PubMed

Cancer Med. 2024 Dec;13(23):e70424. doi: 10.1002/cam4.70424.ABSTRACTBACKGROUND: Colorectal cancer (CRC) is one of the most common cancers. Various options are available for treatment, but prognosis is still poor in the more advanced stages. Current screening methods are not as accurate for distinguishing between benign and malignant growths, resulting in unnecessary invasive procedures. Recently a focus has been placed on identifying metabolites. Of these, taurine has frequently been detected, and this particular compound has a multifactorial role in human physiology.METHODS: We conducted a systematic review of studies up till November 2023. Searches were done in three databases- MEDLINE, CINAHL-Ebsco, and PubMed. Three independent reviewers filter titles, abstracts, and full-texts according to selection criteria. Ten studies (samples = 1714) were identified showing a differential level of taurine in CRC patient samples. Quality assessment accounted for the risk of bias of each study using the 'robvis' tool. Where meaningful comparisons could be made, meta-analyses were carried out using the 'R' program for precalculated effect sizes with 'metagen' in R. The 'meta' package was utilised for creation of forest plots.FINDINGS: Taurine was shown to significantly increase odds of CRC. It was also significantly associated with being a discriminator for CRC as a diagnostic metabolite. This was maintained at various stages of CRC. Taurine had increased expression in CRC patients, especially when the matrix utilised was blood. Nevertheless, there was significant heterogeneity for some outcomes.INTERPRETATION: In conclusion, these findings highlight the potential of using taurine as well as other bile acid metabolites (lithocholic and ursodeoxycholic acid) to diagnose CRC and illustrate the link with microbiome interactions. Overall increased taurine concentration are associated with significantly increased odds for CRC. There was mostly an increase in relative expression of taurine in CRC samples, excluding results from Wang et al.PMID:39632512 | DOI:10.1002/cam4.70424

Int J Food Sci Nutr. 2024 Dec 4:1-14. doi: 10.1080/09637486.2024.2437469. Online ahead of print.ABSTRACTPhosphatidylcholine (PC) has garnered considerable attention due to its involvement in a wide array of crucial biological functions. However, there is still much to active explore regarding the precise mechanisms that underlie PC's actions in the context of high-fat diet. In this study, we found that both PC intervention and treatment significantly mitigated lipid accumulation, liver damage, and body weight gaining triggered by the high-fat diet. Untargeted and targeted metabolomic analyses uncovered substantial effects of PC on bile acid metabolism, especially led to a substantial reduction in elevated levels of free bile acids. 16S rRNA gene sequencing revealed that PC modulated the gut microbiota structures and compositions in high-fat diet mice, particularly exhibiting a positive association with Pseudoflavonifractor abundance, and a negative correlation with Olsenella, Parasutterella, and Allobaculum abundance. Our study suggested that PC held promise as a potential candidate for alleviating lipid metabolism injury, liver disease or obesity.PMID:39632393 | DOI:10.1080/09637486.2024.2437469

Gut Microbes. 2024 Jan-Dec;16(1):2434675. doi: 10.1080/19490976.2024.2434675. Epub 2024 Dec 4.ABSTRACTAutism spectrum disorder (ASD) currently lacks effective diagnostic and therapeutic approaches. Disruptions in the gut ecosystem have been observed in individuals with ASD, suggesting that targeting gut microbiota through probiotic and dietary supplementation may serve as a potential treatment strategy. This two-phase study aimed to characterize the fecal metagenome of children with ASD and investigate the beneficial effects of a combined probiotic and medium-carbohydrate intervention in ASD. Fecal metagenomes of children with ASD were compared to those of typically developing children, revealing intestinal dysbiosis in ASD, characterized by reduced levels of Prevotella sp. Dialister invisus, and Bacteroides sp. along with increased predicted abundances of inosine, glutamate, xanthine, and methylxanthine. The gut bacteriome and phageome exhibited high cooperativity. In a 3-month pilot study, Bifidobacterium animalis subsp. lactis Probio-M8 (Probio-M8) was administered alongside a medium-carbohydrate diet to Chinese children with ASD. The primary endpoint was the Childhood Autism Rating Scale (CARS), while the secondary endpoint was the Gastrointestinal Symptom Rating Scale (GSRS). A total of 72 autistic children were initially recruited for the intervention study, but only 53 completed the intervention. Probio-M8, in combination with dietary intervention, significantly improved CARS and GSRS scores, increased fecal levels of Bifidobacterium animalis, Akkermansia muciniphila, Fusicatenibacter saccharivorans, and Sutterella sp. while also reducing Blautia obeum (Benjamini-Hochberg corrected p ≤ 0.05 for all cases). The intervention also modulated fecal metabolites associated with the metabolism of amino acids (lysine), neurotransmitters (glutamate, γ-aminobutyric acid), polyunsaturated fatty acids (arachidonate, myristic acid), and vitamin B3. In conclusion, Probio-M8 combined with medium-carbohydrate diet effectively improved ASD symptoms, with associated changes in the gut microbiome and metabolome, supporting its potential as an adjunctive therapy for ASD.PMID:39632378 | DOI:10.1080/19490976.2024.2434675

Ecotoxicol Environ Saf. 2024 Dec 3;289:117444. doi: 10.1016/j.ecoenv.2024.117444. Online ahead of print.ABSTRACTPerfluorooctanoic acid (PFOA) and tetrabromobisphenol A (TBBP-A) are emerging environmental contaminants with recognized potential health and ecological risks. This study investigated the effects of PFOA and TBBP-A exposure on the global of metabolites of silkworm gut with GC-MS metabolomics. Our results revealed distinct metabolic alterations in silkworms exposed to PFOA and TBBP-A, highlighting their differential impacts on silkworm health and productivity. Exposure to these chemicals significantly altered metabolic profiles, leading to disruptions in pathways related to lipid, carbohydrate, and amino acid metabolism. These findings suggest that PFOA and TBBP-A disrupt crucial metabolic processes in silkworms, indicating potential toxicity and prompting further investigation into their effects on human health and the environment. Ongoing research is crucial to develop safer alternatives and mitigate the risks associated with these persistent contaminants.PMID:39632329 | DOI:10.1016/j.ecoenv.2024.117444

New Phytol. 2024 Dec 4. doi: 10.1111/nph.20303. Online ahead of print.ABSTRACTThe plant community has a strong track record of RNA sequencing technology deployment, which combined with the recent advent of spatial platforms (e.g. 10× genomics) has resulted in an explosion of single-cell and nuclei datasets that can be positioned in an in situ context within tissues (e.g. a cell atlas). In the genomics era, application of proteomics technologies in the plant sciences has always trailed behind that of RNA sequencing technologies, largely due in part to upfront cost, ease-of-use, and access to expertise. Conversely, the use of early analytical tools for characterizing small molecules (metabolites) from plant systems predates nucleic acid sequencing and proteomics analysis, as the search for plant-based natural products has played a significant role in improving human health throughout history. As the plant sciences field now aims to fully define cell states, cell-specific regulatory networks, metabolic asymmetry and phenotypes, the measurement of proteins and metabolites at the single-cell level will be paramount. As a result of these efforts, the plant community will unlock exciting opportunities to accelerate discovery and drive toward meaningful translational outcomes.PMID:39632263 | DOI:10.1111/nph.20303

Food Chem. 2024 Nov 24:142224. doi: 10.1016/j.foodchem.2024.142224. Online ahead of print.ABSTRACTThis study explored the changes in nutrients, metabolites, and enzyme activity in Citrus reticulata peel powders (CRPP) under conventional or ultrasound-assisted solid-state fermentation (SSF) using Aspergillus niger CGMCC 3.6189. Compared to nonfermented CRPP (NF-CRPP), ultrasound-assisted fermented CRPP (UIS-CRPP) significantly increased total protein and carotenoid levels by 85.26 % and 179.68 %, respectively, surpassing conventionally-fermented CRPP (FO-CRPP). Among the 521 identified differential metabolites, organic acids, lipids, and flavonoids were predominant. Flavonoid accumulation was primarily driven by the flavone and flavonol biosynthesis pathway, with 90.47 % and 90.00 % of differential flavonoids upregulated in FO-CRPP and UIS-CRPP, respectively. SSF significantly increased phenylalanine, tyrosine, and methionine levels, and tyrosine ammonia-lyase and β-D-glucosidase activities, with higher levels in UIS-CRPP. These findings suggest that conventional and ultrasound-assisted fermentation enhances flavonoid levels in CRPP by modulating key enzyme activities in flavonoid biosynthesis and biotransformation. Our study offers a feasible approach for producing value-added products from citrus peel waste.PMID:39632168 | DOI:10.1016/j.foodchem.2024.142224

Ann Thorac Cardiovasc Surg. 2024;30(1). doi: 10.5761/atcs.oa.24-00126.ABSTRACTPURPOSE: Although the clinical outcomes of on-pump (ONCAB) and off-pump CABG (OPCAB) are well established, their metabolomic impacts remain underexplored. This study aims to compare the metabolic profiles of ONCAB and OPCAB to identify differential metabolites associated with clinical outcomes.METHODS: In a prospective cohort study conducted between January 2023 and September 2023, 100 plasma samples from 20 patients undergoing isolated elective CABG (10 per group) were analyzed. Samples were collected preoperatively and at multiple postoperative time points (Days 0-3) and processed using proton nuclear magnetic resonance (1H-NMR). Advanced statistical modeling was applied to identify differential metabolites.RESULTS: No significant differences were found in clinical outcomes, although ONCAB showed higher postoperative CKMB levels. Both procedures induced metabolomic alterations, with ONCAB demonstrating a more substantial impact, particularly on Day 0. Key metabolites, including leucine, succinate, creatine, glucose, and adenine, affected starch and sucrose metabolism.CONCLUSION: ONCAB induces more pronounced metabolic shifts immediately postsurgery, involving protein and energy turnover, oxidative stress, and disrupted glucose metabolism, indicative of cellular stress responses. A comprehensive understanding of these metabolic changes is critical for informing targeted interventions and supports the use of OPCAB as a preferred strategy for patients with elevated metabolic risks.PMID:39631940 | DOI:10.5761/atcs.oa.24-00126

Zhongguo Fei Ai Za Zhi. 2024 Oct 20;27(10):725-734. doi: 10.3779/j.issn.1009-3419.2024.106.28.ABSTRACTBACKGROUND: Metabolic change is one of the important characteristics of radiation pneumonitis. Radiotherapy, as a conventional method for the treatment of thoracic tumors, can not only effectively kill tumor cells, but also cause adverse reactions such as local inflammation and fibrosis, which leads to limited therapeutic effect and profound impact on the quality of life of patients. Therefore, it is of great significance to explore the metabolic changes caused by radiotherapy. The aim of this study was to investigate the effects of X-ray irradiation on the metabolism of a mouse lung epithelial cell line (murine lung epithelial-12, MLE12).METHODS: MLE12 cells were' cultured in vitro and randomly divided into radiation group (IR) and control group (NC). Cells in the IR group were irradiated at a dose of 10 Gy using a Hitachi X-ray irradiator. Cell supernatant samples were collected at 48 h after irradiation. Metabolomic analysis of the samples was performed by liquid chromatograph mass spectrometer (LC/MS).RESULTS: LC/MS metabolomics analysis revealed the metabolic changes of MLE12 cells at 48 h after irradiation. A total of 38 secretory metabolites were altered in the IR group compared with the NC group. According to the annotation of Kyoto Encyclopedia of Genes and Genomes (KEGG) database, the differential metabolites are mainly involved in nucleotide metabolism, amino acid metabolism and lipid metabolism, among which the difference in nucleotide metabolism is the most significant.CONCLUSIONS: The metabolism of MLE12 cells was significantly affected by X-ray irradiation, mainly affecting the nucleotide metabolic pathways, including purine and pyrimidine metabolites and related metabolic pathways.PMID:39631829 | DOI:10.3779/j.issn.1009-3419.2024.106.28

J Microbiol Biotechnol. 2024 Jul 17;34(12):2558-2567. doi: 10.4014/jmb.2312.12033. Online ahead of print.ABSTRACTSun-drying constitutes a traditional method employed in the preparation of dried oysters within the coastal regions of South China. However, its ramifications on nutritional attributes and the genesis of flavor-contributory compounds in the resultant dried oysters remain significantly unexplored. This research endeavors to scrutinize the repercussions of the production process on the microbiota and metabolites within dried oysters. Utilizing 16s rRNA amplicon sequencing, the identification of 409 operational taxonomic units (OTUs) ensued, wherein Proteobacteria, Bacteroidetes, Firmicutes, Tenericutes, and Actinobacteria surfaced as the primary pathogenic bacteria present in oyster samples. Analysis of the dried oyster sample metabolomes via LC-MS unveiled a discernible augmentation in compounds associated with steroid hormone biosynthesis, arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, and linoleic acid metabolism throughout the entirety of the drying process. Subsequent exploration into the association between metabolites and bacterial communities highlighted the prevailing coexistence of Mycoplasma, Psychrilyobacter, and Vibrio demonstrating negative correlations with a substantial number of metabolites across categories including organic acid and its derivatives, nucleotide and its metabolites, free fatty acids, and amino acids. Conversely, Shewanella and Arcobacter exhibited positive correlations with these metabolite categories. This exhaustive investigation offers invaluable insights into the dynamic alterations within the microbiota and metabolites of dried oysters across diverse drying periods. These findings are anticipated to significantly contribute to the advancement of production techniques and the formulation of enhanced safety measures for the processing of dried oysters.PMID:39631783 | DOI:10.4014/jmb.2312.12033

J Ethnopharmacol. 2024 Dec 2:119197. doi: 10.1016/j.jep.2024.119197. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Huangkui Capsule (HKC) is a traditional Chinese medicinal preparation. Numerous clinical studies have reported that HKC has a good nephroprotection effect. The clinical application of cisplatin is greatly limited by its nephrotoxicity, and HKC shows promise in preventing cisplatin-induced nephrotoxicity (CIN).AIM OF THE STUDY: To evaluate the effectiveness of HKC in alleviating CIN and explore its underlying action mechanisms.MATERIALS AND METHODS: A rat model of CIN was established via single-dose injection of cisplatin. The effectiveness of HKC was evaluated by biochemical indices and pathological sections. Then, serum, kidney, and cecal endogenous metabolic profiles as well as the gut microbiota were characterized using lipidomics, metabolomics, and 16S rRNA high-throughput sequencing technique. Spearman's correlation analysis was carried out between gut microbiota, biomarkers, and biochemical indices. Finally, antibiotic treatment was performed to establish pseudo-sterile rat model and validate the nephroprotection of HKC in a gut microbiota-dependent manner.RESULTS: HKC could significantly attenuate the abnormal elevation of serum creatinine and urea nitrogen, kidney index, and kidney injury score in CIN rats, remarkably alleviate the disturbance of metabolic profiles of serum, kidney, and cecal contents, corresponding to the endogenous metabolites such as fatty acids, phosphatidylcholines, amino acids, acylcarnitines, and short-chain fatty acids, and enrich the diversity of gut microbiota. Spearman's correlation analysis revealed that Clostridium_sensu_stricto_1 was positively correlated with the altered short-chain fatty acids in serum and negatively correlated with the altered acylcarnitine in the kidney. In the pseudo-sterile rat model, the attenuation effect of HKC on the abnormal elevation of serum creatinine and urea nitrogen, along with the alleviation of metabolic profile disorders, was greatly diminished or even abolished, demonstrating the nephroprotective effect of HKC in a gut microbiota-dependent manner.CONCLUSIONS: HKC exerted the nephroprotective effect on CIN in a gut microbiota-dependent manner, mainly by regulating Clostridium_sensu_stricto_1 mediated metabolisms of phosphatidylcholines, acylcarnitines, fatty acids, tryptophan and short-chain fatty acids, thereby reducing the inflammatory response. The present study could provide reliable scientific evidence for gut microbiota-dependent mechanisms of HKC in the treatment of kidney injury and may widen the clinical application of HKC in cisplatin-containing cancer therapy.PMID:39631718 | DOI:10.1016/j.jep.2024.119197

J Proteomics. 2024 Dec 2:105360. doi: 10.1016/j.jprot.2024.105360. Online ahead of print.ABSTRACTInflammatory bowel disease is characterized by severe imbalance of intestinal flora and metabolic disorders. Recent studies have demonstrated that probiotics can effectively alleviate inflammatory bowel disease by restoring the intestinal flora structure and modulating the immune response. However, the role of probiotics in regulating intestinal metabolism disorders is still unclear. This study explores the role of probiotic B. cereus in alleviating DSS-induced colitis. The findings indicated probiotic B. cereus treatment mitigated tissue damage and apoptosis during inflammation. Metabolome and transcriptome analysis revealed B. cereus activated the cholic acid-FXR axis by increasing cholic acid levels, which promoted the gene expression level of NF-κB inhibitor α, reduced the IL-1β, IL-6, IL-18 and TNF-α concentrations. Furthermore, it effectively mitigated the DSS-induced disruption of bile acid metabolism, arginine metabolism, and linoleic acid metabolism. This study explores the effect and mechanisms of probiotic B. cereus on alleviating DSS-induced colitis. It aims to provide a theoretical basis for microbial therapy in inflammatory bowel disease. SIGNIFICANCE: This study used metabolome and transcriptome to reveal the roles and mechanisms, which probiotic Bacillus cereus modulates metabolic disorders and alleviate DSS-induced colitis. We identified the cholic acid-FXR axis as an important target for alleviating DSS-induced colitis. These findings provide new insights into microbial treatment strategies for IBD.PMID:39631667 | DOI:10.1016/j.jprot.2024.105360

Biochim Biophys Acta Bioenerg. 2024 Dec 2:149530. doi: 10.1016/j.bbabio.2024.149530. Online ahead of print.ABSTRACTThe temperate climate-adapted brown hare (Lepus europaeus) and the cold-adapted mountain hare (Lepus timidus) are closely related and interfertile species. However, their skin fibroblasts display distinct gene expression profiles related to fundamental cellular processes. This indicates important metabolic divergence between the two species. Through targeted metabolomics and metabolite tracing, we identified species-specific variations in glycerol 3-phosphate (G3P) metabolism. G3P is a key metabolite of the G3P shuttle, which transfers reducing equivalents from cytosolic NADH to the mitochondrial electron transport chain (ETC), consequently regulating glycolysis, lipid metabolism, and mitochondrial bioenergetics. Alterations in G3P metabolism have been implicated in multiple human pathologies including cancer and diabetes. We observed that mountain hare mitochondria exhibit elevated G3P shuttle activity, alongside increased membrane potential and decreased mitochondrial temperature. Silencing mitochondrial G3P dehydrogenase (GPD2), which couples the conversion of G3P to the ETC, uncovered its species-specific role in controlling mitochondrial membrane potential and highlighted its involvement in skin fibroblast thermogenesis. Unexpectedly, GPD2 silencing enhanced wound healing and cell proliferation rates in a species-specific manner. Our study underscores the pivotal role of the G3P shuttle in mediating physiological, bioenergetic, and metabolic divergence between these hare species.PMID:39631556 | DOI:10.1016/j.bbabio.2024.149530

Genomics. 2024 Dec 2:110973. doi: 10.1016/j.ygeno.2024.110973. Online ahead of print.ABSTRACTMany studies on the adaptability of Tibetan sheep to hypoxia have been reported, but little attention has been paid to the reproduction of Tibetan sheep living at an altitude of more than 4000 m. In this study, the ovaries of Alpine Merino sheep (AM) living in middle-high altitude areas (2500 m) and the ovaries of Gangba Tibetan sheep (GB) and Huoba Tibetan sheep (HB) living in ultra-high altitude areas (4400 m or more) were collected. Through morphological, transcriptomics and metabolomics, the effects of ultra-high altitude areas on Tibetan sheep ovarian development and the molecular mechanism of sheep's adaptability to ultra-high altitude environment were explored. The results showed that the number of granulosa cells in AM was significantly higher than that in GB and HB. The transcriptome revealed several genes related to follicular development, such as DAPL1, IGFBP1, C5, GPR12, STRA6, BMPER, etc., which were mainly enriched in related pathways such as cell growth and development. Through metabolomics analysis, it was found that the differential metabolites between the three groups of sheep were mainly lipids and lipid-like small molecules, such as Glycerol 3-Phosphate, PC (16: 0 / 18: 3 (9Z, 12Z, 15Z)), mainly enriched in lipid metabolism and other related pathways. The results of combined analysis showed that Tryptophan metabolism and Steroid hormone biosynthesis may have a significant effect on Tibetan sheep follicular development. Some genes (including HSD17B7, CYP11A1, CYP19, HSD3B1, CYP17, etc.) and some metabolites (including Cortisone, 2-Methoxyestrone, etc.) are enriched in these pathways, regulating ovarian and follicular development by affecting estrogen, progesterone, etc.. The results further revealed the molecular mechanism of Tibetan sheep to adapt to the ultra-high altitude environment and maintain normal ovarian and follicular development through the regulation of genes and metabolites.PMID:39631551 | DOI:10.1016/j.ygeno.2024.110973

Sci Total Environ. 2024 Dec 3;957:177851. doi: 10.1016/j.scitotenv.2024.177851. Online ahead of print.ABSTRACTIncreasing evidence indicates that plants under environmental stress can actively seek the help of microbes ('cry-for-help' hypothesis). However, empirical evidence underlying this strategy is limited under metal-stress conditions. Here, we employed integrated microbial community profiling in cadmium (Cd) polluted soil and culture-based methods to investigate the three-way interactions between the industrial hemp (Cannabis Sativa L.), rhizospheric microbes, and Cd stress. Results from the pot and three cycles of the successful hemp planting experiments showed that Cd stress significantly affected the composition of rhizosphere fungi in industrial hemp and induced enrichment of the fungal operational taxonomic unit (OTU)3 (Cladosporium). A representative of OTU3 (strain DM-2) was successfully isolated. In a hydroponic experiment, inoculation of DM-2 significantly increased the shoot length (by 25.84 %) and fresh weight (by 92.66 %) of hemp seedlings when compared to the absence of DM-2 under the Cd stress. The findings indicate that DM-2 inoculation could effectively alleviate the Cd stress in hemp seedlings. Metabolomic analysis of spent media with or without DM-2 revealed the association of DM-2 with the transformation of root exudates to melatonin, which may be a key chemical in plant-microbe interactions against abiotic stresses. The findings will inform efforts to manipulate the root microbiome to enhance plant growth in polluted environments.PMID:39631339 | DOI:10.1016/j.scitotenv.2024.177851

PLoS One. 2024 Dec 4;19(12):e0315213. doi: 10.1371/journal.pone.0315213. eCollection 2024.ABSTRACT[This corrects the article DOI: 10.1371/journal.pone.0270593.].PMID:39630706 | DOI:10.1371/journal.pone.0315213

Plant Biol (Stuttg). 2024 Dec 4. doi: 10.1111/plb.13747. Online ahead of print.ABSTRACTThe exceptionally high growth rate and high flavonoid content make the giant duckweed Spirodela polyrhiza (L.) Schleid. (Arales: Lemnaceae Martinov) an ideal organism for food production and metabolic engineering. To facilitate this, identification of the genetic basis underlying growth and metabolic traits is essential. Here, we analysed growth and content of 42 metabolites in 137 S. polyrhiza genotypes and characterized the genetics underpinning these traits using a genome-wide association (GWA) approach. We found that biomass positively correlated with the content of many free amino acids, including L-glutamine, L-tryptophan, and L-serine, but negatively correlated with specialized metabolites, such as flavonoids. GWA analysis showed that several candidate genes involved in processes such as photosynthesis, protein degradation, and organ development were jointly associated with multiple metabolic traits. The results suggest the above genes are suitable targets for simultaneous optimization of duckweed growth and metabolite levels. This study provides insights into the metabolic diversity of S. polyrhiza and its underlying genetic architecture, paving the way for industrial applications of this plant via targeted breeding or genetic engineering.PMID:39630110 | DOI:10.1111/plb.13747

Adv Sci (Weinh). 2024 Dec 4:e2403309. doi: 10.1002/advs.202403309. Online ahead of print.ABSTRACTN6-acetyl-L-lysine residue is abundant in dietary protein but little is known about its potential influences on the diet-consumers. Herein, it is reported that Lysyl-tRNA synthetase (KARS) mediates co-translational deposition of diet-derived N6-acetyl-L-lysine (AcK) in nascent proteins to contribute to the acetylome in cells. Acetylated dietary protein is a direct source of AcK that can widely and substantially regulate the acetylome in multiple organs of mice. By analyzing the mechanisms underlying AcK contributing to the acetylome in mammalian cells, it is found that KARS can utilize AcK as an alternative substrate to produce N6-acetyl-l-lysyl-tRNA. The crystal structure of KARS in complex with AcK at 2.26 Å resolution shows that AcK shares the same substrate-binding pocket as L-lysine, allowed by a sidechain flip of Tyr499. The generated N6-acetyl-L-lysyl-tRNA introduces AcK into growing nascent polypeptide and results in protein acetylation, including the regions buried inside folded proteins that are post-translational modification (PTM)-inaccessible and functionally important. This undocumented protein modification mechanism is inherently different from PTM and termed as co-translational modification (coTM). It is expected to extend the repertoire of acetylome and improve the understanding of protein modification mechanisms in cells.PMID:39630081 | DOI:10.1002/advs.202403309

Mol Carcinog. 2024 Dec 4. doi: 10.1002/mc.23851. Online ahead of print.ABSTRACTCirculating metabolic profiles have shown promising potential in identifying high-risk populations for various diseases, while metabolic perturbation plays an important role in gastric cancer. In this study, we conducted a cross-sectional study with 1800 participants to identify plasma metabolite signatures associated with environmental risk factors of gastric cancer. Subsequently, we evaluated the association between these signatures and gastric cancer risk in a nested case-control study involving 326 gastric cancer cases and 326 matched cancer-free controls. We conducted mediation analyses to elucidate the potential impact of metabolites on the association between environmental factors and gastric cancer. In the cross-sectional study, we identified 46 metabolites associated with Helicobacter pylori (H. pylori) infection, 365 with alcohol drinking, and 154 with smoking status. In the nested case-control study, 60 plasma metabolites, comprising 30 lipids, 15 amino acids, 6 xenobiotics, 3 nucleotides, 2 cofactors and vitamins, 2 carbohydrate, 1 energy, and 1 peptide, were associated with gastric cancer risk. A one-standard deviation increment in the H. pylori infection-related metabolomic signature was associated with an increased risk of gastric cancer (OR = 1.66, 95% CI: 1.32-2.09, p = 1.62 × 10-5). Furthermore, the effect of H. pylori infection on gastric cancer was partially mediated by the metabolomic signature (23.28%, 95% CI: 0.09-0.56) or adenine (13.69%, 95% CI: 0.05-0.31). In conclusion, we have identified metabolites associated with environmental factors and demonstrated the association between the H. pylori infection signature and gastric cancer risk. The findings provide novel insights into characterizing high-risk population for gastric cancer.PMID:39630052 | DOI:10.1002/mc.23851

J Physiol. 2024 Dec 4. doi: 10.1113/JP287342. Online ahead of print.ABSTRACTIt has been hypothesised that skeletal muscle protein turnover is affected by menstrual cycle phase with a more anabolic environment during the follicular vs. the luteal phase. We assessed the influence of menstrual cycle phase on muscle protein synthesis and myofibrillar protein breakdown in response to 6 days of controlled resistance exercise in young females during peak oestrogen and peak progesterone, using stable isotopes, unbiased metabolomics and muscle biopsies. We used comprehensive menstrual cycle phase-detection methods, including cycle tracking, blood samples and urinary test kits, to classify menstrual phases. Participants (n = 12) completed two 6 day study phases in a randomised order: late follicular phase and mid-luteal phase. Participants performed unilateral resistance exercise in each menstrual cycle phase, exercising the contralateral leg in each phase in a counterbalanced manner. Follicular phase myofibrillar protein synthesis (MPS) rates were 1.33 ± 0.27% h-1 in the control leg and 1.52 ± 0.27% h-1 in the exercise leg. Luteal phase MPS was 1.28 ± 0.27% h-1 in the control leg and 1.46 ± 0.25% h-1 in the exercise leg. We observed a significant effect of exercise (P < 0.001) but no effect of cycle phase or interaction. There was no significant effect of menstrual cycle phase on whole-body myofibrillar protein breakdown (P = 0.24). Using unbiased metabolomics, we observed no notable phase-specific changes in circulating blood metabolites associated with any particular menstrual cycle phase. Fluctuations in endogenous ovarian hormones influenced neither MPS, nor MPB in response to resistance exercise. Skeletal muscle is not more anabolically responsive to resistance exercise in a particular menstrual cycle phase. KEY POINTS: It has been hypothesised that the follicular (peak oestrogen) vs. the luteal (peak progesterone) phase of the menstrual cycle is more advantageous for skeletal muscle anabolism in response to resistance exercise. Using best practice methods to assess menstrual cycle status, we measured integrated (over 6 days) muscle protein synthesis (MPS) and myofibrillar protein breakdown (MPB) following resistance exercise in females (n = 12) in their follicular and luteal phases. We observed the expected differences in oestrogen and progesterone concentrations that confirmed our participants' menstrual cycle phase; however, there were no notable metabolic pathway differences, as measured using metabolomics, between cycle phases. We observed that resistance exercise stimulated MPS, but there was no effect of menstrual cycle phase on either resting or exercise-stimulated MPS or MPB. Our data show no greater anabolic effect of resistance exercise in the follicular vs. the luteal phase of the menstrual cycle.PMID:39630025 | DOI:10.1113/JP287342

Adv Sci (Weinh). 2024 Dec 4:e2411276. doi: 10.1002/advs.202411276. Online ahead of print.ABSTRACTMetabolic studies at the single cell level can directly define the cellular phenotype closest to physiological or disease states. However, the current single cell metabolome (SCM) study using mass spectroscopy has difficulty giving a complete view of the metabolic activity in the cell, and the prediction of the metabolism-phenotype relationship is limited by the potential inconsistency between transcriptomic and metabolic levels. Here, the single-cell simultaneous metabolome and transcriptome profiling method (scMeT-seq) is developed at one single cell, based on sub-picoliter sampling from the cell for the initial metabolome profiling followed by single cell transcriptome sequencing. This design not only provides sufficient cytoplasm for SCM but also nicely keeps the cellular viability for the accurate transcriptomic analysis in the same cell. Integrative analysis of scMeT-seq reveals both dynamical and cell state-specific associations between metabolome and transcriptome in the macrophages with defined metabolic perturbations. Moreover, metabolite signatures are mapped to the single-cell trajectory and gene correlation network of macrophage transition, which allows the unsupervised functional interpretation of metabolome. Thus, the established scMeT-seq should lead to a new perspective in metabolic research by transforming metabolomics from a metabolite snapshot to a functional approach.PMID:39629980 | DOI:10.1002/advs.202411276