PubMed

Proteomes. 2025 Jan 15;13(1):4. doi: 10.3390/proteomes13010004.ABSTRACTNelumbo nucifera is an aquatic plant with a high ornamental value due to its flower. Despite the release of several versions of the lotus genome, its annotation remains inefficient, which makes it difficult to obtain a more comprehensive knowledge when -omic studies are applied to understand the different biological processes. Focusing on the petaloid of the lotus flower, we conducted a comparative proteomic analysis among five major floral organs. The proteogenomic strategy was applied to analyze the mass spectrometry data in order to dig out novel proteoforms that are involved in the petaloids of the lotus flower. The results revealed that a total of 4863 proteins corresponding to novel genes were identified, with 227 containing single amino acid variants (SAAVs), and 72 originating from alternative splicing (AS) genes. In addition, a range of post-translational modifications (PTMs) events were also identified in lotus. Through functional annotation and homology analysis with 24 closely related plant species, we identified five candidate proteins associated with floral organ development, which were not identified by ordinary proteomic analysis. This study not only provides new insights into understanding the mechanism of petaloids in lotus but is also helpful in identifying new proteoforms to improve the annotation of the lotus genome.PMID:39846635 | DOI:10.3390/proteomes13010004

Zool Res. 2025 Jan 18;46(1):177-192. doi: 10.24272/j.issn.2095-8137.2024.223.ABSTRACTIncreasing evidence implicates disruptions in testicular fatty acid metabolism as a contributing factor in non-obstructive azoospermia (NOA), a severe form of male infertility. However, the precise mechanisms linking fatty acid metabolism to NOA pathogenesis have not yet been fully elucidated. Multi-omics analyses, including microarray analysis, single-cell RNA sequencing (scRNA-seq), and metabolomics, were utilized to investigate disruptions in fatty acid metabolism associated with NOA using data from public databases. Results identified ACSL6, ACSBG2, and OLAH as key genes linked to fatty acid metabolism dysregulation, suggesting their potential causative roles in NOA. A marked reduction in omega-3 polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), was observed, potentially contributing to the pathological process of NOA. Sertoli cells in NOA patients exhibited apparent fatty acid metabolic dysfunction, with PPARG identified as a key transcription factor (TF) regulating this process. Functional analyses demonstrated that PPARG is crucial for maintaining blood-testis barrier (BTB) integrity and promoting spermatogenesis via regulation of fatty acid metabolism. These findings reveal the pivotal role of fatty acid metabolism in NOA and identify PPARG as a potential therapeutic target.PMID:39846195 | DOI:10.24272/j.issn.2095-8137.2024.223

Rheumatol Adv Pract. 2025 Jan 8;9(1):rkaf005. doi: 10.1093/rap/rkaf005. eCollection 2025.ABSTRACTAPS is an autoimmune disorder characterized by thrombosis and pregnancy complications, primarily driven by aPLs such as LA, aCL and anti-β2 glycoprotein I (a-β2GPI). Despite advances in anticoagulation therapies, managing refractory APS cases remains challenging. Emerging therapies, including rituximab, eculizumab and HCQ, show potential in addressing the underlying mechanisms of APS. Additionally, research into genetic and environmental factors, particularly the gut microbiome's role through molecular mimicry, suggests new therapeutic pathways. Diagnostic advancements, such as the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), metabolomic profiling and MRI, have improved risk stratification and early detection. Non-traditional biomarkers like anti-phosphatidylserine/prothrombin (aPS/PT) and anti-Domain I antibodies further enhance risk assessment. Future research should aim to validate these approaches, optimizing patient outcomes and minimizing long-term APS complications.PMID:39846052 | PMC:PMC11751690 | DOI:10.1093/rap/rkaf005

Front Immunol. 2025 Jan 8;15:1477902. doi: 10.3389/fimmu.2024.1477902. eCollection 2024.ABSTRACTBACKGROUND: A stable and reproducible experimental bacterial pneumonia model postintracerebral hemorrhage (ICH) is necessary to help investigating the pathogenesis and novel treatments of Stroke-associated pneumonia (SAP).AIM: To establish a Gram-negative bacterial pneumonia-complicating ICH rat model and an acute lung injury (ALI)-complicating ICH rat model.METHODS: We established two standardized models of post-ICH pneumonia by nasal inoculation with Klebsiella pneumoniae (Kp) or intratracheal inoculation with lipopolysaccharide (LPS). Survival and neurological scores were monitored. Magnetic resonance imaging was performed to evaluate hematoma volume. Abdominal aortic blood was collected for leukocyte counting, serum was isolated to determine concentrations of S100β and proinflammatory cytokines using ELISAs. Histopathological changes of brain, lung and gut were assessed using hematoxylin-eosin staining. Lung was isolated for immunofluorescence staining for myeloperoxidase (MPO). Bronchoalveolar lavage fluid was collected for leukocyte counting, and supernatant was prepared to measure MPO activity. Ileum was isolated for immunofluorescence staining for tight junction proteins ZO-1 and γδ TCRs/IL-17A and for Alcian blue-nuclear fast red staining of acidic mucins. Feces were collected, 16S rRNA sequencing, untargeted metabolomics and Spearman's correlation analyses were performed to explore changes of gut microbiota, metabolites and their interactions.RESULTS: In Kp-induced bacterial pneumonia-complicating ICH rats, we demonstrated that Kp challenge caused more severe neurological deficits, brain damage, neuroinflammation, and aggravated pneumonia and lung injury. Disruptions of the intestinal structure and gut barrier and the reductions of the protective intestinal IL-17A-producing γδT cells were also observed. Kp challenge exacerbated the gut microbiota dysbiosis and fecal metabolic profile disorders, which were characterized by abnormal sphingolipid metabolism especially elevated ceramide levels; increased levels of neurotoxic quinolinic acid and an upregulation of tryptophan (Trp)-serotonin-melatonin pathway. Spearman's correlation analyses further revealed that the reduction or depletion of some beneficial bacteria, such as Allobaculum and Faecalitalea, and the blooming of some opportunistic pathogens, such as Turicibacter, Dietzia, Corynebacterium and Clostridium_sensu_stricto_1 in Kp-induced SAP rats were associated with the disordered sphingolipid and Trp metabolism. Using an LPS-induced ALI complicating ICH model, we also characterized SAP-induced brain, lung and gut histopathology injuries; peripheral immune disorders and intense pulmonary inflammatory responses.CONCLUSIONS: These two models may be highly useful for investigating the pathogenesis and screening and optimizing potential treatments for SAP. Moreover, the differential genera and sphingolipid or Trp metabolites identified above seem to be promising therapeutic targets.PMID:39845950 | PMC:PMC11750689 | DOI:10.3389/fimmu.2024.1477902

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