PubMed

Brief Bioinform. 2024 Sep 23;25(6):bbae564. doi: 10.1093/bib/bbae564.ABSTRACTCisplatin is one of the most commonly used chemotherapy drugs for treating solid tumors. As a genotoxic agent, cisplatin binds to DNA and forms platinum-DNA adducts that cause DNA damage and activate a series of signaling pathways mediated by various DNA-binding proteins (DBPs), ultimately leading to cell death. Therefore, DBPs play crucial roles in the cellular response to cisplatin and in determining cell fate. However, systematic studies of DBPs responding to cisplatin damage and their temporal dynamics are still lacking. To address this, we developed a novel and user-friendly stand-alone software, DEWNA, designed for dynamic entropy weight network analysis to reveal the dynamic changes of DBPs and their functions. DEWNA utilizes the entropy weight method, multiscale embedded gene co-expression network analysis and generalized reporter score-based analysis to process time-course proteome expression data, helping scientists identify protein hubs and pathway entropy profiles during disease progression. We applied DEWNA to a dataset of DBPs from A549 cells responding to cisplatin-induced damage across 8 time points, with data generated by data-independent acquisition mass spectrometry (DIA-MS). The results demonstrate that DEWNA can effectively identify protein hubs and associated pathways that are significantly altered in response to cisplatin-induced DNA damage, and offer a comprehensive view of how different pathways interact and respond dynamically over time to cisplatin treatment. Notably, we observed the dynamic activation of distinct DNA repair pathways and cell death mechanisms during the drug treatment time course, providing new insights into the molecular mechanisms underlying the cellular response to DNA damage.PMID:39487085 | DOI:10.1093/bib/bbae564

Carbohydr Polym. 2025 Jan 1;347:122708. doi: 10.1016/j.carbpol.2024.122708. Epub 2024 Sep 7.ABSTRACTSoluble starch synthase IIIa (SSIIIa) is a key enzyme involved in amylopectin biosynthesis in rice, and deficiency of SSIIIa results in high content of resistant starch, which is benefit to human health. However, little is known about metabolic differences and carbon re-allocation in the seeds of the indica rice ss3a mutant. We found that SSIIIa deficiency impaired the storage of starch, but increased the soluble sugars, free amino acids and lipids. By multi-omic analyses, we found inactivation of SSIIIa triggered carbon repartitioning by downregulating sucrose synthase, grain incomplete filling 1, fructokinase and hexokinase (HK), and promoted the accumulation of soluble sugars. Meanwhile, the downregulation of HK and upregulation of plastidic phosphoglucomutase reduced the carbon flow through glycolysis and promoted glycogenesis. The downregulation of OsbZIP58 and the deleterious effect on ribosome formation might result in the reduction of storage protein synthesis and increased free amino acids content in ss3a. The higher levels of amylose and lipids could form more amylose-lipid complexes (starch phospholipids), resulting in a higher resistant starch content. Taken together, our study unraveled a functional cross talk between starch, protein and lipids in rice endosperm during seed development of ss3a, providing new insights for formation of high resistant starch in rice.PMID:39486949 | DOI:10.1016/j.carbpol.2024.122708

Carbohydr Polym. 2025 Jan 1;347:122702. doi: 10.1016/j.carbpol.2024.122702. Epub 2024 Sep 5.ABSTRACTSanghuangporus vaninii showed great activities of anti-inflammation and anti-tumor, due to its bioactive macromolecules. However, the hypolipidemic properties of polysaccharides isolated from S. vaninii have not been systematically reported. In this research, a polysaccharide of S. vaninii was obtained and its hypolipidemic activity was investigated. SVP3, a neutral hetero-galactan from S. vaninii, has a →6)-α-Galp-(1→ backbone with partial H-2 branches of α-Manp-(1→ or α-Manp-(1→2)-α-Fucp-(1→. In a hyperlipidemia mouse model, SVP3 significantly inhibited body weight gain and suppressed serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol. SVP3 inhibited the expansion of adipocytes in three types of white adipose tissues and attenuated hepatic injury and hepatic lipid deposition in the mice. The combined analysis of gut microbiota, serum metabolomics, and liver proteomics revealed that SVP3 effectively regulated the abundance of specific gut microbiota and serum metabolites and mediated the inhibitory effect on inflammation-associated toll-like receptor 4/nuclear factor kappa-B pathway by regulating the expression levels of glutathione S-transferase P1, stromal cell derived factor 2-like 1, ribosomal protein L10, thiosulfate sulfurtransferase, and biliverdin reductase A in liver, ultimately realizing the hypolipidemic activity. The results of the present study provide experimental evidence for the development of clinical adjuvant therapeutic drugs to treat hyperlipidemia.PMID:39486943 | DOI:10.1016/j.carbpol.2024.122702

Carbohydr Polym. 2025 Jan 1;347:122665. doi: 10.1016/j.carbpol.2024.122665. Epub 2024 Aug 27.ABSTRACTThis study aims to investigate the effects of levan on the progression of hyperuricemia (HUA) rats and elucidate its underlying mechanisms. After levan intervention, both low and high-dose groups exhibited a significant decrease in serum uric acid (UA) levels, reaching 71.0 % and 77.5 %, respectively, compared to the model group. Furthermore, levan could alleviate renal pathological damage caused by glomerular cell vacuolation, inflammatory infiltration and collagen deposition. The results of enzyme activity assay and real-time fluorescence quantitative PCR showed that levan decreased UA production by inhibiting adenosine deaminase (ADA) activity and gene expression in liver; it upregulated ATP-binding cassette subfamily G member 2 protein (ABCG2) and organic anion transporter 1 (OAT1) transporter gene expression in the kidney, promoting UA excretion. Gut microbiome analysis indicated that levan regulated gut flora dysbiosis induced by HUA, resulting in up-regulated the abundance of beneficial bacteria (Muribaculaceae, Faecalibaculum, Bifidobacterium, and Lactobacillus) and decreased conditioned pathogenic bacteria (Escherichia_Shigella and Proteus). Non-targeted metabolomics showed changes in various serum metabolites associated with glycerophospholipid metabolism, lipid metabolism, and inflammation following oral administration of levan. Therefore, levan may be a promising functional dietary supplement for regulating the gut flora and remodeling of metabolic disorders in individuals with HUA.PMID:39486924 | DOI:10.1016/j.carbpol.2024.122665

Carbohydr Polym. 2025 Jan 1;347:122536. doi: 10.1016/j.carbpol.2024.122536. Epub 2024 Jul 29.ABSTRACTMixed-linkage (1,3; 1,4)-β-D-glucan (MLG) impacts the food and industrial end-uses of barley, but the molecular mechanism of variations in MLG content remains unclear. MLG content usually increases in Waxy-mutated barley. This study applied transcriptomic, proteomic, and metabolomic analyses to Waxy-mutated recombinant inbred lines with higher MLG content and wild-type lines with lower MLG content, and identified candidate genes and pathways regulating MLG content through combining preliminary gene function analysis. MLG biosynthesis differed significantly during late grain development in the Waxy-mutated and wild-type barley lines. The MLG increase was closely associated with strongly active sugar and starch metabolism and stress-responsive plant hormones, particularly abscisic acid (ABA) signaling process. Stress-responsive transcript factors ILR3, BTF3, RGGA, and PR13 protein bind to CslF6, which is critical for barley MLG biosynthesis, and the stress-responsive gene ASR1 also had a positive effect on MLG increase. Waxy mutation enhances barley stress responses by activating ABA- or other stress-responsive plant hormones signaling processes, which facilitates MLG biosynthesis. This study provides a new approach for elucidating the variations in MLG content of barley grains.PMID:39486912 | DOI:10.1016/j.carbpol.2024.122536

J Heart Lung Transplant. 2024 Oct 30:S1053-2498(24)01905-3. doi: 10.1016/j.healun.2024.10.020. Online ahead of print.ABSTRACTBACKGROUND: In lung transplantation (LuTx), various ischemic phases exist, yet the rewarming ischemia time (RIT) during implantation has often been overlooked. During RIT, lungs are deflated and exposed to the body temperature in the recipient's chest cavity. Our prior clinical findings demonstrated that prolonged RIT increases the risk of primary graft dysfunction. However, the molecular mechanisms of rewarming ischemic injury in this context remain unexplored. We aimed to characterize the rewarming ischemia phase during LuTx by measuring organ temperature and comparing transcriptome and metabolome profiles in tissue obtained at the end versus the start of implantation.METHODS: In a clinical observational study, 34 double-LuTx with ice preservation were analyzed. Lung core and surface temperature (n=65 and 55 lungs) was measured during implantation. Biopsies (n=59 lungs) were wedged from right middle lobe and left lingula at start and end of implantation. Tissue transcriptomic and metabolomic profiling were performed.RESULTS: Temperature increased rapidly during implantation, reaching core/surface temperatures of 21.5°C/25.4°C within 30min. Transcriptomics showed increased pro-inflammatory signaling and oxidative stress at the end of implantation. Upregulation of NLRP3 and NFKB1 correlated with RIT. Metabolomics indicated elevated levels of amino acids, hypoxanthine, uric acid, cysteineglutathione disulfide alongside decreased levels of glucose and carnitines. Arginine, tyrosine, and 1-carboxyethylleucine showed correlation with incremental RIT.CONCLUSIONS: The final rewarming ischemia phase in LuTx involves rapid organ rewarming, accompanied by transcriptomic and metabolomic changes indicating pro-inflammatory signaling and disturbed cell metabolism. Limiting implantation time and lung cooling represent potential interventions to alleviate rewarming ischemic injury.PMID:39486771 | DOI:10.1016/j.healun.2024.10.020

Free Radic Biol Med. 2024 Oct 30:S0891-5849(24)01016-5. doi: 10.1016/j.freeradbiomed.2024.10.308. Online ahead of print.ABSTRACTOsteoradionecrosis of the jaw (ORNJ) is a severe complication following head and neck radiotherapy that significantly impacts the quality of life of patients. Currently, there is a lack of comprehensive understanding of the microenvironmental factors involved in ORNJ. In this study, we reveal the activation of taurine metabolism in irradiated mandibular stromal cells using scRNA-Seq and demonstrate a decrease in taurine levels in irradiated bone marrow mesenchymal stromal cells (BMSCs) through metabolomics. Compared with unirradiated BMSCs, taurine uptake in irradiated BMSCs increases. Taurine concentrations in the peripheral blood and jaws of irradiated mice are significantly lower than those in unirradiated mice (P = 0.0064 and 0.0249 respectively). Supplementation with taurine promotes osteogenic differentiation, reduces oxidative stress, and decreases DNA damage in irradiated BMSCs. Oral administration of taurine significantly improves the survival rate of irradiated mice and enhances osteogenesis in irradiated jaws. Our study highlights the role of taurine in the recovery from radiation-induced jaw injury, and suggests its potential as a non-invasive therapeutic option for combating ORNJ.PMID:39486749 | DOI:10.1016/j.freeradbiomed.2024.10.308

Int J Biol Macromol. 2024 Oct 30:137134. doi: 10.1016/j.ijbiomac.2024.137134. Online ahead of print.ABSTRACTLignin utilization is one of the key challenges in the valorziation of lignocellulose. Filamentous fungi are promising candidates for lignin degradation and mineralization. However, novel lignin-degrading species are underexplored and the mechanism of lignin degradation is not fully understood. Here we isolated and characterized a novel species, Myrothecium wuxin, capable of utilizing lignosulfonate as the sole carbon source. To understand the mechanism of lignin degradation, genomic, transcriptomic and metabolic analyses were performed. The genome was sequenced, and assembled to a size of 48.55 Mb, with a contig N50 size of 5.67Mb. A total of 14,221 protein-coding genes were predicted, including a high number of potential ligninolytic enzymes. Transcriptomic analysis revealed a pronounced effect of lignosulfonate on gene expression profiles. More than twenty intermediate aromatic metabolites were identified during lignosulfonate utilization. Through genomic annotation, the genes potentially involved in lignin degradation were identified, and more than nine metabolic pathways of lignin-derived aromatic intermediates were predicted, including the homogentisate pathway, benzoic acid pathway, as well as the tree-branched β-ketoadipate pathway. The genomic information will provide a valuable resource for lignin degradation, while the elucidated catabolic pathways and associated enzymes provide exciting biotechnological opportunities for lignin valorization and production of valuable chemicals.PMID:39486701 | DOI:10.1016/j.ijbiomac.2024.137134

Environ Pollut. 2024 Oct 30:125188. doi: 10.1016/j.envpol.2024.125188. Online ahead of print.ABSTRACTUrban road traffic environmental stress impacts outdoor population health, with oxidative damage serving as an early indicator of xenobiotic exposure. Polycyclic aromatic hydrocarbons (PAHs) as priority carcinogens pose significant public health burden, yet knowledge remains limited regarding the endogenous metabolic alternations associated with oxidative DNA injury. This cross-sectional study focused on the cohort consisting of 109 sanitation workers ("traffic exposure group") and 112 demographics-matched common residents ("controls") in South China. The goal was to elucidate the occurrence of internal exposure to nine hydroxyl PAHs, and the interrelations with oxidative DNA damage (indicated by 8-hydroxy-2'-deoxyguanosine, 8-OHdG) by linear mixed-effect regression model. T-test and orthogonal partial least squares discriminant analysis were used to determine differential metabolites in non-targeted metabolomics. Results revealed outdoor workers suffered from the heavier PAH exposure burden and exhibited a stronger dose-dependent correlation with 8-OHdG, evidenced by the higher regression coefficient (0.244, 95% CI: 0.154-0.334) than controls (0.203, 95% CI: 0.079-0.328). In total 42 differential endogenous metabolites witnessed significant expression under traffic emission scenario, mainly implicated in phenylalanine, tyrosine and tryptophan biosynthesis. The down-expressed uric acid was the unique metabolite that inversely correlated with the increased intake of ∑8PAH especially in cases. Partially attributed to the traffic-derived PAHs, the dysregulated amino acid, nicotinamide, purine, and steroid hormones metabolic pathways encompassing 11 metabolites were determined as underlying biomarkers in mediating DNA damage. Notably, our findings proposed uric acid may act as a potential antioxidant, as evidenced by the negative correlation with 8-OHdG. The study illustrates outcomes of metabolomics can collaboratively indicate DNA oxidative damage caused by PAHs linked to urban traffic exposure, which holds significant implications for future toxicological research.PMID:39486674 | DOI:10.1016/j.envpol.2024.125188

Microb Pathog. 2024 Oct 30:107093. doi: 10.1016/j.micpath.2024.107093. Online ahead of print.ABSTRACTBACKGROUND: Persistent lymphopenia can be regarded as an important index of acquired immune dysfunction in sepsis. Whether the specific immune factor changes in septic patients with lymphopenia and the correlation to gut microbiota and metabolites remain unclear.METHODS: This single-center prospective observation conducted lymphocyte subgroup analysis of blood samples and 16S rRNA gene amplicons sequencing and untargeted metabolomics analysis of fecal samples from 36 subjects with the persistent (≥3d) (n=21) and non-persistent lymphopenia (<3d) (n=15).RESULTS: The persistent lymphopenia showed higher the 28d mortality and 90d mortality, while significantly lower CD3+T/LY, CD3+T cells, CD3+CD4+T cells, CD3+CD8+T cells, Th1 cells, Th2 cells, CD45RA+Treg cells. The 16S rRNA results showed that Staphylococcus, Peptostreptococcus, Bulleidia, Leuconostoc were significant enriched in the persistent lymphopenia. The metabolomics analysis showed that α-Ketoisovaleric acid was increased and 7-DHCA, α-MCA, β-MCA, HCA, LCA-3S, CA, UCA and Citramalic acid were decreased in the persistent lymphopenia.CONCLUSION: In the process of interaction between host receptors and gut microbiota in patients with persistent lymphopenia sepsis, with a significant reduction in gut microbiota diversity and bile acid metabolites. That can affect various inflammatory pathways of gut immune cells, causing immune dysfunction in the body, which may be one of the main causes of death.PMID:39486555 | DOI:10.1016/j.micpath.2024.107093

J Nutr. 2024 Oct 30:S0022-3166(24)01120-9. doi: 10.1016/j.tjnut.2024.10.043. Online ahead of print.ABSTRACTDiet affects the intestinal microbiota. Increasingly, research is linking the intestinal microbiota to various human health outcomes. Consumption of traditional prebiotics (inulin, fructooligosaccharides, and galactooligosaccharides) confers health benefits through substrate utilization by select intestinal microorganisms, namely Bifidobacterium and Lactobacilli. A similar but distinct concept focused on microorganisms to support human health is through direct consumption of certain live microorganisms recognized as probiotics, which classically include Lactobacilli or Bifidobacterium strains. With advances in sequencing technologies and culturing techniques, other novel functional intestinal microorganisms are being increasingly identified and studied to determine how they may underpin human health benefits. These novel microorganisms are targeted for enrichment within the autochthonous intestinal microbiota through dietary approaches and are also gaining interest as next-generation probiotics because of their purported beneficial properties. Thus, characterizing dietary approaches that nourish select microorganisms in situ is necessary to propel biotic-focused research forward. As such, we reviewed the literature to summarize findings on dietary approaches that nourish the human intestinal microbiota and benefit health to help fill the gap in knowledge on the connections between certain microorganisms, the metabolome, and host physiology. The overall objective of this systematic review was to summarize the impact of dietary interventions with the propensity to nourish certain intestinal bacteria, affect microbial metabolite concentrations, and support gastrointestinal, metabolic, and cognitive health in healthy adults. Findings from the 17 randomized controlled studies identified in this systematic review indicated that dietary interventions providing dietary fibers, phytonutrients, or unsaturated fatty acids differentially enriched Akkermansia, Bacteroides, Clostridium, Eubacterium, Faecalibacterium, Roseburia, and Ruminococcus, with variable effects on microbial metabolites, and subsequent associations with physiological markers of gastrointestinal and metabolic health. These findings have implications for biotic-focused research on candidate prebiotic substrates as well as next-generation probiotics.PMID:39486521 | DOI:10.1016/j.tjnut.2024.10.043

Radiother Oncol. 2024 Oct 30:110608. doi: 10.1016/j.radonc.2024.110608. Online ahead of print.ABSTRACTBACKGROUND AND PURPOSE: Radiation-induced intestinal injury (RIII) compromises the clinical utility of pelvic radiotherapy (RT). We aimed to explore the protective effect and underlying mechanism of (-)-epigallocatechin-3-gallate (EGCG) on RIII.MATERIALS AND METHODS: We evaluated the protective effect of EGCG on intestine in RIII mouse model and pelvic cancer patients, while explored the underlying mechanism through (1) 16S rRNA sequencing, (2) metabolomic profiles, (3) fresh sterile fecal filtrate (SFF) transplantation, and (4) transcriptome sequencing.RESULTS: EGCG efficiently prevented RIII in mouse, as reflected by improved survival, alleviated intestinal structure damage, promoted intestinal regeneration, and ameliorated gut microbiota dysbiosis. Prophylactic EGCG intervention reduced the severity of RIII in patients receiving pelvic RT. Mechanistically, the protective effect of EGCG could be transferred to other mice by SFF transplantation. EGCG enriched gut microbiota-derived metabolite D-tagatose, and oral administration of D-tagatose reproduced the radio-protective effect of EGCG via activating AMPK.CONCLUSION: Oral EGCG may be a promising strategy for preventing RIII clinically, and warrant further investigation in prospective randomized phase III trials.PMID:39486483 | DOI:10.1016/j.radonc.2024.110608

J Pharm Biomed Anal. 2024 Oct 28;253:116553. doi: 10.1016/j.jpba.2024.116553. Online ahead of print.ABSTRACTColitis-associated colorectal cancer (CAC) is fatal and can develop spontaneously or as a complication of inflammatory bowel diseases. Although co-administration of azoxymethane/dextran sulfate sodium (AOM/DSS) is a classic method for CAC modeling, its limitations need to be addressed. Accordingly, we aimed to optimize the AOM/DSS model to study CAC extensively and further investigate its pathogenic mechanisms relative to microbiota and metabolism. We optimized the CAC model via a single or enhanced injection of AOM combined with different administration modes and varying DSS concentrations. Subsequently, the fecal-microbiota composition was examined using 16S RNA sequencing, and fecal-colon-metabolome profiles were evaluated via ultra-high performance liquid chromatography-mass spectrometry. Two interval injections of AOM combined with 1.5 % DSS-free drinking resulted in a high tumor formation rate, uniform tumor formation, and low mortality. Based on this model, we innovatively divided the pathogenesis of CAC into three stages, namely inflammation induction, proliferation initiation, and tumorigenesis, and examined the pathological characteristics in each stage. Gut microbial dysbiosis and metabolic alteration drove colorectal tumorigenesis by aggravating inflammation while promoting cell proliferation and carcinogenesis in mice. For the first time, we dynamically demonstrated the process of colon "inflammation to cancer" transformation and provided novel insights to clarify the role of amino acid metabolism in the formation of CAC.PMID:39486392 | DOI:10.1016/j.jpba.2024.116553

J Hazard Mater. 2024 Oct 29;480:136357. doi: 10.1016/j.jhazmat.2024.136357. Online ahead of print.ABSTRACTThe use of nano-chemicals in agriculture has been shown to enhance crop production through soil additions or foliar sprays. However, the accumulation pattern, translocation efficiency, mode of action of nanomaterials (NMs) via different application methods remain unclear. In this study, wheat was treated with CuO-NPs/CeO2-NPs (50 and 100 nm) for 21 days using soil and foliar application separately. Foliar spray resulted in higher accumulation and more efficient translocation of NMs compared to soil addition. Smaller NMs exhibited higher accumulation and transfer capabilities under the same application method. The accumulation of CuO-NPs was approximately 20 times greater than that of CeO2-NPs, particularly under the soil addition treatment. Scanning electron microscopy analysis demonstrated that NMs could directly enter wheat leaves via stomata during foliar application. Wheat growth was inhibited by roughly 15 % following CuO-NPs exposure, whereas no significant effects on growth were observed with CeO2-NPs. By integrating nontargeted metabolomics analysis with targeted physiological characteristics assessments, it was revealed that CuO-NPs mainly disturbed nitrogen metabolism pathways and induced oxidative damage. In contrast, CeO2-NPs enhanced carbohydrates related biological processes such as starch and sucrose metabolism, glycolysis, and TCA cycle, which are crucial for carbon metabolism. These findings suggest that the type of nanomaterial is a crucial factor to consider when evaluating their foliar or soil application in agriculture.PMID:39486329 | DOI:10.1016/j.jhazmat.2024.136357

J Hazard Mater. 2024 Oct 30;480:136370. doi: 10.1016/j.jhazmat.2024.136370. Online ahead of print.ABSTRACTTriclocarban (TCC) is a widely used antimicrobial agent and known endocrine-disrupting chemical found in various products. While its potential toxicities on endocrine-related organs have been highlighted in previous studies, the effects of TCC on non-endocrine organs, particularly the spleen, remain largely unknown. Here, we employed a novel approach combining long-term TCC exposure in a mouse model with spatial metabolomics and lipidomics to investigate the effects of TCC on the spleen. Our results showed that TCC exposure significantly altered the splenic organ weight and coefficient and induced obvious pathological alterations. Omic analysis revealed that TCC exposure disrupted the splenic homeostasis, as indicated by the upregulation of glutathione metabolism, ceramide-to-sphingomyelin signaling and biosynthesis of glycerophospholipids. Notably, the data of mass spectrometry imaging (MSI) revealed that TCC accumulated in the red pulp of the mouse spleen, while its metabolites concentrated in the white pulp. Further MSI analyses identified region-specific metabolic disruptions, including upregulated ceramide signaling in the red pulp, indicating localized inflammation, and upregulated glutathione metabolism throughout the spleen, suggesting widespread oxidative damage. Our findings provide crucial insights into the spatial distribution and biochemical impact of TCC on mice spleens, highlighting the potential risks of long-term TCC exposure to immune function.PMID:39486321 | DOI:10.1016/j.jhazmat.2024.136370

Clin Rheumatol. 2024 Nov 1. doi: 10.1007/s10067-024-07201-1. Online ahead of print.ABSTRACTRheumatoid arthritis (RA) is widespread globally, with the emergence of metabolites derived from both the host and microbes playing a pivotal role in its pathogenesis. This study aims to elucidate the relationships between serum metabolites and the immunological and clinical features of RA. Serum samples were collected from 35 RA patients and 37 healthy controls (HC). Metabolite profiling was performed using gas chromatography-mass spectrometry (GC/MS). Principal component analysis revealed a significant distinction between the RA and HC cohorts. Employing univariate statistical analysis, we identified 36 differential metabolites. Among these, 9 metabolites, including galactose and glucose, were found to be enriched, while the remaining metabolites, such as citric acid, fumaric acid, and inosine, were depleted in RA. These diverse metabolites encompassed various metabolic processes, including the biosynthesis of fatty acids, amino acids, and glucose. The enrichment of glucose and galactose in RA exhibited a substantial correlation with elevated IgG levels, as determined through correlation analysis. Conversely, the depletion of citric acid was correlated with elevated levels of C3 and CRP. Methionine, which also declined in RA patients, displayed a negative correlation with ESR. Furthermore, galactose and glucose exhibited significant positive correlations with naïve B cells, while the decreased eicosanoic acid level in RA was significantly associated with an increase in natural killer cells. Our findings suggest that the altered serum metabolite profile in RA is closely linked to disease severity and the dysregulated immune responses observed in RA patients. Key Points • Identified nine metabolites with upregulated expression and twenty-seven metabolites with downregulated expression. • Established a correlation between alterations in serum metabolite levels and inflammatory markers in RA patients. • Discovered a significant association between changes in serum metabolites and immune cell profiles in RA patients.PMID:39485556 | DOI:10.1007/s10067-024-07201-1

Bioresour Bioprocess. 2024 Nov 1;11(1):105. doi: 10.1186/s40643-024-00817-w.ABSTRACTComparative transcriptomics uncovered distinct expression patterns of genes associated with cofactor and vitamin metabolism in the high-yielding mutant strain Saccharopolyspora erythraea HL3168 E3, as compared to the wild-type NRRL 2338. An in-depth analysis was conducted on the effects of nine vitamins, and it was determined that thiamine pyrophosphate (TPP), vitamin B2, vitamin B6, vitamin B9, vitamin B12, and hemin are key enhancers in erythromycin production in E3, increasing the erythromycin titer by 7.96-12.66%. Then, the Plackett-Burman design and the path of steepest ascent were applied to further optimize the vitamin combination for maximum production efficiency, enhancing the erythromycin titer in shake flasks by 39.2%. Otherwise, targeted metabolomics and metabolic flux analysis illuminated how vitamin supplementation modulates the central carbon metabolism with notable effects on the TCA cycle and methionine synthesis to augment the provision of energy and precursors essential for erythromycin synthesis. This work highlights the capacity for precise vitamin supplementation to refine metabolic pathways, thereby boosting erythromycin production, and provides valuable directions for application on an industrial scale.PMID:39485551 | DOI:10.1186/s40643-024-00817-w

Acta Diabetol. 2024 Nov 1. doi: 10.1007/s00592-024-02336-8. Online ahead of print.ABSTRACTAIMS: Diabetic retinopathy (DR) is a severe complication of diabetes mellitus (DM), and it is challenging to diagnose DR at an early stage by conventional methods. The aim of the present work is to propose an innovative approach to monitor the process of DR from scratch.METHODS: The plasma metabolites changed with DM were obtained by time-dependent metabolomics and lipidomics; the change of retinal function was measured by b-wave amplitude and total Ops-wave amplitude in electroretinography (ERG). Multivariate statistical analysis, logistic regression and correlation analysis were employed to identify metabolic markers from metabolites for the monitoring of DR and investigate the relationship between metabolic markers and retinal function.RESULTS: The metabolic markers LPE18:0, LPC15:0, SM d14:2/26:0, SM d12:0/28:2 and MG 21:0 associated with DR can be utilized as metabolic markers to monitor the process of DR; The decrease in myo-inositol and LPC22:5 and increase in xylonic acid and TAG10:0/16:0/18:1 indicated retinal dysfunction.CONCLUSIONS: The levels of metabolic markers can be used as an indicator of the onset of DR or as a means of monitoring changes in retinal function.PMID:39485549 | DOI:10.1007/s00592-024-02336-8

J Proteome Res. 2024 Nov 1. doi: 10.1021/acs.jproteome.4c00437. Online ahead of print.ABSTRACTThe hospitalization and mortality rates of patients gradually increase following the onset and progression of liver cirrhosis (LC). We aimed to help define clinical stage and better target interventions by detecting the expression of specific metabolites in patients with different stages of LC via Q Exactive hybrid quadrupole orbitrap mass spectrometry (UPLC-Q-Exactive) technology. This noninterventional observation case-control study involved 139 patients with LC or acute-on-chronic liver failure (ACLF) in a Chinese hospital between October 2022 and April 2023. Serum specimens were analyzed for multiple metabolite levels using UPLC-Q-Exactive. Data were processed to screen for differentially accumulated metabolites (DAMs). Short time-series expression miner (STEM) analysis and enrichment analysis were performed to assess cirrhosis progression biomarkers. Following univariate and multivariate analyses, a Venn diagram indicated nine significant DAMs in common among groups. STEM analysis showed 8'-hydroxyabscisic acid, HDCA, pyruvate-3-phosphate, indospicine, eplerenone, and DEHP as significant; their levels first peaked [Child-Turcotte-Pugh (CTP) class B peaked] and then decreased with CTP grade aggravation. Significant differences among 8'-hydroxyabscisic acid, eplerenone, and DEHP were observed among LC comorbidities and between subgroups. Therefore, serum levels of six DAMs may characterize metabolomic changes, determine the severity of LC, and predict the development of ACLF.PMID:39485280 | DOI:10.1021/acs.jproteome.4c00437

Elife. 2024 Nov 1;13:RP94811. doi: 10.7554/eLife.94811.ABSTRACTThe mRNA 5'-cap structure removal by the decapping enzyme DCP2 is a critical step in gene regulation. While DCP2 is the catalytic subunit in the decapping complex, its activity is strongly enhanced by multiple factors, particularly DCP1, which is the major activator in yeast. However, the precise role of DCP1 in metazoans has yet to be fully elucidated. Moreover, in humans, the specific biological functions of the two DCP1 paralogs, DCP1a and DCP1b, remain largely unknown. To investigate the role of human DCP1, we generated cell lines that were deficient in DCP1a, DCP1b, or both to evaluate the importance of DCP1 in the decapping machinery. Our results highlight the importance of human DCP1 in decapping process and show that the EVH1 domain of DCP1 enhances the mRNA-binding affinity of DCP2. Transcriptome and metabolome analyses outline the distinct functions of DCP1a and DCP1b in human cells, regulating specific endogenous mRNA targets and biological processes. Overall, our findings provide insights into the molecular mechanism of human DCP1 in mRNA decapping and shed light on the distinct functions of its paralogs.PMID:39485278 | DOI:10.7554/eLife.94811