PubMed

Heliyon. 2024 Dec 13;11(1):e41217. doi: 10.1016/j.heliyon.2024.e41217. eCollection 2025 Jan 15.ABSTRACTAIM OF THE STUDY: This study investigated the mechanism by which the Postoperative Tongqi Formula (PTQF) treats postoperative ileus (POI) through regulation of the p38 MAPK signaling pathway, Zona occludens 1 (ZO-1) protein, and metabolism.METHODS: The primary components of PTQF were characterized using UHPLC-Q-TOF-MS/MS. The identified compounds subsequently employed network pharmacology to predict the signaling pathways associated with the inflammatory phase of POI. The anti-inflammatory effects of PTQF were evaluated in vitro using RAW264.7 cells. A rat model of POI was used to assess efficacy based on the spleen index and charcoal powder propulsion rat in the small intestine. Furthermore, pathological damage to the small intestine was analyzed using hematoxylin and eosin (HE) staining as well as immunofluorescence to evaluate ZO-1 protein expression. Inflammatory cytokine levels were quantified using enzyme-linked immunosorbent assay (ELISA). Subsequently, Western blot analysis was performed to examine the p38 MAPK signaling pathway. Finally, a metabolomics approach was employed to analyze serum samples to identify potential metabolic pathways.RESULTS: A total of 130 chemical constituents were identified in PTQF. Following the network pharmacology analysis of these compounds, the p38 MAPK signaling pathway was chosen for further investigation. In vitro, PTQF effectively inhibited inflammatory responses in RAW264.7 cells. Results from the spleen index and charcoal powder propulsion rate indicated that PTQF alleviated the inflammatory phase of POI in rats by mitigating systemic and intestinal inflammation. This was supported by reduced levels of inflammatory factors, modulation of ZO-1 protein expression, and a decrease in p38 MAPK phosphorylation levels. Furthermore, serum metabolomics revealed nine differential metabolites linked to intestinal inflammation.CONCLUSION: PTQF mitigates inflammation and intestinal damage in POI rats by modulating inflammatory factors, ZO-1 protein expression, the p38 MAPK signaling pathway, and metabolic disturbances.PMID:39811334 | PMC:PMC11732544 | DOI:10.1016/j.heliyon.2024.e41217

Heliyon. 2024 Dec 18;11(1):e41246. doi: 10.1016/j.heliyon.2024.e41246. eCollection 2025 Jan 15.ABSTRACTHyaluronic acid (HA) is a popular surface modifier in targeted cancer delivery due to its receptor-binding abilities. However, HA alone faces limitations in lipid solubility, biocompatibility, and cell internalization, making it less effective as a standalone delivery system. This comprehensive study aimed to explore a dynamic landscape of complexation in HA-based nanoparticles in cancer therapy, examining diverse aspects from influential modifiers to emerging trends in cancer diagnostics. We discovered that certain active substances, such as 5-aminolevulinic acid, adamantane, and protamine, have been on trend in terms of their usage over the past decade. Dextran, streptavidin, and catechol emerge as intriguing conjugates for HA, coupled with nanostar, quantum dots, and nanoprobe structures for optimal drug delivery and diagnostics. Strategies like hypoxic conditioning, dual responsiveness, and pulse laser activation enhance controlled release, targeted delivery, and real-time diagnostic techniques like ultrasound imaging and X-ray computed tomography (X-ray CT). Based on our findings, conventional bibliometric tools fail to highlight relevant topics in this area, instead producing merely abstract and broad-meaning keywords. Extraction using Named Entity Recognition and topic search with Latent Dirichlet Allocation successfully revealed five representative topics with the ability to exclude irrelevant keywords. A shift in research focuses from optimizing chemical toxicity to particular targeting tactics and precise release mechanisms is evident. These findings reflect the dynamic landscape of HA-based nanoparticle research in cancer therapy, emphasizing advancements in targeted drug delivery, therapeutic efficacy, and multimodal diagnostic approaches to improve overall patient outcomes.PMID:39811313 | PMC:PMC11729671 | DOI:10.1016/j.heliyon.2024.e41246

Curr Res Food Sci. 2024 Dec 18;10:100964. doi: 10.1016/j.crfs.2024.100964. eCollection 2025.ABSTRACTSelenium-enriched probiotics have attracted much attention due to the physiological activities of both probiotics and selenium (organic selenium). In this study, we investigated the mitigating effect of selenium-enriched Lactobacillus rhamnosus GG (LGG@Se) and its pathway on alcohol-induced liver injury (ALI) in mice. The results showed that LGG@Se was superior to LGG and sodium selenite in alleviating ALI. Oral LGG@Se effectively prevented lipid metabolism disorders and liver oxidative damage in mice caused by excessive alcohol intake. 16S amplicon sequencing showed that LGG@Se intervention increased the abundance of beneficial bacteria and suppressed the growth of harmful bacteria in the intestinal tract of over-drinking mice, and thus effectively modulated the homeostasis of intestinal flora, which were highly correlated with the improvement of liver function. Liver metabolomics analysis indicated that LGG@Se intervention altered liver metabolic profiling, and the characteristic biomarkers were mainly involved in amino acid metabolism, including alanine, aspartate and glutamate metabolism, arginine biosynthesis, etc. In addition, LGG@Se intervention modulated the expression of genes and proteins related to lipid metabolism and oxidative stress in liver of over-drinking mice. Western blot analysis revealed that LGG@Se intervention up-regulated the expression of intestinal barrier function-related proteins, thereby ameliorating alcohol-induced intestinal barrier damage. Collectively, these findings provide scientific evidence that LGG@Se possesses the biological activity of improving alcohol-induced lipid metabolism and intestinal microbiota disorder.PMID:39811256 | PMC:PMC11732223 | DOI:10.1016/j.crfs.2024.100964

J Inflamm Res. 2025 Jan 10;18:505-517. doi: 10.2147/JIR.S493338. eCollection 2025.ABSTRACTPURPOSE: Psoriasis is a complex inflammatory skin disorder that is closely associated with metabolic syndrome (MetS). Limited information is available on skin metabolic changes in psoriasis; the effect of concurrent MetS on psoriatic skin metabolite levels is unknown. We aimed to expand this information through skin metabolomic analysis.PATIENTS AND METHODS: Untargeted metabolomics was conducted using skin samples from 38 patients with psoriasis vulgaris with MetS (PVMS), 23 patients with psoriasis vulgaris without MetS (PVNMS), and 10 healthy controls (HC). Data analyses, including multivariate statistical analysis, KEGG pathway enrichment analysis, correlation analysis, and receiver operating characteristic curve analysis, were performed.RESULTS: Significant discrepancies were found between skin metabolites in the HC and PVNMS groups, particularly those involved in nucleotide and glycerophospholipid metabolism. Fifteen of these metabolites were positively correlated with psoriasis severity. Furthermore, MetS was found to affect the metabolic profiles of patients with psoriasis. There were some metabolites with consistent alterations in both the PVNMS/HC and PVMS/PVNMS comparisons.CONCLUSION: This study may provide new insights into the link between skin metabolism and psoriatic inflammation and the mechanism underlying the interaction between psoriasis and MetS.PMID:39810975 | PMC:PMC11730757 | DOI:10.2147/JIR.S493338

Prz Gastroenterol. 2024;16(4):347-361. doi: 10.5114/pg.2024.145833. Epub 2024 Dec 11.ABSTRACTThis scoping review highlights the role of microbiota modifications in prehabilitation for surgical patients. It emphasises the importance of optimising gut microbiota through probiotics, synbiotics, and postbiotics to reduce surgical complications, such as surgical site infections (SSIs). The review highlights that gut dysbiosis, worsened by surgery, stress, antibiotics, and poor diet, can lead to increased infection risk and slower recovery. Evidence from systematic reviews, meta-analyses, and randomised controlled trials suggests that microbiota-targeted interventions can reduce SSIs, enhance immune responses, and promote quicker recovery. The review advocates for an individualised approach to prehabilitation, incorporating microbiota modifications based on patient-specific factors and surgery type. However, it also notes the need for further research to standardise therapeutic regimens and confirm the safety and efficacy of these interventions in clinical practice.PMID:39810873 | PMC:PMC11726224 | DOI:10.5114/pg.2024.145833

World Allergy Organ J. 2024 Dec 19;18(1):101013. doi: 10.1016/j.waojou.2024.101013. eCollection 2025 Jan.ABSTRACTBACKGROUND: Childhood rhinitis and asthma are allergic respiratory diseases triggered by common allergens, but they affect different parts of the respiratory system, leading to distinct symptoms. However, a comprehensive multi-biofluid metabolomics-based approach to uncover valuable insights into childhood allergies and allergen sensitization remains unaddressed.METHODS: Seventy-six children, comprising 26 with rhinitis, 26 with asthma, and 24 healthy controls, were enrolled. Fecal, blood, and urine metabolomic analyses using 1H nuclear magnetic resonance (NMR) spectroscopy were conducted. An integrative analysis of their associations with allergen-specific IgE levels in the context of allergic rhinitis and asthma were also assessed.RESULTS: The analysis of 228 various biofluid samples revealed strong positive correlations between stool and blood metabolites, while blood metabolites exhibited negative correlations with most urine metabolites. Five and 19 metabolites were significantly different in children with rhinitis and asthma, respectively (P < 0.05). Among them, blood isovaleric acid correlated positively with stool IgE levels in rhinitis, while stool butyric acid and acetic acid in asthma exhibited strong negative correlations with total serum and mite allergen-specific IgE levels (P < 0.01). Blood metabolic profiles appeared to have the highest area under the curve (AUC) of 0.732 for rhinitis, whereas stool metabolic profiles had the highest AUC of 0.799 for asthma.CONCLUSIONS: Multiple biofluid metabolomics provides comprehensive insights into childhood allergies, with blood profiles associated with allergic rhinitis and fecal profiles linked to asthma. Their short-chain fatty acid metabolites related to IgE levels emphasize the significant role of the gut microbiota in childhood rhinitis and asthma.PMID:39810829 | PMC:PMC11731466 | DOI:10.1016/j.waojou.2024.101013

BME Front. 2024 Jan 13;6:0084. doi: 10.34133/bmef.0084. eCollection 2025.ABSTRACTSpatial monoomics has been recognized as a powerful tool for exploring life sciences. Recently, spatial multiomics has advanced considerably, which could contribute to clarifying many biological issues. Spatial monoomics techniques in epigenomics, genomics, transcriptomics, proteomics, and metabolomics can enhance our understanding of biological functions and cellular identities by simultaneously measuring tissue structures and biomolecule levels. Spatial monoomics technology has evolved from monoomics to spatial multiomics. Moreover, the spatial resolution, high-throughput detection capability, capture efficiency, and compatibility with various sample types of omics technology have considerably advanced. Despite the technological advances in this field, data analysis frameworks have stagnated. Current challenges include incomplete spatial monoomics data analysis pipeline, overly complex data analysis tasks, and few established spatial multiomics data analysis strategies. In this review, we systematically summarize recent developments of various spatial monoomics techniques and improvements in related data analysis pipeline. On the basis of the spatial multiomics technology, we propose a data integration strategy with cross-platform, cross-slice, and cross-modality. We summarize the potential applications of spatial monoomics technology, aiming to provide researchers and clinicians with a better understanding of how such applications have advanced. Spatial multiomics technology is expected to substantially impact biology and precision medicine through measurements of cellular tissue structures and the extraction of biomolecular features.PMID:39810754 | PMC:PMC11725630 | DOI:10.34133/bmef.0084

Diabetes Metab Res Rev. 2025 Jan;41(1):e70027. doi: 10.1002/dmrr.70027.ABSTRACTAIMS: Gestational diabetes mellitus (GDM) poses a significant risk for developing type 2 diabetes mellitus (T2D) and exhibits heterogeneity. However, understanding the link between different types of post-GDM individuals without diabetes and their progression to T2D is crucial to advance personalised medicine approaches.MATERIALS AND METHODS: We employed a discovery-based unsupervised machine learning clustering method to generate clustering models for analysing metabolomics, clinical, and biochemical datasets. For this analysis, we selected 225 women who later developed T2D during the 12-year follow-up period from the cohort of 1010 women who returned to a non-diabetic state at 6-9 weeks (study baseline) after a GDM pregnancy based on 2-h 75 g research OGTTs. The optimal model was selected by assessing Bayesian Information Criterion values, class separation performance, and the potential for clinically distinguishable clusters, accounting for participant prenatal and early postpartum characteristics.RESULTS: The selected model comprises three clusters: pancreatic beta cell dysfunction (cluster-β: median HOMA-B 161.3 and median HOMA-IR 3.8), insulin-resistance (cluster-IR: median HOMA-B 630.5 and median HOMA-IR 16.8), and a mixed cluster (cluster-mixed: median HOMA-B 307.2 and median HOMA-IR 8.6). These clusters are distinguishable based on postpartum blood test parameters such as glucose tolerance, HOMA indices, and fasting lipid profiles including triglycerides, leptin, HDL-c, and adiponectin, as well as participant age and BMI. Metabolomic analysis identified unique molecular signatures for each cluster. However, the time to T2D onset was not statistically significant among the three clusters (p = 0.22).CONCLUSION: This study enhances our understanding of the heterogeneity of early postpartum metabolic profiles that characterise the future onset of T2D diabetes in a diverse cohort of women with GDM, revealing insights into distinct mechanisms and personalised intervention strategies for the prevention of T2D.PMID:39810724 | DOI:10.1002/dmrr.70027

Integr Zool. 2025 Jan 14. doi: 10.1111/1749-4877.12948. Online ahead of print.ABSTRACTOver the past few decades, ocean hypoxia has been increasing due to human activities. Hypoxic stress, characterized by a reduced level of dissolved oxygen, is an escalating threat to marine ecosystems, with potentially devastating effects on the viability of endangered species such as the tri-spine horseshoe crab Tachypleus tridentatus. Even though this species is remarkably resilient to low oxygen levels, persistent hypoxia can negatively impact its population's survivability. The objective of this research was to examine the impact of short-term hypoxia on the behavior, gut microbiota, and metabolomics of juvenile T. tridentatus. First instar juvenile horseshoe crabs were subjected to hypoxic stress (2 mg O2/L) for 14 days and then recovered for 7 days in an environment with normal dissolved oxygen. The findings demonstrated that short-term hypoxia reduced the rates of swimming and burrowing of horseshoe crabs, and induced the change of tissue metabolites and intestinal flora malfunction. Additionally, in the hypoxia groups on day 14, 86 distinct metabolites showed a trend of downregulation, while 29 metabolites showed an upregulation trend. Arginine biosynthesis; histidine metabolism; vitamin B6 metabolism; aminoacyl-tRNA biosynthesis; and alanine, aspartate, and glutamate metabolism were the top five metabolic KEGG pathways (p < 0.05) enriched with 8 metabolites. In conclusion, our results provided new insights related to the behaviors, microbiota, and metabolites involved in juvenile T. tridentatus exposed to short-term hypoxic conditions and confirmed that hypoxia impairs their behavioral and physiological status.PMID:39810487 | DOI:10.1111/1749-4877.12948

Microbiome. 2025 Jan 14;13(1):10. doi: 10.1186/s40168-024-01990-y.ABSTRACTBACKGROUND: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) with a global prevalence of 30% is multifactorial and the involvement of gut bacteria has been recently proposed. However, finding robust bacterial signatures of NAFLD has been a great challenge, mainly due to its co-occurrence with other metabolic diseases.RESULTS: Here, we collected public metagenomic data and integrated the taxonomy profiles with in silico generated community metabolic outputs, and detailed clinical data, of 1206 Chinese subjects w/wo metabolic diseases, including NAFLD (obese and lean), obesity, T2D, hypertension, and atherosclerosis. We identified highly specific microbiome signatures through building accurate machine learning models (accuracy = 0.845-0.917) for NAFLD with high portability (generalizable) and low prediction rate (specific) when applied to other metabolic diseases, as well as through a community approach involving differential co-abundance ecological networks. Moreover, using these signatures coupled with further mediation analysis and metabolic dependency modeling, we propose synergistic defined microbial consortia associated with NAFLD phenotype in overweight and lean individuals, respectively.CONCLUSION: Our study reveals robust and highly specific NAFLD signatures and offers a more realistic microbiome-therapeutics approach over individual species for this complex disease. Video Abstract.PMID:39810263 | DOI:10.1186/s40168-024-01990-y

J Transl Med. 2025 Jan 14;23(1):68. doi: 10.1186/s12967-024-05915-z.ABSTRACTMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex and multifaceted disorder that defies simplistic characterisation. Traditional approaches to diagnosing and treating ME/CFS have often fallen short due to the condition's heterogeneity and the lack of validated biomarkers. The growing field of precision medicine offers a promising approach which focuses on the genetic and molecular underpinnings of individual patients. In this review, we explore how machine learning and multi-omics (genomics, transcriptomics, proteomics, and metabolomics) can transform precision medicine in ME/CFS research and healthcare. We provide an overview on machine learning concepts for analysing large-scale biological data, highlight key advancements in multi-omics biomarker discovery, data quality and integration strategies, while reflecting on ME/CFS case study examples. We also highlight several priorities, including the critical need for applying robust computational tools and collaborative data-sharing initiatives in the endeavour to unravel the biological intricacies of ME/CFS.PMID:39810236 | DOI:10.1186/s12967-024-05915-z

World J Microbiol Biotechnol. 2025 Jan 15;41(2):37. doi: 10.1007/s11274-025-04254-5.ABSTRACTRevealing the differences of metabolite profiles of H. pluvialis during hyperaccumulation of astaxanthin under the high salinity and nitrogen deficiency conditions was the key issues of the present study. To investigate the optimum NaCl and NaNO3 concentration and the corresponding metabolic characteristic related to the astaxanthin accumulation in H. pluvialis, a batch culture experiment was conducted. The results indicated that 7.5 g·L- 1 and 0 g·L- 1 (nitrogen deficiency) were the optimum NaCl and NaNO3 levels for the astaxanthin accumulation respectively, under which the highest astaxanthin contents reached up to 7.51mg·L- 1 and 5.60mg·L- 1. A total of 132 metabolites were identified using LC-MS/MS technique, among which 30 differential metabolites with statistical significance were highlighted. Subsequently, 18 and 10 differential metabolic pathways in the high salinity (HS) and nitrogen-deficient (ND) treatments were extracted and annotated respectively. The values of Fv/Fm, Yield and NPQ were all at the highest level in the ND group during the experiment. The levels of the metabolites in the ND group were almost lower than those both in the control (CK) and HS group, while which in the HS group were substantially at the higher or close levels compared to the CK group. Finally, 7 metabolic markers related to the astaxanthin accumulation were highlighted in the HS and ND group respectively. L-Proline, L-Aspartate, Uridine 5'-monophosphate (UMP), Succinate, L-2-Hydroxygluterate, L-Valine and Inosine 5'-monophosphate (IMP) were identified as the metabolic markers in the HS group, whose fold change were 0.85, 4.14, 0.31, 0.66, 3.10, 1.32 and 0.30. Otherwise, the metabolic markers were Glyceric acid, Thymine, sn-Glycerol 3-phosphate, Glycine, Allantoic acid, L-Valine and IMP in the ND group, with the fold change 0.23, 2.11, 0.38, 0.41, 0.50 and 2.96 respectively. The results provided the comparative metabolomic view of astaxanthin accumulation in H. pluvialis under the different cultivation conditions, moreover showed a novel insights into the astaxanthin production.PMID:39810003 | DOI:10.1007/s11274-025-04254-5

Nat Metab. 2025 Jan 14. doi: 10.1038/s42255-024-01190-w. Online ahead of print.ABSTRACTAlthough diabetes is now a global epidemic, China has the highest number of affected people, presenting profound public health and socioeconomic challenges. In China, rapid ecological and lifestyle shifts have dramatically altered diabetes epidemiology and risk factors. In this Review, we summarize the epidemiological trends and the impact of traditional and emerging risk factors on Chinese diabetes prevalence. We also explore recent genetic, metagenomic and metabolomic studies of diabetes in Chinese, highlighting their role in pathogenesis and clinical management. Although heterogeneity across these multidimensional areas poses major analytic challenges in classifying patterns or features, they have also provided an opportunity to increase the accuracy and specificity of diagnosis for personalized treatment and prevention. National strategies and ongoing research are essential for improving diabetes detection, prevention and control, and for personalizing care to alleviate societal impacts and maintain quality of life.PMID:39809974 | DOI:10.1038/s42255-024-01190-w

Planta. 2025 Jan 14;261(2):36. doi: 10.1007/s00425-025-04609-0.ABSTRACTInoculation with the PGPB Herbaspirillum seropedicae shapes both the structure and putative functions of the wheat microbiome and causes changes in the levels of various plant metabolites described to be involved in plant growth and health. Plant growth promoting bacteria (PGPB) can establish metabolic imprints in their hosts, contributing to the improvement of plant health in different ways. However, while PGPB imprints on plant metabolism have been extensively characterized, much less is known regarding those affecting plant indigenous microbiomes, and hence it remains unknown whether both processes occur simultaneously. In this study, both 16S amplicon and ITS sequencing analyses were carried out to study both the structural as well as the putative functional changes in the seed-borne endophytic microbiome of wheat plants inoculated with the PGPB Herbaspirillum seropedicae strain RAM10. Concomitantly, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) analyses were used to investigate the alterations in the root metabolome of PGPB-inoculated plants. PGPB inoculation led to marked differences in the composition of the root microbiome, accompanied by the differential enrichment of microorganisms with putative roles in both plant energy and nitrogen metabolism. In addition, metabolome analyses showed that the levels of 16 metabolites belonging to the phenylpropanoid, terpenoid, and unsaturated fatty acid families were significantly altered in PGPB-inoculated plants. These findings shed light on the interplay between PGPB, the plant and its associated microbiome, indicating that PGPB can act as the driving force mediating long-lasting changes in both the plant metabolome and the plant microbiome.PMID:39809904 | DOI:10.1007/s00425-025-04609-0

Sci Rep. 2025 Jan 14;15(1):1922. doi: 10.1038/s41598-025-85229-2.ABSTRACTCommunity-acquired pneumonia (CAP) has a significant impact on public health, especially in light of the recent SARS-CoV-2 pandemic. To enhance disease characterization and improve understanding of the underlying mechanisms, a comprehensive analysis of the plasma lipidome, metabolome and proteome was conducted in patients with viral and bacterial CAP infections, including those induced by SARS-CoV-2. Lipidomic, metabolomic and proteomic profiling were conducted on plasma samples of 69 patients suffering either from viral or bacterial CAP. Lipid and metabolite analyses were LC-MS-based, while proteomic analyses were performed using multiple panels of the Olink platform. Statistical methods, machine learning and pathway analyses were conducted investigating differences between the infection types. Through comparison of the bacterial and viral pathogen groups, distinct signatures were observed in the plasma profiles. Notably, linoleic acid-derived inflammation signaling metabolites (EpOME and DiHOME) were increased in viral CAP compared to bacterial CAP. Similarly, proteins involved in cellular immune response and apoptosis (LAG-3 and TRAIL) showed elevated levels in viral CAP, while bacterial CAP exhibited notable elevation in pattern-recognizing receptors (CLEC4D and EN-RAGE). Additionally, within the lipidomic profile at baseline, several lipids displayed notable differences between viral and bacterial pneumonia, including bile acids (GCA, TCA, TCDCA), various tri- and diglycerides (TGs and DGs), and several phosphatidylcholines (PCs). These findings hold promise for facilitating the differential diagnosis of viral and bacterial pulmonary infections based on the systemic lipidome, metabolome and proteome, enabling timely treatment decisions. Additionally, they highlight potential targets for drug research, advancing therapeutic interventions in CAP. By providing valuable insights into the molecular characterization of CAP, this study contributes to the improvement of understanding the disease and, ultimately, the development of effective treatment strategies.PMID:39809876 | DOI:10.1038/s41598-025-85229-2

Mol Psychiatry. 2025 Jan 14. doi: 10.1038/s41380-025-02891-8. Online ahead of print.ABSTRACTSuicide is a major public health concern, and the number of deaths by suicide has been increasing in recent years in the US. There are various biological risk factors for suicide, but causal molecular mechanisms remain unknown, suggesting that investigation of novel mechanisms and integrative approaches are necessary. Transfer (t)RNAs and their modifications, including cytosine methylation (m5C), have received little attention regarding their role in normal or diseased brain function, though they are dynamic mediators of protein synthesis. tRNA regulation is highly interconnected with proteomic and metabolomic outcomes, suggesting that investigating these multiple levels of molecular regulation together may elucidate more information on neural function and suicide risk. In the current study, we used an integrative 'omics' approach to probe tRNA dysregulation, including tRNA expression and tRNA m5C, proteomics, and amino acid metabolomics in prefrontal cortex from 98 subjects who died by suicide during an episode of major depressive disorder (MDD) and neurotypical controls. While no changes were detected in amino acid content, results showed increased tRNAGlyGCC expression in the suicide brain that is not driven by changes in m5C. Proteomics revealed increased expression of proteins with high glycine codon GGC content, demonstrating a strong association between isoacceptor-specific tRNA expression and proteomic outcomes in the suicide brain, which is in line with previous work linking tRNAGly with alterations in glycine-rich proteins in a translational rodent model of depression. Further, we confirmed using a rodent model that tRNAGlyGCC overexpression was sufficient to increase the expression of proteins with high glycine codon GGC content that were upregulated in the suicide brain. By characterizing the effects of MDD-suicide in human PFC tissue, we now begin to elucidate a novel molecular signature with downstream consequences for psychiatric outcomes.PMID:39809846 | DOI:10.1038/s41380-025-02891-8

Cell Death Dis. 2025 Jan 14;16(1):16. doi: 10.1038/s41419-025-07334-4.ABSTRACTMitochondrial oxidative phosphorylation (OXPHOS) is a therapeutic vulnerability in glycolysis-deficient cancers. Here we show that inhibiting OXPHOS similarly suppresses the proliferation and tumorigenicity of glycolytically competent colorectal cancer (CRC) cells in vitro and in patient-derived CRC xenografts. While the increased glycolytic activity rapidly replenished the ATP pool, it did not restore the reduced production of aspartate upon OXPHOS inhibition. This shortage in aspartate, in turn, caused nucleotide deficiencies, leading to S phase cell cycle arrest, replication fork stalling, and enrichment of the p53 pathway, manifestations of replication stress. The addition of purine nucleobases adenine and guanine along with the pyrimidine nucleoside uridine restored replication fork progression and cell proliferation, whereas the supplementation of exogenous aspartate recovered the nucleotide pool, demonstrating a causal role of the aspartate shortage in OXPHOS inhibition-induced nucleotide deficiencies and consequently replication stress and reductions in proliferation. Moreover, we demonstrate that glutamic-oxaloacetic transaminase 1 (GOT1) is critical for maintaining the minimum aspartate pool when OXPHOS is inhibited, as knockdown of GOT1 further reduced aspartate levels and rendered CRC cells more sensitive to OXPHOS inhibition both in vitro and in vivo. These results propose GOT1 targeting as a potential avenue to sensitize cancer cells to OXPHOS inhibitors, thus lowering the necessary doses to efficiently inhibit cancer growth while alleviating their adverse effects.PMID:39809754 | DOI:10.1038/s41419-025-07334-4

Annu Rev Anal Chem (Palo Alto Calif). 2025 Jan 14. doi: 10.1146/annurev-anchem-061424-090547. Online ahead of print.ABSTRACTThe use of cell culture techniques to model human disease is an indispensable tool that has helped improve the health and well-being of the world. Monolayer cultures have most often been used for biomedical research, although not accurately recapitulating an in vivo human tumor. Tumor spheroids are a form of three-dimensional cell culture that better mimics an avascularized human tumor through their cell-cell contacts in all directions, development of various chemical gradients, and distinct populations of cells found within the spheroid. In this review, we highlight how mass spectrometry has propelled the utility of the spheroid model to understand cancer biology. We discuss how mass spectrometry imaging can be utilized to determine the penetration efficiency of various chemotherapeutics, how proteomics can be used to understand the biology in the various layers of a spheroid, and how metabolomics and lipidomics are used to elucidate how various spheroids behave toward chemotherapeutics.PMID:39809466 | DOI:10.1146/annurev-anchem-061424-090547

Phytochem Anal. 2025 Jan 14. doi: 10.1002/pca.3500. Online ahead of print.ABSTRACTINTRODUCTION: Aqueous stem bark extracts of Aspidosperma rigidum Rusby, Couroupita guianensis Aubl., Monteverdia laevis (Reissek) Biral, and Protium sagotianum Marchand have been reported as traditional remedies in several countries of the Amazonian region. Despite previous research, further investigation to characterize secondary metabolites and the biological activity of extracts is needed to derive potential applications.MATERIAL AND METHODS: Metabolic profiling was carried out using liquid and gas chromatography coupled with mass spectrometry (UHPLC-MS/MS and GC-MS). The chemical composition of the studied plants was further compared by principal component analysis (PCA). Additionally, chemical profiles were correlated with antimicrobial and toxicity activities, which suggested potential metabolites for future research.RESULTS: We identified 16 and 32 compounds by UHPLC-MS/MS and GC-MS analysis, respectively. Antimicrobial activity was detected in three stem bark extracts. C. guianensis showed inhibition of all tested microorganisms, including antibiotic-resistant strains. Molecular networking approaches, in silico tools, and Pearson's correlation showed that antifungal compounds could be a terpene glycoside (r = 0.918) and/or a phenolic (r = 0.882) metabolite class.CONCLUSION: This study highlights the use of the established procedure in exploring the metabolomes of these species, which could be a novel source of antimicrobial drug discovery. Coupling the observed biological potential with UHPLC-MS/MS data has also accelerated the tracing of their bioactive compounds. These findings update the state of the art regarding the chemical composition and biological activity of the plant extracts, defining potential new applications for the pharmaceutical applications.PMID:39809459 | DOI:10.1002/pca.3500

J Adv Res. 2025 Jan 12:S2090-1232(25)00037-2. doi: 10.1016/j.jare.2025.01.018. Online ahead of print.ABSTRACTINTRODUCTION: Soil nutrient supply drives the ecological functions of soil micro-food webs through bottom-up and top-down mechanisms in degraded agroecosystems. Nutrient limitation responds sensitively to variations in degraded agroecosystems through restoration practices, such as legume intercropping.OBJECTIVES: This study examined the effects of legume intercropping on trophic cascade dynamics through resource supply in degraded purple soil ecosystems.METHODS: A field experiment was conducted with three plantation types: Camellia oleifera monoculture (CK), C. oleifera-Arachis hypogaea (peanut) intercropping (CP), and C. oleifera-Senna tora intercropping (CS). Using soil nutrient limitation as a premise, modified by legume intercropping, we assessed the biodiversity of soil biotic taxa, analysed their community composition, and applied partial least squares path modelling (PLS-PM) to link trophic cascade with ecological functions.RESULTS: Legume intercropping altered the abundance of biotic taxa, leading to changes in biotic diversity and microbial life strategies. The PLS-PM results indicated that legume intercropping enhanced bacterial diversity by aggravating soil P limitation, which subsequently increased protist consumer diversity and omnivore-predator nematode abundance through a bottom-up effect. Omnivore-predator nematodes and protist consumers indirectly influenced soil P metabolism, down-regulated through bacteria in the top-down effect. We observed high consistency between the untargeted metabolomic analysis and soil nutrient limitations. These findings indicate that soil micro-food web structure and function responded sensitively to legume intercropping in degraded ecosystems.CONCLUSION: The results highlight the role of soil nutrient limitation in shaping micro-food webs and suggest that soil P limitation controls the down-regulation of soil P-related ecological functions through bottom-up and top-down effects.PMID:39809362 | DOI:10.1016/j.jare.2025.01.018