PubMed

Metabolomics. 2025 Apr 5;21(2):50. doi: 10.1007/s11306-025-02238-y.ABSTRACTINTRODUCTION: Infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) leads to COVID19 disease and caused a worldwide pandemic in 2019. Since the first wave of infections, there has been significant antigenic shifts, leading to the emergence of new variants. Today, infections have shifted away from the severe, fatal infection seen in 2019.OBJECTIVE: This study aimed to assess how the plasma metabolomes from patients varied with infection with different strains and could reflect disease severity.METHODS: Patients with COVID19 not requiring intensive care were recruited between January 2021 and May 2022 from the Queen Elizabeth Hospital Birmingham; 33 patients with alpha, 13 delta and 14 omicron variants. These were compared to 26 age matched contemporaneously recruited controls. Plasma samples were extracted into chloroform/methanol/water (1:2.5/1 v/v) and assessed by flow injection electrospray mass spectrometry (FIE-MS) using an Exactive Orbitrap mass spectrometer. Derived data were assessed using the R based MetaboAnalyst platform.RESULTS: Plasma metabolomes from COVID19 patients were clearly different from controls. Metabolite variation could be related to infection with different SARS-CoV2 variants. Variant showed different levels of some phospholipids, ganglioside GD1a and a dihydroxyvitamin D3 derivative. Correlations of the plasma metabolomes indicated negative correlations between selected phospholipids and the levels of C-reactive protein, creatinine, neutrophil and D-dimer.CONCLUSION: The plasma metabolomes of COVID19 patients show changes, particularly in phospholipids, which could reflect disease severity and SARS-CoV2 variant infection.PMID:40186806 | DOI:10.1007/s11306-025-02238-y

Microb Biotechnol. 2025 Apr;18(4):e70140. doi: 10.1111/1751-7915.70140.ABSTRACTThe EU Green Deal prioritises the transformation of the chemical industry to a more environmentally sustainable model. This involves using microorganisms, such as Saccharomyces cerevisiae, to produce molecules more sustainably through biotechnological approaches. In this study, we demonstrate an example of serotonin production using S. cerevisiae as a cell factory, along with its optimisation and upscaling. To achieve this, we introduced two heterologous genes, the combination of tryptophan decarboxylase from Clostridium sporogenes (CsTDC) and tryptamine 5-hydroxylase from Oryza sativa (OsT5H), to complete the serotonin biosynthetic pathway using L-tryptophan (L-TRP) as a precursor. By modifying ARO4 to a feedback-resistant version (ARO4*), the flux of the shikimate pathway was significantly increased and serotonin production was achieved at levels up to 120 mg/L directly from the glucose source. After a medium optimisation, a final concentration of 80 g/L glucose and 300 mg/L of nitrogen resulted in better conditions for increasing serotonin titres. Using this medium in a 1 L bioreactor fermentation resulted in approximately 250 mg/L of serotonin. A targeted metabolomic study of the bioreactor growth medium identified potential bottlenecks in the serotonin-overproducing strain and future targets for increasing its titre. We have constructed a strain of S. cerevisiae that represents the first steps towards feasible industrial production of serotonin using a sustainable and environmentally friendly approach, paving the way for the development of similar biotechnological strategies in the future.PMID:40186557 | DOI:10.1111/1751-7915.70140

Pest Manag Sci. 2025 Apr 5. doi: 10.1002/ps.8816. Online ahead of print.ABSTRACTBACKGROUND: Meloidogyne incognita is one of the pathogenic nematodes with the widest range and most serious damage, which can infest many food and cash crops. We screened a strain of Streptomyces aquilus JXGZ01, whose culture filtrate showed excellent nematicidal activity and egg hatching inhibition activity against M. incognita. In this study, we performed metabolomic analysis of the culture filtrate of this strain.RESULTS: The data showed that of the total 304 differential metabolites, 244 were significantly up-regulated and 60 were significantly down-regulated. Seven compounds with large fold changes were selected from the up-regulated metabolites to test the nematicidal activity against M. incognita. The mortality of M. incognita in both 5 and 10 mg mL-1 of 4-acetylaminobutyric acid was more than 85%. The mortality of M. incognita in both 10 and 100 mg mL-1 of (R)-(-)-2-phenylglycinol was more than 70%. The mortality rate of M. incognita in 100 mg of N-acetyl-l-glutamic acid was 78.25%. In addition, the hatching inhibition rate of egg masses were more than 90% for both 5 and 10 mg mL-1 of 4-acetylaminobutyric acid. The hatching inhibition rate of egg masses were more than 80% for 100 mg and 10 mg (R)-(-)-2-phenylglycinol. The hatching inhibition rate of 100 mg N-acetyl-l-glutamic acid on eggs was 93.47%.CONCLUSION: The results demonstrate that S. aquilus can be a candidate microorganism for the biological control of M. incognita, and its metabolites 4-acetylaminobutyric acid and (R)-(-)-2-phenylglycinol had great potential as nematicides. © 2025 Society of Chemical Industry.PMID:40186508 | DOI:10.1002/ps.8816

Phytochem Anal. 2025 Apr 4. doi: 10.1002/pca.3531. Online ahead of print.ABSTRACTINTRODUCTION: The SARS-CoV-2 pandemic has revealed a deficiency in antiviral agents. Plants, traditionally used for respiratory infections, are valuable sources of antiviral compounds. Such a plant is the Sideritis L. taxa (mountain tea), traditionally used against cold and cough.OBJECTIVES: Accordingly, this study aimed to investigate the potential protective effects of dichloromethane extracts from Sideritis species against SARS-CoV-2.MATERIALS AND METHODS: Eight Sideritis extracts were tested in an in vitro pretreatment assay to assess the protective effect against SARS-CoV-2. Therefore, infectious virus particles were pre-incubated with the extract, then incubated with Vero E6 cells to finally measure cell viability as a surrogate for virus infection. Untargeted analyses (GC-MS and LC-PDA-HRESIMS) were performed to determine metabolite profiles.RESULTS: Using an orthogonal approach that combines untargeted metabolomics and biological data from a screening assay, we characterized the phytochemical profiles of the different extracts and prioritized samples for targeted isolation. The dichloromethane extract of Sideritis cypria exhibited a notable protective effect. Untargeted analysis revealed coumarins as key compounds, with varying amounts across Sideritis species. Accordingly, fractionation of extract resulted in the isolation of two coumarin derivatives. Structure elucidation was performed using one- and two-dimensional nuclear magnetic resonance experiments. The coumarin, more abundant in S. cypria, demonstrated a slight protective effect in the SARS-CoV-2 pretreatment assay.CONCLUSION: This study highlights the antiviral effects of Sideritis taxa, although further investigations are necessary to clarify the full potential of the herb. Additionally, the methodology presented herein can serve as a valuable resource for future phytochemical investigations focused on coumarin content within Sideritis genus.PMID:40186332 | DOI:10.1002/pca.3531

Eur J Med Res. 2025 Apr 5;30(1):245. doi: 10.1186/s40001-025-02526-2.ABSTRACTBACKGROUND: Gestational diabetes mellitus (GDM) is the most common pregnancy complication, significantly affecting maternal and neonatal health. Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by metabolic abnormalities, which notably elevates the risk of developing GDM during pregnancy.METHODS: In this study, we utilized ultra-high-performance liquid chromatography for untargeted metabolomics analysis of serum samples from 137 pregnant women in the early-to-mid-pregnancy. The cohort consisted of 137 participants, including 70 in the PCOS group (36 who developed GDM in mid-to-late pregnancy and 34 who did not) and 67 in the non-PCOS group (37 who developed GDM and 30 who remained GDM-free). The aim was to investigate metabolic profile differences between PCOS and non-PCOS patients and to construct early GDM prediction models separately for the PCOS and non-PCOS groups.RESULTS: Our findings revealed significant differences in the metabolic profiles of PCOS patients, which may help elucidate the higher risk of GDM in the PCOS population. Moreover, tailored early GDM prediction models for the PCOS group demonstrated high predictive performance, providing strong support for early diagnosis and intervention in clinical practice.CONCLUSIONS: Untargeted metabolomics analysis revealed distinct metabolic patterns between PCOS patients and non-PCOS patients, particularly in pathways related to GDM. Based on these findings, we successfully constructed GDM prediction models for both PCOS and non-PCOS groups, offering a promising tool for clinical management and early intervention in high-risk populations.PMID:40186293 | DOI:10.1186/s40001-025-02526-2

J Nanobiotechnology. 2025 Apr 4;23(1):270. doi: 10.1186/s12951-025-03331-z.ABSTRACTBACKGROUND: Acute lung injury (ALI) is a severe respiratory disease accompanied by diffuse inflammatory responses induced by various clinical causes. Many fresh medicinal plants have shown better efficacy than their dried forms in preventing and treating diseases like inflammation. As a classical Chinese herb, platycodon grandiflorum (PG) has been demonstrated effective in treating pneumonia, but most of previous studies focused on the efficacy of processed or dried PG formats, while the specific benefits of its fresh form are still underexplored. Exosome-like nanoparticles derived from medicinal plants are expected to point out an important direction for exploring the material basis and mechanism of this fresh herbal medicine.RESULTS: The fresh form of PG could effectively improve ALI induced by lipopolysaccharide (LPS), relieve lung histopathological injury and weight loss, and reduce levels of inflammatory factors in mice, exhibiting better efficacy than dried PG in the treatment of ALI. Further extraction and purification of PG exosome-like nanoparticles (PGLNs) demonstrated that PGLNs had good biocompatibility, with characteristics consistent with general exosome-like nanoparticles. Besides, proteomic analysis indicated that PGLNs were rich in a variety of proteins. Animal experiments showed that PGLNs improved the pathological changes in LPS-induced lung tissues, inhibited the expression of inflammatory factors and promoted the expression of anti-inflammatory factors, and exerted a regulatory effect on the polarization of lung macrophages. Cell experiments further confirmed that PGLNs could be effectively taken up by RAW264.7 cells and repolarize M1 macrophages into M2 type, therefore reducing the secretion of harmful cytokines. Moreover, non-targeted metabolomics analysis reveals that PGLNs reduce inflammation and control macrophage polarization in a manner closely linked to pathways including glycolysis and lipid metabolism, highlighting a potential mechanism by which PGLNs protect the lungs from inflammatory damage like ALI.CONCLUSION: Fresh PG has better anti-inflammatory and repair effects than its dried form. As one of the most effective active substances in fresh PG, PGLNs may regulate macrophage inflammation and polarization by regulating metabolic pathways including lipid metabolism and glycolysis, so as to reduce inflammation and repair lung injury.PMID:40186259 | DOI:10.1186/s12951-025-03331-z

Biotechnol Biofuels Bioprod. 2025 Apr 4;18(1):42. doi: 10.1186/s13068-025-02638-1.ABSTRACTBACKGROUND: Pharmaceutical safety is an increasing global priority, particularly as the demand for therapeutic compounds rises alongside population growth. Phytocannabinoids, a class of bioactive polyketide molecules derived from plants, have garnered significant attention due to their interaction with the human endocannabinoid system, offering potential benefits for managing a range of symptoms and conditions. Traditional extraction from cannabis plants poses regulatory, environmental, and yield-related challenges. Consequently, microbial biosynthesis has emerged as a promising biotechnological alternative to produce cannabinoids in a controlled, scalable, and sustainable manner. Developing diatom-based biofactories represent a crucial step in advancing this biotechnology, enabling the efficient production of high-valued compounds such as cannabinoids.RESULTS: We engineered the diatom Phaeodactylum tricornutum, a unicellular photosynthetic model organism prized for its naturally high lipid content, to produce olivetolic acid (OA), a key metabolic precursor to most cannabinoids. The genes encoding tetraketide synthase and olivetolic acid cyclase from cannabis were cloned onto episomal vectors and introduced using bacterial conjugation in two separate P. tricornutum transconjugant lines to evaluate enzyme activity and OA production in vivo. Both genes were successfully expressed, and the corresponding enzymes accumulated within the transconjugant lines. However, despite testing the cell extracts individually and in combination, OA accumulation was not detected suggesting potential conversion or utilization of OA by endogenous metabolic pathways within the diatoms. To investigate this further, we analyzed the impact of CsTKS expression on the diatom's metabolome, revealing significant alterations that may indicate metabolic flux redirection or novel pathway interactions.CONCLUSIONS: Our study demonstrates the successful expression of cannabinoid biosynthetic genes in P. tricornutum but highlights challenges in OA accumulation, likely due to endogenous metabolic interactions. These findings underscore the complexity of metabolic engineering in diatoms and suggest the need for further pathway optimization and metabolic flux analysis to achieve efficient cannabinoid biosynthesis. This research contributes to advancing sustainable biotechnological approaches for cannabinoid production.PMID:40186218 | DOI:10.1186/s13068-025-02638-1

BMC Pregnancy Childbirth. 2025 Apr 4;25(1):395. doi: 10.1186/s12884-025-07542-y.ABSTRACTBACKGROUND: Telomere length (TL) is a marker of cellular aging associated with risk for age-related diseases and is known to be influenced by various factors, including oxidative stress and inflammation, in the contexts of stress and aging. The physiological demands of pregnancy may impact maternal TL, though research in this area is sparse. We tested oxidative stress and explored inflammation as predictors of maternal TL in a sample of women with normative pregnancies.METHODS: Participants (N = 88, aged 18 to 46 years, 25% non-Hispanic Black, 65% non-Hispanic White) were recruited during their 2nd or 3rd trimester. TL was measured using saliva via qPCR as absolute TL. Oxidative stress was derived from principal component analysis of selected metabolites measured via urinary metabolomics. Inflammation was quantified as total IL-6 in serum. Hypotheses were tested with stepwise generalized linear models.RESULTS: Longer TL was predicted by higher oxidative stress (b = 0.20 ± 0.08; P =.019), controlling for maternal age, gestational age, race/ethnicity, maternal BMI, and income-to-needs ratio. In our exploratory analysis, longer TL was also predicted by higher IL-6 (b = 0.76 ± 0.20; P =.0003) controlling for covariates. There was no significant interaction between oxidative stress and inflammation predicting TL.CONCLUSION: Our findings suggest that in normative pregnancies, both oxidative stress and inflammation are independently associated with longer telomere length. Given that these associations are inconsistent with the role of oxidative stress and inflammation on telomere biology in non-pregnant samples, future work should aim to replicate these findings in both normal and high-risk pregnancies, explore mechanisms underlying these associations using longitudinal designs, and examine how these relationships influence maternal and fetal health.PMID:40186152 | DOI:10.1186/s12884-025-07542-y

BMC Cancer. 2025 Apr 4;25(1):611. doi: 10.1186/s12885-025-13680-5.ABSTRACTBACKGROUND: Oral squamous cell carcinoma is a malignant tumor with high morbidity and mortality, and changes in microflora have a close relationship with tumor development. In this study, we tried to identify the changes in oral microbial characteristics and metabolite levels in OSCC patients.METHODS: In this study, saliva samples were collected from 40 oral cancer cases and 39 healthy controls. The microbiome was analysed by 16 S rDNA gene sequencing, and the metabolome was detected by Liquid Chromatography-Mass Spectrometry (LC-MS) with metabolite traceability using the Metorigin platform. Correlations between the microbiome and metabolome were analysed using the Spearman correlation method.RESULTS: The study found a significant difference in the β diversity of oral microbiota between the oral cancer group and healthy controls, while α diversity showed no significant difference. At the phylum level, Deferribacterota significantly increased, and Cyanobacteria significantly decreased in the oral cancer group. At the genus level, Vibrio and Lactococcus were significantly elevated, while Bifidobacterium and Faecalibacterium were significantly reduced. Metabolomic analysis identified 36 differentially abundant metabolites; 13(S)-HOTrE and 13-HODE were significantly downregulated, while docosanamide was significantly upregulated in the oral cancer group. Six bacteria-specific metabolites, including Indole, were also downregulated. Correlation analysis showed that N-Acetylneuraminic acid had a significant negative correlation with Pseudoalteromonas and Vibrio (r < -0.4).CONCLUSION: This study found large differences in microbiome levels at the portal level, at the genus level, and significant differences in the levels of a variety of metabolites labeled by indoles, providing a new and potentially valuable direction for the diagnosis and treatment of oral squamous carcinoma.PMID:40186151 | DOI:10.1186/s12885-025-13680-5

BMC Plant Biol. 2025 Apr 4;25(1):429. doi: 10.1186/s12870-025-06480-3.ABSTRACTSelenium (Se) is an essential trace element that plays a critical role in human tissue formation, metabolism, and physiological functions. However, many individuals worldwide suffer from Se deficiency diseases. This study aims to evaluate the impact of Se-tolerant LF-17 agents and exogenous Na2SeO3 application on the growth, enzyme activity, and metabolic characteristics of rape seedlings. Treatment LF-3 (inoculation of Se-tolerant LF-17 agent and exogenous Na2SeO3, with the soil Se concentration of 5 mg/kg) led to a 38.62% increase in plant height and a 116.7% increase in fresh weight. And the Se-tolerant LF-17 agent in treatment LF-3 also reduced the oxidative stress induced by exogenous Na2SeO3 compared to that of treatment LF-2 (with the same amount exogenous Na2SeO3 only), as evidenced by the lower activities of SOD, POD, and CAT, as well as less content of malondialdehyde. Furthermore, the upregulation of metabolic pathways such as "cuticle, suberine, and wax biosynthesis" "flavonoid biosynthesis," and "terpenoid backbone biosynthesis" enhanced the plant's stress resistance as revealed by non-targeted metabolomics sequencing method. This approach offers promising applications for improving Se bioavailability in crops, mitigating Se toxicity, addressing global Se deficiency challenges and is expected to contribute to fulfilling the Se supplementation needs of the population.PMID:40186103 | DOI:10.1186/s12870-025-06480-3

Pediatr Res. 2025 Apr 4. doi: 10.1038/s41390-025-04021-0. Online ahead of print.ABSTRACTPrecision medicine is a transformative healthcare model that utilizes an understanding of a person's genome, environment, lifestyle, and interplay to deliver customized healthcare. Precision medicine has the potential to improve the health and productivity of the population, enhance patient trust and satisfaction in healthcare, and accrue health cost-benefits both at an individual and population level. Through faster and cost-effective genomics data, next-generation sequencing has provided us the impetus to understand the nuances of complex interactions between genes, diet, and lifestyle that are heterogeneous across the population. The emergence of multiomics technologies, including transcriptomics, proteomics, epigenomics, metabolomics, and microbiomics, has enhanced the knowledge necessary for maximizing the applicability of genomics data for better health outcomes. Integrative multiomics, the combination of multiple 'omics' data layered over each other, including the interconnections and interactions between them, helps us understand human health and disease better than any of them separately. Integration of these multiomics data is possible today with the phenomenal advancements in bioinformatics, data sciences, and artificial intelligence. Our review presents a broad perspective on the utility and feasibility of a genomics-first approach layered with other omics data, offering a practical model for adopting an integrated multiomics approach in pediatric health care and research. IMPACT: Precision medicine provides a paradigm shift from a conventional, reactive disease control approach to proactive disease prevention and health preservation. Phenomenal advancements in bioinformatics, data sciences, and artificial intelligence have made integrative multiomics feasible and help us understand human health and disease better than any of them separately. The genotype-first approach or reverse phenotyping has the potential to overcome the limitations of the phenotype-first approach by identifying new genotype-phenotype associations, enhancing the subclassification of diseases by widening the phenotypic spectrum of genetic variants, and understanding functional mechanisms of genetic variations.PMID:40185865 | DOI:10.1038/s41390-025-04021-0

Int J Biol Macromol. 2025 Apr 2:142620. doi: 10.1016/j.ijbiomac.2025.142620. Online ahead of print.ABSTRACTGalloylated catechins are major catechins in tea, resulting in a bitter and astringent taste. In this study, to identify the key genes involved in the hydrolysis of astringency-associated galloylated catechins in Camellia sinensis, multiomics association analysis, including enzyme activity assays, transcriptomics, and metabolomics, was performed. Subsequently, seven candidate genes involved in the hydrolysis of galloylated catechin were screened from tea genomes using correlation analysis. Phylogenetic analysis revealed that these genes were clustered into caffeoyl shikimate esterase, acetate esterase, and tannase groups. In vitro, the purified recombinant enzymes rCSS0031888 and rCSS0049322 catalyzed the hydrolysis of galloylated catechins into nongalloylated catechins. This study provides an efficient method for mining functional genes and identifying key genes involved in the hydrolysis of galloylated catechins in vitro, thereby reducing the bitterness and astringency of tea and offering a molecular basis for cultivating high-quality tea varieties.PMID:40185441 | DOI:10.1016/j.ijbiomac.2025.142620

Metabolism. 2025 Apr 2:156258. doi: 10.1016/j.metabol.2025.156258. Online ahead of print.ABSTRACTBACKGROUND: More and more steatotic livers undergo resection or transplantation but they exhibit higher susceptibility to ischemia-reperfusion injury (IRI), which results in increased perioperative complication morbidity and mortality. IRI is driven by various cytokines and receptors, both of which are extensively modified by N-glycosylation. We aim to elucidate susceptibility of steatotic livers to IRI from the perspective of N-glycosylation.METHODS: Differentially expressed genes and glycoproteins were identified with RNA-seq and N-glycoproteomics. Myeloid LIF or hepatocyte LIFR knockout mice were developed to examine the function of LIF and LIFR. Modalities including phosphoproteomics, ChIP-seq, single cell RNA-seq, metabolomics and immunoblotting were utilized to investigate underlying mechanisms.RESULTS: LIF transcription in myeloid cells and LIFR N-glycosylation in hepatocytes were substantially induced by IRI of normal livers. LIF and LIFR protected normal livers from IRI through activating STAT3 and promoting downstream TNFAIP3 expression, which was facilitated by LIFR N-glycosylation. Mechanistically, N-glycosylation at N238 stabilized LIFR protein by disrupting TRIM28-mediated K48 ubiquitination at LIFR K254. Furthermore, N-glycosylation at N358/N658/N675 of LIFR facilitated LIF/LIFR/gp130 complex formation and subsequent signal transduction. However, in steatotic livers, myeloid cell LIF transcription was partially inhibited due to hepatic microenvironment L-arginine insufficiency, while hepatocyte LIFR N-glycosylation was defective due to intracellular UDP-GlcNAc exhaustion. Importantly, combined L-arginine and GlcNAc treatment reversed LIF expression and LIFR N-glycosylation insufficiency, which represents potential therapeutic strategy to protect steatotic livers.CONCLUSIONS: LIF expression and LIFR N-glycosylation insufficiency aggravates steatotic liver IRI, which can be reversed by combined L-arginine and GlcNAc treatment.PMID:40185397 | DOI:10.1016/j.metabol.2025.156258

Mol Cell Endocrinol. 2025 Apr 2:112536. doi: 10.1016/j.mce.2025.112536. Online ahead of print.ABSTRACTPolycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age, yet the molecular mechanisms influencing its pathophysiology remain poorly defined. A comprehensive prospective case-control study was conducted to elucidate the follicular fluid (FF) hormone and metabolite profile in women with PCOS and its implications for oocyte maturation and fertilization. The study involved 40 age- and body mass index (BMI)-matched women undergoing in vitro fertilization (IVF), including 20 diagnosed with PCOS and 20 controls with infertility due to tubal or male factors. A distinctive hormone profile in the FF of women with PCOS was identified, characterized by significantly higher anti-Müllerian hormone (AMH) levels (24.90±17.61 vs. 16.68±17.67 pmol/L, p=0.0039) and lower progesterone (8253±4748 vs. 25362±10862 ng/mL, p<0.0001) and estradiol levels (388.23±210.58 vs. 651.48±390.79 ng/mL, p=0.0208) compared to normoovulatory controls. Moreover, a metabolite fingerprint associated with glycolytic and mitochondrial dysfunction was observed, as evidenced by lower lactate (4575.44±1507.76 vs. 5595.34±1073.32 μmol/L, p=0.0182) and formate (64.51±16.06 vs. 75.81±16.63 μmol/L, p=0.0351) levels and higher citrate levels (136.93±52.53 vs. 109.15±24.17 μmol/L, p=0.0409) in the FF of women with PCOS. These findings suggest that the molecular profile of the FF in women with PCOS is related to granulosa cell glycolytic and mitochondrial dysfunction, which can have a negative impact on oocyte fertilization potential. The study provides an integrative analysis of the FF hormone and metabolite profile in women with PCOS, offering insights into the molecular mechanisms underlying the reproductive dysfunctions associated with this condition.PMID:40185328 | DOI:10.1016/j.mce.2025.112536

Eur J Pharmacol. 2025 Apr 2:177590. doi: 10.1016/j.ejphar.2025.177590. Online ahead of print.ABSTRACTRecently, interest in imidazoline receptors (IRs) has been increasing. Over the years, a growing number of studies have highlighted the therapeutic potential of ligands targeting these receptors, however, the potential role of imidazoline I2 receptor agonists in cancer treatment has not been thoroughly investigated. Colorectal cancer (CRC) is among the most prevalent and lethal forms of cancer worldwide. The complexity of CRC necessitates individualized approaches. One promising area of research within CRC therapy is the regulation of autophagy. Recent studies have explored the relationship between autophagy and cancer progression, revealing that autophagy modulation could be a potential strategy for CRC treatment. However, the mechanisms underlying autophagy regulation remain poorly understood. This study aimed to evaluate the effect of the imidazoline I2 receptor agonist, namely 2-(2-benzofuranyl)-2-imidazoline hydrochloride (2-BFI), on colorectal cancer cells, HT-29 and HCT-116 cell lines, particularly its impact when co-incubated with the autophagy inhibitor, hydroxychloroquine (HCQ). The results showed that 2-BFI synergistically increased the cytotoxic effect of HCQ by inducing oxidative stress and apoptosis. Furthermore, our investigation indicated impairment autophagic influx in colon cancer cells treated by 2-BFI. The comprehensive metabolomic analysis revealed significant alterations in key metabolic pathways including MAO activity, oxidative stress responses, energy-related metabolites and amino acids metabolism. Altogether, these findings demonstrate potential a new therapeutic strategy based on autophagy regulation and the selective induction of oxidative stress in colorectal cancer cells. Moreover, this study provides a foundation for further investigation into the therapeutic potential of imidazoline receptor agonists in cancer therapy.PMID:40185322 | DOI:10.1016/j.ejphar.2025.177590

Environ Res. 2025 Apr 2:121534. doi: 10.1016/j.envres.2025.121534. Online ahead of print.ABSTRACTExposure to metals has been linked to an increased risk of gestational hypothyroidism (GHT), but the combined effects of metal mixtures and the role of serum metabolites in this relationship remain poorly understood. Therefore, this study aimed to examine the associations between metal exposure and GHT risk and to explore the mediating role of serum metabolites. In a case-control study with 30 pairs of GHT patients and controls matched by age, gestational age, parity, and obesity status, we measured serum metabolites and whole blood metal levels using UPLC-MS/MS and ICP-MS, respectively. Conditional logistic regression was employed to assess the individual effects of metals on GHT risk, while Bayesian kernel machine regression (BKMR) and quantile g-computation evaluated the combined effects of metal co-exposure. Mediation analyses were conducted to investigate the role of serum metabolites in these associations. arsenic (As), chromium (Cr), nickel (Ni), and Selenium (Se) were significantly associated with increased GHT risk (ORs: Se = 1.62, Cr = 1.11, Ni = 1.14, As = 1.21). Joint exposure to As, Ni, and Se was positively associated with GHT risk. Mediation analyses revealed that free fatty acids (FFA, 18:5) mediated the associations of Ni and Se with GHT, explaining 31.33% and 49.16% of the associations, respectively. Our findings suggest that blood levels of As, Ni, and Se are associated with an increased risk of GHT, and that the Ni- and Se-GHT associations are mediated by FFA (18:5), providing insights into the mechanisms linking metal exposure, serum metabolites, and GHT risk.PMID:40185263 | DOI:10.1016/j.envres.2025.121534

Environ Pollut. 2025 Apr 2:126187. doi: 10.1016/j.envpol.2025.126187. Online ahead of print.ABSTRACTBile salt hydrolase (BSH) is produced by gut bacteria and is responsible for deconjugating amino acids from the aliphatic side chains of conjugated bile acids (BAs), initiating the critical first step in BAs metabolism. Lead (Pb) is known to cause gut microbial dysbiosis, but whether it affects BAs profiles by reshaping the gut microbiota remains elusive. Here, using targeted BAs metabolomics and metagenomics sequencing, we found that 200 μg/L Pb treatment led to a significant increase in the abundance of BSH-producing microbiota (e.g., Eubacterium and Yersinia), thus promoting the deconjugation of taurocholic acid (TCA) and taurochenodeoxycholic acid (TCDCA). Consequently, the accumulation of relatively hydrophobic BAs cholic acid (CA) and chenodeoxycholic acid (CDCA) may cause damage to enterocytes (e.g., reduced microvilli and enterocyte heights), which attenuated tadpole digestion and ultimately led to significant reductions in morphological parameters. The inhibition of tadpole growth by Pb toxicity may negatively affect their survival and even increase their risk of death. Overall, these results revealed for the first time the toxicological mechanism by which Pb reshapes the gut microbiota and thus disrupts the BAs profile, shedding new insights into the detrimental effects of Pb toxicity on amphibian growth.PMID:40185186 | DOI:10.1016/j.envpol.2025.126187

Biotechnol Adv. 2025 Apr 2:108577. doi: 10.1016/j.biotechadv.2025.108577. Online ahead of print.ABSTRACTThe inert nature, durability, low cost, and wide applicability of plastics have made this material indispensable in our lives. This dependency has resulted in a growing number of plastic items, of which a substantial part is disposed in landfills or dumped in the environment, thereby affecting terrestrial and aquatic ecosystems. Among plastic materials, polyolefins are the most abundant and are impervious to biodegradation, owing to the presence of strong CC and CH bonds. Nevertheless, naturally occurring biodegradation of polyolefins, albeit limited, has been reported. This observation has sparked research on microbial polyolefin degradation. More efficient and targeted versions of this process could be developed also in the laboratory by designing synthetic microbial consortia with engineered enzymes. In this review, we discuss strategies for the development of such microbial consortia and identification of novel polyolefin-degrading microorganisms, as well as the engineering of polyethylene-oxidizing enzymes with greater catalytic efficacy. Finally, different techniques for the design of synthetic microbial consortia capable of successful polyolefin bioremediation will be outlined.PMID:40185175 | DOI:10.1016/j.biotechadv.2025.108577

Microb Pathog. 2025 Apr 2:107533. doi: 10.1016/j.micpath.2025.107533. Online ahead of print.ABSTRACTBACKGROUND: s: Polycystic ovary syndrome (PCOS) is a metabolic disorder disease strongly associated with gut microbiota (GM). Zishen Qingre Lishi Huayu recipe (ZQLHR), a traditional Chinese medicinal compound, has patented and shown therapeutic effects in treating PCOS in clinical trials without clear pharmacological mechanisms. This study aimed to disclose the potential therapeutic mechanism of ZQLHR on PCOS.METHODS: We firstly confirmed the therapeutic effects of ZQLHR treatment in PCOS patients. 16S rRNA sequencing, untargeted metabolomics, fecal microbiota transplantation (FMT), high performance liquid chromatography (HPLC) and Person's correlation analysis were conducted to elucidate the potential therapeutic mechanism.RESULTS: These results showed that PCOS symptoms in ZQLHR patients were significantly ameliorated. ZQLHR could increase the levels of butyrate-producing Lachnospira and Faecalibacterium and decrease the abundance of Escherichia-Shigella. Untargeted metabolomics showed that ZQLHR significantly improved host metabolic function, particularly butyrate metabolism and citrate cycle (TCA cycle) metabolism. The combined Faecalibacterium and butyrate metabolism datasets were correlated. Stool samples from ZQLHR patients could ameliorate ovarian architecture, significantly reduce testosterone (T), estradiol (E2) and luteinizing hormone (LH) levels and increased follicle-stimulating hormone (FSH) levels and increase the content of butyric acid in PCOS mice (P < 0.01). Moreover, the correlation analysis showed that some biochemical parameters (T, E2, LH levels and FSH) and butyric acid were correlated.CONCLUSION: We firstly depicted that ZQLHR could alleviate the series of symptom in women with PCOS by regulating gut microbiota and butyrate metabolism. This study provides a scientific basis and new ideas for the therapy of PCOS.PMID:40185172 | DOI:10.1016/j.micpath.2025.107533

Am J Physiol Lung Cell Mol Physiol. 2025 Apr 4. doi: 10.1152/ajplung.00111.2025. Online ahead of print.NO ABSTRACTPMID:40185106 | DOI:10.1152/ajplung.00111.2025