PubMed

Heliyon. 2024 Nov 2;10(21):e40096. doi: 10.1016/j.heliyon.2024.e40096. eCollection 2024 Nov 15.ABSTRACTAround the world, oral cancer (OC) is a major public health problem, resulting in a significant number of deaths each year. Early detection and treatment are crucial for improving patient outcomes. Recent progress in DNA sequencing and transcriptome profiling has revealed extensive non-coding RNAs (ncRNAs) transcription, underscoring their regulatory importance. NcRNAs influence genomic transcription and translation and molecular signaling pathways, making them valuable for various clinical applications. Combining spatial transcriptomics (ST) and spatial metabolomics (SM) with single-cell RNA sequencing provides deeper insights into tumor microenvironments, enhancing diagnostic and therapeutic precision for OC. Additionally, the exploration of salivary biomarkers offers a non-invasive diagnostic avenue. This article explores the potential of ncRNAs as diagnostic and therapeutic tools for OC.PMID:39583806 | PMC:PMC11582460 | DOI:10.1016/j.heliyon.2024.e40096

Neurobiol Stress. 2024 Nov 4;33:100686. doi: 10.1016/j.ynstr.2024.100686. eCollection 2024 Nov.ABSTRACTBACKGROUND: Alterations in gut-brain axis communication pathways and the gut microbiota ecosystem caused by early life stress have been extensively described as critical players in the pathophysiology of stress-induced disorders. However, the extent to which stress-induced gut microbiota alterations manifest in early life and contribute to the sex-specific susceptibility to distinct gut-brain phenotypes in adulthood has yet to be defined.METHODS: Male and female Sprague-Dawley rat offspring underwent maternal separation (3h/day from postnatal day 2-12). Faecal samples were collected before weaning for gut microbiota 16S rRNA sequencing and metabolomic analysis. Visceral pain sensitivity and negative valence behaviours were assessed in adulthood using colorectal distension and the forced swim test respectively. Behavioural data were processed in a two-step cluster analysis to identify groupings within the dataset. Multi-omics analysis was carried out to investigate if the microbial signatures following early life stress were already defined according to the membership of the adult behavioural phenotypes.RESULTS: Maternal separation resulted in increased visceral hypersensitivity while showing a trend for a sex-dependent increase in negative valence behaviour in adulthood. The cluster analysis revealed four clusters within the dataset representing distinct pathophysiological domains reminiscent of the behavioural consequences of early-life stress: 1. resilient, 2. pain, 3. immobile and 4. comorbid. The early life gut microbiota of each of these clusters show distinct alterations in terms of diversity, genus level differential abundance, and functional modules. Multi-omic integrations points towards a role for different metabolic pathways underlying each cluster-specific phenotype.CONCLUSION: Our study is the first to identify distinct phenotypes defined by susceptibility or resilience to gut-brain dysfunction induced by early life stress. The gut microbiota in early life shows sex-dependent alterations in each cluster that precede specific behavioural phenotypes in adulthood. Future research is warranted to determine the causal relationship between early-life stress-induced changes in the gut microbiota and to understand the trajectory leading to the manifestation of different behavioural phenotypes in adulthood.PMID:39583744 | PMC:PMC11582825 | DOI:10.1016/j.ynstr.2024.100686

ACS Omega. 2024 Nov 6;9(46):45746-45758. doi: 10.1021/acsomega.4c02557. eCollection 2024 Nov 19.ABSTRACTConcerns about the SARS-CoV-2 outbreak (COVID-19) continue to persist even years later, with the emergence of new variants and the risk of disease severity. Common clinical symptoms, like cough, fever, and respiratory symptoms, characterize the noncritical patients, classifying them from mild to moderate. In a more severe and complex scenario, the virus infection can affect vital organs, resulting, for instance, in pneumonia and impaired kidney and heart function. However, it is well-known that subclinical symptoms at a metabolic level can be observed previously but require a proper diagnosis because viral replication on the host leaves a track with a different profile depending on the severity of the illness. Metabolomic profiles of mild, moderate, and severe COVID-19 patients were obtained by multiple platforms (LC-HRMS and MALDI-MS), increasing the chance to elucidate a prognosis for severity risk. A strong link was discovered between phenylalanine metabolism and increased COVID-19 severity symptoms, a pathway linked to cardiac and neurological consequences. Glycerophospholipids and sphingolipid metabolisms were also dysregulated linearly with the increasing symptom severity, which can be related to virus proliferation, immune system avoidance, and apoptosis escaping. Our data, endorsed by other literature, strengthens the notion that these pathways might play a vital role in a patient's prognosis.PMID:39583673 | PMC:PMC11579725 | DOI:10.1021/acsomega.4c02557

Cureus. 2024 Oct 23;16(10):e72239. doi: 10.7759/cureus.72239. eCollection 2024 Oct.ABSTRACTLiver cancer, particularly hepatocellular carcinoma (HCC), poses a significant global health challenge due to its high mortality rate. Hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC) are the two main types of primary liver cancer (PLC), each with its own set of complexities. Secondary or metastatic liver cancer is more common than PLC. It is frequently observed in malignancies such as colorectal, pancreatic, melanoma, lung, and breast cancer. Liver cancer is often diagnosed at an advanced stage, making it difficult to treat. This highlights the need for focused research on early detection and effective treatment strategies. This review explores the epidemiology, risk factors, and diagnostic techniques for HCC. The development of HCC involves various risk factors, including chronic liver diseases, hepatitis B and C infections, alcohol consumption, obesity, smoking, and genetic predispositions. Various invasive and non-invasive diagnostic techniques, such as biopsy, liquid biopsy, and imaging modalities like ultrasonography, computed tomography scans (CT scans), magnetic resonance imaging (MRI), and positron emission tomography (PET) scans, are utilized for HCC detection and monitoring. Advances in imaging technology and biomarker research have led to more accurate and sensitive methods for early HCC detection. We also reviewed advanced research on emerging techniques, including next-generation sequencing, metabolomics, epigenetic biomarkers, and microbiome analysis, which show great potential for advancing early diagnosis and personalized treatment strategies. This literature review provides insights into the current state of liver cancer diagnosis and promising future advancements. Ongoing research and innovation in these areas are essential for improving early diagnosis and reducing the global burden of liver cancer.PMID:39583507 | PMC:PMC11584332 | DOI:10.7759/cureus.72239

J Pain Res. 2024 Nov 20;17:3897-3918. doi: 10.2147/JPR.S487156. eCollection 2024.ABSTRACTBACKGROUND: Previous metabolomics studies have indicated a close association between blood metabolites and pain. However, the causal relationship between blood metabolites and spinal pain (SP) remains unclear. This study employs a bidirectional two-sample Mendelian randomization (MR) analysis to evaluate the causal relationship between 452 blood metabolites and SP.METHODS: We used bidirectional two-sample MR analysis to assess the causal relationship between blood metabolites and SP, including neck pain (NP), thoracic spine pain (TSP), low back pain (LBP), and back pain (BP). Genome-wide association studies (GWAS) data for 452 metabolites (7,824 participants) were used as exposure variables. Summary data for NP were obtained from the UK Biobank, for TSP from the FinnGen Biobank, and for LBP from both the UK Biobank and the FinnGen Biobank. Summary data for BP were obtained from the UK Biobank. Inverse-variance weighting (IVW) was used to estimate the causal relationships between metabolites and SP, complemented by various sensitivity analyses to account for pleiotropy and heterogeneity, ensuring robust results.RESULTS: The IVW analysis identified 155 metabolites associated with SP risk and 142 metabolites influenced by SP. No significant heterogeneity or horizontal pleiotropy was observed through other analytical methods.CONCLUSION: This study demonstrates potential causal effects between blood metabolites and SP, providing new insights into the pathogenesis of SP. These findings lay a theoretical foundation for preventing and treating SP through targeted interventions on specific blood metabolites, potentially elucidating underlying biological mechanisms.PMID:39583190 | PMC:PMC11585999 | DOI:10.2147/JPR.S487156

PeerJ. 2024 Nov 19;12:e18496. doi: 10.7717/peerj.18496. eCollection 2024.ABSTRACTRice grown in Yunnan Province is known for its excellent taste and consumer preference. However, the metabolite composition of this unique rice remains unclear. In this study, the metabolic profile of different rice planted in various producing regions was evaluated. A total of 1,005 metabolites were identified, including nucleotides and their derivatives, amino acids and their derivatives, alkaloids, organic acids, phenolic acids, lignans and coumarins, lipids, terpenoids, quinones, flavones, tannins, and others. Procucing region and varieties can be clearly distinguished on the PCA diagram. Differential metabolites accumulated in the MSD502 vs. MSR88 (138)/LHHG (234)/LHR88 (188) comparison groups. The results in this study provide scientific information for the origin tracing and variety differentiation of raw rice materials.PMID:39583111 | PMC:PMC11583909 | DOI:10.7717/peerj.18496

PeerJ. 2024 Nov 19;12:e18534. doi: 10.7717/peerj.18534. eCollection 2024.ABSTRACTBACKGROUND: Research on serum metabolite profiles in thyroid autoimmunity (TAI) patients during early pregnancy is currently limited.AIM & METHODS: The current study aimed to identify differential serum metabolites and assess the relationship between pregnancy outcomes and metabolic abnormalities in individuals with TAI. This research included 26 pregnant women with TAI and 30 healthy controls (HC). We employed a liquid chromatograph mass spectrometer (LC-MS) to analyze changes between the two groups.RESULTS: Newborns in the TAI patients had lower birth weights than those in the control group (P = 0.007). We identified 92 differential metabolites (including 50 upregulated and 42 downregulated) belonging to amino acids, fatty acyls, glycerophosphocholines, steroid and other categories and four significantly enrichment Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including taurine and hypotaurine metabolism, citrate cycle (TCA cycle), glyoxylate and dicarboxylate metabolism and 2-oxocarboxylic acid metabolism. We further identified 15 characteristic metabolites (6-Methylquinoline, D-erythrose 4-phosphate, 4-Hydroxyisoleucine, phosphatidylcholine (PC)(16:2e/16:0), N3,N4-Dimethyl-L-arginine, N-desmethyltramadol, 3-Methoxybenzaldehyde, sphingomyelin (SM)(d14:3/28:2), gamma-Glutamylleucine, NSI-189, 3-(1-cyano-1,2-dihydroisoquinolin-2-yl)-3-oxopropyl propionate, lysophosphatidylinositol (LPI) 16:0, cis-Aconitic acid, polyamide (PA)(18:1/18:2) and fatty acyl esters of hydroxy fatty acid (FAHFA)(17:0/18:0)) using least absolute shrinkage and selection operator (LASSO) regression. Correlation analyses revealed that 6-Methylquinoline, D-erythrose 4-phosphate, gamma-Glutamylleucine, and LPI 16:0 exhibited a positive correlation with anemia before delivery, while 3-(1-cyano-1,2-dihydroisoquinolin-2-yl)-3-oxopropyl propionate had a negative correlation. LPI 16:0 displayed a positive correlation with uric acid (UA) during both middle and late pregnancy, whereas 3-Methoxybenzaldehyde exhibited a negative correlation with UA in late pregnancy. Cis-Aconitic acid showed a positive correlation with fasting blood glucose (FBG) in middle pregnancy. Conversely, 6-Methylquinoline and 4-Hydroxyisoleucine had a negative correlation with birth weight. Thyroid autoantibodies were found to be associated with 14 metabolites identified using LASSO, with the exception of PA (18:1/18:2).CONCLUSIONS: Our findings provide new evidence supporting the early screening of serum metabolites and their potential for predicting adverse pregnancy outcomes in women with TAI.PMID:39583110 | PMC:PMC11583911 | DOI:10.7717/peerj.18534

J Allergy Clin Immunol Glob. 2024 Oct 18;4(1):100353. doi: 10.1016/j.jacig.2024.100353. eCollection 2025 Feb.ABSTRACTBACKGROUND: Hereditary angioedema (HAE) is a rare inherited disorder that predisposes an individual to develop vasogenic edema. Bradykinin release, which increases vascular permeability, results in angioedema. C1 esterase inhibitor (C1-INH) is a major regulator of critical enzymes involved in bradykinin generation and mutations in genes that encode the C1 inhibitor of complement factor 1, which prevent its synthesis (type I HAE), form a dysfunctional protein (type II HAE), or have normal functioning C1-INH (type III HAE, aka HAE-III).OBJECTIVES: The goals of this study were to use a systems biology analysis to identify novel biomarkers to aid in the diagnosis of HAE-III and to elucidate its underlying pathogenic mechanisms.METHODS: Blood samples were obtained from HAE-III subjects and age- and sex-matched healthy controls. DNA, RNA, and protein purified from the samples were subjected to multiomics analysis using a 1-shot liquid chromatography-mass spectrometry-based multiomics platform (Omni-MS, Dalton Bioanalytics) to profile proteins, lipids, electrolytes, and metabolites enabling concurrent analysis of diverse analyte classes.RESULTS: A total of 1647 novel identifications that included genes, proteins, and metabolites were made when comparing HAE-III samples to control samples. Our identification library included MSFragger for protein identification, LipiDex for lipid identification, and Compound Discoverer for metabolite identification, enabling differential expression analysis. Key findings included a significant increase in the expression levels of galectin-3, lysosomal α-glucosidase, platelet factor 4, and platelet-derived growth factor subunit A in HAE-III subjects compared to controls, all of which generate an immunomodulatory response.CONCLUSION: Galectin-3 plays a critical role in eosinophil recruitment and airway allergic inflammation. It may contribute to chronic inflammation and fibrosis resulting in leaky vasculature, and it could be a potential therapeutic target in HAE-III.PMID:39583036 | PMC:PMC11583700 | DOI:10.1016/j.jacig.2024.100353

Front Vet Sci. 2024 Nov 8;11:1456790. doi: 10.3389/fvets.2024.1456790. eCollection 2024.ABSTRACTThe rearing system of livestock plays a vital role in animal production, meat quality, and overall welfare. This study aimed to assess the influence of cage-rearing system and forest-rearing system on the ileum microbiota, metabolome, and ileal mucosa transcriptome in meat rabbits. Moreover, 16S rDNA sequencing revealed significant differences in the ileal microbiome composition: caged rabbits exhibited a higher abundance of the genera uncultured Erysipelotrichaceae and Delftia, whereas the levels of Muribaculaceae, unclassified Burkholderiales, and uncultured Eubacteriaceae were lower compared to rabbits reared in the forest. Metabolome analysis identified 372 differentially accumulated metabolites in the ileum content, which were predominantly mapped to amino acid metabolism, nucleotide metabolism, and energy metabolism pathways. The cage-rearing system was found to positively correlate with the efficient utilization of nutrient sources. Additionally, transcriptome analysis of the ileal mucosa revealed 984 differentially expressed genes, predominantly involved in metabolic pathways, signal transduction pathways, and immune response processes. Through Pearson correlation analysis, we were able to elucidate the metabolic pathway, immune responses, and disease resistance mechanisms were affected by the rearing system. Overall, the findings suggested that metabolic adaptation, nutrient utilization, and immune response play crucial roles in how rabbits adjust to different rearing systems. While the cage system may enhance nutrient efficiency, it appears to suppress immune function and disease resistance.PMID:39582888 | PMC:PMC11582050 | DOI:10.3389/fvets.2024.1456790

Front Immunol. 2024 Nov 8;15:1469163. doi: 10.3389/fimmu.2024.1469163. eCollection 2024.ABSTRACTINTRODUCTION: During an immune response, macrophages undergo systematic metabolic rewiring tailored to support their functions. Branched-chain amino acid (BCAA) metabolism has been reported to modulate macrophage function; however, its role in macrophage alternative activation remain unclear. We aimed to investigate the role of BCAA metabolism in macrophage alternative activation.METHOD: The metabolomics of BMDM-derived M0 and M2 macrophages were analyzed using LC-MS. BCAAs were supplemented and genes involved in BCAA catabolism were inhibited during M2 macrophage polarization. The expression of M2 marker genes was assessed through RT-qPCR, immunofluorescence, and flow cytometry.RESULTS AND DISCUSSION: Metabolomic analysis identified increased BCAA metabolism as one of the most significantly rewired pathways upon alternative activation. M2 macrophages had significantly lower BCAA levels compared to controls. BCAA supplementation promoted M2 macrophage polarization both in vitro and in vivo and increased oxidative phosphorylation in M2 macrophages. Blocking BCAA entry into mitochondria by knockdown of SLC25A44 inhibited M2 macrophage polarization. Furthermore, M2 macrophages polarization was suppressed by knockdown of Branched-chain amino-acid transaminase 2 (BCAT2) and branched chain keto acid dehydrogenase E1 subunit alpha (BCKDHA), both of which are key enzymes involved in BCAA oxidation. Overall, our findings suggest that BCAA catabolism plays an important role in polarization toward M2 macrophages.PMID:39582859 | PMC:PMC11582057 | DOI:10.3389/fimmu.2024.1469163

Food Chem (Oxf). 2024 Nov 6;9:100228. doi: 10.1016/j.fochms.2024.100228. eCollection 2024 Dec 30.ABSTRACTThe flavor of guava, an important tropical fruit, is influenced by secondary metabolites. However, the mechanisms and processes underlying flavor formation in guava remain unclear. In this study, dynamic changes in volatile organic compounds (VOCs), sugars, and organic acids in guava peel and flesh across different developmental stages were investigated using headspace solid-phase microextraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). Here, we identified 90 VOCs, three sugars and eight organic acids. The dynamics of VOCs differ between the flesh and peel. The early developmental stages are more critical in influencing the variation of VOCs in the flesh, while VOC changes in peel occur more progressively across the developmental stages. By integrating transcriptomic and metabolomic analyses, we identified several key genes involved in VOC, sugar, and acid metabolism. This is the first study to describe the expression patterns of these genes throughout guava development, providing new insights into guava flavor development.PMID:39582733 | PMC:PMC11583725 | DOI:10.1016/j.fochms.2024.100228

Food Chem X. 2024 Nov 5;24:101971. doi: 10.1016/j.fochx.2024.101971. eCollection 2024 Dec 30.ABSTRACTAvocado is widely grown in tropical and subtropical regions of China. Diverse germplasms have been generated through natural hybridization and selective breeding. Here, to screen high-quality avocado germplasms, we characterized the nutritional quality of 95 avocado germplasms grown in China based on metabolomics. The oil content of the 95 avocado germplasms was 2.18 %-16.60 % and followed a normal distribution. We further profiled nine fatty acids, 16 hydrolyzed amino acids, and eight mineral elements in avocado fruit, which varied widely among different germplasms. Correlation analysis revealed significant positive correlations between fatty acid components, as well as between amino acid components and between mineral elements. Clustering analysis and evaluation of the 95 avocado germplasms identified 14 germplasms with high nutritional quality. These findings provide a basis for evaluation of avocado fruit quality and utilization of high-quality avocado germplasms, as well as important implications for the breeding of avocado.PMID:39582637 | PMC:PMC11585822 | DOI:10.1016/j.fochx.2024.101971

Curr Res Food Sci. 2024 Nov 7;9:100919. doi: 10.1016/j.crfs.2024.100919. eCollection 2024.ABSTRACTThis work was aimed to explore the antioxidative properties, bioavailability and the safety of bioactive peptides obtained by the enzymatic hydrolysis of ultrasound-treated (UO) and untreated (nUO) soybean okara proteins. Particularly, the peptidomic profiles of both hydrolysates were examined using an untargeted metabolomics technique for suspect screening that was specifically designed for the profiling of short-chain peptides and relied on ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) and bioinformatics. Next, both UO and nUO hydrolysates reduce Dipeptidyl peptidase-IV (DPP-IV) enzyme activity until 39.54 ± 0.26 % and 43.29 ± 0.36 % respectively and inhibit angiotensin converting enzyme (ACE) activities by 30.54 ± 0.42 % and 30.76 ± 0.02 %, respectively. Moreover, they demonstrate to exerted antioxidant properties. Particularly, they show a comparable in vitro antioxidant activity but when the oxidative stress is induced by H2O2 in Caco-2 cells, UO hydrolysate is more active in lowering the levels of reactive oxygen species (ROS) and of lipid peroxidation induced of 48% and 20% respectively. In addition, UO- and nUO-derived peptides trans-epithelial transported by human differentiated intestinal cell monolayer, were identified. Lastly, the possible hepatotoxicity of UO and nUO hydrolysates in HepG2 cells has not been observed by measuring alanine transferase (ALT) and aspartate transferase (AST) levels and cytotoxic effects.PMID:39582575 | PMC:PMC11582538 | DOI:10.1016/j.crfs.2024.100919

J Pediatr Gastroenterol Nutr. 2024 Nov 25. doi: 10.1002/jpn3.12420. Online ahead of print.ABSTRACTOBJECTIVES: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common pediatric liver disease and can progress to liver fibrosis. Latino adolescents have increased MASLD and fibrosis risk. While fibrosis is diagnosed by biopsy or imaging, more accessible, noninvasive, and economical screening methods are needed. We aimed to use plasma metabolomics/lipidomics to identify potential fibrosis biomarkers in Latino adolescents with obesity.METHODS: Liver stiffness (LS) was measured in 93 Latino adolescents with obesity using magnetic resonance elastography. Metabolites and lipids were extracted from plasma and identified on Compound Discoverer. Associations between metabolites/lipids and fibrosis (LS > 2.73 kPa) were determined using linear regression models after covariate adjustment. False discovery rate (FDR) adjusted Pearson's correlations were performed. Analytes yielding significant FDR-adjusted correlations were examined further by receiver operator curve analysis.RESULTS: Mean (±standard deviation) alanine transaminase (ALT) was 45.7(±65.2) IU/L, hepatic fat fraction was 12.7(±9.1)%, and LS was 2.4(±0.3) kPa. We identified 795 metabolites and 413 lipids in plasma, but only one single metabolite, dihydroxyacetone phosphate (DHAP), a marker of triglyceride synthesis, was significantly associated with fibrosis after FDR adjustment (p < 0.05). In terms of predicting fibrosis, ALT had an area under the curve (AUC) of 0.79, and DHAP had an AUC of 0.79. When combined, ALT + DHAP had an AUC of 0.89.CONCLUSIONS: The combination of ALT + DHAP may have the potential as an accurate, noninvasive test for liver fibrosis. Our data is limited to Latino children with obesity, and a larger cohort should be examined to further validate this novel biomarker.PMID:39582475 | DOI:10.1002/jpn3.12420

Microb Biotechnol. 2024 Nov;17(11):e70011. doi: 10.1111/1751-7915.70011.ABSTRACTMicrobial biosurfactants have garnered significant interest from industry due to their lower toxicity, biodegradability, activity at lower concentrations and higher resistance compared to synthetic surfactants. The deep-sea Rhodococcus sp. I2R has been identified as a producer of glycolipid biosurfactants, specifically succinoyl trehalolipids, which exhibit antiviral activity. However, genome mining of this bacterium has revealed a still unexplored repertoire of biosurfactants. The microbial genome was found to host five non-ribosomal peptide synthetase (NRPS) gene clusters containing starter condensation domains that direct lipopeptide biosynthesis. Genomics and mass spectrometry (MS)-based metabolomics enabled the linking of two NRPS gene clusters to the corresponding lipopeptide families, leading to the identification of 20 new cyclolipopeptides, designated as rhodoheptins, and 33 new glycolipopeptides, designated as rhodamides. An integrated in silico gene cluster and high-resolution MS/MS data analysis allowed us to elucidate the planar structure, inference of stereochemistry and reconstruction of the biosynthesis of rhodoheptins and rhodamides. Rhodoheptins are cyclic heptapeptides where the N-terminus is bonded to a β-hydroxy fatty acid forming a macrolactone ring with the C-terminal amino acid residue. Rhodamides are linear 14-mer glycolipopeptides with a serine- and alanine-rich peptide backbone, featuring a distinctive pattern of acetylation, glycosylation and succinylation. These molecules exhibited biosurfactant activity in the oil-spreading assay and showed moderate antiproliferative effects against human A375 melanoma cells.PMID:39582288 | DOI:10.1111/1751-7915.70011

NPJ Biofilms Microbiomes. 2024 Nov 24;10(1):135. doi: 10.1038/s41522-024-00612-7.ABSTRACTThe rapid development of high-throughput sequencing techniques provides an unprecedented opportunity to generate biological insights into microbiome-related diseases. However, the relationships among microbes, metabolites and human microenvironment are extremely complex, making data analysis challenging. Here, we present NMFGOT, which is a versatile toolkit for the integrative analysis of microbiome and metabolome data from the same samples. NMFGOT is an unsupervised learning framework based on nonnegative matrix factorization with graph regularized optimal transport, where it utilizes the optimal transport plan to measure the probability distance between microbiome samples, which better dealt with the nonlinear high-order interactions among microbial taxa and metabolites. Moreover, it also includes a spatial regularization term to preserve the spatial consistency of samples in the embedding space across different data modalities. We implemented NMFGOT in several multi-omics microbiome datasets from multiple cohorts. The experimental results showed that NMFGOT consistently performed well compared with several recently published multi-omics integrating methods. Moreover, NMFGOT also facilitates downstream biological analysis, including pathway enrichment analysis and disease-specific metabolite-microbe association analysis. Using NMFGOT, we identified the significantly and stable metabolite-microbe associations in GC and ESRD diseases, which improves our understanding for the mechanisms of human complex diseases.PMID:39582023 | DOI:10.1038/s41522-024-00612-7

Am J Chin Med. 2024 Nov 25:1-33. doi: 10.1142/S0192415X24500745. Online ahead of print.ABSTRACTAcupuncture and moxibustion are widely acknowledged as effective complementary therapies for managing inflammatory bowel disease (IBD) in traditional Chinese medicine. However, the regulatory mechanisms by which these two therapies exert their therapeutic effects in IBD are yet to be fully elucidated. The objective of this study was to investigate the mechanisms of action underlying acupuncture and moxibustion and the regulative differences between them as therapeutic interventions for IBD. Using a dextran sodium sulfate-induced IBD mice model, the effects of the two treatments were evaluated by examination of body weight, stool samples, colon morphology, inflammatory factors, gut microbiota, and metabolites. The results indicated that both acupuncture and moxibustion mitigated body weight reduction; improved the structural characteristics of intestinal tissues; increased levels of anti-inflammatory cytokines including interleukin (IL)-10; and decreased levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-[Formula: see text]), nuclear factor kappa B (NF-[Formula: see text]B), IL-6, IL-1[Formula: see text], and IL-17. Acupuncture and moxibustion had distinct effects on the regulation of the intestinal microbiota and metabolic pathways in IBD mice. Moxibustion regulated a greater number of metabolic pathways than acupuncture, the majority of which were associated with amino acid metabolism, brain signal transmission, energy metabolism, and anti-inflammatory pathways. These findings provide a scientific basis for the differential applications of acupuncture and moxibustion in clinical practice.PMID:39581856 | DOI:10.1142/S0192415X24500745

Br J Pharmacol. 2024 Nov 24. doi: 10.1111/bph.17393. Online ahead of print.ABSTRACTBACKGROUND AND PURPOSE: While pain and itch are both commonly associated with chronic dermatitis (CD), the molecular mechanisms underlying these debilitating symptoms is not well understood. This study aims to identify novel, endogenous compounds that mediate CD-associated pain and itch.EXPERIMENTAL APPROACH: Lesional skin of CD model mice was examined using unbiased metabolomic analysis to identify candidate pain or itch inducing compounds in CD. Sphingosine-1-phosphate (S1P) concentration in CD model skin was analysed using UPLC/MS/MS. Behaviour, calcium imaging and immunofluorescence staining were used to determine the pain and itch effects and mechanisms of the identified CD-related compounds.KEY RESULTS: In the lesional skin of CD model mice, 136 compounds were significantly changed. These compounds are predominately associated with the sphingolipids metabolism pathway. S1P is significantly increased in the lesional skin . The TRPV4 channel was critical for S1P induced itch and pain. Sphingosine kinase 2 (SPHK2), the key enzyme controlling S1P synthesis, was significantly increased in lesional skin. ABC294640, a SPHK2 inhibitor, significantly decreased S1P concentration in lesional CD model skin, as well as in model associated epidermal hyperplasia and chronic pain and itch. In CD patients, SPHK2 expression and S1P concentration were significantly elevated compared to healthy control skin.CONCLUSION AND IMPLICATIONS: Our results indicate that, in CD, increased S1P induces chronic pain and itch partly through TRPV4. Inhibition of S1P synthesis or the S1P/S1P receptor-TRPV4 pathway are promising treatment strategies for CD-associated pain and itch.PMID:39581852 | DOI:10.1111/bph.17393

Urol Oncol. 2024 Nov 23:S1078-1439(24)00724-5. doi: 10.1016/j.urolonc.2024.11.008. Online ahead of print.ABSTRACTThis review assesses the current understanding of the relationship between the human microbiome and BCa. Recognizing how the microbiome affects the tumor microenvironment provides valuable insights into cancer biology, potentially uncovering interactions that could be leveraged to develop innovative therapeutic approaches. By clarifying these intricate microbial-tumor dynamics, novel targets for microbiome-based interventions can be identified, ultimately improving treatment effectiveness and patient outcomes. Current literature lacks comprehensive insights into the effects of BCa treatment on the microbiome and the prevalence of immunotherapy-related toxicities. Further research into the microbiome's role in BCa development could bridge the gap between fundamental research and therapeutic applications. Implementing microbiome surveillance, metagenomic sequencing, and metabolomics in clinical trials could deepen our understanding of BCa and its treatment. This review explores the existing understanding of the urine, tissue, and gut microbiomes and their connections to BCa. Enhanced knowledge of these relationships can pave the way for future research to identify reliable disease predictors, prognostic markers, and novel therapeutic targets.PMID:39581825 | DOI:10.1016/j.urolonc.2024.11.008

BMJ Open. 2024 Nov 24;14(11):e087430. doi: 10.1136/bmjopen-2024-087430.ABSTRACTINTRODUCTION: Suspected preterm labour (SPL) is an obstetric complication that occurs in 9% of all pregnancies and is the leading cause of antenatal hospital admissions. More than half of women with SPL deliver a premature baby which is a known risk factor for developing cardiovascular and metabolic disorders in childhood and later in adult life. On the other hand, the other half of these women will deliver at term, labelled as 'false preterm labour'. Although this has been thought to be a benign condition, accumulating evidence reported in recent years showed long-term effects for the foetus, neonate and infant even when birth occurs at term. However, the impact of SPL on cardiovascular and metabolic programming has not been studied yet. The aim of this prospective cohort study is to evaluate the impact of SPL on cardiac remodelling and function and on cardiovascular and metabolic profiles independently of gestational age at birth.METHODS AND ANALYSIS: Prospective cohort study of subjects exposed and not exposed to an episode of SPL. Women with singleton pregnancies who are admitted at a tertiary hospital due to SPL and matched controls will be recruited. Evaluation of cardiovascular remodelling by foetal echocardiography will be performed during admission. Cord blood will be collected at birth in order to analyse different metabolomic footprints and several cardiovascular and metabolic risk biomarkers. Moreover, children will undergo an echocardiography 6 months after birth. The relationship between SPL and cardiovascular and metabolic programming will be modelled considering different covariates such as socioeconomic factors, perinatal characteristics, lifestyle, diet and exercise.ETHICS AND DISSEMINATION: Ethical approval was granted in April 2020 from CEIC Aragón (CEICA) (C.P.-C.I. PI20/136). Study outcomes will be disseminated at international conferences and published in peer-reviewed scientific journals.TRIAL REGISTRATION NUMBER: NCT05670665.PMID:39581725 | DOI:10.1136/bmjopen-2024-087430