PubMed

J Transl Med. 2024 Nov 1;22(1):989. doi: 10.1186/s12967-024-05801-8.ABSTRACTBACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood.METHODS: To investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC). This included mass cytometry, cytokine arrays, and targeted metabolomics. We then analyzed the peripheral changes of NMOSD, and features related to NMOSD's disease severity. Furthermore, an integrative analysis was conducted to identify the distinguishing characteristics of NMOSD from HC. Additionally, we unveiled the variations in peripheral features among different clinical subgroups within NMOSD. An independent cohort of 40 individuals with NMOSD was utilized to assess the serum levels of fibroblast activation protein alpha (FAP).RESULTS: Our analysis revealed a distinct peripheral immune and metabolic signature in NMOSD patients. This signature is characterized by an increase in monocytes and a decrease in regulatory T cells, dendritic cells, natural killer cells, and various T cell subsets. Additionally, we found elevated levels of inflammatory cytokines and reduced levels of tissue-repair cytokines. Metabolic changes were also evident, with higher levels of bile acids, lactates, triglycerides, and lower levels of dehydroepiandrosterone sulfate, homoarginine, octadecadienoic acid (FA[18:2]), and sphingolipids. We identified distinctive biomarkers differentiating NMOSD from HC and found blood factors correlating with disease severity. Among these, fibroblast activation protein alpha (FAP) was a notable marker of disease progression.CONCLUSIONS: Our comprehensive blood profile analysis offers new insights into NMOSD pathophysiology, revealing significant peripheral immune and metabolic alterations. This work lays the groundwork for future biomarker identification and mechanistic studies in NMOSD, highlighting the potential of FAP as a marker of disease progression.PMID:39487546 | DOI:10.1186/s12967-024-05801-8

BMC Microbiol. 2024 Nov 1;24(1):445. doi: 10.1186/s12866-024-03560-6.ABSTRACTBACKGROUND: Sponge-associated microorganisms are promising resources for the production of bioactive compounds with cytotoxic potential. The main goal of our study is to isolate the fungal endophytes from the Red Sea sponge Hyrtios sp. followed by investigating their cytotoxicity against number of cell lines.RESULTS: The fungal strain UR3 was isolated from the Red Sea sponge using Sabouraud dextrose agar media. It was identified based on partial 18 S rRNA gene and ITS sequence analyses as Cladosporium sp. UR3. The in vitro cytotoxic potential of the ethyl acetate extract of the fungal isolate was evaluated using MTT assay against three cancer cell lines: CACO2, MCF7, and HEPG2. Metabolomics profiling of the obtained ethyl acetate extract using LC-HR-ESI-MS, along with molecular docking and pharmacological network studies for the dereplicated compounds were performed to explore its chemical profile and the possible cytotoxic mechanism of the sponge-associated fungi.CONCLUSION: These results highlighted the role of sponge-associated fungi as a fruitful resource for the discovery of cytotoxic metabolites.PMID:39487417 | DOI:10.1186/s12866-024-03560-6

Metabolomics. 2024 Nov 2;20(6):122. doi: 10.1007/s11306-024-02192-1.ABSTRACTINTRODUCTION AND OBJECTIVES: Since the use of a bio stimulant should provide a response to a problem that depends on the production system implemented (crops, plant model, soil, climate, the farmer's practices…), the agricultural sector is facing concomitant challenges of choosing the best bio stimulant that suits their needs. Thus, understanding bio stimulant-plant interactions, at molecular level, using metabolomics approaches is a prerequisite, for the development of a bio stimulant, leading to an effective exploration and application of formulations in agriculture. AGRO-K®, is commercialized as a plant-based bio stimulant that improve vigor and enhance resistance to lodging in cereal crops. A recent previous untargeted metabolomics study has demonstrated the ability of this bio stimulant to improve wheat resistance to lodging, in real open-field conditions. However, the reproducibility of the impact of this bio stimulant in other filed crops is not yet investigated.METHODS: Therefore, the present study aimed to assess the changes in primary and secondary metabolites in the roots, stems, and leaves of fiber flax (Linum usitatissimum L), treated with the bio stimulant, using NMR and LC-MS-based untargeted metabolomics approach.RESULTS AND CONCLUSIONS: In addition to the previous result conducted in wheat, the present analysis seemed to show that this bio stimulant led to a similar pathway enhancement in flax. The pathways which seem to be reproducibly impacted are hydroxycinnamic acid amides (HCAAs), phenylpropanoids and flavonoids. Impacting these pathways enhance root growth and elongation and cell wall lignification, which can aid in preventing crop lodging. These results confirm that HCAAs, flavonoids, and phenylpropanoids could serve as signatory biomarkers of the impact of AGRO-K® on improving lodging resistance across various plant species.PMID:39487363 | DOI:10.1007/s11306-024-02192-1

Metabolomics. 2024 Nov 2;20(6):121. doi: 10.1007/s11306-024-02188-x.ABSTRACTBACKGROUND: Chronic kidney disease (CKD) is common in patients with diabetes mellitus (DM). Volatile organic compounds (VOCs) are widespread pollutants that may impact DM development.OBJECTIVE: This study aims to explore the association between urinary VOC metabolites and CKD in patients with DM.METHODS: Adult National Health and Nutrition Examination Survey (NHANES) 2011 to 2018 participants with DM were included in this study. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Multivariable regression models were used to analyze the associations between urinary VOC metabolites and CKD.RESULTS: A total of 1,295 participants with DM and a mean age of 59 years were included. After adjustment for demographic and clinical characteristics, elevated levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) (tertile 2: adjusted odds ratio (aOR) = 1.81, 95% confidence interval (CI): 1.15-2.85, p = 0.012), N-acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC) (tertile 2: aOR = 1.84, 95% CI: 1.10-3.08, p = 0.021), DHBMA (tertile 3: aOR = 1.93, 95% CI: 1.12-3.35, p = 0.020), and phenylglyoxylic acid (PGA) (tertile 3: aOR = 1.71, 95% CI: 1.11-2.63, p = 0.017) were significantly associated with increased likelihood of CKD.CONCLUSION: Specific urinary VOC metabolite levels are positively associated with an increased risk of CKD in patients with DM. These findings suggest that monitoring urinary VOC metabolites could be important for the prevention and management of CKD in this population. Future longitudinal studies should focus on establishing causality and elucidating the underlying mechanisms of these associations.PMID:39487359 | DOI:10.1007/s11306-024-02188-x

Metabolomics. 2024 Nov 2;20(6):123. doi: 10.1007/s11306-024-02191-2.ABSTRACTINTRODUCTION: Breast Cancer (BC) is one of the most diagnosed malignancies among women and the second leading cause of cancer related death in North America. Triple Negative BC (TNBC), one of the most severe subtypes of BC, is extremely aggressive and has a higher chance of occurrence in women under 50 years of age. Due to a lack of regular mammographic testing in women under 50, many individuals with TNBC are diagnosed late which can decrease their survival rate. Currently, liquid biopsy is being investigated as a potentially less-invasive alternative to traditional breast tissue biopsy, but this approach is not completely reliable. Blood contains extracellular vesicles (EVs), which carry biomolecular cargo and play a role in BC progression and metastasis. Examination of small EVs could potentially yield metabolite biomarkers for early BC diagnosis.OBJECTIVE: We aim to study metabolites in small EVs to find biomarkers for BC diagnosis.METHODS: In this work, an untargeted nano-LC MS/MS metabolomics approach was used to analyze metabolites from small EVs derived from metastatic MDA-MB-231 and compare it with a non-cancerous MCF10A cell line.RESULTS: Two metabolites, LysoPC 22:6/0:0 and N-acetyl-L-Phenylalanine, unique to sEVs of MDA-MB-231, were identified, validated, and proposed as potential BC biomarkers.CONCLUSION: Metabolites from sEVs may be used for BC diagnosis.PMID:39487276 | DOI:10.1007/s11306-024-02191-2

Sci Rep. 2024 Nov 1;14(1):26290. doi: 10.1038/s41598-024-76637-x.ABSTRACTStuccoes are very delicate decorative elements of Roman age. Very few of them survived almost intact to present days and, for this reason, they are of great interest to restorers and conservators. In this study, we combined metabarcoding and untargeted metabolomics to characterise the taxonomic and metabolic profiles of the microorganisms forming biofilms on the stuccoes located on the ceiling of the laconicum, a small thermal environment in the archaeological park of Baia (southern Italy). We found that some samples were dominated by bacteria while others by eukaryotes. Additionally, we observed high heterogeneity in the type and abundance of bacterial taxa, while the eukaryotic communities, except in one sample (at prevalence of fungi), were dominated by green algae. The metabolic profiles were comparable across samples, with lipids, lipid-like molecules and carbohydrates accounting for roughly the 50% of metabolites. In vitro and in vivo tests to remove biofilms on stuccoes using essential oils blends were successful at a 50% dilution for one hour and half. This integrative study advanced our knowledge on taxonomic and metabolic profiles of biofilms on ancient stuccoes and highlighted the potential impacts of these techniques in the field of cultural heritage conservation.PMID:39487240 | DOI:10.1038/s41598-024-76637-x

Sci Rep. 2024 Nov 1;14(1):26291. doi: 10.1038/s41598-024-77909-2.ABSTRACTPorphyromonas gingivalis (P. gingivalis), the main pathogen responsible for periodontitis, is linked to systemic disorders via the oral-gut axis. Short-chain fatty acids (SCFAs) are vital for gut health, but their role in P. gingivalis-induced gut disorders remains unclear. This study utilized metabolomics and 16 S rRNA sequencing to explore gut microbiota and SCFAs levels in P. gingivalis-induced periodontitis mouse models. Significant changes were observed in gut, including a reduction in SCFAs-producing bacteria, such as Lactobacillus, Ligilactobacillus, Allobucalum, and a notable decrease in Firmicutes and Actinobacteriota. The intestinal permeability tests and histological analyses revealed that periodontitis led to epithelial inflammation, reduced mucin secretion, and compromised gut barrier integrity. In vitro experiments with Caco-2 cells co-cultured with P. gingivalis showed that the bacterium disrupted cellular junctions by impairing autophagy, specifically through the ATG5-LC3 pathway, leading to decreased expression of tight junction proteins and reduced SCFA absorption. Remarkably, rapamycin treatment both in vitro and in vivo restored gut barrier function by enhancing autophagy, increasing tight junction protein expression, and promoting SCFAs absorption via MCT1 and SMCT1, alongside GPR43/GPR109a pathway activation. These findings reveal autophagy's novel role in regulating SCFAs metabolism in P. gingivalis-induced gut dysbiosis, offering insights for preventing and treating periodontitis-related systemic diseases.PMID:39487211 | DOI:10.1038/s41598-024-77909-2

J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Oct 24;1248:124342. doi: 10.1016/j.jchromb.2024.124342. Online ahead of print.ABSTRACTThis study has developed a new targeted methodology for the separation, detection, and quantification of metabolites from the wider energy metabolome of industrially important microorganisms such as Saccharomyces cerevisiae in a single analytical sample. This has been achieved using UHPLC-MS technology in HILIC mode. Absolute concentrations of metabolites nicotinamide adenine dinucleotide (NAD), nicotinamide adenine dinucleotide reduced (NADH), nicotinamide adenine dinucleotide phosphate (NADP), nicotinamide adenine dinucleotide phosphate reduced (NADPH), flavin adenine dinucleotide (FAD), adenosine-monophosphate (AMP), adenosine-diphosphate (ADP), and adenosine-triphosphate (ATP) were determined in a single extraction and analytical methodology. This study demonstrated the development of a rapid, statistically robust, and reproducible methodology through regression calibrations of standard samples from 0.1 to 100 µMol providing a correlation value of r2 = >0.98 for all metabolites. Sample preparation, extraction and analytical methodologies used showed high accuracy, sensitivity, and recovery. With an LOD and LOQ for the targeted analysis of metabolites from the wider energy metabolism in a single sample and analytical run with the lowest LOD of 0.055 nMol (±0.002) and lowest LOQ of 0.167 nMol (±0.006). This method was then applied to Saccharomyces cerevisiae cell culture to evaluate the methodology in industrially used microbial cultures. Results obtained have been statistically determined to be robust and reproducible through recovery analysis using deuterated and isotopically labelled internal standards AMP-15N, ADP-15N and ATP-d14.PMID:39486264 | DOI:10.1016/j.jchromb.2024.124342

Environ Int. 2024 Oct 22;193:109092. doi: 10.1016/j.envint.2024.109092. Online ahead of print.ABSTRACTFluorotelomer sulfonates (FTSs) are widely used as novel substitutes for perfluorooctane sulfonate, inevitably leading to FTSs accumulation in various environmental media and subsequent exposure to humans. This accumulation eventually poses environmental hazards and health risks. However, their toxicity mechanisms remain unclear. Herein, the mechanisms of two FTSs (6:2 and 8:2 FTS) induced toxicity in human hepatocellular carcinoma cells were investigated via non-targeted metabolomics and lipidomics based on liquid chromatography-high resolution mass spectrometry. Our results revealed that amino acid, purine, acylcarnitine and lipid levels were significantly perturbed by 6:2 and 8:2 FTS exposure. The effects of 8:2 FTS exposure were largely characterized by up-regulation of pyruvate metabolism pathway and down-regulation of purine metabolism pathway, whereas the opposite trends were induced by 6:2 FTS exposure. The opposite trends were confirmed by the mRNA expression levels of four key genes (glyoxalase 1, adenylosuccinate lyase, inosine monophosphate dehydrogenase 1 (IMPDH1) and IMPDH2) determined by real-time PCR. Common lipid perturbations included significantly increased ceramide/sphingomyelin ratios, and obvious accumulation of hexosylceramides and lysoglycerophospholipids. 6:2 FTS exposure induced sharp accumulation of glycerides, including monoglycerides, diglycerides and triglycerides. 8:2 FTS exposure induced decreased levels of acylcarnitines and fatty acids. Both of 6:2 and 8:2 FTS exposure induced increased levels of intracellular reactive oxygen species, an imbalance in energy metabolism homeostasis, and mitochondrial dysfunction. The results of integrated omics analysis are expected to serve as valuable information for the health risk assessment of 6:2 FTS and 8:2 FTS.PMID:39486253 | DOI:10.1016/j.envint.2024.109092

Mar Pollut Bull. 2024 Oct 31;209(Pt B):117197. doi: 10.1016/j.marpolbul.2024.117197. Online ahead of print.ABSTRACTThe neurotoxin β-N-methylamino-L-alanine (BMAA) produced by marine diatoms has been implicated in some neurological disorders, and there is a need to elucidate the biological processes involved in the production of BMAA-containing proteins. In this study, growth of seven diatoms was suppressed under nitrogen limitation, however the production of BMAA-containing proteins was significantly increased in six of them, up to 5.22-fold increase in Thalassiosira andamanica. These variations were associated with reduced concentration of dissolved inorganic nitrogen (DIN) and changes in photosynthetic efficiency. Analytical results of non-targeted metabolomics showed that the obvious changes in amino acids, lipids and sugars may help diatoms to adjust growth and physiological parameters. Combined with previous transcriptomic data, a decrease in N-acetyl-D-glucosamine (GlcNAc) leads to an increase in N-glycan terminal modifications, which in turn increases protein misfolding. In addition, the reduced efficiency of vesicular transport in the COPII system may have exacerbated the accumulation of BMAA-containing proteins.PMID:39486208 | DOI:10.1016/j.marpolbul.2024.117197

Org Lett. 2024 Nov 1. doi: 10.1021/acs.orglett.4c03470. Online ahead of print.ABSTRACTMoon snails (family: Naticidae) lay egg masses that are rich in bacterial species distinct from the surrounding environment. We hypothesized that this microbiome chemically defends the moon snail eggs from predation and pathogens. Herein, we report the discovery of bokeelamides, new lipopeptides from the egg mass-associated bacterium, Ectopseudomonas khazarica, which were discovered using mass spectrometry (MS)-based metabolomics. The structures of the bokeelamides were elucidated using two-dimensional (2D) nuclear magnetic resonance (NMR), tandem MS, Marfey's, and genomic analyses.PMID:39486159 | DOI:10.1021/acs.orglett.4c03470

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