacteroidetes ratio and were enriched in bacterial genera associated with domestication and modern feeding practices. Metabolomic analysis showed distinct profiles, with WB significantly enriched in the Pantothenate and CoA biosynthesis pathway, highlighting dietary and environmental influences on host metabolism. Additionally, DP had a distinct gut virome composition, particularly enriched in lytic phages of the Chaseviridae family. ARG analysis indicated a higher abundance of tetracycline resistance genes in DP, likely due to antibiotic use in pig farms. Furthermore, variations in HPB composition underscored potential health risks associated with contact with pig feces. These findings provide valuable insights into the microbial ecology of domestic pigs and wild boars, emphasizing the importance of these comparisons in identifying zoonotic pathogen transmission pathways and managing antibiotic resistance. Continued research in this area is essential for developing effective strategies to mitigate public health risks and promote sustainable livestock management practices.PMID:39193431 | PMC:PMC11347354 | DOI:10.3389/fmicb.2024.1450306

Clin Mass Spectrom. 2018 Aug 3;10:16-24. doi: 10.1016/j.clinms.2018.08.001. eCollection 2018 Dec.ABSTRACTMelanoma accounts for more than 60% of deaths associated with skin cancer, making its early detection through dermatological screening essential for improved treatment outcomes. Early detection and successful treatment of melanoma can dramatically increase the 5-year survival rate from 14 to 98%. To support such efforts, comprehensive identification of metabolite patterns capable of describing cancer progression will help support the foundational knowledge necessary to build early detection platforms for intervention prior to metastasis. Using an UPLC-MS, as part of a cell-based, untargeted metabolomics approach, we profiled the metabolomes of WM-226-4 and WM-115 cells. Derived from the metastatic and the primary sites of the same individual, these two cell lines represent a paired melanoma cancer cell line. Progenesis and MetaboAnalyst, platforms dedicated to metabolomics data analysis, were used to establish a panel of differentially expressed metabolites across these two stages of melanoma. In addition, mummichog was used to identify the affected pathways. A total of 12 differentially expressed metabolites including amino acids, carnitine, acylcarnitine, and a limited set of lipids were identified. The significantly differing metabolites are components of a diverse set of metabolic pathways (e.g., glycerophospholipid metabolism, carnitine shuttle, tryptophan metabolism), that have biological implications for the survival and dissemination of metastatic melanoma cells.PMID:39193356 | PMC:PMC11322782 | DOI:10.1016/j.clinms.2018.08.001

Front Pharmacol. 2024 Aug 13;15:1437738. doi: 10.3389/fphar.2024.1437738. eCollection 2024.ABSTRACTIntroduction: Elevated glucagon levels are a characteristic feature of type 2 diabetes. This abnormal increase in glucagon can lead to an accelerated rate of gluconeogenesis. Glucagon also stimulates hepatic metabolism of amino acids, particularly promoting the formation of urea. The specific role of carbamoyl phosphate synthetase 1 (CPS1), a rate-limiting enzyme in the urea cycle, in the development versus the persistence of glucagon-induced hyperglycemia has not been previously established. Methods: The study employed both in vivo and in vitro approaches to assess the impact of CPS1 modulation on glucagon response. CPS1 was knockdown or overexpression to evaluate its influence on hepatic gluconeogenesis. In addition, an in-silico strategy was employed to identify a potential CPS1 inhibitor. Results: Knockdown of CPS1 significantly reduced the glucagon response both in vivo and in vitro. Conversely, overexpression of CPS1 resulted in an overactive hepatic gluconeogenic response. Mechanistically, CPS1 induced the release of calcium ions from the endoplasmic reticulum, which in turn triggered the phosphorylation of CaMKII. The activation of CaMKII then facilitated the dephosphorylation and nuclear translocation of FOXO1, culminating in the enhancement of hepatic gluconeogenesis. Furthermore, cynarin, a natural CPS1 inhibitor derived from the artichoke plant, had the capacity to attenuate the hepatic glucagon response in a CPS1-dependent manner. Discussion: CPS1 played a pivotal role in mediating glucagon-induced hepatic gluconeogenesis. The discovery of cynarin as a natural inhibitor of CPS1 suggested its potential as a therapeutic agent for diabetes treatment.PMID:39193349 | PMC:PMC11347310 | DOI:10.3389/fphar.2024.1437738

Front Pharmacol. 2024 Aug 9;15:1434988. doi: 10.3389/fphar.2024.1434988. eCollection 2024.ABSTRACTBACKGROUND: It is unknown how cancer cells override apoptosis and maintain progression under nutrition-deprived conditions within the tumor microenvironment. Phosphoenolpyruvate carboxykinase (PEPCK or PCK) catalyzes the first rate-limiting reaction in gluconeogenesis, which is an essential metabolic alteration that is required for the proliferation of cancer cells under glucose-limited conditions. However, if PCK-mediated gluconeogenesis affects apoptotic cell death of non small cell lung cancer (NSCLC) and its potential mechanisms remain unknown.METHODS: RNA-seq, Western blot and RT-PCR were performed in A549 cell lines cultured in medium containing low or high concentrations of glucose (1 mM vs. 20 mM) to gain insight into how cancer cells rewire their metabolism under glucose-restriction conditions. Stable isotope tracing metabolomics technology (LC-MS) was employed to allow precise quantification of metabolic fluxes of the TCA cycle regulated by PCK2. Flow Cytometry was used to assess the rates of early and later apoptosis and mitochondrial ROS in NSCLC cells. Transwell assays and luciferase-based in vivo imaging were used to determine the role of PCK2 in migration and invasion of NSCLC cells. Xenotransplants on BALB/c nude mice to evaluate the effects of PCK2 on tumor growth in vivo. Western blot, Immunohistochemistry and TUNEL assays to evaluate the protein levels of mitochondrial apoptosis.RESULTS: This study report that the mitochondrial resident PCK (PCK2) is upregulated in dependent of endoplasmic reticulum stress-induced expression of activating transcription factor 4 (ATF4) upon glucose deprivation in NSCLC cells. Further, the study finds that PCK2-mediated metabolism is required to decrease the burden of the TCA cycles and oxidative phosphorylation as well as the production of mitochondrial reactive oxygen species. These metabolic alterations in turn reduce the activation of Caspase9-Caspase3-PARP signal pathway which drives apoptotic cell death. Importantly, silencing PCK2 increases apoptosis of NSCLC cells under low glucose condition and inhibits tumor growth both in vitro and in vivo.CONCLUSION: In summary, PCK2-mediated metabolism is an important metabolic adaptation for NSCLC cells to acquire resistance to apoptosis under glucose deprivation.PMID:39193344 | PMC:PMC11347759 | DOI:10.3389/fphar.2024.1434988

Front Pharmacol. 2024 Aug 13;15:1435166. doi: 10.3389/fphar.2024.1435166. eCollection 2024.ABSTRACTIntroduction: Stress-related gastric mucosal lesions (SGMLs) are the most common complication in critical care patients. Previous studies have demonstrated that herbal pair (HP), Polygonum hydropiper-Coptis chinensis (HP P-C) has the anti-SGML effect. However, the underlying mechanism of HP P-C against SGML remains elusive. This study aimed to elucidate how HP P-C extracts exert their protective effects on SGML by examining the role of gut microbiota and metabolites. Methods: SD rats were pretreated with different doses of HP P-C extracts for 6 days, followed by inducing SGML with water-immersion restraint stress (WIRS). After a comprehensive evaluation of serum and gastric tissue indicators in rats, 16S rRNA sequencing and metabolomics analyses were conducted to assess the impact of HP P-C on the fecal microorganisms and metabolites and their correlation. Results: Animal experiment suggested that pretreatment with HP P-C effectively reduced the gastric mucosal lesions, remarkably increased superoxide dismutase (SOD) activity in SGML model rats induced by WIRS. 16S rRNA sequencing analysis showed that HP P-C altered the composition of gut microbiota by raising the abundance of Lactobacillus and Akkermansia. In addition, metabolomics data identified seventeen main differential metabolites related to WIRS-induced gastric mucosal injury, primarily involving in tyrosine metabolism and betalain biosynthesis. HP P-C was found to regulate tyrosine metabolism and betalain biosynthesis by down-regulating the tyramine, L-tyrosine and L-dopa and up -regulating the gentisic acid and dopaquinone. Conclusion: Taken together, this study indicated that HP P-C could effectively protect against WIRS-induced gastric mucosal lesions by modulating intestinal flora and metabolites.PMID:39193339 | PMC:PMC11347758 | DOI:10.3389/fphar.2024.1435166

Front Mol Biosci. 2024 Aug 13;11:1403844. doi: 10.3389/fmolb.2024.1403844. eCollection 2024.ABSTRACTINTRODUCTION: Multifactorial Eye disorders are a significant public health concern and have a huge impact on quality of life. The pathophysiological mechanisms underlying these eye disorders were not completely understood since functional and low-throughput biological tests were used. By identifying biomarkers linked to eye disorders, metabolomics enables early identification, tracking of the course of the disease, and personalized treatment.METHODS: The electronic databases of PubMed, Scopus, PsycINFO, and Web of Science were searched for research related to Age-Related macular degeneration (AMD), glaucoma, myopia, and diabetic retinopathy (DR). The search was conducted in August 2023. The number of cases and controls, the study's design, the analytical methods used, and the results of the metabolomics analysis were all extracted. Using the QUADOMICS tool, the quality of the studies included was evaluated, and metabolic pathways were examined for distinct metabolic profiles. We used MetaboAnalyst 5.0 to undertake pathway analysis of differential metabolites.RESULTS: Metabolomics studies included in this review consisted of 36 human studies (5 Age-related macular degeneration, 10 Glaucoma, 13 Diabetic retinopathy, and 8 Myopia). The most networked metabolites in AMD include glycine and adenosine monophosphate, while methionine, lysine, alanine, glyoxylic acid, and cysteine were identified in glaucoma. Furthermore, in myopia, glycerol, glutamic acid, pyruvic acid, glycine, cysteine, and oxoglutaric acid constituted significant metabolites, while glycerol, glutamic acid, lysine, citric acid, alanine, and serotonin are highly networked metabolites in cases of diabetic retinopathy. The common top metabolic pathways significantly enriched and associated with AMD, glaucoma, DR, and myopia were arginine and proline metabolism, methionine metabolism, glycine and serine metabolism, urea cycle metabolism, and purine metabolism.CONCLUSION: This review recapitulates potential metabolic biomarkers, networks and pathways in AMD, glaucoma, DR, and myopia, providing new clues to elucidate disease mechanisms and therapeutic targets. The emergence of advanced metabolomics techniques has significantly enhanced the capability of metabolic profiling and provides novel perspectives on the metabolism and underlying pathogenesis of these multifactorial eye conditions. The advancement of metabolomics is anticipated to foster a deeper comprehension of disease etiology, facilitate the identification of novel therapeutic targets, and usher in an era of personalized medicine in eye research.PMID:39193222 | PMC:PMC11347317 | DOI:10.3389/fmolb.2024.1403844

Front Plant Sci. 2024 Aug 13;15:1389379. doi: 10.3389/fpls.2024.1389379. eCollection 2024.ABSTRACTFlooding, as a natural disaster, plays a pivotal role in constraining the growth and development of plants. Flooding stress, including submergence and waterlogging, not only induces oxygen, light, and nutrient deprivation, but also alters soil properties through prolonged inundation, further impeding plant growth and development. However, hypoxia (or anoxia) is the most serious and direct damage to plants caused by flooding. Moreover, flooding disrupts the structural integrity of plant cell walls and compromises endoplasmic reticulum functionality, while hindering nutrient absorption and shifting metabolic processes from normal aerobic respiration to anaerobic respiration. It can be asserted that flooding exerts comprehensive effects on plants encompassing phenotypic changes, transcriptional alterations, protein dynamics, and metabolic shifts. To adapt to flooding environments, plants employ corresponding adaptive mechanisms at the phenotypic level while modulating transcriptomic profiles, proteomic characteristics, and metabolite levels. Hence, this study provides a comprehensive analysis of transcriptomic, proteomic, and metabolomics investigations conducted on flooding stress on model plants and major crops, elucidating their response mechanisms from diverse omics perspectives.PMID:39193215 | PMC:PMC11347887 | DOI:10.3389/fpls.2024.1389379

Front Plant Sci. 2024 Aug 13;15:1427688. doi: 10.3389/fpls.2024.1427688. eCollection 2024.ABSTRACTINTRODUCTION: Ascochyta blight (AB) caused by the necrotrophic fungus Ascochyta rabiei is one of the most significant diseases that limit the production of chickpea. Understanding the metabolic mechanisms underlying chickpea-A.rabiei interactions will provide important clues to develop novel approaches to manage this disease.METHODS: We performed metabolite profiling of the aerial tissue (leaf and stem) of two chickpea accessions comprising a moderately resistant breeding line (CICA1841) and a highly susceptible cultivar (Kyabra) in response to one of the highly aggressive Australian A. rabiei isolates TR9571 via non-targeted metabolomics analysis using liquid chromatography-mass spectrometry.RESULTS: The results revealed resistance and susceptibility-associated constitutive metabolites for example the moderately resistant breeding line had a higher mass abundance of ferulic acid while the levels of catechins, phthalic acid, and nicotinic acid were high in the susceptible cultivar. Further, the host-pathogen interaction resulted in the altered levels of various metabolites (induced and suppressed), especially in the susceptible cultivar revealing a possible reason for susceptibility against A.r abiei. Noticeably, the mass abundance of salicylic acid was induced in the aerial tissue of the susceptible cultivar after fungus colonization, while methyl jasmonate (MeJA) was suppressed, elucidating the key role of phytohormones in chickpea-A. rabiei interaction. Many differential metabolites in flavonoid biosynthesis, phenylalanine, Aminoacyl-tRNA biosynthesis, pentose and glucuronate interconversions, arginine biosynthesis, valine, leucine, and isoleucine biosynthesis, and alanine, aspartate, and glutamate metabolism pathways were up- and down-regulated showing the involvement of these metabolic pathways in chickpea-A. rabiei interaction.DISCUSSION: Taken together, this study highlights the chickpea - A. rabiei interaction at a metabolite level and shows how A. rabiei differentially alters the metabolite profile of moderately resistant and susceptible chickpea accessions and is probably exploiting the chickpea defense pathways in its favour.PMID:39193211 | PMC:PMC11347347 | DOI:10.3389/fpls.2024.1427688

Front Public Health. 2024 Aug 13;12:1401006. doi: 10.3389/fpubh.2024.1401006. eCollection 2024.ABSTRACTINTRODUCTION: Air pollution is a significant contributor to morbidity and mortality globally and has been linked to an increased risk of dementia. Previous studies within the Betula cohort in Northern Sweden have demonstrated associations between air pollution and dementia, as well as distinctive metabolomic profiles in dementia patients compared to controls. This study aimed to investigate whether air pollution is associated with quantitative changes in metabolite levels within this cohort, and whether future dementia status would modify this association.METHODS: Both short-term and long-term exposure to air pollution were evaluated using high spatial resolution models and measured data. Air pollution from vehicle exhaust and woodsmoke were analyzed separately. Metabolomic profiling was conducted on 321 participants, including 58 serum samples from dementia patients and a control group matched for age, sex, and education level, using nuclear magnetic resonance spectroscopy.RESULTS: No statistically significant associations were found between any metabolites and any measures of short-term or long-term exposure to air pollution. However, there were trends potentially suggesting associations between both long-term and short-term exposure to air pollution with lactate and glucose metabolites. Notably, these associations were observed despite the lack of correlation between long-term and short-term air pollution exposure in this cohort. There were also tendencies for associations between air pollution from woodsmoke to be more pronounced in participants that would later develop dementia, suggesting a potential effect depending on urban/rural factors.DISCUSSION: While no significant associations were found, the trends observed in the data suggest potential links between air pollution exposure and changes in lactate and glucose metabolites. These findings provide some new insights into the link between air pollution and metabolic markers in a low-exposure setting. However, addressing existing limitations is crucial to improve the robustness and applicability of future research in this area. The pronounced associations in participants who later developed dementia may indicate an influence of urban/rural factors, warranting further investigation.PMID:39193206 | PMC:PMC11348805 | DOI:10.3389/fpubh.2024.1401006

Expert Rev Gastroenterol Hepatol. 2024 Aug 28. doi: 10.1080/17474124.2024.2393180. Online ahead of print.ABSTRACTINTRODUCTION: Colorectal cancer (CRC) is one of the most deadly cancers on a global scale. Diagnosis of CRC is challenging and it is often detected at a late stage. Identification of relevant biomarkers could lead to the development of effective diagnostic methods for CRC.AREAS COVERED: We reviewed the literature on lipid (including exosomal) biomarkers that have the potential to become common, minimally invasive and effective diagnostic tools for CRC. We showed that differences in lipid levels (single compounds and entire panels) make it possible to classify patients into diseased or healthy groups, determine the stage of CRC, as well as accompanying inflammation and immune reactions associated with tumorigenesis. We also discussed exosomes which are important components of the tumor microenvironment that influence tumor progression and for which only a small number of studies were conducted so far in this area.EXPERT OPINION: A rapid development in the field of lipid-based biomarkers, including exosomal lipid biomarkers, is expected as growing evidence shows their potential application and good accuracy. However, one of the major issues that needs to be addressed within this topic is to translate findings into a noninvasive and versatile diagnostic test robustly validated in clinical conditions.PMID:39192805 | DOI:10.1080/17474124.2024.2393180

Alzheimers Dement. 2024 Aug 27. doi: 10.1002/alz.14194. Online ahead of print.ABSTRACTINTRODUCTION: Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early Alzheimer's disease (AD) pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify cerebrospinal fluid (CSF) biomarkers for AD-related central nervous system (CNS) pathophysiologic changes using tissue and fluids with early pathology, free of post mortem artifact.METHODS: We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes.RESULTS: AD pathology on biopsy correlates with CSF β-amyloid-42/40, neurofilament light chain (NfL), and phospho-tau-181(p-tau181)/β-amyloid-42, while several gene expression modules correlate with NfL. Proteomic analysis highlights seven core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease-relevant groups that correlate with biopsy data.DISCUSSION: As additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking.HIGHLIGHTS: AD CSF biomarkers correlate with CNS pathology and transcriptomic changes. Seven proteins correlate with CNS pathology and gene expression changes. Inflammatory and neuronal gene expression changes correlate with YKL-40 and NPTXR, respectively. CSF metabolomic analysis identifies pathways that correlate with biopsy data. Fatty acid metabolic pathways correlate with β-amyloid pathology.PMID:39192661 | DOI:10.1002/alz.14194

Curr Med Chem. 2024 Aug 26. doi: 10.2174/0109298673302394240823114448. Online ahead of print.ABSTRACTINTRODUCTION: In this study, the molecular mechanisms through which Lascorbate (Vitamin C) potentially treats Chronic Obstructive Pulmonary Disease (COPD) were identified. A non-targeted metabolomics analysis revealed metabolic disorders and significantly reduced levels of L-ascorbate in COPD patients compared to healthy subjects.METHOD: The COPD rat model was established by exposing them to Cigarette Smoke (CS). The L-ascorbate intervention reduced lung inflammation and histological damage in COPD rat models. Network pharmacology analysis revealed 280 common targets between L-ascorbic acid (drug) and COPD (disease), of which seven core targets were MMP3, MME, PCNA, GCLC, SOD2, EDN1, and EGF. According to molecular docking prediction, L-ascorbate had the highest affinity with EGF. Molecular dynamics simulation indicated relatively stable EGF and L-ascorbate complexes.RESULTS: The PI3K/AKT signaling pathway was significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analysis.CONCLUSION: Finally, the in vivo and in vitro experiments confirmed that L-ascorbate affected COPD by regulating the EGF/PI3K/AKT pathway. In summary, based on network pharmacology and molecular docking analyses, this study revealed that L-ascorbate affects COPD development by regulating the PI3K/AKT signaling pathway through EGF, and thus contributes to the understanding and clinical application of Lascorbate in the treatment of COPD.PMID:39192652 | DOI:10.2174/0109298673302394240823114448

Sci Total Environ. 2024 Aug 25:175772. doi: 10.1016/j.scitotenv.2024.175772. Online ahead of print.ABSTRACTIn this study, sophorolipids (SLs)-modified biochar (BC-SLs) was used to enhance the bioremediation of petroleum hydrocarbons (PHs) contaminated soil. The biodegradation rate of petroleum hydrocarbons (PHs) by BC-SLs and BC treatments were 62.86 % and 52.64 % after 60 days of remediation experiments, respectively, higher than non-biochar treatment group (24.09 %). The metagenomic analysis showed that the abundance of petroleum-degrading bacteria Actinobacteria and Proteobacteria were increased by 3.8 % and 5.3 %, respectively in BC-SLs treatment, and the abundance of functional genes for PHs degradation, such as alkB, nidA and pcaG, were significantly increased by 12.85 %, 30.08 % and 21.01 %, respectively. The metabolomic analysis showed that BC-SLs facilitated the metabolic process of PHs, the microbial metabolism of petroleum hydrocarbons (PHs) became more active. Fatty acid degradation and polycyclic aromatic hydrocarbons (PAHs) degradation were up-regulated, indicating the promoting effect of the BC-SLs for PHs metabolism. The combined metagenomic and metabolomic analysis demonstrated the strong positive correlations between PHs metabolites and PHs-degrading bacteria, such as lauric acid vs. Actinobacteria, benzoic vs. Proteobacteria. The strong positive correlations between PHs metabolites and PHs-degrading genes were also observed, such as o-ehyltoluene vs. nahD, 4-isopropylbenzoic acid vs. etbAa. The modification of biochar with SLs increased the oxygen-containing functional groups on the surface of biochar. Meanwhile, the emulsification and solubilization of SLs promoted the bioavailability of PHs. The effects of BC-SLs on the nitrogen cycle during PHs remediation showed that it facilitated the accumulation of nitrogen-fixing genes, promoted nitrification but inhibited denitrification process. This study confirms that the application of BC-SLs is an effective remediation of PHs contamination and a sustainable method for controlling agricultural waste resources.PMID:39191326 | DOI:10.1016/j.scitotenv.2024.175772

Phytomedicine. 2024 Aug 22;134:155955. doi: 10.1016/j.phymed.2024.155955. Online ahead of print.ABSTRACTBACKGROUND: Fever is one of the main pathophysiological reactions that occurs during the acute phase of various diseases. Excessive body temperature can lead to various adverse consequences such as brain tissue damage and abnormal immune responses. Phillyrin (Phr) is the main active ingredient in Forsythia suspensa (Thunb.) Vahl (Lian Qiao) and has antipyretic effects; however, its antipyretic mechanism of action remains unclear.PURPOSE: This study aimed to explore the antipyretic mechanisms of Phr and provide a new treatment plan for fever.METHODS: The antipyretic effects of Phr were evaluated using a mouse model of pneumonia fever. The main metabolites of Phr involved in its antipyretic function were identified using a mitochondrial temperature-sensitive probe. Further synthesis of the main metabolite, phillygenin (Phg), an alkynylated probe, was performed, and chemical proteomics was used to capture and analyze its direct target for antipyretic effects. The mechanism of action of Phg and its antipyretic targets was explored using metabolomics and various molecular biology methods.RESULTS: Phr showed significant antipyretic and anti-inflammatory effects in a mouse model of lipopolysaccharide-induced fever. Phg reversibly targeted the nicotinamide adenine dinucleotide (NAD+) binding domain of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), malate dehydrogenase 2 (MDH2), and isocitrate dehydrogenase 2 (IDH2) to inhibit their enzymatic activity. In-depth analysis of cellular metabolomics and mitochondrial stress testing indicated that inhibition of GAPDH, MDH2, and IDH2 enzyme activity by Phg led to a decrease in cellular energy supply and heat production regulated by glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation signaling pathways. Phg specifically targeted macrophages and inhibited LPS-induced macrophage activation by downregulating GAPDH enzyme activity, thereby exerting anti-inflammatory effects. In vivo experiments also confirmed that the antipyretic effect of Phr in LPS-induced fever model mice was related to its main metabolites, Phg and Phg-sulfonate (Phg-S), which directly targeted the NAD+ binding domain of GAPDH, IDH2, and MDH2, inhibiting the activity of these enzymes, thereby reducing energy supply and regulating febrile-related inflammatory factors.CONCLUSION: This study reported for the first time that the antipyretic effect of Phr is produced by targeting GAPDH, IDH2, and MDH2 to regulate energy supply and febrile-related inflammatory factors through its main metabolites Phg and Phg-S. This study not only provides potential drugs for fever treatment but also provides new ideas for improving clinical fever treatment plans.PMID:39191169 | DOI:10.1016/j.phymed.2024.155955

Ecotoxicol Environ Saf. 2024 Aug 26;284:116925. doi: 10.1016/j.ecoenv.2024.116925. Online ahead of print.ABSTRACTMicroplastic (MP) are an emerging environmental pollutant, which has toxic effects on organisms, and it has received extensive attention currently. Studying the transcriptomic and metabolic responses of mice to nanoplastic-contaminated water is critical for understanding molecular-level toxicity of nanoplastics (NPs), but there are few studies on this topic. To analyze the effects of different concentrations of polystyrene (PS) nanoplastic-contaminated water on mice at the transcriptome and metabolism of spleens to study the molecular toxicity. Here, testing of histopathology of spleen of female mice was performed after drinking water containing 0.1 μm PS-NPs (1 mg/mL and 50 mg/mL) at different concentrations for 49 days, respectively. The spleen tissue samples were subjected to metabolome and transcriptome sequencing. Four differentially expressed genes were randomly chosen for qRT-PCR to confirm the correctness of transcriptome sequencing. Common Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that a large number of differential genes and differential metabolites mainly focused on immune, inflammation, neurodegenerative disease, cardiovascular disease, nervous, etc. in the organism systems module; lipid, amino acid, taurine and hypotaurine metabolisms, etc. in the metabolism module; signaling translation, signaling molecules and interaction, and neuroactive ligand-receptor interaction, etc. in the environmental information processing. The results showed that pathway analysis at transcriptome and metabolome levels confirmed that the immune system of mice was affected after drinking water contaminated with polystyrene nanoplastics.PMID:39191138 | DOI:10.1016/j.ecoenv.2024.116925