PubMed

J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Nov 20;1250:124385. doi: 10.1016/j.jchromb.2024.124385. Online ahead of print.ABSTRACTMS imaging (MSI) is a powerful technique for investigating the spatial distribution of metabolites in complex biological samples. However, due to the absence of liquid chromatography (LC) separation in routine MSI analysis, matrix effect is obvious and isomers identification remains challenging. To overcome these shortcomings of classical MSI tools (e.g., DESI-MSI and MALDI-MSI) for isomer differentiation and insufficient datapoints for quantification, online extraction-liquid chromatogram-hybrid triple quadrupole-time-of-flight mass spectrometry (OLE-LC-Qtof-MS) platform has been developed for spatial metabolome. As a proof-of-concept, two species flowers namely Forsythia viridissima (FV) and Jasminum nudiflorum (JN) that bloom in early spring were collected, dried, and cut into small pieces (1.0 mm × 1.0 mm). All pieces successively underwent OLE-LC-Qtof-MS measurements. As a result, 46 and 41 metabolites were observed and identified from FV and JN petals, respectively. Particularly, each compound corresponded to a chromatographic peak and isomeric differentiation was achieved amongst a set of chlorogenic acid derivatives. The peak areas of high intensity metabolites were aligned and combined within either species. The datasets were individually converted into heatmaps for all compounds, 87 ones in total, and each grid of any heatmap was assigned to the original location in the petal. Then, the spatial-resolved distribution style of each compound crossing the petal was reflected by the re-organized heatmap bearing the petal shape. As expected, regio-specific occurrence and accumulation were observed for several compounds, particularly among the chlorogenic acid isomers. Above all, OLE-LC-Qtof-MS is an alternative tool for spatial-resolved metabolome attributing to the advantages of isomeric separation and reliable quantification.PMID:39603011 | DOI:10.1016/j.jchromb.2024.124385

Food Chem. 2024 Nov 22;466:142199. doi: 10.1016/j.foodchem.2024.142199. Online ahead of print.ABSTRACTDouchi is traditional Chinese condiment. In this study, electronic sense, GC-IMS and metabolomics were combined to analyse the changes in flavour profiles and metabolites of Yangjiang douchi at different fermentation stages. The results showed that umami was the primary taste characteristic of douchi. Aldehydes, esters, and ketones representing the predominant flavour compounds. Metabolomic analysis identified 13 compounds as key differential metabolites, which were mainly enriched in the arachidonic acid metabolic pathway in lipid metabolism. The correlation analysis indicated that heptanal, hexanal, phenyl acetaldehyde, benzene acetaldehyde and abhexone may be the key aroma substances during fermentation. The major free fatty acids that may act as key flavour precursors are palmitic acid, oleic acid and linoleic acid. This study provides a scientific basis for the industrial regulation of Yangjiang douchi fermentation.PMID:39602999 | DOI:10.1016/j.foodchem.2024.142199

Clin Exp Allergy. 2024 Nov 27. doi: 10.1111/cea.14607. Online ahead of print.NO ABSTRACTPMID:39602883 | DOI:10.1111/cea.14607

Sci Transl Med. 2024 Nov 27;16(775):eadk0636. doi: 10.1126/scitranslmed.adk0636. Epub 2024 Nov 27.ABSTRACTIn liver transplantation, donor livers are typically stored in a preservation solution at 4°C for up to 12 hours. However, this short preservation duration can lead to various issues, such as suboptimal donor-recipient matching and limited opportunities for organ sharing. Previous studies have developed a long-term preservation method called supercooling liver preservation (SLP) to address these issues. However, in this study using a rat model, we observed that long-term SLP led to more severe liver damage compared with clinically prevalent traditional static cold storage (SCS) for durations less than 8 hours. To understand the potential mechanism of SLP-induced liver injury, we conducted an integrative metabolomic, transcriptomic, and proteomic analysis. We identified the PDE3B-cAMP-autophagy pathway as a key determinant of SLP-induced liver injury. Specifically, we found that PDE3B was elevated during SLP, which promoted a reduction of cAMP metabolites, triggering an AMPK-dependent autophagy process that led to liver injury in rats. We found that blocking the reduction in cAMP using the PDE3B inhibitor cilostamide inhibited autophagy and substantially ameliorated liver injury during 48-hour SLP in rat livers. Furthermore, we validated the effectiveness of cilostamide treatment in preventing liver injury in pig and human liver 48-hour SLP models. In summary, our results reveal that metabolic reprogramming involving the PDE3B-cAMP-autophagy axis is the key determinant of liver injury in long-term SLP and provide an early therapeutic strategy to prevent liver injury in this setting.PMID:39602509 | DOI:10.1126/scitranslmed.adk0636

Chin Med J (Engl). 2024 Nov 18. doi: 10.1097/CM9.0000000000003360. Online ahead of print.ABSTRACTBACKGROUND: Endoscopic sphincterotomy (EST) is widely used to treat common bile duct stones (CBDS); however, long-term studies have revealed the increasing incidence of recurrent CBDS after EST. Loss of sphincter of Oddi function after EST was the main cause of recurrent CBDS. Reparation of the sphincter of Oddi is therefore crucial. This study aims to investigate the effectiveness and safety of endoclip papilloplasty (ECPP) for repairing the sphincter of Oddi and elucidate its mechanism.METHODS: Eight healthy Bama minipigs were randomly divided into the EST group and the ECPP group at a 1:1 ratio, and bile samples were collected before endoscopy and 6 months later. All minipigs underwent transabdominal biliary ultrasonography for the diagnosis of cholelithiasis 6 months after endoscopy. The biliary microbiota composition and alpha and beta diversity were analyzed by 16S rRNA gene sequencing. Differential metabolites were analyzed by bile acid metabolomics to explore the predictive indicators of cholelithiasis.RESULTS: Three minipigs were diagnosed with cholelithiasis in the EST group, while none in the ECPP group showed cholelithiasis. The biliary Firmicutes/Bacteroidota (F/B) ratio was increased after EST and decreased after ECPP. The Chao1 and observed species index significantly decreased 6 months after EST (P = 0.017 and 0.018, respectively); however, the biliary α-diversity was similar before and 6 months after ECPP. The β-diversity significantly differed in the EST group before and 6 months after EST, as well as in the ECPP group before and 6 months after ECPP (analysis of similarities [ANOSIM]: R = 0.917, P = 0.040; R = 0.740, P = 0.035; respectively). Glycolithocholic acid (GLCA) and taurolithocholic acid (TLCA) accumulated in bile 6 months after EST.CONCLUSIONS: ECPP has less impact on the biliary microenvironment than EST and prevents duodenobiliary reflux by repairing the sphincter of Oddi. The bile levels of GLCA and TLCA may be used to predict the risk of cholelithiasis.PMID:39602330 | DOI:10.1097/CM9.0000000000003360

Proc Natl Acad Sci U S A. 2024 Dec 3;121(49):e2419175121. doi: 10.1073/pnas.2419175121. Epub 2024 Nov 27.ABSTRACTWhile hydroxyl radical is commonly named as the Fenton product responsible for DNA and RNA damage in cells, here we demonstrate that the cellular reaction generates carbonate radical anion due to physiological bicarbonate levels. In human and Escherichia coli models, their transcriptomes were analyzed by RNA direct nanopore sequencing of ribosomal RNA and chromatography coupled to electrochemical detection to quantify oxidation products in order to follow the bicarbonate dependency in H2O2-induced oxidation. These transcriptomic studies identified physiologically relevant levels of bicarbonate focused oxidation on the guanine base favorably yielding 8-oxo-7,8-dihydroguanine (OG). In human cells, the bicarbonate-dependent oxidation was further analyzed in the metabolome by mass spectrometry, and a glycosylase-dependent qPCR assay to quantify oxidation sites in telomeres. These analyses further identify guanine as the site of oxidation when bicarbonate is present upon H2O2 exposure. Labile iron as the catalyst for forming carbonate radical anion was demonstrated by repeating the bicarbonate-dependent oxidations in cells experiencing ferroptosis, which had a >fivefold increase in redox-active iron, to find enhanced overall guanine-specific oxidation when bicarbonate was present. The complete profiling of nucleic acid oxidation in the genome, transcriptome, and metabolome supports the conclusion that a cellular Fe(II)-carbonate complex redirects the Fenton reaction to yield carbonate radical anion. Focusing H2O2-induced oxidative modification on one pathway is consistent with the highly evolved base excision repair suite of enzymes to locate G-oxidation sites for repair and gene regulation in response to oxidative stress.PMID:39602264 | DOI:10.1073/pnas.2419175121

Rev Endocr Metab Disord. 2024 Nov 27. doi: 10.1007/s11154-024-09934-5. Online ahead of print.ABSTRACTGestational diabetes mellitus (GDM) is a common complication of pregnancy that has short- and long-term adverse effects. Therefore, further exploration of the pathophysiology of GDM and related biomarkers is important. In this study, we performed a systematic review and meta-analysis to investigate the associations between metabolites in blood detected via metabolomics techniques and the risk of GDM and to identify possible biomarkers for predicting the occurrence of GDM. We retrieved case‒control and cohort studies of metabolomics and GDM published in PubMed, Embase, and Web of Science through March 29, 2024; extracted metabolite concentrations, odds ratios (ORs), or relative risks (RRs); and evaluated the integrated results with metabolites per-SD risk estimates and 95% CIs for GDM. We estimated the results via the random effects model and the inverse variance method. Our study is registered in PROSPERO (CRD42024539435). We included a total of 28 case‒control and cohort studies, including 17,370 subjects (4,372 GDM patients and 12,998 non-GDM subjects), and meta-analyzed 67 metabolites. Twenty-five of these metabolites were associated with GDM risk. Some amino acids (isoleucine, leucine, valine, alanine, aspartate, etc.), lipids (C16:0, C18:1n-9, C18:1n-7, lysophosphatidylcholine (LPC) (16:0), LPC (18:0), and palmitoylcarnitine), and carbohydrates and energy metabolites (glucose, pyruvate, lactate, 2-hydroxybutyrate, 3-hydroxybutyrate) were discovered to be associated with increased GDM risk (hazard ratio 1.06-2.77). Glutamine, histidine, C14:0, and sphingomyelin (SM) (34:1) were associated with lower GDM risk (hazard ratio 0.75-0.84). These findings suggest that these metabolites may play essential roles in GDM progression, and serve as biomarkers, contributing to the early diagnosis and prediction of GDM.PMID:39602052 | DOI:10.1007/s11154-024-09934-5

Geroscience. 2024 Nov 27. doi: 10.1007/s11357-024-01453-0. Online ahead of print.ABSTRACTComplex lipids, essential components in biological processes, exhibit conserved age-related changes that alter membrane properties and cellular functions and are implicated as biomarkers and contributors to longevity and age-related diseases. While physical activity alleviates age-related comorbidities and physical impairments, comprehensive exploration of the underlying biological mechanisms, particularly at the level of complex lipids, remains limited. However, clinical studies suggest that physical activity may counteract these age-related lipidomic changes, presenting a promising avenue for intervention. We performed lipidomic profiling of plasma from an extensively characterized cohort of young and aged individuals. Annotating 1446 unique lipid species across 24 lipid classes, we found the most prominent difference in older adults was an accumulation of triacylglycerols (TGs), with lower physical activity levels associated with higher TG levels in plasma and reduced physical functionality. Remarkably, lipid species in the TG class did not accumulate uniformly. Rather, our study unveiled a negative correlation between higher physical activity levels and TGs with shorter chain lengths and more double bonds in this demographic. Overall, our research highlights that plasma TG length and saturation level can help mark healthy aging groups in humans. These findings deepen our understanding of how aging affects complex lipids and the influence of physical activity on this process.PMID:39601998 | DOI:10.1007/s11357-024-01453-0

J Nat Prod. 2024 Nov 27. doi: 10.1021/acs.jnatprod.4c00740. Online ahead of print.ABSTRACTMarine microorganisms are a treasure trove of natural products, especially those in extreme marine environments, which may produce novel natural products. Herein, biosynthetic gene cluster analysis combined with an integrated metabolomic strategy incorporating matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), nuclear magnetic resonance (NMR), and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) based Global Natural Products Social Molecular Networking (GNPS) was used to discover new compounds from the Mariana trench anemone-derived fungus Hamigera ingelheimensis MSC5. As a result, 12 new cyclic pentapeptides, avellanins D-O (1-12), were isolated, together with a known cyclic pentapeptide avellanin C (13). All the structures and absolute configurations were elucidated using NMR, mass spectrometry, X-ray diffraction analysis, and Marfey's method. A plausible biosynthetic pathway for the avellanins was proposed based on the gene cluster analysis of H. ingelheimensis MSC5. Bioassay revealed that compound 6 exhibited potent antimalarial activity with an IC50 value of 0.19 ± 0.09 μM.PMID:39601657 | DOI:10.1021/acs.jnatprod.4c00740

Rapid Commun Mass Spectrom. 2025 Feb 15;39(3):e9946. doi: 10.1002/rcm.9946.ABSTRACTBACKGROUND: Zhenzhu Tongluo pills (ZZTL) have been utilized for the treatment of neurobrucellosis (NB) in the Inner Mongolia region of China. However, the specific mechanism underlying the neuroprotective effects of ZZTL in NB remains insufficiently explored. Therefore, this study aimed to analyze the metabolite profiles across different groups to identify potential biomarkers for the diagnosis and treatment of NB.METHODS: LC-MS analysis was used to screen differential metabolites in cerebrospinal fluid (CSF) samples from control subjects, NB patients, and NB patients undergoing ZZTL therapy.RESULTS: We identified 225 common metabolites across two comparison groups (NB vs. control group and NB + ZZTL vs. NB group). Among these metabolites, 138 were downregulated, and 87 were upregulated in the NB group compared to the control group, while the levels of these metabolites were reversed by ZZTL therapy. Creatinine exhibited the highest VIP score in both comparison groups, with elevated levels observed in CSF samples from NB patients compared to controls; however, its levels were reduced following ZZTL therapy. Additionally, hypoxanthine and uric acids levels were also increased in CSF samples from NB patients, indicating dysregulation of purine metabolism in NB; however, these changes were reversed by ZZTL. Furthermore, pantothenic acid (vitamin B5) and niacinamide (vitamin B3) levels were decreased in CSF samples from NB patients, suggesting a potential link between NB and vitamin B3 and B5 deficiency; however, these changes were reversed by ZZTL.CONCLUSION: Collectively, CSF metabolomics may effectively differentiate NB patients from control subjects, providing valuable insights for NB diagnosis and treatment.PMID:39601633 | DOI:10.1002/rcm.9946

Plant Biol (Stuttg). 2024 Nov 27. doi: 10.1111/plb.13741. Online ahead of print.ABSTRACTIsoprenoids comprise the largest group of plant specialized metabolites. 1-deoxy-D-xylulose-5-phosphate synthase (DXS) is one of the major rate-limiting enzymes in their biosynthesis. The DXS family expanded structurally and functionally during evolution and is believed to have significantly contributed to metabolic complexity and diversity in plants. This family has not yet been studied in Physcomitrium patens or other bryophytes. Here, we assessed the degree of evolutionary expansion in the DXS family in bryophytes and, more specifically, in P. patens using phylogenetic analysis. Transcriptome profiling was applied to investigate tissue-specific, developmental, and environmental responses, such as salt stress, in the DXS family. Moreover, the effect of salt stress on terpenoid biosynthesis was monitored through metabolomics. The phylogenetic analysis of DXS revealed that a structural expansion occurred in bryophytes, but not in P. patens. Functional complementation assay revealed functional activity in all four copies. Comparative transcriptomics showed tissue- and condition-specific divergence in the expression profiles of DXS copies and demonstrated specific stress responses for PpDXS1D, particularly to salt stress. These findings coincide with increased flux in the pathway towards downstream metabolites under salt stress. Additionally, co-expression network analysis revealed significant differences between the co-expressed genes of the DXS copies and illustrated enrichment of stress-responsive genes in the PpDXS1D network. These results suggest that the DXS family in P. patens is conserved but undergoes differential transcriptional regulation, which might allow P. patens to fine-tune DXS levels under different conditions, such as abiotic stress.PMID:39601615 | DOI:10.1111/plb.13741

Nutrients. 2024 Nov 6;16(22):3804. doi: 10.3390/nu16223804.ABSTRACTBACKGROUND: Alterations in maternal lipid metabolism have been elucidated by several studies in relation to macrosomia. However, the lipidome of the intrauterine compartment associated with macrosomia, particularly in early pregnancy, remains largely unknown.OBJECTIVES: (1) To compare the lipidomic profile of early 2nd trimester amniotic fluid (AF) of healthy mothers with normal body mass index who gave birth to large-for-gestational age (LGA) versus appropriate-for-gestational age (AGA) infants; and (2) to examine if insulin and glucose concentrations in AF were associated with the AF lipidomic profile.METHODS: In this nested case-control study, bio-banked AF samples were collected from pregnant women undergoing routine amniocentesis at 12-22 weeks of gestation. A subsample of 15 LGA infants (cases) were contrasted with 15 AGA infants (controls). An untargeted lipidomics analysis using liquid chromatography quadrupole time-of-flight mass spectrometry was conducted. Univariate and multivariate statistical analyses (principal component analysis and partial least-squares discriminant analysis) were used to extract differentially abundant (DA) features with high variable importance in projection (VIP) scores.RESULTS: LGA AF was characterized by elevations of 30 phosphatidic acid species. Among other DA features, sphingomyelin (SM 14:0;O2/20:1) had the highest VIP score and was markedly elevated in LGA AF. Neither insulin nor glucose was associated with 2nd trimester AF lipidomic profiles in these healthy, normal-weight mothers.CONCLUSION: These findings provide evidence of early dysregulated lipid metabolism in healthy, normal-weight mothers with LGA infants.PMID:39599591 | DOI:10.3390/nu16223804

Food Funct. 2024 Nov 27. doi: 10.1039/d4fo01878h. Online ahead of print.ABSTRACTEmerging evidence suggests that Parkinson's disease (PD) is strongly associated with altered gut microbiota. The present study investigated the prophylactic effects of anthocyanins (ACNs) from Lycium ruthenicum Murray on Parkinson's disease based on microbiomics and metabolomics. In this study, sixty-six adult male C57BL/6J mice were randomized into the control group, model group, positive drug (Madopar) group, and low-, medium- and high-dose ACN groups. Behavioral experiments were conducted and pathological indicators were determined. Fresh feces were collected for microbiomic analysis using 16S rRNA sequencing. Urine and serum were analyzed by the UPLC-MS method for untargeted metabolomics. The results demonstrated that ACNs ameliorated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor deficits, dopamine neuron death, and glial cell activation, while 100 mg kg-1 and 200 mg kg-1 ACNs were more neuroprotective than 50 mg kg-1. Mice with PD-like phenotypes have an altered gut microbiota composition, and ACNs may regulate this disorder by causing an increase in Firmicutes/Bacteroidota ratio and abundance of norank_f__Eubacterium_coprostanoligenes_group and a decrease in the abundance of norank_f__Muribaculaceae, Coriobacteriaceae_UCG-002 and Parvibacter. Furthermore, ACNs increased 14 urinary key metabolites such as DIMBOA-Glc and tauroursodeoxycholic acid, decreased N,N-dimethyllysine, and increased 12 serum key metabolites such as 1-methylguanine and 1-nitro-5-glutathionyl-6-hydroxy-5,6-dihydronaphthalene, and decreased lamivudine-monophosphate and 5-butyl-2- methylpyridine. The present study reveals that ACNs are protective against MPTP-induced PD in mice by modulating anti-inflammatory flora in the gut and endogenous metabolites in serum/urine, and the key mechanisms may be related to Coriobacteriaceae_UCG-002 and glycerophospholipid metabolic pathways. Our findings provide new insights into the pathogenesis and potential treatment of Parkinson's disease.PMID:39601125 | DOI:10.1039/d4fo01878h

Front Endocrinol (Lausanne). 2024 Nov 12;15:1443330. doi: 10.3389/fendo.2024.1443330. eCollection 2024.ABSTRACTBACKGROUND: Recently, serum metabolites have shown potential in predicting survival outcomes and may be related to the pathogenesis of prostate cancer. Nevertheless, the precise impact concerning the genetic effect of metabolites on prostate cancer risk remains obscure. In this context, we conducted a Mendelian randomization (MR) study aiming to explore the causality between genetically determined metabolites and the risk of prostate cancer.METHODS: We conducted a two-sample MR analysis aiming to identify the underlying metabolites associated with prostate cancer. Exposure information was obtained from the largest metabolome-based genome-wide association (GWAS) data containing 7,824 Europeans. Genome-wide association analysis was utilized to detect instrumental variables (IVs) for metabolites. We applied the inverse-variance weighted (IVW) approach as the primary method, and to augment the reliability and robustness of our findings, additional analysis methods encompassing weighted median, MR-Egger, and leave-one-out analysis were utilized. MR-Egger intercept test was implemented to explore the pleiotropy. Cochran's Q test was utilized to quantify the degree of heterogeneity. Additionally, we performed metabolic pathway analysis and single-cell RNA sequencing analysis.RESULTS: We found that three serum metabolites were causally associated with prostate cancer after utilizing rigorous screening standards. Utilizing single nucleotide polymorphisms as IVs, a 1-SD increase in fructose was associated with 77% higher risk of prostate cancer (OR:1.77, 95%CI: 1.05-2.97, PIVW=0.031), a 1-SD increase in N1-methyl-3-pyridone-4-carboxamide was associated with 29% higher risk of prostate cancer (OR:1.29, 95%CI: 1.05-1.58, PIVW=0.017), and a 1-SD increase in 12-hydroxyeicosatetraenoate (12-HETE) was associated with 18% higher risk of prostate cancer (OR:1.18, 95%CI: 1.07-1.31, PIVW=0.0008). Metabolites that were causally linked to the risk of prostate cancer were mainly enriched in the valine, leucine and isoleucine biosynthesis pathway (P=0.026) and the nicotinate and nicotinamide metabolism pathway (P=0.048).CONCLUSIONS: Our MR analysis provided suggestive evidence supporting the causal relationships between three identified serum metabolites and prostate cancer, necessitating further investigation to elucidate the underlying mechanisms through which these blood metabolites and metabolic pathways may impact the initiation and progression of prostate cancer.PMID:39600951 | PMC:PMC11590024 | DOI:10.3389/fendo.2024.1443330

Front Endocrinol (Lausanne). 2024 Nov 12;15:1409079. doi: 10.3389/fendo.2024.1409079. eCollection 2024.ABSTRACTBACKGROUND: The pathological and physiological characteristics between HBsAg-positive HBV infection and occult hepatitis B infection (OBI) are currently unclear. This study aimed to explore the immune microenvironment in the peripheral circulation of OBI patients through integration of proteomic and metabolomic sequencing, and to identify molecular biomarkers for clinical diagnosis of HBsAg-positive HBV and OBI.METHODS: This research involved collection of plasma from 20 patients with OBI (negative for HBsAg but positive for HBV DNA, with HBV DNA levels < 200 IU/mL), 20 patients with HBsAg-positive HBV infection, and 10 healthy individuals. Mass spectrometry-based detection was used to analyze the proteome, while nuclear magnetic resonance spectroscopy was employed to study the metabolomic phenotypes. Differential molecule analysis, pathway enrichment and functional annotation, as well as weighted correlation network analysis (WGCNA), were conducted to uncover the characteristics of HBV-related liver disease. Prognostic biomarkers were identified using machine learning algorithms, and their validity was confirmed in a larger cohort using enzyme linked immunosorbent assay (ELISA).RESULTS: HBsAg-positive HBV individuals showed higher ALT levels (p=0.010) when compared to OBI patients. The influence of HBV infection on metabolic functions and inflammation was evident through the analysis of distinct metabolic pathways in HBsAg-positive HBV and OBI groups. Tissue tracing demonstrated a connection between Kupffer cells and HBsAg-positive HBV infection, as well as between hepatocytes and OBI. Immune profiling revealed the correlation between CD4 Tem cells, memory B cells and OBI, enabling a rapid response to infection reactivation through cytokine secretion and antibody production. A machine learning-constructed and significantly expressed molecule-based diagnostic model effectively differentiated HBsAg-positive and OBI groups (AUC values > 0.8). ELISA assay confirmed the elevation of FGB and FGG in OBI samples, suggesting their potential as biomarkers for distinguishing OBI from HBsAg-positive infection.CONCLUSIONS: The immune microenvironment and metabolic status of HBsAg-positive HBV patients and OBI patients vary significantly. The machine learning-based diagnostic model described herein displayed impressive classification accuracy, presenting a non-invasive means of differentiating between OBI and HBsAg-positive HBV infections.PMID:39600945 | PMC:PMC11588476 | DOI:10.3389/fendo.2024.1409079

Front Plant Sci. 2024 Nov 12;15:1461442. doi: 10.3389/fpls.2024.1461442. eCollection 2024.ABSTRACTCamellia japonica 'High Fragrance' is a camellia hybrid known for its unique and intense floral scent. The current understanding of the dynamic changes in its fragrance and the underlying mechanisms are still limited. This study employed a combination of metabolomic and transcriptomic approaches to reveal the characteristics of the metabolites involved in the remarkable fragrance of this camellia and their biosynthetic mechanisms along three flower developmental stages (flower bud, initial bloom, and full bloom). Among the 349 detected volatile organic compounds (VOCs), the majority were terpenes (57, 16.33%) and esters (53, 15.19%). Of these, 136 VOCs exhibited differential accumulation over time. Transcriptomic data from floral organs at different flowering stages identified 56,303 genes, with 13,793 showing significant differential expression. KEGG enrichment analysis revealed 57, 91, and 33 candidate differential genes related to the biosynthesis of terpenes, phenylpropanoids, and fatty acid derivatives, respectively. This indicates that terpenes, esters, and their related synthetic genes might play a crucial role in the formation of 'High Fragrance' characteristics. During the entire flowering process, the majority of genes exhibited an elevated expression pattern, which correlated with the progressive accumulation of VOCs. Interestingly, the expression patterns of the differentially expressed genes in the mevalonate (MVA) and 2-C-methyl-D-erythritol 4-phosphate (MEP) pathways, associated with terpene synthesis, showed opposite trends. A transcriptional-metabolic regulatory network linking terpenoid compounds, related synthetic enzymes, and potential transcription factors could be outlined for 'High Fragrance' camellia, thus providing a theoretical basis for further exploring these events and breeding more fragrant camellias.PMID:39600898 | PMC:PMC11588446 | DOI:10.3389/fpls.2024.1461442

J Inflamm Res. 2024 Nov 22;17:9407-9422. doi: 10.2147/JIR.S488638. eCollection 2024.ABSTRACTOBJECTIVE: This study aimed to investigate the role of immune inflammation in recurrent spontaneous abortions (RSA).METHODS: In this study, decidua tissues from 12 patients were collected. These included six individuals with RSA in the RSA group and six in the control group. The differences in gene and metabolite expression in the decidua of the placenta between normal pregnancies and patients with RSA were compared using transcriptomic and metabolomic analyses. The differentially expressed genes and metabolites were further analyzed through functional enrichment analysis using high-throughput sequencing technology.RESULTS: There was a significant upregulation of genes associated with immunity and inflammation in the RSA group compared to the control group. The TNF signaling pathway was upregulated in the RSA group. Inflammatory mediators were expressed at higher levels in the RSA group, and arachidonic acid metabolism was the most significant differential metabolite set. The regulation of inflammatory mediators of transient receptor potential (TRP) channels were enriched in RSA cases. The integrated analysis of the data further suggests that the immune-inflammatory response might be an important factor in RSA. The expression levels of genes related to inflammation and hypoxia in tissues from patients with RSA were verified using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and this revealed that the expression of MARK10 and TNFAIP3 genes was significantly upregulated in samples from RSA patients compared to normal tissues.CONCLUSION: The findings suggest a strong association between immune-related inflammation and RSA. Addressing metabolic and inflammatory aspects in patients with RSA may potentially help enhance pregnancy outcomes.PMID:39600677 | PMC:PMC11590633 | DOI:10.2147/JIR.S488638

Ther Adv Musculoskelet Dis. 2024 Nov 25;16:1759720X241299535. doi: 10.1177/1759720X241299535. eCollection 2024.ABSTRACTBACKGROUND: Osteoarthritis (OA) is a common degenerative joint disease that poses a significant global healthcare challenge due to its complexity and limited treatment options. Advances in metabolomics have provided insights into OA by identifying dysregulated metabolites and their connection to altered signaling pathways. However, a comprehensive understanding of these biomarkers in OA is still required.OBJECTIVES: This systematic review aims to identify metabolomics biomarkers associated with dysregulated signaling pathways in OA, using data from various biological samples, including in vitro models, animal studies, and human research.DESIGN: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.DATA SOURCES AND METHODS: Data were gathered from literature published between August 2017 and May 2024, using databases such as "PubMed," "Scopus," "Web of Science," and "Google Scholar." Studies were selected based on keywords like "metabolomics," "osteoarthritis," "amino acids," "molecular markers," "biomarkers," "diagnostic markers," "inflammatory cytokines," "molecular signaling," and "signal transduction." The review focused on identifying key metabolites and their roles in OA-related pathways. Limitations include the potential exclusion of studies due to keyword selection and strict inclusion criteria.RESULTS: The meta-analysis identified dysregulated metabolites and associated pathways, highlighting a distinct set of related metabolites consistently altered across the studies analyzed. The dysregulated metabolites, including amino acids, lipids, and carbohydrates, were found to play critical roles in inflammation, oxidative stress, and energy metabolism in OA. Metabolites such as alanine, lysine, and proline were frequently linked to pathways involved in inflammation, cartilage degradation, and apoptosis. Key pathways, including nuclear factor kappa B, mitogen-activated protein kinase, Wnt/β-catenin, and mammalian target of rapamycin, were associated with changes in metabolite levels, particularly in proinflammatory lipids and energy-related compounds.CONCLUSION: This review reveals a complex interplay between dysregulated metabolites and signaling pathways in OA, offering potential biomarkers and therapeutic targets. Further research is needed to explore the molecular mechanisms driving these changes and their implications for OA treatment.PMID:39600593 | PMC:PMC11590150 | DOI:10.1177/1759720X241299535

Research (Wash D C). 2024 Nov 26;7:0539. doi: 10.34133/research.0539. eCollection 2024.ABSTRACTBackground: Clear cell renal cell carcinoma (ccRCC) is a prevalent malignant tumor of the urinary system. While tyrosine kinase inhibitors (TKIs) are currently the first-line treatments for advanced/metastatic ccRCC, patients often develop resistance after TKI therapy. Lipid metabolic reprogramming, a hallmark of tumor progression, contributes to acquired drug resistance in various malignant tumors. Mitophagy, a process that maintains mitochondrial homeostasis, aids tumor cells in adapting to microenvironmental changes and consequently developing drug resistance. Solute carrier family 27 member 3 (SLC27A3), highly expressed in lipid-rich tumors like ccRCC, has been associated with poor prognosis. However, the impact of SLC27A3 and the transcription factor complex containing STAT2 on lipid metabolic reprogramming, mitophagy in ccRCC, and their role in TKI resistance remain unexplored. Methods: 786-O to pazopanib resistance was induced by gradient increase of concentration, and the genes related to lipid metabolism were screened by RNA sequencing. Bioinformatics was used to analyze the differential expression of SLC27A3 and its effect on patient prognosis, and to predict the activated pathway in pazopanib-resistant cells. Lipid droplets (LDs) were detected by Red Oil O and BODIPY probe. Micro-targeted lipidomic of acyl-coenzyme A (CoA) and lipid metabolomics were performed to screen potential metabolites of SLC27A3. The differential expression of SLC27A3 was detected in clinical samples. The differential expression of SLC27A3 and its effect on drug resistance of ccRCC tumor were detected in vitro and in vivo. Mitophagy was detected by electron microscopy, Mtphagy probe, and Western blot. The mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels were detected by JC-1 and DCF probes. The binding site of the transcription factor complex to the SLC27A3 promoter was detected by dual-luciferase reporter gene assay. Results: SLC27A3, highly expressed in lipid-rich tumors such as ccRCC and glioblastoma, predicts poor prognosis. SLC27A3 expression level also increased in pazopanib-resistant 786-O cells (786-O-PR) with more LD accumulation compared to parental cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis from RNA sequencing showed that PINK1/Parkin-mediated mitophagy pathway was enriched in 786-O-PR. Knockdown of SLC27A3 markedly suppressed LD accumulation and mitophagy, and overcame pazopanib resistance in vitro and in vivo. Moreover, SLC27A3 functions as an acyl-CoA ligase catalyzing the formation of acyl-CoA, which refers to fatty acid oxidation accompanied by ROS production and synthesis of lipid. Overproduced acyl-CoA oxidation in mitochondria resulted in MMP decrease and amounts of ROS production, subsequently triggering PINK1/Parkin-mediated mitophagy. Moreover, mitophagy inhibition led to more ROS accumulation and cell death, indicating that mitophagy can keep ROS at an appropriate level by negative feedback. Mitophagy, simultaneously, prevented fatty acid oxidation in mitochondria by consuming CPT1A, forcing synthesis of triglycerides and cholesterol esters stored in LDs by transforming acyl-CoA, to support ccRCC progression. Besides, we found that STAT2 expression was positively correlated to SLC27A3. Transcriptional factor complex containing STAT2 could bind to the promoter of SLC27A3 mRNA to promote SLC27A3 transcription proved by dual-luciferase reporter assay, which also regulated LD metabolism and activated mitophagy during pazopanib resistance. Conclusion: SLC27A3 is up-regulated in pazopanib-resistant ccRCC and predicts poor prognosis. High expression of SLC27A3 produces excessive metabolites of various long-chain fatty acyl-CoA (12:0-, 16:0-, 17:0-, 20:3-CoA) to enter mitochondria for β-oxidation and produce amounts of ROS activating mitophagy. Subsequent mitophagy/ROS negative feedback controls ROS homeostasis and consumes CPT1A protein within mitochondria to suppress fatty acid β-oxidation, forcing acyl-CoA storage in LDs, mediating pazopanib resistance in ccRCC. Furthermore, STAT2 was identified as a core component of a potential upstream transcriptional factor complex for SLC27A3. Our findings shed new light on the underlying mechanism of SLC27A3 in ccRCC TKI resistance, which may provide a novel therapeutic target for the management of ccRCC.PMID:39600540 | PMC:PMC11588985 | DOI:10.34133/research.0539

Front Genet. 2024 Nov 12;15:1450064. doi: 10.3389/fgene.2024.1450064. eCollection 2024.ABSTRACTBACKGROUND: Aging can impair the ability of elderly individuals to fight infections and trigger persistent systemic inflammation, a condition known as inflammaging. However, the mechanisms underlying the development of inflammaging remain unknown.METHODS: We conducted 16S rRNA sequencing of intestinal contents from young and old C57BL/6J mice to elucidate changes in gut microbiota diversity and microbial community composition after aging. Aging-related differential bacterial taxa were then identified, and their abundance trends were validated in human samples. The variances in intestinal barrier function and circulating endotoxin between groups were also assessed. Furthermore, widely targeted metabolomics was conducted to characterize metabolic profiles after aging and to investigate the key metabolic pathways enriched by the differential metabolites.RESULTS: Our findings demonstrated an increase in relative proportion of pathogenic bacteria with age, a trend also revealed in healthy populations of different age groups. Additionally, aging individuals exhibited reduced intestinal barrier function and increased circulating endotoxin levels. Widely targeted metabolomics revealed a significant increase in various secondary bile acid metabolites after aging, positively correlated with the relative abundance of several aging-related bacterial taxa. Furthermore, old group had lower levels of various anti-inflammatory or beneficial metabolites. Enrichment analysis identified the starch and sucrose metabolism pathway as potentially the most significantly impacted signaling pathway during aging.CONCLUSION: This study aimed to provide insights into the complex interactions involved in organismal inflammaging through microbial multi-omics. These findings lay a solid foundation for future research aimed at identifying novel biomarkers for the clinical diagnosis of aging-related diseases or potential therapeutic targets.PMID:39600316 | PMC:PMC11588687 | DOI:10.3389/fgene.2024.1450064