PubMed

Stem Cell Res Ther. 2025 Apr 12;16(1):177. doi: 10.1186/s13287-025-04311-8.ABSTRACTINTRODUCTION: Mesenchymal stem cell (MSC)-derived conditioned media is emerging as a promising alternative to stem cell therapy, owing to its abundant content of growth factors and cytokines.OBJECTIVE: This review evaluates the clinical applications of MSC-conditioned media in improving scars, promoting wound healing, stimulating hair growth, and rejuvenating the skin.MATERIALS AND METHODS: A thorough search of relevant databases was performed to identify studies meeting the inclusion criteria. From an initial pool of 75 articles, 16 studies published up to 2024 were selected based on their relevance, focus, and alignment with the research objectives.RESULTS: Among the 17 selected studies, 5 examined the role of conditioned media in skin rejuvenation, 3 investigated its effects on hair growth, 5 assessed its efficacy in scar treatment, 2 assessed its efficacy in Inflammatory Dermatologic Disease and 2 explored its role in wound healing. All studies reported favorable outcomes, demonstrating significant improvements in scars, hair regrowth, and skin rejuvenation with the application of conditioned media.CONCLUSION: This review underscores the potential of MSC-derived conditioned media in dermatology. Several studies also highlighted its enhanced therapeutic effects when combined with adjunctive treatments, such as laser therapy and microneedling, showcasing improved outcomes in dermatological care.PMID:40221781 | DOI:10.1186/s13287-025-04311-8

BMC Complement Med Ther. 2025 Apr 12;25(1):138. doi: 10.1186/s12906-025-04880-4.ABSTRACTBACKGROUND: The emergence of antimicrobial resistance (AMR) is imperiling global health, hence, the need to remedy this challenge by discovering new therapeutic strategies and agents. Quorum sensing inhibition (QSI) is opined as a potential novel strategic approach in the fight against AMR by abrogation of bacterial virulence and pathogenicity. Currently, there are no clinically approved QSI drugs. Based on this, this study evaluated the QSI properties of South African plant species.METHODS: Twenty-nine extracts and their corresponding 203 fractions generated using solid phase extraction were screened for QSI activity in vitro against Chromobacterium violaceum ATCC 12472. Active and inactive fractions of the most potent plant species were analysed using UPLC-HRMS. The acquired mass spectral data was subjected to chemometric analysis.RESULTS: From the QSI assays, three plant species showed remarkable QSI activity, measured by dose-dependent inhibition of violacein production (IVP), at sublethal concentrations. Terminalia phanerophlebia emerged as the most active species, with the extract and five of its fractions showing good activity in IVP (IVP IC50 ≤ 0.1 mg/mL). This was closely followed by Momordica cardiospermoides whose crude extract and two of its corresponding fractions showed good activity (IVP IC50 ≤ 0.1 mg/mL). Three fractions of Helichrysum odoratissimum also had good activity (IVP IC50 ≤ 0.1 mg/mL) marking it one of the most potent selected species. Chemometric analysis identified five compounds including olivetol and hydroxytyrosol as chemical markers positively associated with the QSI activity of T. phanerophlebia.CONCLUSION: In conclusion, the findings of our study provided insight into the QSI properties of South African plant species. Further studies will focus on the isolation of the putative active compounds and the in vitro evaluation of their QSI activity.PMID:40221765 | DOI:10.1186/s12906-025-04880-4

BMC Vet Res. 2025 Apr 12;21(1):262. doi: 10.1186/s12917-025-04705-z.ABSTRACTBACKGROUND: The forest musk deer (FMD, Moschus berezovskii), an endangered small ruminant, is listed as a class I protected wild animals in China. However, compared to their wild counterparts, captive FMD are more prone to gastrointestinal diseases caused by gut microbial dysbiosis, which severely limits population growth and increases the risk of mortality. Active dry yeast (ADY), as a commonly used feed additive, has been widely applied in domestic livestock to improve gut microbiota and enhance immune function. Whether dietary supplementation with ADY in captive FMD contributes to gut microbial homeostasis and physical health is still unclear. Thus, the study aimed to evaluate the effects of dietary supplementation with ADY on the immunity, gut microbial composition, and serum metabolites in FMD.METHODS: Fourteen male FMD from the Chongqing Institute of Medicinal Plant Cultivation (Chongqing, China), with similar initial bodyweights (7.0±0.3kg) and an average age of 4.5 years, were selected and randomly divided into two groups. The control group was fed a standard diet, while the ADY group received the standard diet supplemented with ADY at a dosage of 10 g/kg DM.RESULTS: ADY supplementation significantly increased the concentrations of immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) in the serum. ADY improved the richness and diversity of the gut microbiota, increased the relative abundance of the Firmicutes and Bacteroidota, but decreased the relative abundance of the Proteobacteria. A widely targeted metabolomics analysis identified a total of 25 differential metabolites, with 10 being upregulated and 15 downregulated. Many differential metabolites, for example phosphatidylcholine, Glu-His, L-cysteine and other differential metabolites contributed to strengthening the immunity of the FMD by affecting arachidonic acid metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, and so on.CONCLUSION: Dietary supplementation with ADY positively impacts the immunity of FMD by modulating the composition of the gut microbial communities and serum metabolites.PMID:40221712 | DOI:10.1186/s12917-025-04705-z

Nat Commun. 2025 Apr 12;16(1):3497. doi: 10.1038/s41467-025-58887-z.ABSTRACTLipid droplets (LDs) are the main cellular storage sites for triacylglycerols (TAGs), playing an important role in energy homeostasis and cell signaling. Hydrolysis of the stored TAGs begins with conversion of TAGs into diacylglycerols (DAGs) by adipose triglyceride lipase (ATGL), followed by hydrolysis of DAGs by hormone-sensitive lipase (HSL). Despite the central role of HSL in lipolysis, the molecular determinants for its LD association have remained elusive. Here, we report the cryo-EM structure of human HSL at 3.4 Å. Combining this with hydrogen-deuterium exchange mass spectrometry, biochemical and cellular assays, we identify residues 489-538, referred to as the "H-motif", and the N-terminal 4-helix bundle of HSL as LD-binding motifs mediating direct interaction of HSL with LDs. LD binding mediated by the LD-binding motifs is independent of HSL phosphorylation catalyzed by the cAMP-dependent kinase PKA. Our findings provide insight into the LD binding mechanism of HSL, advancing our understanding of the regulation of lipolysis.PMID:40221426 | DOI:10.1038/s41467-025-58887-z

Semin Nephrol. 2025 Apr 12:151580. doi: 10.1016/j.semnephrol.2025.151580. Online ahead of print.ABSTRACTAcute kidney injury (AKI) is a common condition linked to increased morbidity, mortality, and substantial health care costs both in the United States and globally. Early diagnosis, prompt intervention, and effective therapeutic management of AKI are vital for improving patient outcomes. Recent advancements in renal imaging and omics technologies have provided new perspectives and deeper insights into kidney injury while also presenting challenges in developing a comprehensive cellular and molecular atlas of the condition. This review focuses on the application of mass spectrometry imaging-based spatial metabolomics in studying ischemia- and toxin-induced AKI in animal models and human patients. Spatial metabolomics offers a deeper understanding of the pathophysiological connections between various processes, such as dysregulated lipid metabolism and the shift from the tricarboxylic acid cycle to glycolytic flux, which contribute to functional impairment and structural damage in AKI. Continued research in renal multimodal imaging and omics is essential to further our understanding of kidney injury from diagnostic, mechanistic, and therapeutic perspectives. Semin Nephrol 36:x-xx © 20XX Elsevier Inc. All rights reserved.PMID:40221281 | DOI:10.1016/j.semnephrol.2025.151580

Anal Chim Acta. 2025 Jun 1;1353:343951. doi: 10.1016/j.aca.2025.343951. Epub 2025 Mar 17.ABSTRACTTrimethylamine N-oxide (TMAO) serves as a crucial biomarker for early detection and prevention of cardiovascular and chronic kidney diseases. In this study, we design and implement a novel pixel array-based urine biosensor to explore the relationship between TMAO levels and glucose in urine and the urine albumin-creatinine ratio (UACR). The urine biosensor, incorporating a specialized readout circuit, measures TMAO across various UACR ranges, revealing a linear correlation with a slope of 8.5 mV per mg/g up to 1100 mg/g UACR. Although glucose levels also rise with UACR, significant discrepancies occur beyond 30 mg/g, indicating that glucose does not consistently correlate with UACR increases. The biosensor demonstrates a sensitivity of 41 ADC counts/μM (4.5 mV/μM), a 10-s response time, 98 % reproducibility, and a drift of 0.3 mV over extended periods. It requires only 5 μL of urine for a comprehensive analysis of TMAO and glucose. This approach significantly improves time efficiency, offering a faster and more convenient solution for monitoring the risk for chronic kidney disease, such as those with diabetes.PMID:40221198 | DOI:10.1016/j.aca.2025.343951

Anal Chim Acta. 2025 Jun 1;1353:343947. doi: 10.1016/j.aca.2025.343947. Epub 2025 Mar 22.ABSTRACTBACKGROUND: The relationship between diet, human health, and disease prevention is well-established, with food bioactive compounds (FBs) widely recognized for their beneficial effects. Metabolism is key in transforming precursor FBs molecules and facilitating their circulation in the human body. Urine has proven to be a valuable biofluid for monitoring dietary exposure. However, the low concentrations of FBs metabolites, their chemical variability, and the lack of appropriate reference standards present challenges in metabolite identification. To address these challenges, developing urine preparation methods for scalable metabolite isolation and unambiguous structure elucidation could significantly improve the coverage and accurate annotation of urine metabolites.RESULTS: Urine samples were collected from a healthy volunteer after hydroxytyrosol (HT) supplementation. Traditional urine pretreatment protocols, such as liquid-liquid extraction (LLE) and solid-phase extraction (SPE), were tested alongside enrichment methods using resins (XAD-4, XAD-7, ion-exchange). Extracts were analyzed in parallel using HPLC-DAD/ELSD, UPLC-HRMS, and NMR to assess profiles and annotate metabolites. Methods were evaluated based on extraction yield, metabolite chemical and biochemical diversity, metabolite coverage, selectivity, as well as cost, ease and time. The most promising protocols were further tested on a larger scale. Among the methods evaluated, XAD-7 resin and LLE (Urine/EtOAc 1:3) showed the best performance. Furthermore, detailed identification of metabolites (endogenous and exogenous) per protocol was performed using LC-HRMS/MS and NMR. Additionally, investigation of each protocol performance in respect to the biochemical pathway in which metabolites are implicated was assessed.SIGNIFICANCE: The suggested workflow is compatible with both profiling and isolation set-ups and could provide essential insights into urine metabolome and FBs biotransformation. It ensures confident identification and high coverage of metabolites, providing more complete and accurate interpretation of metabolism studies' results and, therefore, valuable input in profiling approaches towards the role of diet on human health.PMID:40221194 | DOI:10.1016/j.aca.2025.343947

J Immunother Cancer. 2025 Apr 12;13(4):e010924. doi: 10.1136/jitc-2024-010924.ABSTRACTBACKGROUND: Triple-negative breast cancer (TNBC) is the most malignant breast cancer, highlighting the need for effective immunotherapeutic targets. The immune checkpoint molecule B7-H3 has recently gained attention as a promising therapeutic target due to its pivotal role in promoting tumorigenesis and cancer progression. However, the therapeutic impact of B7-H3 inhibitors (B7-H3i) remains unclear.METHODS: Transcriptomic and metabolomic analyses were conducted to explore the underlying mechanisms of B7-H3 inhibition in TNBC. The therapeutic efficacy of the combined treatment strategy was substantiated through comprehensive phenotypic assays conducted in vitro and validated in vivo using animal models.RESULTS: B7-H3 blockade induces a "primed for death" stress state in cancer cells, leading to distinct alterations in metabolic pathways. Specifically, B7-H3 knockdown activated the AKT signaling pathway and upregulated sterol regulatory element-binding protein 1 (SREBP1), which in turn elevated FASN expression. The simultaneous inhibition of both B7-H3 and FASN more effectively attenuated the malignant progression of TNBC.CONCLUSIONS: Our findings propose an "immune attack-metabolic compensation" dynamic model and suggest the feasibility of a dual-targeting strategy that concurrently inhibits both B7-H3 and FASN to enhance therapeutic efficacy in TNBC patients.PMID:40221152 | DOI:10.1136/jitc-2024-010924

J Insect Physiol. 2025 Apr 10:104800. doi: 10.1016/j.jinsphys.2025.104800. Online ahead of print.ABSTRACTSpodoptera frugiperda is among the most significant pests affecting food crops globally. Our findings indicate that the mortality rates of 1st and 2nd instar larvae are significantly higher than those of 3rd instar and older larvae following tobacco consumption. In this study, we employed integrated transcriptomic and metabolomic analyses to investigate the changes in gene expression and metabolic processes in 2nd and 3rd instar larvae after consuming tobacco and maize. Transcriptome analysis revealed that the majority of differentially expressed genes (DEGs) involved in xenobiotic biodegradation and metabolism were upregulated, particularly cytochrome P450s. Metabolomic analysis identified alkaloid metabolites in the bodies of larvae that had fed on tobacco. The 3rd instar larvae that consumed tobacco exhibited increased production of metabolites via cytochrome P450. Correlation analysis of the transcriptome and metabolome demonstrated that, when comparing the 3rd instar larvae fed on tobacco to those fed on maize, both DEGs and differentially accumulated metabolites (DAMs) shared pathways related to cytochrome P450, fatty acid metabolism, and glutathione metabolism. Transcriptome and metabolome analysis shows cytochrome P450 play an important role in the detoxification and adaptability of S. frugiperda larvae to tobacco. This study provides a preliminary explanation of the detoxification metabolism and adaptive mechanisms of S. frugiperda larvae in response to tobacco.PMID:40221127 | DOI:10.1016/j.jinsphys.2025.104800

Environ Pollut. 2025 Apr 10:126232. doi: 10.1016/j.envpol.2025.126232. Online ahead of print.ABSTRACTBaicalein has pharmacological functions, such as antioxidant and anti-inflammatory properties, and has been shown to alleviate damage to organs caused by environmental pollutants. However, the mechanism by which baicalein reduces the toxic effects of metals needs further research. This study used Pelophylax nigromaculatus tadpoles as a model to explore the toxicological effects of lead (Pb) on the gut-liver axis, and the mechanism by which baicalein alleviates lead toxicity. Analysis of the gut microbiota showed that baicalein alleviated abnormal changes in the gut microbiota following Pb exposure, mainly by increasing the abundance of beneficial bacterial genera, including Cetobacterium, Clostridioides, and Monoglobus. Liver metabolomics showed that compared to a natural recovery, baicalein treatment significantly increased the content of metabolites such as uridine, 17α-hydroxypregnenolone, niacin, and cucurbitacin E, and significantly reduced the content of metabolites such as linoleic, gluconic acid, and tetrahydrocortisone. These differential metabolites could be enriched in pathways such as pyrimidine metabolism, nicotinic acid and nicotinamide metabolism, and steroid hormone biosynthesis, which were beneficial for the treatment of liver injury. There was a significant correlation between the gut microbiota and the main differential metabolites in the liver with the addition of baicalein. The improvement of these metabolic pathways by baicalein is beneficial for the repair of the liver and intestines. Therefore, baicalein can increase the abundance of beneficial gut microbiota, improve liver metabolism, and thus reduce the damage of Pb exposure to the gut-liver axis.PMID:40221113 | DOI:10.1016/j.envpol.2025.126232

Gene. 2025 Apr 10:149483. doi: 10.1016/j.gene.2025.149483. Online ahead of print.ABSTRACTSpinocerebellar ataxia type 14 (SCA14) is an autosomal dominant disorder characterized by progressive cerebellar dysfunction and neurodegeneration. To date, it is rarely reported in China. SCA14 is caused by mutations in the PRKCG gene, which encodes protein kinase C gamma (PKCγ). Although nearly eighty distinct mutations of PRKCG gene have been identified, the pathological mechanisms of SCA14 remain unclear. In this study, we performed whole exome sequencing to screen causative genes in patients with unexplained progressive cerebellar ataxias, and identified three PRKCG mutations (c.302A > G, p.H101R, c.520C > G, p.H174D and c.2063C > G, p.P688R) that have not been previously reported in Chinese patients with SCA14. To explore the pathogenicity and function of these SCA14-associated PRKCG mutations, HEK293T and HeLa cells were transfected with the plasmids of empty vector, wild-type PRKCG and indicated PRKCG mutants. Protein stability, aggregation propensity, phosphorylation status, mitochondrial function and cytotoxicity were then measured. We found that H101R mutant PKCγ protein is unstable, prone to aggregate, exhibits reduced basal phosphorylation, and is resistant to agonist-mediated dephosphorylation. Also, H101R mutant PKCγ protein could result in increased apoptosis and reduced cell viability. These findings are similar to other pathogenic mutations. Additionally, cellular mitochondrial dysfunction was observed for the first time in cells expressing mutant PKCγ. Together, we identified three PRKCG mutations, expanding the mutation spectrum of PRKCG in China. The c.302A > G, p.H101R variant is likely pathogenic and mitochondrial dysfunction is suggested involved in the pathogenesis of SCA14.PMID:40221062 | DOI:10.1016/j.gene.2025.149483

J Dairy Sci. 2025 Apr 10:S0022-0302(25)00218-8. doi: 10.3168/jds.2024-26102. Online ahead of print.ABSTRACTThis study aimed to investigate the impact of preweaning nutrient intake on milk production of the 2 first lactations, risk of culling and metabolomic profiles in dairy cows fed a restricted (RES) or an elevated (ELE) milk supply preweaning. A total of 86 Holstein Friesian female calves were randomly assigned to either 5.4 Mcal of ME in 8 L of MR/d (ELE) or 2.7 Mcal of ME in 4 L of MR/d (RES) from d 2 after birth until they were stepped down by 50% from d 42 to d 49 and fully weaned at d 50. Starting from d 50, animals from both treatments were fed and managed in the same way, with treatments being blinded, for the entire study duration. At 60 d in milk (DIM) in first lactation, blood samples were taken for metabolomics analysis. Heifers fed the ELE diet exhibited higher ADG (0.79 vs. 0.49 kg/d) in the pre-weaning period, leading to higher BW at 70 d of age (94 vs. 85 kg). In the first lactation, cows fed the ELE diet preweaning exhibited higher DMI (+ 0.7 kg/d), higher milk fat yield (+ 50 g/d) and milk fat content (+0.24%) but lower feed efficiency (-0.04) compared with the RES group. In the second lactation, fat- protein corrected milk yield (+ 1.8 kg/d), milk fat yield (+115 g/d), milk fat content (+0.22%) and feed efficiency (+0.06) were all higher in ELE cows. Throughout these 2 lactations, ELE cows were leaner as indicated by a lower BCS. Cows fed the ELE diet preweaning had a higher first service conception rate during the second lactation compared with RES (40.7 vs. 13.0%). Moreover, the likelihood to be culled before third, fourth, or fifth calving was halved when calves were fed ELE as compared with RES. Metabolomic profiling revealed distinct metabolomic profiles at 60 DIM in response to preweaning milk supply. The major metabolic pathways affected by preweaning nutrient supply at 60 DIM were pyrimidine, sphingosine, guanidino and acetamido, purine metabolism, and the tricarboxylic acid cycle. The metabolic profile differences between the groups describe a metabolic configuration that was sustained into adulthood and that may explain the improved productivity and resilience of cows fed a greater milk supply during the preweaning period.PMID:40221032 | DOI:10.3168/jds.2024-26102

J Dairy Sci. 2025 Apr 10:S0022-0302(25)00219-X. doi: 10.3168/jds.2024-26103. Online ahead of print.ABSTRACTMilk lipolysis refers to the breakdown of triacylglycerols by lipoprotein lipase. Our aim was to identify the drivers of spontaneous lipolysis in skimmed ewe's milk. To achieve this, feed restriction was used as a lever to generate contrasting samples with respect to lipolysis. We combined multivariate statistical methods to identify the effects of feed restriction on ewes, the molecular composition of skim milk, and the drivers of spontaneous lipolysis in milk. The high spontaneous lipolysis in skimmed ewe's milk was driven by a combination of variables consisting of 12 milk proteins (ANGPT1, FN1, COL14A1, W5PDQ9, W5QH04, CLSTN1, PPIB, PLIN3, ITIH2, ASAH1, SMPD1 and FST), 7 milk fatty acids (C6:0, C14:0, C14:1 cis9, C10:1 cis9, C10:0, C11:0 and C12:0), milk urea, plasma acetate, plasma urea, plasma IGF1, milk yield and NEL. In particular, the proteins ANGPT1, SMPD1 and ASAH1 were identified as players in the lipolytic process in milk, whatever the level of nutrition, which could be considered in future tools to manage milk lipolysis.PMID:40221030 | DOI:10.3168/jds.2024-26103

Fish Shellfish Immunol. 2025 Apr 10:110312. doi: 10.1016/j.fsi.2025.110312. Online ahead of print.ABSTRACTAmyloodinium ocellatum is a pathogenic parasitic dinoflagellate that infects most marine fish, including the Acanthopagrus latus. This study combined transcriptomics and metabolomics analyses to investigate the pathogenesis of A. ocellatum infection in A. latus. The results indicated that A. ocellatum infection significantly up-regulated 1,556 genes and 326 metabolites while down-regulating 1,668 genes and 399 metabolites in the gills of A. latus. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that numerous differentially expressed genes (DEGs) and differential metabolites (DMs) were enriched in pathways associated with oxidative stress, inflammation, and apoptosis, suggesting that these factors may be key drivers of disease pathogenesis and mortality in infected fish. The effects of A. ocellatum infection on reactive oxygen species (ROS) levels, apoptosis, antioxidant capacity, and gene expression in the gills of A. latus were also investigated, alongside hematological and histopathological analyses of the internal organs. The results revealed that A. ocellatum infection induced overproduction of ROS, triggering apoptosis, altered oxidase and antioxidant enzyme activities, and increased mRNA expression of inflammation-related (COX-2, IL-1β, IL-8) and apoptosis-related genes (CatB, CASP3) in the gills of A. latus. Moreover, cholesterol (CHO) concentrations and aspartate transaminase (AST) activity in the serum, as well as the number and density of melanomacrophage centers (MMCs) in the spleen, were significantly higher (P < 0.05) in the infected fish. In conclusion, this study reports that A. ocellatum infection causing oxidative stress, inflammation, and apoptosis in the gills of A. latus, which contribute to fish mortality.PMID:40220926 | DOI:10.1016/j.fsi.2025.110312

Mech Ageing Dev. 2025 Apr 10:112057. doi: 10.1016/j.mad.2025.112057. Online ahead of print.ABSTRACTGrowing old is the major risk factor for hundreds of distinct conditions. Thus, ageing of the global population will pose major social, medical, and economic challenges unless this ill health can be ameliorated or reversed. Accordingly, it is increasingly clear that cross-disciplinary approaches to understanding ageing, although not essential, allow collaborative teams to develop new methodologies which can accelerate translation of research into interventions. Co-creation of new concepts and technologies also brings reciprocal benefits to the individual disciplines involved. The evolution of human ageing is a case in point. Whilst there is broad consensus concerning the process and factors shaping the evolution of ageing in general their relative contributions to the evolution of human ageing remain less clear. This is due to three distinct factors. The extended genetic bottlenecks to which H. sapiens was exposed until the termination of the last ice age which sharply distinguishes our species from almost all current ageing models. Sociality, which humans share with many, but not all, living primate species; and finally, an extended post reproductive menopausal period which is extremely rare in the biosphere and uniquely long in humans. Accordingly, a symposium on the physiology and demography of early human evolution was organised by the authors at which palaeodemographers, archaeologists, population biologists and geroscientists discussed human ageing. This has generated important interdisciplinary research priorities which could accelerate the development of treatments for older people in the present and transform key aspects of our understanding of the ageing process in the past.PMID:40220913 | DOI:10.1016/j.mad.2025.112057

Int J Biol Macromol. 2025 Apr 10:143051. doi: 10.1016/j.ijbiomac.2025.143051. Online ahead of print.ABSTRACTIn this study, low molecular weight chondroitin sulfates (LMCSs) with different structures, named LMCSO, LMCSD, and LMCSH, were prepared by oxidative degradation, deamidation cleavage, and hydrothermal depolymerization, respectively. In vitro fermentation modeling was used to study the effects of CS and LMCSs on gut microbiota and metabolite composition. The degree of carbohydrate metabolism was in the order of CS > LMCSH > LMCSO > LMCSD. Significantly, GlcA in chondroitin-6-sulfate (CSC) was more readily utilized by gut microbiota during fermentation, and this trend was more pronounced in LMCSs. The LMCSs group notably increased microbial richness and evenness, especially in the LMCSD group. Bacteroides fragilis was identified as a potential primary degrader of CS and LMCSs through species-level analysis. The abundance of Escherichia-Shigella was reduced by LMCSs, and short-chain fatty acids production was enhanced, particularly by LMCSO, while the production of beneficial metabolites such as N-acetyl-D-Glucosamine 6-Phosphate (GlcNAc-6P), lactate, and progesterone was stimulated. Among these, the metabolism of the key metabolite GlcNAc-6P was significantly and positively correlated with the abundance of Bacteroides, Clostridium_sensu_stricto_1, and Parabacteroides. Exploring the mechanisms by which gut microbiota metabolize LMCSs with different structures can provide theoretical support for the targeted preparation of LMCSs that modulate the gut microbiota.PMID:40220808 | DOI:10.1016/j.ijbiomac.2025.143051

EBioMedicine. 2025 Apr 11;115:105686. doi: 10.1016/j.ebiom.2025.105686. Online ahead of print.ABSTRACTBACKGROUND: Gut microbiota dysbiosis has been implicated in pulmonary arterial hypertension (PAH). However, the exact roles and underlying mechanisms of multi-kingdom gut microbiota, including bacteria, archaea, and fungi, in PAH remain largely unclear.METHODS: The shotgun metagenomics was used to analyse multi-kingdom gut microbial communities in patients with idiopathic PAH (IPAH) and healthy controls. Furthermore, fecal microbiota transplantation (FMT) was performed to transfer gut microbiota from IPAH patients or monocrotaline (MCT)-PAH rats to normal rats and from normal rats to MCT-PAH rats.FINDINGS: Gut microbiota analysis revealed substantial alterations in the bacterial, archaeal, and fungal communities in patients with IPAH compared with healthy controls. Notably, FMT from IPAH patients or MCT-PAH rats induced PAH phenotypes in recipient rats. More intriguingly, FMT from normal rats to MCT-PAH rats significantly ameliorated PAH symptoms; restored gut bacteria, archaea, and fungi composition; and shifted the plasma metabolite profiles of MCT-PAH rats toward those of normal rats. In parallel, RNA-sequencing analysis demonstrated the expression of genes involved in key signalling pathways related to PAH. A panel of multi-kingdom markers exhibited superior diagnostic accuracy compared with single-kingdom panels for IPAH.INTERPRETATION: Our findings established an association between multi-kingdom gut microbiota dysbiosis and PAH, thereby indicating the therapeutic potential of FMT in PAH. More importantly, apart from gut bacteria, gut archaea and fungi were also significantly associated with PAH pathogenesis, highlighting their indispensable role in PAH.FUNDING: This work was supported by Noncommunicable Chronic Diseases-National Science and Technology Major Projects No. 2024ZD0531200, No. 2024ZD0531201 (Research on Prevention and Treatment of Cancer, Cardiovascular and Cerebrovascular Diseases, Respiratory Diseases, and Metabolic Diseases), the National Natural Science Foundation of China of China (No. 82170302, 82370432), Financial Budgeting Project of Beijing Institute of Respiratory Medicine (Ysbz2025004, Ysbz2025007), National clinical key speciality construction project Cardiovascular Surgery, Reform and Development Program of Beijing Institute of Respiratory Medicine (Ggyfz202417, Ggyfz202501), Clinical Research Incubation Program of Beijing Chaoyang Hospital Affiliated to Capital Medical University (CYFH202209).PMID:40220715 | DOI:10.1016/j.ebiom.2025.105686

Chemosphere. 2025 Apr 11;378:144399. doi: 10.1016/j.chemosphere.2025.144399. Online ahead of print.ABSTRACTLead (Pb), a toxic heavy metal prevalent in the environment, poses serious health risks due to its persistence and bioaccumulation. While certain Lactiplantibacillus plantarum strains have demonstrated the ability to mitigate Pb toxicity in vivo, the molecular mechanisms remain unclear. We hypothesized that Pb-resistant L. plantarum strains employ unique physiological adaptations to survive and counteract Pb stress. To test this, tandem mass tag (TMT) proteomics and LC-MS metabolomics were applied to compare the Pb-tolerant strain CCFM8661 and Pb-sensitive strain CCFM578 under 128 mg/L Pb exposure. Metabolomics revealed that Pb stress altered levels of key metabolites, including proline, arginine, glutamic acid, and mannitol. Proteomics showed that Pb stress decreased the abundance of 30 key proteins, such as 1-phosphofructokinase, pyruvate kinase, and β-galactosidase, while increasing 10 key proteins, including thioredoxin, GTP pyrophosphokinase, and tRNA-binding protein. Integration of metabolomics and proteomics data indicated that Pb stress disrupted amino acid metabolism, suppressed energy pathways, and upregulated nucleic acid repair mechanisms. Notably, the Pb-resistant strain CCFM8661 demonstrated strong antioxidant defenses and could cope with Pb stress through ABC transporters, low-energy metabolism, membrane modification, and osmotic regulation. In contrast, CCFM578 exhibited inhibited transport activity, compromised DNA repair, and disrupted energy metabolism. Our findings suggest that L. plantarum's Pb resistance relies on coordinated regulation of antioxidant systems, amino acid/osmolyte synthesis, and transporter activity, along with adaptive energy conservation. This study offers valuable insights into microbial Pb detoxification strategies.PMID:40220651 | DOI:10.1016/j.chemosphere.2025.144399

J Pharm Biomed Anal. 2025 Apr 7;262:116874. doi: 10.1016/j.jpba.2025.116874. Online ahead of print.ABSTRACTAcute pancreatitis (AP) is a common gastrointestinal disease characterized by pancreatic cell damage and inflammation. Given the early clinical diagnosis and management challenges, exploring novel analytical frameworks from new orientations for interrogating AP is urgent. The release of damage-associated molecular patterns (DAMPs) and their receptor recognition initiate sterile inflammation, serving as key drivers in the development and progression of AP. Thus, this study aimed to delineate the underlying correlations between alterations in the DAMP profile and the AP state. We have developed a new framework combining potential DAMPs profiles obtained from pseudotargeted metabolomics method with machine learning (ML) models for AP prediction. 2-(1-Piperazinyl) pyrimidine chemical labeling was utilized to provide characteristic fragment ions and improve the quantitative sensitivity of targeted metabolites. A total of 49 potential DAMPs were identified and semi-quantified from collected serum samples (n = 84), positive or negative for APs. For modeling obtained datasets with five different ML algorithms, the support vector machine model was chosen as the optimal model to differentiate with high accuracy, achieving an area under the receiver-operating characteristic curve (AUROC) of 0.944. It also showed a strong performance in an external independent validation set (AUROC: 0.907). Moreover, the model was interpreted using the Shapley Additive exPlanations analysis to specify the important features and identify specific free fatty acids as key contributors. Overall, the novel framework enables high accuracy in predicting the presence of AP status. Meanwhile, it underlines the utility of DAMPs in inflammatory diseases and provides reference values for diagnosing in first-line clinics.PMID:40220635 | DOI:10.1016/j.jpba.2025.116874

Food Chem. 2025 Apr 7;483:144233. doi: 10.1016/j.foodchem.2025.144233. Online ahead of print.ABSTRACTGarden strawberry (Fragaria × ananassa) is a hybrid species with a narrowed allelic diversity due to intensive breeding. We studied the chemical composition and sensory properties of 13 progenies (reconstructed garden strawberry from diverse F. chiloensis and F. virginiana germplasms) and compared to cultivars 'Honeoye', 'Korona' and 'Polka'. Polar metabolite profiles (1H NMR) were associated with ripeness and origin of the wild parent. Volatile compounds not commonly present in commercial cultivars were observed, and the total content of volatiles and specifically esters were present in higher concentrations in the hybrids (HS-SPME-GC-MS). Descriptive sensory analysis indicated the hybrids were less red, and the anthocyanin contents (UHPLC-DAD), especially pelargonidin glycosides, were lower in the hybrid strawberries. Hybrids were also smaller, and had higher overall odour and overall flavour intensities. Hence, the reconstruction from wild sources enabled the introduction of new chemical, colour and flavour properties of high interest into the garden strawberry.PMID:40220444 | DOI:10.1016/j.foodchem.2025.144233