PubMed

Anim Nutr. 2024 Nov 7;20:303-310. doi: 10.1016/j.aninu.2024.10.002. eCollection 2025 Mar.ABSTRACTGut microbiota disruption during the weaning process is a significant factor of intestinal injury. Our previous studies have suggested that Prevotella may play a critical role in causing intestinal inflammation. This study aimed to clarify the impact of Prevotella copri on intestinal injury and the protecting effect by dihydroquercetin (DHQ) in weaned piglets. A total of 108 healthy Duroc × Landrace × Yorkshire weaned piglets, aged 21 d, were randomly allocated into 3 groups with 6 replicates and 6 piglets per replicate. The piglets were the following diets for 28 d: 1) a basal diet, 2) basal diet containing 1.0 × 108 CFU/kg P. copri, 3) basal diet supplemented with 1.0 × 108 CFU/kg P. copri and 100 mg/kg DHQ. Results showed that P. copri decreased significantly the average daily gain (ADG) (P < 0.001), which was recovered by supplementation of DHQ with decreased serum levels of malondialdehyde (MDA), interleukin (IL)-2 and IL-8 but increased total superoxide dismutase (T-SOD) activity and IL-10 in weaned piglets (P < 0.001). Moreover, DHQ increased the expression of tight junction proteins (claudin-2, occludin and tight junction protein zonula occludens protein-1 (ZO-1) and the mRNA expression of glutathione peroxidase 4 (GPX-4) in ileum (P < 0.001). Intestinal flora analysis showed that P. copri increased the relative abundance of Prevotella (P = 0.026) and Eubacterium coprostanoligenes group (P < 0.001), but decreased the relative abundance of Lachnospiraceae NK4A136 group (P < 0.001), while supplementation of DHQ reduced the relative abundance of Prevotella (P = 0.026). Metabolomics results indicated that P. copri enhanced the content of 12-OH bile acid, but decreased the contents of glycodeoxycholic acid (GDCA) and glycochenodeoxycholic acid (GCDCA) (P < 0.001), while DHQ reduced the 12-OH bile acid content (P < 0.001) and increased the GDCA content (P = 0.020). In summary, P. copri caused intestinal injury and reduced growth performance in weaned piglets, and DHQ showed a protective effect by modulating gut microbiota and bile acids metabolism.PMID:39995524 | PMC:PMC11849659 | DOI:10.1016/j.aninu.2024.10.002

Anim Nutr. 2024 Nov 28;20:277-290. doi: 10.1016/j.aninu.2024.11.004. eCollection 2025 Mar.ABSTRACTThe synchronized absorption of amino acids and glucose in the gut is essential for amino acid utilization and protein synthesis in the body. The study aimed to investigate how the starch digestion rate and amino acid levels impact the growth and intestinal starch and amino acid digestion, transport, and metabolism in juvenile broilers. The experiment was conducted with 702 Arbor Acres Plus broilers at 1 d old, which were randomly divided into 9 treatments with 6 replicates of 13 chickens each. The treatments included 3 different starch sources (corn, waxy corn, and tapioca) with 3 different apparent ileal digestible lysine (AID Lys) levels (1.08%, 1.20%, and 1.32%). A notable interaction was noted for dietary starch sources and AID Lys levels in the feed-to-gain ratio (F/G) and distal ileal starch digestibility (P < 0.01). The tapioca starch and waxy corn starch diets with 1.32% of AID Lys significantly decreased F/G compared with corn starch (P < 0.01). There was no significant difference in F/G of broilers among waxy corn starch diet with 1.08% AID Lys level, tapioca starch diet with 1.20% AID Lys level, and corn starch diet with 1.32% AID Lys level (P > 0.05). The 1.32% AID Lys level and the waxy corn starch both improved the body weight (BW) of broilers from 0 to 3 weeks of age, intestinal starch digestibility, and intestinal villi height or the ratio of villi height to crypt depth (P < 0.05). Compared with the corn starch diet, waxy corn starch and tapioca starch diets significantly elevated the AID of Met, Glu, Lys, Arg, Asp, His, Ile, Tyr, Gly, and Val levels (P < 0.05). The carbon metabolomics results revealed that the waxy corn starch diet significantly reduced malic acid and cis-aconitic acid levels (P < 0.05) in the tricarboxylic acid cycle compared to the corn starch diet. It was concluded that a waxy corn starch diet improves the growth performance of broilers by improving intestinal morphology, increasing the absorption and transport of amino acids, reducing the amino acid oxidation for energy supply in the intestinal mucosa, and promoting protein synthesis in muscles, which not only reduces the need for dietary AID Lys but also saves on production costs.PMID:39995521 | PMC:PMC11847748 | DOI:10.1016/j.aninu.2024.11.004

Curr Res Food Sci. 2025 Jan 31;10:100990. doi: 10.1016/j.crfs.2025.100990. eCollection 2025.ABSTRACTThis study was designed to explore the role of gut microbiota and its metabolites in the treatment of estrogen-induced cholestasis (EIC) in rats with a soybean pulp-rich diet and to clarify the effects of daidzein (DAI), a principal active ingredient of soybean pulp. The findings demonstrated that the soybean pulp-rich diet could relieve cholestasis by decreasing the levels of total bile acids (TBA) and alkaline phosphatase and enhancing the bile flow rate. Through gut microbiota and metabolomics analyses, it was revealed that this diet might alter the abundances of certain bacterial taxa including Akkermansia, Bacteroides, and Turicibacter, thus influencing lipid metabolism, tryptophan metabolism, and steroid metabolism, which led to disparities between the groups fed with and without the soybean pulp-rich diet. Moreover, the soybean pulp-rich diet could modulate the abundances of Prevotella spp. and Tyzzerella, reducing EIC by regulating lipid metabolism and short-chain fatty acids synthesis. Notably, DAI treatment significantly alleviated the abnormalities in serum TBA, alanine aminotransferase, and aspartate aminotransferase levels and mitigated the liver tissue damage in the EIC model. In summary, during cholestasis, variations in gut microbiota and metabolite profiles occurred. The intervention of soybean pulp affected the abundances of bacteria (such as Prevotella spp. and Tyzzerella) and regulated lipid metabolism-related pathways. Importantly, DAI was identified as a crucial component for the protective effects associated with the soybean pulp diet.PMID:39995468 | PMC:PMC11849669 | DOI:10.1016/j.crfs.2025.100990

ISME Commun. 2025 Jan 21;5(1):ycaf007. doi: 10.1093/ismeco/ycaf007. eCollection 2025 Jan.ABSTRACTPolar oceanographic regions are exposed to rapid changes in temperature, salinity, and light fields that determine microbial species distributions, but resilience to an increasingly unstable climate is unknown. To unravel microbial genomic potential of the Northern Baffin Bay's polynya, we constructed eight metagenomes from the same latitude but targeting two sides of Pikialasorsuaq (The North Water) that differ by current systems, stratification, and temperature regimes. Samples from the surface and subsurface chlorophyll maximum (SCM) of both sides were collected 13 months apart. Details of metabolic pathways were determined for 18 bacteria and 10 microbial eukaryote metagenome-assembled genomes (MAGs). The microbial eukaryotic MAGs were associated with the dominant green algae in the Mamiellales and diatoms in the Mediophyceae, which tended to respectively dominate the eastern and western sides of Pikialasorsuaq. We show that microbial community taxonomic and functional signatures were ca. 80% similar at the latitude sampled with only 20% of genes associated with local conditions. From the metagenomes we found genes involved in osmotic regulation, antifreeze proteins, and photosystem protection, with hydrocarbon biodegradation and methane oxidation potential detected. The shared genomic compliment was consistent with adaptation to the Arctic's extreme fluctuating conditions, with implications for their evolutionary history and the long-term survival of a pan-arctic microbiome. In particular, previously unrecognized genetic capabilities for methane bio-attenuation and hydrocarbon metabolism in eukaryotic phytoplankton suggest adaptation to dark conditions that will remain, despite climate warming, in the high latitude offshore waters of a future Arctic.PMID:39995421 | PMC:PMC11847657 | DOI:10.1093/ismeco/ycaf007

Analyst. 2025 Feb 25. doi: 10.1039/d4an01573h. Online ahead of print.ABSTRACTMass spectrometry (MS)-based omics methods have transformed biomedical research with accurate and high-throughput analysis of diverse molecules in biological systems. Recent technological advances also enabled multi-omics to be achieved from the same sample or on a single analytical platform. Sample normalization is a critical step in MS-omics studies but is usually conducted independently for each omics experiment. To bridge this technical gap, we evaluated different sample normalization methods suitable for analyzing proteins, lipids, and metabolites from the same sample for multi-omics analysis. We found that normalizing samples based on tissue weight or protein concentration before or after extraction generated distinct quantitative results. Normalizing samples first by tissue weight before extraction and then by protein concentration after extraction resulted in the lowest sample variation to reveal true biological differences. We then applied this two-step normalization method to investigate multi-omics profiles of mouse brains lacking the GRN gene. Loss-of-function mutations in the GRN gene lead to the deficiency of the progranulin protein and eventually cause neurodegeneration. Comparing the proteomics, lipidomics, and metabolomics profiles of GRN KO and WT mouse brains revealed molecular changes and pathways related to lysosomal dysfunction and neuroinflammation. In summary, we demonstrated the importance of selecting an appropriate normalization method during multi-omics sample preparation. Our normalization method is applicable to all tissue-based multi-omics studies, ensuring reliable and accurate biomolecule quantification for biological comparisons.PMID:39995368 | DOI:10.1039/d4an01573h

Environ Sci Technol. 2025 Feb 25. doi: 10.1021/acs.est.4c13902. Online ahead of print.ABSTRACTPersistent organic pollutants (POPs) are lipophilic environmental contaminants accumulated in the adipose tissue. Weight loss interventions, such as bariatric surgery, can mobilize POPs from adipose tissue into the bloodstream. We hypothesized that this mobilization could contribute to increases in blood pressure among 57 adolescents with severe obesity undergoing bariatric surgery. POPs and metabolic features were measured from visceral adipose tissue collected during surgery using gas and liquid chromatography, coupled with high-resolution mass spectrometry. Blood pressure was assessed at baseline, 6 months, and 5 years post-surgery. We used quantile g-computation to estimate associations of POP mixtures with blood pressure changes. With one quartile increase in POP mixtures, systolic blood pressure (SBP) increased by 6.4% five years after bariatric surgery compared to baseline SBP [95% confidence interval (CI): 0.4%, 12.4%]. The meet-in-the-middle approach identified overlapping metabolic features and pathways linking POP mixtures to SBP changes, highlighting the role of prostaglandin formation via arachidonic acid metabolism. POP mixtures were negatively associated with indole-3-acetate (-0.729, 95% CI: -1.234, -0.223), which was negatively associated with SBP changes at five years (-3.49%, 95% CI: -6.51%, -0.48%). Our findings suggested that lipophilic POP mixtures attenuated the beneficial effect of bariatric surgery on improved blood pressure among adolescents via alterations in lipid metabolism.PMID:39995310 | DOI:10.1021/acs.est.4c13902

Eur Heart J. 2025 Feb 25:ehaf062. doi: 10.1093/eurheartj/ehaf062. Online ahead of print.NO ABSTRACTPMID:39995248 | DOI:10.1093/eurheartj/ehaf062

Food Funct. 2025 Feb 25. doi: 10.1039/d4fo06067a. Online ahead of print.ABSTRACTThis study developed a probiotic Eurotium cristatum-fermented soybean powder (EFSP) and analyzed its nutrient profile, volatile components, and laxative efficacy in rats. After 8 days fermentation, polysaccharide contents significantly decreased, while total flavonoid levels initially increased in the first 6 days, and then decreased rapidly. Isoflavone glycosides were reduced, accompanied by an increase in isoflavone aglycones. Additionally, marked changes were observed in the composition and content of short-chain fatty acids, protein-based amino acids, and volatile compounds. Furthermore, EFSP demonstrated superior laxative effects to non-fermented soybean powder (NFSP) in diphenoxylate-induced constipated rats, primarily by modulating the aquaporins, mucin and enteric neuro factor levels in the colonic tissue. Metabolomics indicated that linoleic acid, primary bile acid synthesis, and taurine and sulfinic acid might be involved in constipation regulation. These findings suggested that Eurotium cristatum fermentation enhances the nutritional properties of soybean, contributing to its distinctive nutritional quality.PMID:39995243 | DOI:10.1039/d4fo06067a

Cancer Biol Med. 2025 Feb 24:j.issn.2095-3941.2024.0385. doi: 10.20892/j.issn.2095-3941.2024.0385. Online ahead of print.ABSTRACTOBJECTIVE: Erianin has potential anticancer activities, especially against lung cancer. The specific mechanisms underlying the anti-cancer effects, including the molecular targets and signaling pathways in lung cancer, remain poorly understood and necessitate further investigation.METHODS: Lung cancer cell viability was evaluated using the CCK-8 assay. Flow cytometry was used to examine the effects of erianin on apoptosis and cell cycle progression. mRNA sequencing and metabolomics analysis were utilized to explore erianin-induced biological changes. Potential targets were identified and validated through molecular docking and Western blot analysis. The roles of mammalian target of rapamycin (mTOR) and carbamoyl-phosphate synthetase/aspartate transcarbamylase/dihydroorotase (CAD) in erianin-induced growth inhibition were studied using gene overexpression/knockdown techniques with uridine and aspartate supplementation confirming pyrimidine metabolism involvement. Additionally, lung cancer-bearing nude mouse models were established to evaluate the anti-lung cancer effects of erianin in vivo.RESULTS: Erianin significantly inhibits the proliferation of lung cancer cells, induces apoptosis, and causes G2/M phase cell cycle arrest. Integrative analysis of mRNA sequencing and metabolomics data demonstrated that erianin disrupts pyrimidine metabolism in lung cancer cells. Notably, uridine supplementation mitigated the inhibitory effects of erianin, establishing a connection between pyrimidine metabolism and anticancer activity. Network pharmacology analyses identified mTOR as a key target of erianin. Erianin inhibited mTOR phosphorylation, thereby blocking downstream effectors (S6K and CAD), which are essential regulators of pyrimidine metabolism.CONCLUSIONS: Erianin is a promising therapeutic candidate for lung cancer. Erianin likely inhibits lung cancer cell growth by disrupting pyrimidine metabolism by suppressing mTOR activation.PMID:39995202 | DOI:10.20892/j.issn.2095-3941.2024.0385

Cancer Prev Res (Phila). 2025 Feb 25. doi: 10.1158/1940-6207.CAPR-24-0383. Online ahead of print.ABSTRACTDiet affects cancer risk and plant-derived polyphenols exhibit cancer-preventive properties. Walnuts are an exceptional source of polyphenolic ellagitannins, converted into urolithins by gut microflora. This clinical study examines the impact of urolithin metabolism on inflammatory markers in blood and colon polyp tissue. We evaluate the effects of walnut consumption on urinary urolithins, serum inflammatory markers and immune cell markers in polyp tissues obtained from 39 subjects. Together with detailed food frequency data, we perform integrated computational analysis of metabolomics data combined with serum inflammatory markers and spatial imaging of polyp tissues using imaging mass cytometry. LC-MS/MS analyses of urine and fecal samples identifies a widely divergent capacity to form nine urolithin metabolites in this patient population. Subjects with higher urolithin A formation exhibit lower levels of several key serological inflammatory markers, including C-peptide, sICAM 1, sIL6R, Ghrelin, TRAIL, sVEGFR2, PDGF and MCP2, alterations that are more pronounced in obese individuals for siCAM-1, ENA-78, Leptin, GLP-1 and MIP-1D. There is a significant increase in levels of PYY associated with urolithin A formation, whereas TNF-α levels show an opposite trend, recapitulated in an in vitro system with ionomycin/PMA-stimulated PBMCs. Spatial imaging of colon polyp tissues shows altered cell cluster patterns, including a significant reduction of vimentin and CD163 expression associated with urolithin A. The ability to form urolithin A is linked to inflammation, warranting further studies to understand the role of urolithins in cancer prevention.PMID:39995164 | DOI:10.1158/1940-6207.CAPR-24-0383

Chem Biol Drug Des. 2025 Feb;105(2):e70066. doi: 10.1111/cbdd.70066.ABSTRACTStachydrine (STA) has therapeutic effects on heart disorders. The current study assessed its effects on Type 2 diabetes (T2D) induced cardiac disorders by focusing on the heart-gut axis. Mice were subjected to high-fat diet (HFD) and streptozocin (STZ) to induce cardiac disorders such as inflammation and structural deteriorations, which were handled with STA. Changes regarding the composition and metabolism of gastrointestinal (GI) microbiota were then determined using a multiomics strategy, including amplicon sequencing and metabolomics. The data showed that STA improved heart function, reduced intestinal permeability, and suppressed inflammation in mice in a dose-dependent manner. However, the compound had little influence on the overall alpha diversity of gut microbiota, while it did influence the beta diversity. The analyses based on the multiomics strategy demonstrated that certain GI microbial groups, including Paramuribaculum, Allobaculum, Bifidobacterium, and Adlercreutzia, responded to the STA administration, which contributed to the alternatives of metabolites in the gut. Correlation analyses showed that Duncaniella and Ruminococcus negatively impacted health, while Muribaculum, Paramuribaculum, and Prevotella positively influenced intestinal permeability and heart health. Collectively, STA attenuated T2D-induced cardiac disorders by improving heart structure and function and suppressing inflammation, during which the GI homeostasis of the T2D mice changed to an alternative state that was different from that of healthy mice.PMID:39994907 | DOI:10.1111/cbdd.70066

Crit Care. 2025 Feb 24;29(1):88. doi: 10.1186/s13054-025-05291-0.ABSTRACTAcute respiratory distress syndrome (ARDS) is a severe complication of critical illness, characterized by bilateral lung infiltrates and hypoxemia. Its clinical and pathophysiological heterogeneity poses challenges for both diagnosis and treatment. This review outlines the evolution of ARDS definitions, discusses the underlying pathophysiology of ARDS, and examines the clinical implications of its heterogeneity. Traditional ARDS definitions required invasive mechanical ventilation and relied on arterial blood gas measurements to calculate the PaO2/FiO2 ratio. Recent updates have expanded these criteria to include patients receiving noninvasive respiratory support, such as high-flow nasal oxygen, and the adoption of the SpO2/FiO2 ratio as an alternative to the PaO2/FiO2 ratio. While these changes broaden the diagnostic criteria, they also introduce additional complexity. ARDS heterogeneity-driven by varying etiologies, clinical subphenotypes, and underlying biological mechanisms-highlights the limitations of a uniform management approach. Emerging evidence highlights the presence of distinct ARDS subphenotypes, each defined by unique molecular and clinical characteristics, offering a pathway to more precise therapeutic targeting. Advances in omics technologies-encompassing genomics, proteomics, and metabolomics-are paving the way for precision-medicine approaches with the potential to revolutionize ARDS management by tailoring interventions to individual patient profiles. This paradigm shift from broad diagnostic categories to precise, subphenotype-driven care holds promise for redefining the landscape of treatment for ARDS and, ultimately, improving outcomes in this complex, multifaceted syndrome.PMID:39994815 | DOI:10.1186/s13054-025-05291-0

Lipids Health Dis. 2025 Feb 24;24(1):69. doi: 10.1186/s12944-025-02475-z.ABSTRACTBACKGROUND: Hepatocellular carcinoma (HCC) is the third deadliest malignant tumor worldwide. Most patients are initially diagnosed as HCC at advanced stages and are too late for radical treatment by surgery, resulting in poor prognosis. Over 50% of the HCC patients are caused by hepatitis B virus (HBV) infection. Therefore, effective early identification of HCC in the high-risk population with HBV infection is crucial for early intervention of HCC.METHODS: We employed plasma lipidomics to identify critical lipid classes associated with tumorigenesis in the high-risk population with HBV infection. Potential regulatory mechanisms are validated at multi-omic levels. A machine learning algorithm is used for feature selection and diagnostic modelling, and performance of the models is evaluated by ROC curves.RESULTS: We unveiled varied profiles of plasma lipid metabolites in a cohort of 57 HBV-related HCC subjects, 57 HBV-related liver cirrhosis (LC) subjects and 61 chronic hepatitis B (CHB) subjects with matched age, sex and HBV status. We identified a correlation of the ether phosphatidylcholine (PC) synthesis with hepatocarcinogenesis in patients with HBV-related liver diseases. The diagnostic models achieved an area under ROC curve (AUC) of 0.849 for discriminating HCC from CHB and an AUC of 0.829 for discriminating HCC from LC.CONCLUSIONS: We illustrate the role of ether PC in hepatocarcinogenesis upon HBV infection and provide novel effective markers for early detection of HCC in a cohort with HBV infection.PMID:39994676 | DOI:10.1186/s12944-025-02475-z

BMC Genomics. 2025 Feb 24;26(1):192. doi: 10.1186/s12864-025-11392-5.ABSTRACTBACKGROUND: Sexual dimorphism, a widespread phenomenon across the animal kingdom, encompasses differences between sexes in size, morphology, and physiological traits. In this study, we investigated sexual dimorphism in the flexor carpi radialis (FCR) muscle, which is critical for amplexus in Asiatic toads (Bufo gargarizans), using integrated transcriptomic and metabolomic approaches.RESULTS: Male toads exhibited significantly larger FCR muscles, reflecting enhanced muscle function required for sustained amplexus. Transcriptomic analysis identified 818 differentially expressed genes (DEGs) between sexes, with 389 upregulated and 429 downregulated in males, predominantly associated with muscle contraction, sarcomere organization, and energy metabolism. Metabolomic profiling revealed 69 differentially expressed metabolites (DEMs), with male-biased enrichment in pathways involved in protein synthesis and degradation, energy metabolism, and material transport. Integrated analysis pinpointed key metabolic pathways-such as glycine, serine, and threonine metabolism; alanine, aspartate, and glutamate metabolism; fatty acid degradation; and the tricarboxylic acid (TCA) cycle-as central to the observed sexual dimorphism. Among these, the genes AGXT, ACADL, ACAT1, MDH2, and SUCLG2 emerged as pivotal regulators.CONCLUSIONS: Collectively, these findings provide novel insights into the genetic and metabolic basis of sexual dimorphism in B. gargarizans, offering a deeper understanding of the evolutionary mechanisms driving sex-specific traits in vertebrates.PMID:39994541 | DOI:10.1186/s12864-025-11392-5

BMC Plant Biol. 2025 Feb 24;25(1):244. doi: 10.1186/s12870-025-06273-8.ABSTRACTTobacco (Nicotiana tabacum L.) is a globally crop due to its distinctive flavor and economic value. In this study, we systematically analyzed the dynamic changes in volatile substances, broad-spectrum metabolites, enzymes, and biochemical compounds in tobacco leaves during flue-curing process. Combining metabolomics with enzyme activity and biochemical analysis, we identified that 43℃ is a critical period for enzyme activity and metabolite transitions, while 45 ℃ requires stringent moisture control. During the T3 stages, phenolic acids, amino acids, and derivatives were notably enriched, with increases of 19.58-fold, 18.59-fold, and 17.33-fold in lmmn001643, MWS20633g, and Lmhn004756, respectively. These compounds may serve as candidate biomarkers for non-volatile compounds. Aroma dynamics primarily contributed to the green and sweet flavor of flue-cured tobacco leaves, and the key aroma components included D114, KMW1317, and KMW0466. Differential volatile and non-volatile metabolites were enriched in four pathways, including monoterpenoid biosynthesis, tyrosine metabolism, phenylalanine metabolism, and phenylpropanoid biosynthesis. These pathways are closely related to phenylalanine ammonia-lyase and the synthesis of chlorogenic acid and rutin, which influence the aroma quality, aroma intensity, irritation, and volatility of tobacco. Additionally, the contents of caffeic acid, ferulic acid, sinapic acid, and PAL activity in phenylpropanoid biosynthesis pathway, increased with the rising temperature, accelerating reactions with alcohols and leading to increase lignin formation. This study enhances our understanding of the dynamic changes in the aroma and metabolic substances of Cuibi 1(CB-1) at the critical stages of the curing process and offers valuable insights for process improvement.PMID:39994521 | DOI:10.1186/s12870-025-06273-8

Sci Rep. 2025 Feb 24;15(1):6593. doi: 10.1038/s41598-025-91314-3.ABSTRACTMesenchymal stem cells (MSCs) have emerged as crucial players within the tumor microenvironment (TME), contributing through their paracrine secretome. Depending on the context, the MSC-derived secretome can either support or inhibit tumor growth. This study investigates the role of MSC-derived secretome in modulating breast cancer (BC) cell behavior, with a focus on ten-eleven translocation 1 (TET1), a DNA demethylase with known oncogenic properties in triple-negative breast cancer (TNBC). We first isolated and characterized human bone marrow-derived MSCs, and then assessed the impact of their secretome on BC cells. Treatment with the MSC-derived secretome significantly inhibited the proliferation and migration of both MDA-MB-231 and MCF-7 BC cell lines, resulting in reduced cell viability and migration rates compared to control cells. Western blot analyses revealed downregulation of Cyclin D1 and c-Myc, along with decreased expression of N-cadherin and increased expression of E-cadherin, indicating potential inhibition of the epithelial-to-mesenchymal transition. Differential gene expression analyses highlighted TET1 as significantly upregulated in TNBC tissues compared to normal samples. Further experiments confirmed that the MSC-derived secretome downregulated TET1 expression in BC cells, as evidenced by RT-qPCR and western blot analyses. To explore TET1's functional role, we silenced TET1 with siRNAs, observing cell cycle arrest and enhanced apoptosis-effects that mirrored those seen with MSC-secretome treatment. Notably, TET1 knockdown also increased MDA-MB-231 cell sensitivity to cisplatin, suggesting a role for TET1 in chemoresistance. These findings provide insight into the ability of MSCs to modulate BC cell progression through their secretome, highlighting the involvement of TET1 downregulation in inhibiting BC cell progression and enhancing cisplatin chemosensitivity. The MSC-derived secretome thus holds promise as an innovative, cell-free therapeutic approach in BC treatment.PMID:39994414 | DOI:10.1038/s41598-025-91314-3

Sci Rep. 2025 Feb 25;15(1):6686. doi: 10.1038/s41598-025-87707-z.ABSTRACTTo study the mechanism of calcitonin gene related peptide(CGRP) protecting acute pancreatitis based on metabolomics. 24 adult male rats were randomly divided into control group (Con), acute pancreatitis model group (AP), CGRP treatment group (CGRP + AP, abbreviated as CGRP) and CGRP antagonist(CGRP(8-37)) pretreatment group (preCGRP(8-37) + AP, abbreviated as CGRP37), with 6 rats in each group. After different interventions, pancreases of rats in each group were collected for pathological analysis, and serum was collected for metabolomics analysis. Pathological examination of the pancreas suggested that the inflammation of pancreatitis in AP group was significant, the inflammation of pancreatitis in CGRP group was significantly reduced, and the pancreatitis in CGRP37 group was aggravated. Metabolomics of rat serum suggested that the differences in metabolites in each group were mainly related to amino acid metabolism, coenzyme/vitamin metabolism, carbohydrate metabolism, lipid metabolism, digestive system and other metabolic pathways. According to the trend of metabolite changes, we found 6 differential metabolites that were significantly correlated with CGRP intervention, including L-Valine, 5-Aminopentanoic acid, 4-oxo-L-proline, L-glutamine, L-proline, and Ornithine, all of which were related to amino acid metabolism. CGRP can effectively protect acute pancreatitis, possibly by regulating amino acid metabolism to alleviate acute pancreatitis.PMID:39994332 | DOI:10.1038/s41598-025-87707-z

Sci Rep. 2025 Feb 24;15(1):6642. doi: 10.1038/s41598-025-91251-1.ABSTRACTSeveral alkaloids found in the Zanthoxylum genus have demonstrated significant anticancer activity. However, the antitumor effects of Ethoxychelerythrine (Eth) have not been previously reported. Cell viability, colony formation, apoptosis and cell cycle analysis, intracellular and reactive oxygen species (ROS), mitochondrial membrane potential (MMP) levels of Eth against SW480 cells were evaluated. Subcutaneously transplanted SW480 cells model was used to determine the effect of Eth on tumor growth in vivo. Inflammation levels, angiogenic factors, pathological observations, quantitative reverse-transcription PCR (qRT-PCR), quantitative proteomics, metabolite profiles and western blotting were conducted. It found that Eth significantly inhibited the proliferation of SW480 and HT29 cells in vitro, with stronger inhibitory activity observed against SW480 cells. Therefore, subsequent studies focused on SW480 cells. In vitro, we observed that Eth arrested the cell cycle at the G0/G1 phase, decreased MMP levels, elevated cellular ROS levels, and induced mitochondrial apoptosis. In vitro, Eth significantly inhibited tumor proliferation and metastasis, and regulated the molecule levels of angiogenesis and inflammatory factors in serum, as well as apoptotic protein in tumor tissues. The serum proteomic revealed that the differential proteins were primarily involved in the PI3K/AKT/mTOR pathway, including laminin β1 (Lamb1), and type I collagen (Col1a1). Metabolomics showed that many abnormal levels of metabolites regulated by the PI3K/AKT/mTOR pathway were obviously reversed towards normal levels after Eth intervention. The correlation analysis between the two-omics revealed that different proteins in the PI3K/AKT pathway, particularly lactate dehydrogenase B (LDHB) and glutathione synthetase (GSS), can interact with most of different metabolites. In summary, Eth exerts anti-tumour effects by inhibiting the activation of the PI3K/AKT/mTOR pathway, which in turn activates mitochondrial apoptosis. Eth may be considered in the development of drugs for relieving colon cancer patients in the future.PMID:39994297 | DOI:10.1038/s41598-025-91251-1

Sci Rep. 2025 Feb 24;15(1):6622. doi: 10.1038/s41598-025-90426-0.ABSTRACTThe clinical manifestations of the cytokine storm (CS) associated with COVID-19 resemble the acute phase of sepsis. Metabolomics may contribute to understanding the specific pathobiology of these two syndromes. The aim of this study was to compare serum metabolomic profiles in CS associated with COVID-19 vs. septic surgery patients. In a retrospective cross-sectional study, serum samples from patients with CS associated with COVID-19, with and without comorbidity, as well as serum samples from patients with surgical sepsis were investigated. Targeted metabolomic analysis was performed on all samples using LC-MS/MS. Analysis revealed that similar alterations in the serum metabolome of patients with COVID-19 and surgical septic patients were associated with amino acid metabolism, nitrogen metabolism, inflammatory status, methionine cycle and glycolysis. The most significant difference was found for serum levels of metabolites of kynurenine synthesis, tricarboxylic acid cycle, gamma-aminobutyric acid and niacinamide. The metabolic pathway of cysteine and methionine metabolism was significantly disturbed in COVID-19 and surgical septic patients. For the first time, the similarities and differences between the serum metabolomic profiles of patients with CS associated with COVID-19 and patients with surgical sepsis were investigated for patients from the Northwest of the Russian Federation.PMID:39994234 | DOI:10.1038/s41598-025-90426-0

Nat Commun. 2025 Feb 24;16(1):1910. doi: 10.1038/s41467-025-57032-0.ABSTRACTImpaired glucose uptake in the brain is an early presymptomatic manifestation of Alzheimer's disease (AD), with symptom-free periods of varying duration that likely reflect individual differences in metabolic resilience. We propose a systemic "bioenergetic capacity", the individual ability to maintain energy homeostasis under pathological conditions. Using fasting serum acylcarnitine profiles from the AD Neuroimaging Initiative as a blood-based readout for this capacity, we identified subgroups with distinct clinical and biomarker presentations of AD. Our data suggests that improving beta-oxidation efficiency can decelerate bioenergetic aging and disease progression. The estimated treatment effects of targeting the bioenergetic capacity were comparable to those of recently approved anti-amyloid therapies, particularly in individuals with specific mitochondrial genotypes linked to succinylcarnitine metabolism. Taken together, our findings provide evidence that therapeutically enhancing bioenergetic health may reduce the risk of symptomatic AD. Furthermore, monitoring the bioenergetic capacity via blood acylcarnitine measurements can be achieved using existing clinical assays.PMID:39994231 | DOI:10.1038/s41467-025-57032-0