PubMed

Front Pharmacol. 2025 Jan 7;15:1518906. doi: 10.3389/fphar.2024.1518906. eCollection 2024.ABSTRACTINTRODUCTION: Salvia miltiorrhiza radix et rhizoma (Danshen) is a crucial medicinal material for treating cardiovascular and cerebrovascular diseases. However, the presence of adulterants and intraspecific variability poses challenges to its clinical safety.METHODS: This study collected samples of S. miltiorrhiza from various regions and commonly encountered adulterants. The composition differences of S. miltiorrhiza radix and its adulterants were analyzed by fingerprint and broad-target metabolomics. Chloroplast genome was used to distinguish intra-genus species and DNA barcoding was used to identify germplasm sources.RESULTS: The fingerprinting analysis proved that there is no chemical composition consistency between S. miltiorrhiza radix and its adulterants. Broad-targeted metabolomics can distinguish S. miltiorrhiza radix from Salvia yunnanensis radix, Dipsacus asperoides radix, and Arctium lappa radix. Additionally, comparative chloroplast genome analysis indicated that atpF and rps4-trnT-UGU were the potential DNA barcodes for S. miltiorrhiza. 259 samples from 13 provinces and 21 origins were amplified and sequenced, resulting in the identification of 62 haplotypes. The unique haplotypes found in Shanxi Luoyang, Shandong Qingdao and other places can be used as molecular geographic markers for the identification of the germplasm source of S. miltiorrhiza.DISCUSSION: This study systematically differentiates S. miltiorrhiza from its adulterants and highlights the potential of unique haplotypes as markers for sourcing. The findings provide strong scientific evidence for the clinical safety of S. miltiorrhiza, emphasizing the importance of proper cultivation, selection, and breeding of varieties.PMID:39845798 | PMC:PMC11753211 | DOI:10.3389/fphar.2024.1518906

Hortic Res. 2024 Sep 28;12(1):uhae277. doi: 10.1093/hr/uhae277. eCollection 2025 Jan.ABSTRACTSugar limitation has dramatic consequences on plant cells, which include cell metabolism and transcriptional reprogramming, and the recycling of cellular components to maintain fundamental cell functions. There is however no description of the contribution of epigenetic regulations to the adaptation of plant cells to limited carbon availability. We investigated this question using nonphotosynthetic grapevine cells (Vitis vinifera, cv Cabernet Sauvignon) cultured in vitro with contrasted glucose concentrations. Sugar depletion in the culture medium led to a rapid cell growth arrest and a major metabolic shift that include the depletion in soluble sugar and total amino acids and modulation of the cell redox status. Consistently, flux modeling showed a dramatic slowdown of many pathways required for biomass accumulation such as cell wall and protein synthesis. Sugar depletion also resulted in a major transcriptional reprogramming, characterized by the induction of genes involved in photosynthesis, and the repression of those related to sucrose mobilization or cell cycle control. Similarly, the epigenetic landscape was deeply modified. Glucose-depleted cells showed a higher global DNA methylation level than those grown with glucose. Changes in DNA methylation mainly occurred at transposable elements, and at genes including some of those differentially expressed, consistent with an important role for methylation to the adaptation of cells to limited sugar availability. In addition, genes encoding histone modifiers were differentially expressed suggesting that additional epigenetic mechanisms may be at work in plant cells under carbon shortage.PMID:39845645 | PMC:PMC11750959 | DOI:10.1093/hr/uhae277

Burns Trauma. 2025 Jan 22;13:tkae057. doi: 10.1093/burnst/tkae057. eCollection 2025.ABSTRACTIn this review, we examine the significance of multi-omics technologies in understanding the plethora of intricate processes that activate gastrointestinal (GI) injury repair. Multi-omics, which includes genomics, transcriptomics, proteomics, and metabolomics, allows intricate mapping of cellular responses and molecular pathways involved in GI repair. We highlight the potential of multi-omics to discover previously unknown therapeutic targets or elucidate the molecular basis of the pathogenesis of GI. Furthermore, we explore the possibilities of integrating omics data to improve prediction models, and summarize the state-of-the-art technological developments and persisting obstacles that hinder the translation of multi-omics into clinical practice. Finally, innovative multi-omics approaches that can improve patient outcomes and advance therapeutic strategies in GI medicine are discussed.PMID:39845194 | PMC:PMC11752642 | DOI:10.1093/burnst/tkae057

Front Microbiol. 2025 Jan 8;15:1524521. doi: 10.3389/fmicb.2024.1524521. eCollection 2024.ABSTRACTINTRODUCTION: Polycystic ovary syndrome (PCOS) is a common gynecological condition affecting individuals of reproductive age and is linked to the gut microbiome. This study aimed to identify the hotspots and research trends within the domain of the gut microbiome in PCOS through bibliometric analysis.METHODS: Utilizing bibliometric techniques, we examined the literature on the gut microbiome in PCOS from the Web of Science Core Collection spanning the period from 2012 to 2023. Analytical tools such as CiteSpace, VOSviewer, and Bibliometric R packages were employed to evaluate various metrics, including countries/regions, institutions, authors, co-cited authors, authors' H-index, journals, co-references, and keywords.RESULTS: A total of 191 publications were identified in the field of gut microbiome in PCOS, with an increase in annual publications from 2018 to 2023. People's Republic of China was the most productive country, followed by the United States of America (USA), India. Shanghai Jiao Tong University, Fudan University, and Beijing University of Chinese Medicine were the top three most publications institutions. Thackray VG was identified as the most prolific author, holding the highest H-index, while Liu R received the highest total number of citations. The journal "Frontiers in Endocrinology" published the most articles in this domain. The most frequently co-cited reference was authored by Qi XY. The analysis of keyword burst detection identified "bile acids" (2021-2023) as the leading frontier keyword. Additionally, "gut dysbiosis," "phenotypes," "adolescents," "metabolomics," "metabolites," "fecal microbiota transplantation," and "IL-22" have emerged as the primary keywords reflecting recent research trends.CONCLUSION: This bibliometric analysis explores how the gut microbiome influences endocrine and metabolic disorders related to PCOS, emphasizing its role in the development of PCOS and treatments targeting the gut microbiome. The findings serve as a valuable resource for researchers, enabling them to identify critical hotspots and emerging areas of investigation in this field.PMID:39845049 | PMC:PMC11753182 | DOI:10.3389/fmicb.2024.1524521

Front Microbiol. 2025 Jan 8;15:1473270. doi: 10.3389/fmicb.2024.1473270. eCollection 2024.ABSTRACTWe investigated the metabolome of the iron- and sulfur-oxidizing, extremely thermoacidophilic archaeon Metallosphaera sedula grown on mineral pyrite (FeS2). The extraction of organic materials from these microorganisms is a major challenge because of the tight contact and interaction between cells and mineral materials. Therefore, we applied an improved protocol to break the microbial cells and separate their organic constituents from the mineral surface, to extract lipophilic compounds through liquid-liquid extraction, and performed metabolomics analyses using MALDI-TOF MS and UHPLC-UHR-Q/TOF. Using this approach, we identified several molecules involved in central carbon metabolism and in the modified Entner-Doudoroff pathway found in Archaea, sulfur metabolism-related compounds, and molecules involved in the adaptation of M. sedula to extreme environments, such as metal tolerance and acid resistance. Furthermore, we identified molecules involved in microbial interactions, i.e., cell surface interactions through biofilm formation and cell-cell interactions through quorum sensing, which relies on messenger molecules for microbial communication. Moreover, we successfully extracted and identified different saturated thiophene-bearing quinones using software for advanced compound identification (MetaboScape). These quinones are respiratory chain electron carriers in M. sedula, with biomarker potential for life detection in extreme environmental conditions.PMID:39845047 | PMC:PMC11750793 | DOI:10.3389/fmicb.2024.1473270

Front Microbiol. 2025 Jan 8;15:1501684. doi: 10.3389/fmicb.2024.1501684. eCollection 2024.ABSTRACTThe gut microbiome was involved in a variety of physiological processes and played a key role in host environmental adaptation. However, the mechanisms of their response to altitudinal environmental changes remain unclear. In this study, we used 16S rRNA sequencing and LC-MS metabolomics to investigate the changes in the gut microbiome and metabolism of the Yarkand toad-headed agama (Phrynocephalus axillaris) at different altitudes (-80 m to 2000 m). The results demonstrated that Firmicutes, Bacteroidetes, and Proteobacteria were the dominant phylum, Lachnospiraceae and Oscillospiraceae were the most abundant family, and the low-altitude populations had higher richness than high-altitude populations; Akkermansiaceae appeared to be enriched in high-altitude populations and the relative abundance tended to increase with altitude. The gut microbiome of three populations of P. axillaris at different altitudes was clustered into two different enterotypes, low-altitude populations and high-altitude populations shared an enterotype dominated by Akkermansia, Kineothrix, Phocaeicola; intermediate-altitude populations had an enterotype dominated by Mesorhizobium, Bradyrhizobium. Metabolites involved in amino acid and lipid metabolism differed significantly at different altitudes. The above results suggest that gut microbiome plasticity drives the extensive adaptation of P. axillaris to multi-stress caused by different altitudes. With global warming, recognizing the adaptive capacity of wide-ranging species to altitude can help plan future conservation strategies.PMID:39845039 | PMC:PMC11751238 | DOI:10.3389/fmicb.2024.1501684

Front Microbiol. 2025 Jan 8;15:1447527. doi: 10.3389/fmicb.2024.1447527. eCollection 2024.ABSTRACTAs the world's population grows, pursuing sustainable agricultural production techniques to increase crop yields is critical to ensuring global food security. The development and application of biological agents is of great significance in promoting the sustainable development of agriculture. This study aimed to investigate the role of JZ (compound microbial agent) and MZ (biological agent made from plant materials) in improving the rhizosphere microecological environment and nutrient availability for rice. This study found that JZ enriched Cyanobacteria with biological nitrogen fixation functions; spraying MZ can enrich some beneficial microbiota, such as Bradyrhizobium, playing a role in symbiotic nitrogen fixation. Meanwhile, JZ and MZ were found to affect rhizosphere soil metabolism and improve potassium and nitrogen availability. JZ may promote the degradation of fungicides in the rhizosphere soil environment. Overall, applying biological agents through optimizing rice growing environment to improve yield showed great potential.PMID:39845035 | PMC:PMC11752750 | DOI:10.3389/fmicb.2024.1447527

Front Microbiol. 2025 Jan 8;15:1514633. doi: 10.3389/fmicb.2024.1514633. eCollection 2024.ABSTRACTINTRODUCTION: Golden Retrievers have a high risk of obesity, which is prevalent in dogs and is associated with inflammation and cancer, impairing the health and life expectancy of companion animals. Microbial and metabolite biomarkers have been proposed for identifying the presence of obesity in humans and rodents. However, the effects of obesity on the microbiome and metabolome of Golden Retrievers remains unknown. Therefore, this study was designed to evaluate the signatures of serum biochemistry indexes, gut microbiota and plasma metabolites in non-obese and obese Golden Retrievers, aiming to recognize potential biomarkers of canine obesity.METHODS: A total of 8 non-obese (Ctrl group) and 8 obese (Obe group) Golden Retrievers were included in the present study to collect blood and feces samples for measurements. The fecal microbiome and plasma metabolome were determined using 16S rRNA amplicon sequencing and liquid chromatography-mass spectrometry, respectively.RESULTS: Results showed that the alanine aminotransferase activity and total bilirubin concentration, which have been measured using serum biochemistry analysis, were higher in the Obe group than in the Ctrl group (p < 0.05). Moreover, there was a significant difference in gut microbiota composition between the two groups (p < 0.05). The phyla Proteobacteria, Fusobacteriota, and Bacteroidota as well as genera Fusobacterium, Prevotella, Faecalibacterium, Escherichia-Shigell, and Alloprevotella were more abundant, while phylum Firmicutes and genera Peptoclostridium, Blautia, Turicibacter, Allobaculum, and Erysipelatoclostridium were less abundant in the Obe group compared to the Ctrl group (p < 0.05). Plasma concentrations of citrulline and 11-dehydrocorticosterone were significantly higher in the Obe group than those in the Ctrl group (p < 0.05). Close correlations between serum biochemistry parameters, gut microbiome, and plasma metabolites were observed in the current study.CONCLUSION: The obesity-induced shifts in serum biochemistry indexes, gut microbiota, and plasma metabolites profiles suggest that obese Golden Retrievers exhibit a different microbiome and metabolome than non-obese ones, and the certain metabolites like citrulline and 11-dehydrocorticosterone could be considered as potential biomarkers to recognize obese Golden Retrievers.PMID:39845032 | PMC:PMC11751222 | DOI:10.3389/fmicb.2024.1514633

Food Chem X. 2024 Dec 24;25:102100. doi: 10.1016/j.fochx.2024.102100. eCollection 2025 Jan.ABSTRACTMixed fermentation can enhance the flavor and aroma of fruit wine, but the mechanisms driving this enhancement remain unclear. This study used non-targeted metabolomics to analyze the effects of mixed versus single fermentation on plum wine flavor. The results showed that compared with single fermentation, mixed fermentation reduced ethanol content and the ability to consume reducing sugars. In single fermentation, volatile compounds increased over time, while in mixed fermentation, they first increased and then declined. Mixed fermentation notably increased esters and reduced higher alcohols, with key differentiators including phenethyl acetate, hexyl acetate, isoamyl acetate, ethyl acetate, isoamyl alcohol, phenethyl alcohol, ethyl caproate, and isobutanol. Furthermore, 40 differential non-volatile flavor compounds were identified, with amino acids emerging as the predominant differentiators. The annotation analysis of these compounds revealed 11 important metabolic pathways for proline, aspartate, glutamate, and β-alanine metabolism. These findings provide insight about producing plum wines with distinct flavor profiles.PMID:39844961 | PMC:PMC11751420 | DOI:10.1016/j.fochx.2024.102100

Food Chem X. 2024 Dec 28;25:102097. doi: 10.1016/j.fochx.2024.102097. eCollection 2025 Jan.ABSTRACTThe quality and flavor of Liuyang Douchi are usually closely related to the metabolites compostion. This work described the metabolic profiles of Liuyang douchi during fermentation. Obvious hydrolysis of carbohydrates, proteins and slight lipids degradation were observed. Notably, the qu-making and pile-fermentation stage of douchi could be easily distinguished according to their metabolites profile, and pile-fermentation stage showed the most abundant metabolites. Specifically, organic acid, such as succinic acid and lactic acid, accumulated during pile-fermentation, as well as amino acids and derivatives. Especially glutamate (Glu), which contributed to the umami taste, increased form 0.82 mg/g to 15.90 mg/g after fermentation. Meanwhile, metabolisms related to amino acids were also the main enrichment metabolic pathways. Among them, some flavor compunds such as phenylacetaldehyde might drived from phenylalanine metabolism. These results could provide a new understanding on the metabolic characteristics during Liuyang douchi fermentation.PMID:39844959 | PMC:PMC11751413 | DOI:10.1016/j.fochx.2024.102097

Food Chem X. 2024 Dec 29;25:102139. doi: 10.1016/j.fochx.2024.102139. eCollection 2025 Jan.ABSTRACTThis study used integrative omics to address the response of key elements of the grapevine holobiont to contrasted pedoclimatic conditions found in distinct subregions of Douro Valley (Portugal). A metabolic OPLS-DA model predicted with 100 % accuracy the geographic origin of berries; higher UV radiation, higher temperature and lower precipitation stimulated the accumulation of phenolic acids, flavonols and malvidin conjugates, in detriment of amino acids, organic acids, flavan-3-ols, proanthocyanidins and non-malvidin anthocyanins. Metabarcoding showed a trade-off between bacteria and fungal diversity among subregions, with Pseudomonas, Lactobacillus, Aspergillus and Penicillium acting as intraregional microbial markers. The high phenotypic plasticity of berries and the role of microbes in this process are relevant upon current projections for increased UV radiation and temperature in Southern European viticulture, in a climate change scenario, with predicted impacts on regional wine quality and on the development of adaptation strategies for resilient viticulture.PMID:39844957 | PMC:PMC11750517 | DOI:10.1016/j.fochx.2024.102139

Se Pu. 2025 Feb;43(2):139-147. doi: 10.3724/SP.J.1123.2024.02015.ABSTRACTBiomarkers for ischemic stroke (IS) are yet to fulfill clinical requirements. This study used non-targeted metabolomics to investigate differential metabolites and metabolic pathways in plasma and brain tissue following IS, with the aim of identifying new potential biomarkers and therapeutic targets. Twelve Tibetan miniature pigs were randomly assigned to a model- or sham-operation group. An electrocoagulation-based anterior temporal approach was employed to occlude the middle cerebral artery, thereby creating a model for IS. Plasma and brain tissue samples were collected 36 h post-surgery and analyzed using liquid chromatography-mass spectrometry. Principal component and partial least squares discriminant analyses were used to screen for differential metabolites and exclude exogenous metabolites at p<0.05. Compounds were classified according to the HMDB (Human Metabolome Database), and subjected to KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway and VIP (variable importance in projection) analyses. Plasma metabolomics revealed that 86 metabolites were upregulated while 149 were downregulated, with (Z)-3-oxo-2-(2-pentenyl)-1-cyclopentylacetic acid, trans-cinnamic acid and cinnamoylglycine determined to be significant metabolites. Fifty-eight differential metabolites were upregulated in brain tissue and 53 were downregulated, with 2,3-dihydroflavon-3-ol, guanidinoacetic acid (GAA), N-acetyl-D-tryptophan, oxidized glutathione, 2-hydroxyquinoline, and N-acetyl-L-aspartate (NAA) identified as significant metabolites. Organic acids and derivatives, lipids and lipid-like molecules, organoheterocyclic compounds, and organic oxygen compounds were found to be common compound categories among the top five types of compound in both plasma and brain tissue. Common metabolic pathways in plasma and brain tissue include amino acid metabolism, digestive system, cancer overview, and lipid metabolism pathways, with the (Z)-3-oxo-2-(2-pentenyl)-1-cyclopentylacetic acid, GAA, oxidized glutathione, and NAA metabolites serving as potential biomarkers. This study provides a theoretical foundation for the early screening and development of clinical treatment strategies for IS.PMID:39844704 | DOI:10.3724/SP.J.1123.2024.02015

Anal Chem. 2025 Jan 23. doi: 10.1021/acs.analchem.4c05015. Online ahead of print.ABSTRACTMetabolite levels and turnover rates are necessary to understand metabolomic dynamics in a living organism fully. Amino acids can play distinct roles in various cellular processes, and their abnormal levels are associated with pathological conditions, including cancer. Therefore, their levels, especially turnover rates, may provide enormous information about a phenotype. 13C- or 13C,15N-labeled amino acids have also been commonly used to trace amino acid metabolism. This study presented a new methodology based on 18O labeling for amino acids that relied on monitoring mass isotopologues to calculate the turnover rates of amino acids. The method optimization studies were carried over for selective amino acid monitoring. This methodology provides a rapid, robust, and simple GC-MS method for analyzing the fluxes of amino acid metabolism. The developed method was applied to fetal human colon (FHC) and human colon carcinoma (Caco-2) cell lines to determine cancer-induced shifts in the turnover rates of amino acids. These results defined metabolic reprogramming in Caco-2 cells through increased glutamate and serine turnovers and sharply decreased turnovers of aspartate, threonine, and methionine, therefore pointing to some metabolic vulnerabilities in the metabolism of cancerous cells. The simple mechanism of the developed methodology, the availability of affordable 18O-enriched water, and the ease of application can open a new arena in fluxomics analysis.PMID:39844690 | DOI:10.1021/acs.analchem.4c05015

Anticancer Agents Med Chem. 2025 Jan 22. doi: 10.2174/0118715206350735241224073200. Online ahead of print.ABSTRACTBACKGROUND: Lung cancer is a highly aggressive tumor with limited therapeutic options. The misregulation of Androgen Receptor (AR) signaling has been observed in lung cancer. Therefore, inhibiting AR signaling is a promising strategy for treating lung cancer.OBJECTIVE: Selective Androgen Receptor Modulators (SARMs) are small molecule drugs with a high affinity for the AR. S4, a member of SARMs was potentially positioned as a promising therapeutic agent in A549 lung cancer cells owing to its high bioavailability, lesser side effects, and novelty in cancer.METHODS: We employed several techniques to investigate the potential anti-carcinogenic effect of S4 on A549 cells at cellular level. The cytotoxicity of S4 was investigated thorough MTT, and the IC50 value was identified as 0.22 mM. Then, the anchorage-dependent and -independent colonization of cells were assessed by colony formation and soft agar assays, respectively. Additionally, migration capacity, apoptosis, proliferation, senescene, cell-cycle progression of cells was examined thoroughly. In addition, gene expression profile and metabolome signature were explored via qRT-PCR and metabolomics, respectively to provide molecular links for S4 mode of action.RESULTS: Our findings demonstrate that S4 inhibited growth, migration, and proliferation while inducing apoptosis. S4 significantly upregulated the BAX, CDKN1A, PUMA, and GADD45A genes while downregulating MKI67, BIRC5, and PCNA expression. S4 treatment drastically altered the metabolome signature, and enrichment of cancer related pathways by altered metabolites was noteworthy.CONCLUSION: We report the first study evaluating the potential anti-carcinogenic effects of S4 on lung cancer invitro which would bridge the gap on the utility of SARMs as inhibitors of lung cancer. Our results suggest that S4 could be considered as a promising drug candidate to test further for lung cancer treatment.PMID:39844407 | DOI:10.2174/0118715206350735241224073200

Curr Neuropharmacol. 2025 Jan 22. doi: 10.2174/1570159X23666250122093451. Online ahead of print.ABSTRACTBACKGROUND: The incidence of Major Depressive Disorder (MDD) is high among adolescent females, and MDD is often accompanied by suicide attempts (SAs), which have a serious negative impact on health. However, changes in lipids, thyroid hormone, and brain metabolism among female adolescents with MDD and the relationships between these three markers and MDD with SA have yet to be elucidated.METHODS: This study enrolled 71 MDD patients with SA (MDD+SA), 66 MDD patients without SA (MDD-SA), and 47 healthy controls (HCs). We analysed the lipid and thyroid hormone levels and magnetic resonance spectroscopy results of the subjects.RESULTS: Low levels of social support, high levels of life stress, and high levels of suicidal ideation (SI) were risk factors for SA. In MDD patients, 1) thyroid stimulating hormone was positively correlated with triglyceride (TG) and N-acetyl aspartic acid (NAA)/creatinine in the prefrontal cortex (PFC) and negatively correlated with high-density lipoprotein and the choline/creatinine in the thalamus; 2) free thyroxine was negatively correlated with the choline/creatinine in the thalamus; 3) total cholesterol, TG, low-density lipoprotein, and choline/NAA in the PFC were positively correlated with the severity of SI and suicide risk; and 4) NAA/creatinine in the thalamus was negatively correlated with the severity of SI and suicide risk.CONCLUSION: In female adolescents with MDD, there are significant synergistic changes in lipids, thyroid hormones, and brain metabolism-related factors, and the changes in these indicators may be related to the pathological mechanism of SA.PMID:39844402 | DOI:10.2174/1570159X23666250122093451

Plant Cell Environ. 2025 Jan 22. doi: 10.1111/pce.15400. Online ahead of print.ABSTRACTPlant internal phosphorus (P) recycling is a complex process, which is vital for improving plant P use efficiency. However, the mechanisms underlying phosphate (Pi) release from internal organic-P form remains to be deciphered in crops. Here, we functionally characterised a Pi-starvation responsive purple acid phosphatase (PAP), GmPAP23 in soybean (Glycine max). GmPAP23 could hydrolyse a series of Pi-containing compounds in vitro, such as trehalose-6-phosphate and glucose-l-phosphate. Moreover, GmPAP23 overexpression led to less P distribution in soybean source organs, including mature leaves and pod shells, but more P distribution in seeds under P sufficient conditions, although no effect was observed for transgenic soybean lines with its suppression. Metabolomic analysis found that a group of P-containing metabolites exhibited differential accumulations in mature leaves between wild type (WT) and GmPAP23 overexpression lines, such as glucose-l-phosphate and trehalose-6-phosphate. Moreover, a MYB transcription factor, GmPHR14 was subsequently found to activate the transcription of GmPAP23 via directly binding to its promoter. Collectively, these findings could highlight that the GmPHR14-GmPAP23 pathway, which controls internal P recycling in soybean, and thus affect yield.PMID:39844392 | DOI:10.1111/pce.15400

Cell Biosci. 2025 Jan 22;15(1):6. doi: 10.1186/s13578-024-01340-3.ABSTRACTBACKGROUND: Japanese encephalitis (JE) induced by Japanese encephalitis virus (JEV) infection is the most prevalent diagnosed epidemic viral encephalitis globally. The underlying pathological mechanisms remain largely unknown. Given that viruses are obligate intracellular parasites, cellular metabolic reprogramming triggered by viral infection is intricately related to the establishment of infection and progression of disease. Therefore, uncovering and manipulating the metabolic reprogramming that underlies viral infection will help elucidate the pathogenic mechanisms and develop novel therapeutic strategies.METHODS: Metabolomics analysis was performed to comprehensively delineate the metabolic profiles in JEV-infected mice brains and neurons. Metabolic flux analysis, quantitative real-time PCR, western blotting and fluorescence immunohistochemistry were utilized to describe detailed glutamine-glutamate metabolic profiles during JEV infection. Exogenous addition of metabolites and associated compounds and RNA interference were employed to manipulate glutamine-glutamate metabolism to clarify its effects on viral replication. The survival rate, severity of neuroinflammation, and levels of viral replication were assessed to determine the efficacy of glutamine supplementation in JEV-challenged mice.RESULTS: Here, we have delineated a novel perspective on the pathogenesis of JE by identifying an aberrant low flux in glutamine-glutamate metabolism both in vivo and in vitro, which was critical in the establishment of JEV infection and progression of JE. The perturbed glutamine-glutamate metabolism induced neurotransmitter imbalance and created an immune-inhibitory state with increased gamma-aminobutyric acid/glutamate ratio, thus facilitating efficient viral replication both in JEV-infected neurons and the brain of JEV-infected mice. In addition, viral infection restrained the utilization of glutamine via the glutamate-α-ketoglutaric acid axis in neurons, thus avoiding the adverse effects of glutamine oxidation on viral propagation. As the conversion of glutamine to glutamate was inhibited after JEV infection, the metabolism of glutathione (GSH) was simultaneously impaired, exacerbating oxidative stress in JEV-infected neurons and mice brains and promoting the progression of JE. Importantly, the supplementation of glutamine in vivo alleviated the intracranial inflammation and enhanced the survival of JEV-challenged mice.CONCLUSION: Altogether, our study highlights an aberrant glutamine-glutamate metabolism during JEV infection and unveils how this facilitates viral replication and promotes JE progression. Manipulation of these metabolic alterations may potentially be exploited to develop therapeutic approaches for JEV infection.PMID:39844330 | DOI:10.1186/s13578-024-01340-3

J Anim Sci Biotechnol. 2025 Jan 23;16(1):12. doi: 10.1186/s40104-024-01142-0.ABSTRACTBACKGROUND: The synchronized absorption of amino acids (AAs) and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body. The study investigated how the starch digestion rate and AA levels impact intestinal AA digestion, transport and metabolism, breast muscle protein metabolism, and growth in grower broilers. A total of 720 21-day-old healthy male Arbor Acres Plus broilers were randomly assigned to 12 treatments, each with 6 replicates of 10 birds. The treatments comprised 3 different starch [corn: control, cassava: rapidly digestible starch (RDS), and pea: slowly digestible starch (SDS)] with 4 different AA levels [based on standardized ileal digestible lysine (SID Lys), 0.92%, 1.02% (as the standard), 1.12% and 1.22%].RESULTS: An interaction between dietary starch sources and SID Lys levels significantly affected breast muscle yield (P = 0.033). RDS and SDS diets, or SID Lys levels of 0.92%, 1.02%, or 1.22%, significantly decreased the breast muscle yield of broilers in contrast to the corn starch diet with 1.12% SID Lys (P = 0.033). The SID Lys levels of 1.12% and 1.22% markedly improved body weight (BW), body weight gain (BWG) from 22 to 42 days of age, and mRNA expression of y+LAT1 and mTOR while reducing feed intake (FI) and feed/gain ratio (F/G) compared to the 0.92% SID Lys level (P < 0.05). The SDS diet significantly decreased BW and BWG of broilers from 22 to 42 days of age, distal ileal starch digestibility, jejunal amylase and chymotrypsin activities, and mRNA expression of GLUT2 and y+LAT1 compared to the corn starch diet (P < 0.05). The RDS diet suppressed the breast muscle mass by down-regulating expression of mTOR, S6K1, and eIF4E and up-regulating expression of MuRF, CathepsinB, Atrogin-1, and M-calpain compared to the corn starch diet (P < 0.05). Targeted metabolomics analysis revealed that the SDS diet significantly increased acetyl-CoA and α-ketoglutaric acid levels in the tricarboxylic acid (TCA) cycle (P < 0.05) but decreased the ileal digestibility of Lys, Tyr, Leu, Asp, Ser, Gly, Pro, Arg, Ile, and Val compared to the corn starch group (P < 0.05).CONCLUSION: The SDS diet impaired broiler growth by reducing intestinal starch digestibility, which inhibited intestinal AA and glucose absorption and utilization, increased AA oxidation for energy supply, and lowered the efficiency of protein synthesis. Although the RDS diet resulted in growth performance similar to the corn starch diet, it reduced breast muscle mass by inhibiting protein synthesis and promoting degradation.PMID:39844287 | DOI:10.1186/s40104-024-01142-0

J Transl Med. 2025 Jan 22;23(1):105. doi: 10.1186/s12967-024-06028-3.ABSTRACTChimeric antigen receptor (CAR) T-cell therapy plays a critical role in the treatment of B-cell hematologic malignancies. The combination of PD-1 inhibitors and CAR-T has shown encouraging results in treating patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, there are still cases where treatment is ineffective. This study aimed to investigate the role of IL4I1 in the poor efficacy of CD19 CAR-T combined with PD-1 inhibitors in R/R DLBCL and to explore potential mechanisms. Transcriptomic and metabolomic correlation analyses were performed on tumor tissue from DLBCL patients. We employed an in vitro co-culture system consisting of Pfeiffer cells, CD19 CAR-T and macrophages to investigate the underlying mechanisms. It was found that IL4I1 levels were significantly increased in the tumor tissues of R/R DLBCL patients compared to responders. Correlation analysis revealed a positive association between IL4I1 and tryptophan (Trp)-kynurenic acid (Kyn) related metabolites. In the in vitro co-culture model, the presence of IL4I1 inhibited the cytotoxicity of CAR-T cells. Depletion of IL4I1 disrupted the IDO-AHR-Kyn signaling pathway, thereby enhancing the effectiveness of PD-1 inhibitors in combination with CD19 CAR-T for DLBCL treatment. CAR-T-mediated cytotoxicity was significantly inhibited when IL4I1 was present in the in vitro co-culture model. These findings suggest that IL4I1 may be a contributing factor to poor prognosis in R/R DLBCL patients. IL4I1 expression enhances immunosuppression via the IDO-AHR-Kyn pathway, inhibiting the effectiveness of PD-1 inhibitors combined with CD19 CAR-T. Therefore, suppression of IL4I1 may represent a potential target for combination therapy in DLBCL.PMID:39844281 | DOI:10.1186/s12967-024-06028-3

Cardiovasc Diabetol. 2025 Jan 22;24(1):36. doi: 10.1186/s12933-025-02586-y.ABSTRACTAtherosclerosis, a chronic inflammatory condition characterized by plaque formation, often leads to instability, particularly under Type 2 diabetes mellitus (T2DM) conditions, which exacerbate cardiovascular risks. However, the molecular mechanisms underlying this process remain incompletely understood. In this study, we investigated the correlation between acute coronary syndrome (ACS) and serum levels of Nε-carboxyethyl-lysin (CEL), a prominent advanced glycation end product (AGE) elevated in T2DM, in a cohort of 225 patients with coronary artery disease. Using a murine model of atherosclerosis complicated by T2DM, we examined the effects of CEL on plaque stability and macrophage autophagy. Our findings revealed that elevated serum CEL levels are independently associated with increased ACS incidence. Metabolomic profiling identified CEL as a key AGE contributing to plaque instability in diabetic conditions. Mechanistically, CEL disrupted macrophage autophagy and plaque stability by perturbing the Receptor for Advanced Glycation End products (RAGE)/Liver Kinase B1 (LKB1)/AMP-activated Protein Kinase 1 (AMPK1)/Sirtuin 1 (SIRT1) signaling cascade. This pathway further regulated autophagic activity through SIRT1-mediated acetylation of Zinc Finger with KRAB and SCAN Domains 3 (ZKSCAN3). These findings highlight CEL's critical role in promoting plaque instability in T2DM by impairing key molecular pathways that regulate autophagy, offering potential therapeutic targets for managing atherosclerosis in diabetic patients.PMID:39844245 | DOI:10.1186/s12933-025-02586-y