PubMed

Endocr Metab Immune Disord Drug Targets. 2025 Apr 3. doi: 10.2174/0118715303309669250319083147. Online ahead of print.ABSTRACTReactive arthritis (ReA) is characterized by immune-mediated sterile synovitis brought on by an infection that enters the body through the gastrointestinal or urogenital tracts from a distance. The diseases known as seronegative spondyloarthropathy (SSA) include undifferentiated arthritis (uSpA) and reactive arthritis (ReA). Cytokines are crucial in orchestrating an effective immune response to eliminate bacterial infections, such as those seen in ReA (Reactive Arthritis) conditions. The balance between Th1 and Th2 cytokines is particularly important in determining the outcome of infections associated with ReA. TNF-α and IFN-γ are key antibacterial Th1 cytokines that promote cell-mediated immunity, essential for effective cellular responses against intracellular bacteria. In contrast, Th2 cytokines like IL-4, IL-5, IL-9, and IL-13 are more involved in generating humoral immunity and allergic responses. The mechanisms underlying the differentiation of T helper lymphocytes, which lead to a skewed cytokine secretion profile, remain unclear. Several factors, including the local inflammatory environment, IL-12 levels during T cell priming, variations among antigen-presenting cells (APCs), and antigen dose, have been suggested as potential contributors. This review will explore the critical role of metabolomics in cytokine production and its profound impact on the pathogenesis of reactive arthritis.PMID:40183265 | DOI:10.2174/0118715303309669250319083147

PeerJ. 2025 Mar 31;13:e19131. doi: 10.7717/peerj.19131. eCollection 2025.ABSTRACTUnderstanding the differences in rhizosphere soil microbial metabolites between severely and mildly rocky desertified areas is crucial for developing ecological restoration strategies and land management measures in rocky desertification regions. This study systematically analyzed the differences in rhizosphere soil microbial metabolites of Toona sinensis, Vernicia fordii, and Cornus wilsoniana in severely and mildly rocky desertified areas of Western Hunan using untargeted metabolomics. The results showed that the types and quantities of primary and secondary metabolites in the rhizosphere soil of severely rocky desertified areas were significantly lower than those in mildly rocky desertified areas. Additionally, under severe rocky desertification conditions, 15 common compounds (e.g., 17a-estradiol, adenine, all-trans-retinoic acid) were significantly increased in the rhizosphere soil microbial metabolites of the three tree species. These compounds may provide defense mechanisms for plants to adapt to harsh environments. KEGG metabolic pathway analysis revealed that under severe rocky desertification conditions, Toona sinensis, Vernicia fordii, and Cornus wilsoniana shared six enriched pathways, which play an important role in the biosynthesis of compounds such as phenylpropanoids and unsaturated fatty acids. By revealing the differences in rhizosphere soil microbial metabolites, this study not only deepens the understanding of rocky desertification ecosystems but also provides valuable scientific evidence for ecological restoration and sustainable land management.PMID:40183063 | PMC:PMC11967436 | DOI:10.7717/peerj.19131

Biol Sport. 2025 Apr;42(2):331-344. doi: 10.5114/biolsport.2025.145912. Epub 2024 Dec 19.ABSTRACTAerobic physical exercise has significant benefits for cardiovascular health; however, some individuals experience no benefit or even adverse effects. One reason for poor tolerance to aerobic exercise may be a low percentage of slow-twitch (oxidative) muscle fibers. This study aims to identify the metabolic signatures associated with low and high response to exercise by comparing the metabolic profiles of participants categorized according to their improvement of the 6-minute walking distance. In this study, pre- and postexercise intervention measurements of the 6-minute walking distance were conducted in forty-three lean and overweight young women, followed by non-targeted metabolomics analysis of 1039 known metabolites. An independent validation cohort comprising 791 individuals from the GTEx project was used to assess the gene expression of selected targets. The results indicated that a low improvement in the 6-minute walking distance (Δ 6-MWD = 27 meters) was associated with higher serum levels of N-lactoyl amino acid metabolites, particularly the exercise-inducible metabolite N-lactoyl phenylalanine (Lac-Phe) (FDR = 0.016), compared to high responders. Our results were corroborated in an independent validation cohort, which showed that the gene expression of cytosolic nonspecific dipeptidase (CNDP2), the enzyme responsible for Lac-Phe synthesis, is negatively associated with the percentage of slow-twitch muscle fibers (p < 0.0001). N-lactoyl amino acids may serve as biomarkers for rapid muscle fatigue and low response to exercise, and could be used as metabolic indicators to differentiate exercise response efficacy.PMID:40182705 | PMC:PMC11963115 | DOI:10.5114/biolsport.2025.145912

Front Mol Biosci. 2025 Mar 13;12:1577050. doi: 10.3389/fmolb.2025.1577050. eCollection 2025.NO ABSTRACTPMID:40182621 | PMC:PMC11966493 | DOI:10.3389/fmolb.2025.1577050

Front Mol Biosci. 2025 Mar 13;12:1553162. doi: 10.3389/fmolb.2025.1553162. eCollection 2025.ABSTRACTBACKGROUND: Chenpi (the dried mature peel of Citrus reticulata Blanco) and Rougui (the dried bark of Cinnamomum cassia Presl) are both edible and medicinal plants, which have therapeutic effects on nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanisms necessitate further exploration. This study evaluated the prevention effect of Chenpi-Rougui herb pair (CRP) on NAFLD using an integrated strategy that combined network pharmacology with metabolomics.METHODS: Initially, the components in CRP decoction were characterized by UPLC-QTOF-MS/MS. Subsequently, a high-fat diet induced NAFLD mouse model was used to assess the efficacy of CRP and its individual constituent, Chenpi and Rougui. Additionally, synergetic pathways and crucial targets for CRP therapy in NAFLD were identified using network pharmacology and serum metabolomics. Finally, real-time polymerase chain reaction (RT-PCR) was utilized to validate relevant genes.RESULTS: CRP exerted a more extensive prevention effect on NAFLD mice compared to the individual herb of Chenpi and Rougui. A total of 105 compounds were characterized from CRP, which were linked to 70 potential therapeutic targets for NAFLD. Thirty-two differential metabolites were identified by metabolomics, which were co-regulated by Chenpi, Rougui and CRP. Pathways associated with the intervention of herb pair in NAFLD included energy metabolism, fatty acid metabolism, glycerophospholipid metabolism, sphingolipids metabolism, arachidonic acid metabolism, sterol and bile acid metabolism. Finally, eight targets were screened through conjoint analysis and experimental verification showed that six of them including FASN, AKT1, CASP3, F2, PTGS2 and PRKCA, could be modulated by CRP in NAFLD mice. Besides, Chenpi primarily regulated FASN, AKT1, CASP3 and PRKCA, which were associated with reducing apoptosis in hepatocytes, while Rougui exceled in regulating F2 and PTGS2, closely linked to its anti-inflammatory properties. The combination of Chenpi and Rougui resulted in a broader influence on metabolites, pathways, and primary targets compared to their individual application.CONCLUSION: These results provided valuable insights into the compatibility mechanism of CRP for treating NAFLD, and could also improve the value of its forthcoming application and development as a natural liver protective agent.PMID:40182620 | PMC:PMC11966411 | DOI:10.3389/fmolb.2025.1553162

Front Mol Biosci. 2025 Mar 20;12:1515276. doi: 10.3389/fmolb.2025.1515276. eCollection 2025.ABSTRACTINTRODUCTION: Exploiting microbial natural products is a key pursuit of the bioactive compound discovery field. Recent advances in modern analytical techniques have increased the volume of microbial genomes and their encoded biosynthetic products measured by mass spectrometry-based metabolomics. However, connecting multi-omics data to uncover metabolic processes of interest is still challenging. This results in a large portion of genes and metabolites remaining unannotated. Further exacerbating the annotation challenge, databases and tools for annotation and omics integration are scattered, requiring complex computations to annotate and integrate omics datasets.METHODS: Here we performed a two-way integrative analysis combining genomics and metabolomics data to describe a new approach to characterize the marine bacterial isolate BRA006 and to explore its biosynthetic gene cluster (BGC) content as well as the bioactive compounds detected by metabolomics.RESULTS AND DISCUSSION: We described BRA006 genomic content and structure by comparing Illumina and Oxford Nanopore MinION sequencing approaches. Digital DNA:DNA hybridization (dDDH) taxonomically assigned BRA006 as a potential new species of the Micromonospora genus. Starting from LC-ESI(+)-HRMS/MS data, and mapping the annotated enzymes and metabolites belonging to the same pathways, our integrative analysis allowed us to correlate the compound Brevianamide F to a new BGC, previously assigned to other function.PMID:40182618 | PMC:PMC11965639 | DOI:10.3389/fmolb.2025.1515276

Front Plant Sci. 2025 Mar 20;16:1547157. doi: 10.3389/fpls.2025.1547157. eCollection 2025.ABSTRACT'Egusi' melon (Colocynthis citrullus L.) plays a critical role in food security and potential biofuel production in West Africa. Its seeds are valued for both their nutritional and potential industrial applications, especially in biodiesel production. However, the crop faces significant challenges, including the impacts of climate change, water scarcity, declining arable land, and increased pressure from pests and diseases. These challenges threaten the stability of 'Egusi' production and may hinder its ability to meet future demand. To address these issues, there is a growing need to complement conventional breeding methods with biotechnological approaches. Molecular approaches; including genomics, transcriptomics, proteomics, and metabolomics; have been utilized for the improvement of several cucurbit species. However, information on molecular breeding of 'Egusi' is very limited. The current review focuses on 'Egusi' melon, its biology, uses, and factors affecting its improvement, and highlights critical knowledge gaps in the molecular breeding of 'Egusi'. The review also examines the potential of omics technologies and outlines the importance of genetic transformation and genome editing methods such as CRISPR that could drive the development of more resilient and high-yielding 'Egusi'varieties that will contribute to sustainability and profitability of 'Egusi' farming.PMID:40182542 | PMC:PMC11965695 | DOI:10.3389/fpls.2025.1547157

RSC Adv. 2025 Apr 3;15(13):10419-10425. doi: 10.1039/d5ra01441g. eCollection 2025 Mar 28.ABSTRACTDespite ongoing efforts to employ structure-based methods to discover targeted protein degraders (TPD), the prevailing strategy continues to be the synthesis of a focused set of heterobifunctional compounds and screening them for target protein degradation. Here we used a fluorescence based live cell imaging screen to identify degraders that target exon 14 skipped hepatocyte growth factor receptor (MET). MET is a known oncogenic driver. MET exon 14 skipping mutations (METex14Δ) are found in lung cancers and result in the loss of a degron that is required for E3-ligase recognition and subsequent ubiquitination, prolonging the half-life and oncogenicity of MET. Since proteolysis targeting chimeras (PROTACs) are heterobifunctional molecules that promote target degradation by the proteosome, we sought to restore degradation of MET lost with METex14Δ using a MET-targeting PROTAC. We generated a library of sixty PROTACs of which 37 used the MET inhibitor capmatinib as the protein of interest targeting ligand. We screened this PROTAC library for targeted degradation of METex14Δ-GFP using live cell imaging. We benchmarked the MET-targeting PROTACs to that of a previously reported MET-targeting PROTAC, SJF8240. Curve fitting live cell imaging data affords determination of time required to degrade 50% of the target protein (DT50), which was used in determining structure activity relationships. A promising candidate, 48-284, identified from the screen, exhibited classic PROTAC characteristics, was >15-fold more potent than SJF8240, had fewer off targets compared to SJF8240, and degraded MET in multiple cell lines.PMID:40182503 | PMC:PMC11967169 | DOI:10.1039/d5ra01441g

Front Immunol. 2025 Mar 20;16:1567833. doi: 10.3389/fimmu.2025.1567833. eCollection 2025.ABSTRACTIdiopathic inflammatory myopathies (IIMs) are heterogeneous autoimmune disorders characterized by muscle inflammation, weakness, and extramuscular manifestations such as interstitial lung disease, skin rash, arthritis, dysphagia, myocarditis and other systemic organ involvement. Although T and B cells have historically been central to the understanding of IIM immunopathology, monocytes and their differentiated progenitor cells, macrophages, are increasingly being recognized as critical mediators of both tissue damage and repair. In subtypes such as dermatomyositis, immune-mediated necrotizing myopathy and antisynthetase syndrome, macrophages infiltrate skeletal muscle and other affected tissues, contributing to inflammation via production of pro-inflammatory cytokines, chemokines, and reactive oxygen species. Dysregulated interferon signaling, mitochondrial stress, and aberrant metabolic states in these cells further perpetuate tissue injury in IIMs. Conversely, certain macrophage subsets can support muscle fiber regeneration and dampen inflammation, underscoring the dual roles these cells can play. Future research into the heterogeneity of monocytes and macrophages, including single-cell transcriptomic and metabolomic approaches, will help clarify disease mechanisms, identify biomarkers of disease activity and prognosis, and guide novel therapeutic strategies targeting these innate immune cells in IIM.PMID:40181992 | PMC:PMC11965591 | DOI:10.3389/fimmu.2025.1567833

Front Immunol. 2025 Mar 20;16:1548735. doi: 10.3389/fimmu.2025.1548735. eCollection 2025.ABSTRACTGiven the inevitable hypoxia and reperfusion injury that occur in organs donated after circulatory death (DCD), the quality and function of these organs are significantly compromised, greatly limiting their application in clinical organ transplantation. Recently, the advancement of functional omics technologies has enabled us to deeply analyze the mechanisms underlying DCD donor organ damage from multiple perspectives. This review systematically integrates the studies from transcriptomics, proteomics, and metabolomics to reveal the key biological mechanisms associated with the declines in DCD donor organ quality, including oxidative stress, inflammatory responses, cell death pathways, and metabolic disturbances. Additionally, we summarized emerging therapeutic strategies based on findings from omics perspectives, offering new possibilities to improve the quality of DCD organ for better transplant prognosis. Finally, we discussed the challenges in current research and future directions to provide scientific evidence for clinical practice and promote the application of DCD donors in organ transplantation.PMID:40181961 | PMC:PMC11965662 | DOI:10.3389/fimmu.2025.1548735

J Anim Sci Biotechnol. 2025 Apr 4;16(1):50. doi: 10.1186/s40104-025-01182-0.ABSTRACTBACKGROUND: Rumen microorganisms are key regulators of ruminant growth and production performance. Identifying probiotic candidates through microbial culturomics presents a promising strategy for improving ruminant production performance. Our previous study identified significant differences in rumen microbial communities of Holstein calves with varying average daily gain (ADG). This study aims to identify a target strain based on the findings from multi-omics analysis and literature review, isolating and evaluating the target microbial strains from both the rumen and hindgut contents for their probiotic potential.RESULTS: Parabacteroides distasonis, a strain closely associated with ADG, was successfully isolated from calf rumen content cultured with Fastidious Anaerobe Agar (FAA) medium and named Parabacteroides distasonis F4. Whole-genome sequencing and pan-genome analysis showed that P. distasonis F4 possesses a core functional potential for carbohydrate and amino acid metabolism, with the ability to produce propionate, acetate, and lactate. The results of targeted and untargeted metabolomics further validated the organic acid production and metabolic pathways of P. distasonis F4. An in vitro simulated rumen fermentation test showed that supplementation with P. distasonis F4 significantly altered rumen microbial community structure and increased the molar proportions of propionate and butyrate in the rumen. Furthermore, an in vivo study demonstrated that dietary supplementation with P. distasonis F4 significantly increased the ADG of pre-weaning calves.CONCLUSIONS: This study represents the first isolation of P. distasonis F4 from rumen, highlighting its potential as a probiotic strain for improving rumen development and growth performance in ruminants.PMID:40181465 | DOI:10.1186/s40104-025-01182-0

BMC Oral Health. 2025 Apr 3;25(1):476. doi: 10.1186/s12903-025-05847-0.ABSTRACTBACKGROUND: Spleen-stomach damp-heat syndrome is one of the most common syndrome types in periodontitis from traditional Chinese medicine theory. However, its pathological mechanism is still uncertain. Tissue metabolism is driven by microbes in the host and its microenvironment. Hostmicrobe-metabolism is an interacting and closely related complex. Lipid metabolomics can find lipid metabolites in disease or healthy state, which is beneficial to explore the metabolic process and change mechanism of lipids that may be involved in organisms in healthy or disease state from the perspective of systems biology.METHODS: In this study, 10 patients in the periodontitis group (CP), 10 patients in the periodontitis with spleen-stomach dampness-heat syndrome group (SP) and 10 patients in the healthy group (H) were recruited for participation, whose unstimulated saliva was collected. The differential metabolites between the groups were detected by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and screened out based on the variable importance in projection (VIP) combined with the P-value and fold change (FC) value of univariate analysis. Finally, KEEG pathway enrichment analysis was performed on these differential metabolites.RESULTS: A total of 1131 metabolites were detected in saliva in this study. 497 metabolites were significantly up-regulated in periodontitis, mainly plasma-membrane-associated lipids, unsaturated fatty acids and oxidized lipids. Compared with the healthy group, the lipid metabolism pathways of periodontitis with or without spleen-stomach dampness-heat syndrome group were mainly characterized by significant enrichment of glycerophospholipid metabolism and unsaturated fatty acid metabolism such as arachidonic acid metabolism.CONCLUSION: Compared with periodontally healthy patients, periodontitis with or without spleen-stomach dampness-heat syndrome can cause changes in lipid metabolism in saliva samples of patients. These metabolites are mainly plasma membrane lipids, unsaturated fatty acids and oxidized lipids quality. These lipids may be potential biomarkers of periodontitis. The downstream metabolites of unsaturated fatty acids in the saliva samples of patients with periodontitis and spleen-stomach dampness-heat syndrome were abnormal, and the oxidized lipid (±)5-HETE was significantly abnormal. We speculate that this may be related to the increased state of oxidative stress in saliva samples in disease states.PMID:40181453 | DOI:10.1186/s12903-025-05847-0

BMC Oral Health. 2025 Apr 3;25(1):480. doi: 10.1186/s12903-025-05792-y.ABSTRACTOBJECTIVE: Saliva, which is a critical component of the oral ecosystem, undergoes dynamic changes, particularly during the onset and progression of periodontitis.SUBJECTS AND METHODS: This study used Gas Chromatography-Mass Spectrometry (GC-MS), a reliable and high-throughput tool for metabolomic analysis, to detect salivary metabolic shifts across various stages of periodontitis (T1-T4). We compared differential changes in metabolites between the HC and T1 groups, the T1 and T2 groups, the T2 and T3 groups, and the T3 and T4 groups.RESULTS: By analysing saliva samples from 116 individuals-10 healthy controls (HC) and 106 patients with periodontitis across stages T1 (22 individuals) to T4 (28 individuals), we identified differential metabolites including Glucose, 3-Aminobutanoic Acid, N-(1-Cyclopropylethyl) Aniline, and Methylmalonic Acid. Compared to HC, the metabolites in patients with periodontitis exhibited progressive concentration changes correlating with the severity of the disease. Furthermore, KEGG pathway analysis was used to elucidate the metabolic pathways involved in the development of periodontitis.CONCLUSIONS: Our findings demonstrate the potential of salivary metabolites as biomarkers for monitoring periodontitis progression and offer valuable insights into its pathogenesis and potential therapeutic targets.PMID:40181365 | DOI:10.1186/s12903-025-05792-y

Autophagy. 2025 Apr 3. doi: 10.1080/15548627.2025.2488563. Online ahead of print.ABSTRACTEndurance exercise triggers adaptive responses especially in slow-twitch myofibers of skeletal muscles, leading to the remodeling of myofiber structure and the mitochondrial network. However, molecular mechanisms underlying these adaptive responses, with a focus on the fiber type-specific perspective, remains largely unknown. In this study we analyzed the alterations of transcriptomics and metabolomics in distinct skeletal myofibers in response to endurance exercise. We determined that genes associated with sphingolipid metabolism, namely those encoding SPHK1, S1PR1, and S1PR2, are enriched in slow-twitch but not fast-twitch myofibers from both mouse and human skeletal muscles, and found that the SPHK1-S1PR pathway is essential for adaptive responses of slow-twitch to endurance exercise. Importantly, we demonstrate that endurance exercise causes the accumulation of ceramides on stressed mitochondria, and the mitophagic degradation of ceramides results in an increase of the sphingosine-1-phosphate (S1P) level. The elevated S1P thereby facilitates mitochondrial adaptation and enhances endurance capacity via the SPHK1-S1PR1/S1PR2 axis in slow-twitch muscles. Moreover, administration of S1P improves endurance performance in muscle atrophy mice by emulating these adaptive responses. Our findings reveal that the SPHK1-S1P-S1PR1/S1PR2 axis through mitophagic degradation of ceramides in slow-twitch myofibers is the central mediator to endurance exercise and highlight a potential therapeutic target for ameliorating muscle atrophy diseases.PMID:40181214 | DOI:10.1080/15548627.2025.2488563

Nat Chem. 2025 Apr 3. doi: 10.1038/s41557-025-01789-w. Online ahead of print.ABSTRACTMicrobiota-mediated drug metabolism can affect pharmacological efficacy. Here we conducted a systematic comparative metabolomics investigation of drug metabolism modes by evaluating the impacts of human gut commensal bacteria on 127 G-protein-coupled receptor (GPCR)-targeted drugs. For the most extensively metabolized drugs in our screen, we elucidated both conventional and unconventional drug transformations and the corresponding activities of generated metabolites. Comparisons of drug metabolism by a gut microbial community versus individual species revealed both taxon intrinsic and collaborative processes that influenced the activity of the metabolized drugs against target GPCRs. We also observed iloperidone inactivation by generating unconventional metabolites. The human gut commensal bacteria mixture incorporated sulfur in the form of a thiophene motif, whereas Morganella morganii used a cascade reaction to incorporate amino-acid-derived tricyclic systems into the drug metabolites. Our results reveal a broad impact of human gut commensal bacteria on GPCR-targeted drug structures and activities through diverse microbiota-mediated biotransformations.PMID:40181149 | DOI:10.1038/s41557-025-01789-w

Sci Rep. 2025 Apr 3;15(1):11502. doi: 10.1038/s41598-025-96038-y.ABSTRACTThis study investigates the role of Cathepsin D (CTSD) in diabetic vascular complications, particularly its impact on the phenotypic transformation of vascular smooth muscle cells (VSMCs) induced by advanced glycation end-products (AGEs), and explores its potential molecular mechanisms. CTSD was overexpressed in VSMCs using lentiviral vectors. Various methods, including CCK-8, immunofluorescence, SA-β-Gal staining, EdU assay, scratch assay, cell cycle analysis, and Western blotting, were employed to assess VSMC viability, proliferation, migration, senescence, and apoptosis. Additionally, transcriptomic and metabolomic analyses were conducted to investigate the molecular mechanisms underlying CTSD overexpression in VSMCs. AGEs treatment significantly inhibited CTSD expression in VSMCs, leading to reduced cell viability, enhanced proliferation and migration, increased senescence, and apoptosis. In contrast, overexpression of CTSD effectively inhibited AGEs-induced VSMCs proliferation, migration, senescence, and apoptosis. Combined transcriptomic and metabolomic analyses suggested that CTSD may affect VSMCs phenotypic transformation by inhibiting the glycolysis pathway. This study highlights the critical role of CTSD in the phenotypic transformation of VSMCs induced by AGEs and provides a new perspective for cardiovascular and cerebrovascular disease treatment. CTSD may emerge as a novel therapeutic target, though its specific molecular mechanisms and clinical application prospects in VSMCs phenotypic transformation require further investigation.PMID:40181129 | DOI:10.1038/s41598-025-96038-y

Nat Commun. 2025 Apr 3;16(1):3174. doi: 10.1038/s41467-025-58525-8.ABSTRACTAnchorage-independent survival of ovarian tumor cells in ascites is the initial and critical step for peritoneal metastasis. How ovarian tumor cells achieve anchorage independence remains unclear. Here we show that a noncanonical role of spermidine/spermine N1-acetyltransferase 1 (SAT1) dictates anchorage-independent cell survival and potentiates metastatic dissemination in ovarian cancer. SAT1-high cancer cells are prevalent in ascitic tumors, and high SAT1 expression in primary tumors is linked to increased peritoneal metastasis rates in ovarian cancer patients. Mechanistically, SAT1 noncanonically acetylates H3K27 domains in multiple mitosis-regulating genes, increasing their transcriptional levels and protecting disseminating cells from aberrant mitosis and mitotic cell death. Notably, the acetylation of H3K27 by SAT1 depends on the reductive carboxylation of glutamine to supply acetyl-CoA in the nucleus. SAT1 inhibition with the small-molecule inhibitor ginkgolide B attenuates the metastatic tumor burden in mouse models. We conclude that SAT1 inhibition is a promising therapeutic strategy for metastatic ovarian cancer.PMID:40180916 | DOI:10.1038/s41467-025-58525-8

Semin Nephrol. 2025 Apr 2:151577. doi: 10.1016/j.semnephrol.2025.151577. Online ahead of print.ABSTRACTThe coupling between energy metabolism and transport processes is a key feature that defines the functional capability of proximal tubule cells. Recent studies using metabolomics and transcriptomics provide insights into the relationships between changes in single-cell transcriptomic profiles and energy metabolism during kidney development and in disease states. In this review, we describe insights from these studies and how mapping of metabolites to functional pathways within cells enables these insights. We also describe our analyses of fatty acid metabolism pathways from single-cell transcriptomic data obtained by the Kidney Precision Medicine Project, which indicate that proximal tubule cell subtypes can be divided into two major groups with high and low levels of mRNAs for fatty acid (beta) oxidation enzymes. On average, patients with CKD have higher levels of cells with low fatty acid oxidation capability. These cells also have lower levels of sodium transporters. Within each group of proximal tubule cell subtypes there is considerable variability between individual patients. Integrating these data with metabolomics analyses can provide insights into how the differential metabolic capabilities of proximal tubule cells are related to disease features in individual patients. Identifying such relationships can lead to development of precision medicine approaches in nephrology.PMID:40180882 | DOI:10.1016/j.semnephrol.2025.151577

J Steroid Biochem Mol Biol. 2025 Apr 2:106741. doi: 10.1016/j.jsbmb.2025.106741. Online ahead of print.NO ABSTRACTPMID:40180878 | DOI:10.1016/j.jsbmb.2025.106741

Methods Cell Biol. 2025;195:143-172. doi: 10.1016/bs.mcb.2023.03.007. Epub 2023 Jul 14.ABSTRACTFlow cytometry has great potential for screening in translational research areas due to its deep quantification of cellular features, ability to collect millions of cells in minutes, and consistently expanding suite of validated antibodies that detect cell identity and functions. However, cytometry remains under-utilized in discovery chemical biology due to the differences in expertise between chemistry groups developing chemical libraries and cell biologists developing single cell assays. This chapter is designed to bridge this gap by providing a detailed protocol aimed at both chemistry and biology audiences with the goal of helping train novice researchers. Assay users select from three elements: a small molecule input, a target cell type, and a module of cytometry readouts. For each, we explore basic and advanced examples of inputs, including screening fractionated microbial extracts and pure compounds, and target cells, including primary human blood cells, mouse cells, and cancer cell lines. One such module of cytometry readouts focuses on cell function and measures DNA damage response (γH2AX), growth (phosphorylated S6), DNA content, apoptosis (cleaved Caspase3), cell cycle M phase (phosphorylated Histone H3), and viability (membrane permeabilization). The protocol can also be adapted to measure different functional readouts, such as cell identity or differentiation and contrasting cell injury mechanisms. The protocol is designed to be used in 96-well plate format with fluorescent cell barcoding and the debarcodeR algorithm. Ultimately, the goal is to encourage the next generation of chemical biologists to use functional cell-based cytometry assays in discovery and translational research.PMID:40180452 | DOI:10.1016/bs.mcb.2023.03.007