PubMed

Front Mol Biosci. 2024 Nov 28;11:1528799. doi: 10.3389/fmolb.2024.1528799. eCollection 2024.NO ABSTRACTPMID:39669675 | PMC:PMC11634746 | DOI:10.3389/fmolb.2024.1528799

Heliyon. 2024 Feb 28;10(5):e26643. doi: 10.1016/j.heliyon.2024.e26643. eCollection 2024 Mar 15.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is an incurable neurodegenerative disease that has become one of the most important diseases threatening global public health security. Dihuang Yinzi (DHYZ) is a traditional Chinese medicine that has been widely used for the treatment of AD and has significant therapeutic effects, but its specific mechanism of action is still unclear.The aim of the study is to investigate the specific mechanism of DHYZ in treating AD based on brain metabolomics and network pharmacology.MATERIALS AND METHODS: In this study, the classic APPswe/PS1E9 (APP/PS1) mice were selected as the AD animal model, and the mechanism of DHYZ was studied. The learning and memory ability of mice was detected by Y-maze test, and the ultrastructure of neural cells in the brain of the mice was observed by transmission electron microscope (TEM). Then, the mechanism of DHYZ intervention in AD was analyzed by constructing network pharmacology, and combined with brain metabolomics based on ultra performance liquid chromatography-mass spectrometry (UPLC-MS) to detect differential metabolic markers and their metabolic pathways. In addition, a joint analysis of differential metabolites and potential targets for DHYZ treatment of AD is conducted to deeply explore the relationship between key targets, differential metabolites, and metabolic pathways.RESULTS: After 30 days of DHYZ treatment, the spatial work and reference memory ability of APP/PS1 mice were significantly improved, the structure of mitochondria and synapses in the neurons of the brain were basically normal. 202 potential targets for DHYZ treatment of AD were screened through network pharmacology, and after enrichment analysis, these targets showed correlation with redox reactions, mitochondrial and synaptic functional pathways. And 7 differential metabolites were identified in brain metabolomics are Nicotinic acid, N-Formyl-L-glutamic acid, 5-(2-Hydroxyethyl)-4-methylthiazole, D-Gulono-1,4-lactone, Norepinephrine, 3-Methylotrophicacid, Palmitic acid. These differential metabolites mainly involve nicotinite and nicotinamide metabolism, pertussis, cAMP signaling pathway, cysteine and methionine metabolism. Notablely, through matching analysis of targets and metabolites, a total of 20 genes were found to match Nicotinic acid, 51 genes were found to match norepinephrine, and 14 genes intersected with the two metabolites, enrichment analysis of the intersected genes showed that neuroactive light receptor interaction, serotonergic synapse, and cAMP signaling were significantly affected, which is consistent with previous network pharmacology results.CONCLUSION: This study identified the main chemical ingredients of DHYZ intervention in AD may originated from Polygala tenuifolia Wild, Dendrobium nobile Line and Ophiogon japonicus (L.f) Ker-Gawl. Combined with Y Maze, TEM and brain metabolomics, revealed that DHYZ can improve the learning and memory abilities and brain pathological morphology of APP/PS1 mice by regulating nicotinic acid, 3-Methylthiopropionic acid, pertussis and their metabolic pathways, including nicotinate and nicotinamide metabolism, cAMP signaling pathway and cysteine and methionine metabolism. In short, this study provides a new research foundation and direction for the treatment of AD with traditional Chinese medicine.PMID:39669488 | PMC:PMC11636838 | DOI:10.1016/j.heliyon.2024.e26643

Int J Endocrinol. 2024 Dec 5;2024:1634072. doi: 10.1155/ije/1634072. eCollection 2024.ABSTRACTIn this study, we evaluated the effects of intrabursal administration of cabergoline and N-acetylcysteine on ovarian hyperstimulation syndrome (OHSS) in an immature rat model. The study assessed body, ovarian, and uterine weights, as well as the concentrations of vascular endothelial growth factor A (VEGF-A). Moreover, levels of MDA, 4-HDA, and nitrites were assessed in ovarian homogenates, and vascular permeability was quantified in the peritoneal cavity. Ovarian morphology was characterized using histology and hematoxylin-eosin staining, determining the count of ovarian follicles and corpus luteum. Our results demonstrated a significant increase in lipoperoxidation, nitrite levels, and VEGF-A concentrations in the OHSS group compared to the control group. These biochemical alterations corroborate the successful induction of OHSS in the experimental model. Direct injection into the ovarian bursa resulted in reduced vascular permeability and VEGF-A levels, suggesting that the effects of cabergoline are predominantly ovarian. Particularly, cabergoline did not significantly alter other parameters such as ovarian weight, lipoperoxidation, nitrite levels, or morphology. Conversely, low concentrations of N-acetylcysteine (25-50 µg/kg) significantly reduced ovarian and uterine weights, VEGF-A levels, and vascular permeability. Interestingly, this dose-response relationship was not observed at higher NAC concentrations (100-200 μg/kg), suggesting a potential threshold beyond which NAC loses efficacy in these specific parameters. Our results suggest that the localized administration of N-acetylcysteine shows promise as a therapeutic strategy for OHSS by modulating key parameters associated with the syndrome. These promising results warrant further investigation into its mechanisms and efficacy, potentially expanding therapeutic options for OHSS management.PMID:39669379 | PMC:PMC11637629 | DOI:10.1155/ije/1634072

Front Pharmacol. 2024 Nov 28;15:1510098. doi: 10.3389/fphar.2024.1510098. eCollection 2024.ABSTRACTINTRODUCTION: Chronic kidney disease (CKD) is a substantial global health issue with high morbidity and mortality. Yishen Paidu Pills (YSPDP) are effective concentrated water pills composed of four herbs developed by Wuhan Union Hospital to treat CKD. However, the mechanism of YSPDP action is largely unknown. This study combined metabolomics, network pharmacology, transcriptomics, and experimental verification to elucidate and identify the effects and potential mechanisms of YSPDP against CKD.METHODS: Firstly, we used metabolomics analyses to identify the chemical components of YSPDP. Then, network pharmacology was conducted and indicated the predicted signaling pathways regulated by YSPDP. Next, we conducted a 5/6 subtotal nephrectomy (5/6 SNx) rat model and treated these rats with YSPDP or Losartan for 10 weeks to evaluate the effect of YSPDP on CKD. To further analyze the underlying mechanism of YSPDP in CKD, the kidney tissues of 5/6 SNx rats treated with vehicle and YSPDP were performed with transcriptome sequencing. Finally, the western blot was performed to validate the signaling pathways of YSPDP against CKD.RESULTS: Twenty-four classes of chemicals were identified by metabolomics in YSPDP. YSPDP markedly hindered CKD progression, characterized by the restoration of body weight and serum albumin levels, improved renal function, diminished tissue injury, and hampered renal fibrosis in 5/6 SNx rats. The efficacy of YSPDP in ameliorating the progression of CKD was comparable to that of losartan. Furthermore, network pharmacology, transcriptomics, and functional enrichment analysis indicated the PI3K/AKT/mTOR signaling pathway was the key pathway regulated by YSPDP. Western blot validated the inhibition of PI3K/AKT/mTOR signaling in the kidney of 5/6 SNx rats treated by YSPDP.CONCLUSION: The study identified the chemicals of YSPDP and revealed that YSPDP prevented the progression of CKD by inhibiting PI3K/AKT/mTOR signaling in 5/6 SNx rats.PMID:39669205 | PMC:PMC11634598 | DOI:10.3389/fphar.2024.1510098

Front Pharmacol. 2024 Nov 28;15:1506767. doi: 10.3389/fphar.2024.1506767. eCollection 2024.ABSTRACTMetformin has become the frontline treatment in addressing the significant global health challenge of type 2 diabetes due to its proven effectiveness in lowering blood glucose levels. However, the reality is that many patients struggle to achieve their glycemic targets with the medication and the cause behind this variability has not been investigated thoroughly. While genetic factors account for only about a third of this response variability, the potential influence of metabolomics and the gut microbiome on drug efficacy opens new avenues for investigation. This review explores the different molecular signatures to uncover how the complex interplay between genetics, metabolic profiles, and gut microbiota can shape individual responses to metformin. By highlighting the insights from recent studies and identifying knowledge gaps regarding metformin-microbiota interplay, we aim to highlight the path toward more personalized and effective diabetes management strategies and moving beyond the one-size-fits-all approach.PMID:39669200 | PMC:PMC11634602 | DOI:10.3389/fphar.2024.1506767

Hepatobiliary Surg Nutr. 2024 Dec 1;13(6):962-973. doi: 10.21037/hbsn-23-645. Epub 2024 Aug 22.ABSTRACTBACKGROUND: Sarcopenia at the time of liver transplantation (LT) is an established risk factor for mortality following LT. However, most studies in this context have defined sarcopenia by one-time, static measurements. The aims of this study were (I) to determine the impact of the rate of muscle loss in waitlisted LT recipients on post-LT outcomes and (II) to identify patterns of serum metabolites associated with patients with more progressive sarcopenia.METHODS: Patients undergoing liver transplant from 2008 to 2018 who received more than one computed tomography (CT) scans within 12 months prior to liver transplant were included (n=61). The psoas muscle index (PMI) was calculated using Slice-O-Matic software and corrected for patient height (m2). Patients were classified into two groups based the rate of reduction in PMI-high wasting [HW; change in PMI (ΔPMI) ≤-1%/month] and low wasting (LW; ΔPMI >-1%/month). Pre-transplant serum metabolic profiles were collected using nuclear magnetic resonance (NMR) spectroscopy. Living kidney donor sera was used as healthy controls.RESULTS: Median ΔPMI was -2.0%/month in HW and -0.15%/month in LW patients (P<0.001). Post-transplant 1-year mortality was significantly higher in HW patients. There were no significant differences in metabolite concentrations between HW and LW patients. However, perturbations in taurine, sarcosine, betaine and the aromatic amino acids (AAAs), were observed in patients with liver disease as compared to healthy controls. Liver disease was also associated with a decrease in lipoprotein profiles, especially high-density lipoprotein (HDL) particles.CONCLUSIONS: In patients undergoing LT, the rate of progression of sarcopenia is a strong prognostic indicator of post-LT death. Serum metabolite profiles were not characteristically unique to HW patients, and most closely resemble derangements associated with chronic liver disease.PMID:39669082 | PMC:PMC11634410 | DOI:10.21037/hbsn-23-645

Front Nutr. 2024 Nov 28;11:1438876. doi: 10.3389/fnut.2024.1438876. eCollection 2024.ABSTRACTBACKGROUND: The global prevalence of the metabolic disease Type 2 Diabetes (T2D) is increasing. Risk factors contributing to the development of T2D include overweight and obesity, lack of physical activity (PA), and an unhealthy diet. In addition, the gut microbiota has been shown to affect metabolic regulation. Since T2D is preventable, efforts should be put into the discovery of new biomarkers for early detection of individuals at risk of developing the disease.OBJECTIVE: The objective of the cross-sectional study was to explore the relationship between gut microbiota and physical activity (PA) and/or metabolic markers such as selected amino acids (AA), markers of glycaemic regulation and lipid metabolism and anthropometric measures.DESIGN: Healthy adults (18 and 65 years) with BMI between 18.5 and 27.5 kg/m2 originally recruited to a randomised controlled trial (RCT) (n = 17: six males, eleven females), were included in this exploratory cross-sectional study. Physical activity data was calculated based on a 3-days registration, and blood metabolome, gut microbiota analyses and anthropometric measures from one visit of the intervention were used in this cross-sectional study.RESULTS: Of the 47 gut bacteria analysed, there were a total of 87 significant correlations with AA, PA, body composition and/or metabolic markers. Several of the gut bacteria correlated with both PA, metabolic or anthropometric markers.CONCLUSION: In this study, we demonstrate associations between gut bacteria and PA and/or metabolic markers including AA in healthy individuals. The results may guide future studies aiming at identifying new and early biomarkers of metabolic health and diseases.PMID:39668899 | PMC:PMC11635997 | DOI:10.3389/fnut.2024.1438876

Anal Methods. 2024 Dec 13. doi: 10.1039/d4ay01672f. Online ahead of print.ABSTRACTLiupao tea (LPT) is a Chinese dark tea known to possess a unique flavour. Microbial fermentation plays a crucial role in flavour development and enrichment. Currently, the phytochemical profiles and bioactivities of LPT with and without fermentation are not fully known. In this study, we compared the chemical composition of raw tea (SF), stale-aroma (SA), and betelnut-aroma (BA) type LPT through the application of GC/LC-MS-based metabolomics, and experimentally investigated their bioactivities via antioxidant, anti-inflammatory, hypolipidemic, and hypoglycemic assays in vitro. The results indicated that fermentation enhanced the flavour of LPT as evidenced by the sweetness-producing substances, decreased bitterness and astringency-related compounds and enriched abundance of aroma-generating compounds. Two and four volatiles were detected to be major contributors to the aroma in SA and BA, respectively. Fatty acids and phosphatidylcholines were the primary lipids, among which the lysing diacylglycerol trimethyl homoserines were found to be a new class of lipids in LPT. Notably, the fermentation resulted in the degradation of compounds, particularly glycerophospholipids and saccharolipids. SF had the highest level of bioactivity, followed by BA and SA. These findings expand the present understanding regarding the development of flavour, nutrition, and medicinal value of LPT. Moreover, they provide a theoretical basis for the identification of BA and SA and serve as a reference value for consumers in their selection of LPT products.PMID:39668786 | DOI:10.1039/d4ay01672f

Food Funct. 2024 Dec 13. doi: 10.1039/d4fo04660a. Online ahead of print.ABSTRACTBifidobacterium species are known for their efficacy in alleviating constipation. This study aimed to compare the constipation-relieving effects of different Bifidobacterium species (Bifidobacterium longum subsp. longum, Bifidobacterium bifidum, Bifidobacterium animalis, Bifidobacterium breve, Bifidobacterium longum subsp. infantis, and Bifidobacterium adolescentis) and to explore the underlying mechanisms from both the bacterial and host perspectives. We evaluated six Bifidobacterium species for their physiological properties, including growth rate, oligosaccharide utilization, osmotic pressure resistance, cell adhesion, and bile acid dissociation capability. Mice with severe constipation induced by loperamide hydrochloride were treated with these bacteria at a density of 109 CFU per mL for 17 days. Gastrointestinal indices such as fecal water content, time to first black stool defecation, and small intestine propulsion rate were measured to assess constipation relief. Microbiome and metabolome (bile acid and tryptophan) analyses were conducted to elucidate the differences in constipation relief among the species. Our results demonstrated that Bifidobacterium longum subsp. longum exhibited superior physiological traits, including rapid growth, extensive oligosaccharide utilization, and high bile salt dissociation capacity. Notably, only Bifidobacterium longum subsp. longum significantly ameliorated constipation symptoms in the mouse model. Furthermore, this strain markedly restored bile acid and short-chain fatty acid levels in the intestines of constipated mice and altered the composition of the intestinal microbiota. These findings suggest that the enhanced efficacy of Bifidobacterium longum subsp. longum in relieving constipation is associated with its ability to modulate intestinal physiology and microbiota structure and metabolism.PMID:39668691 | DOI:10.1039/d4fo04660a

Br J Pharmacol. 2024 Dec 12. doi: 10.1111/bph.17409. Online ahead of print.ABSTRACTBACKGROUND AND PURPOSE: Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease, and the range of current clinical treatments is not ideal. We previously found that polysaccharide of Atractylodes macrocephala Koidz (PAMK) is beneficial in DSS-induced colitis, and we aimed to investigate the underlying mechanisms in this study.EXPERIMENTAL APPROACH: PAMK was used to treat DSS-induced colitis in mice, 16S rRNA sequencing analysis was used to detect changes in the intestinal microbiota, targeted metabolomics analysis was used to determine the content of tryptophan-metabolizing bacteria, and western blotting was used to determine aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) levels. Furthermore, antibiotic-mediated depletion of gut microbiota and faecal microbiota transplantation were performed to assess the role of the gut microbiota in PAMK alleviation of colitis.KEY RESULTS: PAMK treatment relieved intestinal microbiota dysbiosis in mice with colitis, contributed to the proliferation of tryptophan-metabolizing bacteria, and increased the levels of tryptophan metabolites, resulting in a significant increase in the nuclear translocation of PXR and expression of PXR and its target genes, but not AhR. The gut microbiota is important in PAMK treatment of colitis, including in the alleviation of symptoms, inhibition of inflammation, maintenance of the integrity of the intestinal barrier, and the regulation of the Th17/Treg cell balance.CONCLUSION AND IMPLICATIONS: Based on our findings, we elucidate a novel mechanism by which PAMK alleviates DSS-induced colitis and thus provides evidence to support the potential development of PAMK as a new clinical drug against UC.PMID:39667762 | DOI:10.1111/bph.17409

Fitoterapia. 2024 Dec 10:106343. doi: 10.1016/j.fitote.2024.106343. Online ahead of print.ABSTRACTPostprandial hyperglycemia is a hallmark of diabetes, and inhibition of key carbohydrate digestion enzymes such as α-amylase (α-AMY) and α-glucosidase (α-GLU) is an effective therapeutic target. A potential unexplored source of inhibitory compounds of these enzymes is Brassica oleracea var. capitata L (BOCE). This study explored the in vitro inhibition mechanism of BOCE and studied in silico the interaction of its compounds identified and quantified by UPLC-QTOF-MS on α-AMY and α-GLU. BOCE demonstrated IC50 values of 3.08 mg/mL for α-AMY and 22.63 mg/mL for α-GLU, indicating competitive and mixed-type inhibitions, respectively. Untargeted metabolomics identified 21 compounds, primarily phenolic acids such as t-cinnamic, sinapic, and caffeoylquinic acid. In the targeted analysis, 11 compounds were quantified, mainly phenolic acids. The most impactful biosynthetic pathways identified were phenylpropanoids and brassinosteroids. In silico analysis revealed that for α-AMY and α-GLU, castasterone and 26-hydroxybrassinolide displayed the lowest binding free energies with specific hydrogen bond patterns to catalytic residues in the binding site, respectively. B. oleracea is a promising source of compounds with the ability to modulate key enzymes related to hyperglycemia. Specifically, compounds such as castasterone and 26-hydroxybrassinolide show potential against α-AMY and α-GLU inhibition, offering a novel approach to diabetes.PMID:39667674 | DOI:10.1016/j.fitote.2024.106343

Free Radic Biol Med. 2024 Dec 10:S0891-5849(24)01139-0. doi: 10.1016/j.freeradbiomed.2024.12.030. Online ahead of print.ABSTRACTSolar ultraviolet B (UVB) radiation-induced DNA damage is a well-known initiator of skin carcinomas. The UVB-induced DNA damage response (DDR) involves series of signaling cascades that are activated to maintain cell integrity. Among the different biological processes, little is known about the role of energy metabolism in the DDR. We sought to determine whether UVB-induced nuclear and/or mitochondrial cyclobutane pyrimidine dimers (CPDs) alter cellular energy metabolism. To gain insight into this question, we took advantage of keratinocytes expressing nuclear or mitochondrial CPD photolyase. Applying a quantitative proteomic approach and targeted metabolomics, we observed biphasic alterations in multiple metabolic pathways and in the abundance of various metabolites, largely influenced by the presence of genomic CPDs. The heightened oxygen consumption rate post-irradiation, along with mitochondrial structural rearrangements, was found to be dependent on both mitochondrial and nuclear CPDs. Understanding the influence of nuclear and mitochondrial DNA damage on keratinocyte responses to UVB irradiation deepens current knowledge regarding skin cancer prevention, initiation, and therapy.PMID:39667588 | DOI:10.1016/j.freeradbiomed.2024.12.030

Int J Biol Macromol. 2024 Dec 10:138629. doi: 10.1016/j.ijbiomac.2024.138629. Online ahead of print.ABSTRACTA close relationship between the pathogenesis of chronic kidney disease (CKD) and abnormalities in the gut-kidney axis. Paotianxiong polysaccharides (PTXP) that have demonstrated therapeutic effects on CKD. However, the specific mechanism by which PTXP ameliorates CKD through the gut-kidney axis remains to be explored. In this study, the microbiomes and metabolomics were combined to investigate the impact of PTXP on intestinal flora structure and metabolism, further unveiling the relationship through correlation analysis. The results showed that PTXP intervention significantly modulated renal function abnormalities in CKD rats and significantly modulates gut microbial disorders, evidenced by an increased abundance of Lactobacillus murinus, Bacteroides fragilis, and a decreased abundance of Bifidobacterium pseudolongum. Furthermore, PTXP reversed the changes in intestinal metabolites, such as linoleic acid and docosahexaenoic acid, induced by CKD and identified unsaturated fatty acid metabolism as a key metabolic pathway. Correlation analyses also revealed associations among gut microorganisms, metabolites, and renal function indexes, confirming that PTXP alleviated CKD through the gut-kidney axis. Moreover, the above conclusions were verified by fecal bacteria transplantation experiments. These findings provide insights into the mechanism of PTXP for the treatment of CKD and provide new targets for the treatment of CKD.PMID:39667450 | DOI:10.1016/j.ijbiomac.2024.138629

Ecotoxicol Environ Saf. 2024 Dec 11;289:117518. doi: 10.1016/j.ecoenv.2024.117518. Online ahead of print.ABSTRACTThe persistent airway inflammation is the main characteristic of chronic obstructive pulmonary disease (COPD), typically caused by an indoor environment pollution cigarette smoke (CS). METTL16 is an m6A methyltransferase that has been proven to be closely associated with the occurrence of various diseases. However, its exact role in smoking-induced COPD remains to be investigated. In this study, we found that the level of METTL16 was aberrantly decreased in lung tissues of COPD smokers. Similarly, murine model induced by CS and lung epithelial cell model induced by cigarette smoke extract (CSE) also confirmed this discovery. Moreover, in the Mettl16-deficient (Mettl16+/-) mice challenged with CS, airway inflammation was aggravated. To identify the potential target genes and regulatory pathways through METTL16, methylated RNA immunoprecipitation sequencing (meRIP-seq), RNA sequencing (RNA-seq) and metabolomic profiling were used. Knockdown of METTL16 significantly reduced the stability of glutamic-oxaloacetic transaminase 2 (GOT2) and downregulated its expression through m6A modification, while reprogramed glutamine metabolism in lung epithelial cells. Significant reduction in inflammation levels was observed in the 3-month COPD murine model fed a glutamine-supplemented diet. Mechanistically, METTL16 could regulate lung epithelial mitochondrial function by participating in the reprogramming of glutamine metabolism. Our study characterized the role of the METTL16/GOT2/glutamine axis in the occurrence and development of COPD, and emphasized the potential value of METTL16 and glutamine in the therapy of chronic airway inflammation in smoking-induced COPD.PMID:39667326 | DOI:10.1016/j.ecoenv.2024.117518

Food Chem. 2024 Dec 5;468:142384. doi: 10.1016/j.foodchem.2024.142384. Online ahead of print.ABSTRACTIn this study, the bioaccessibility and bioavailability of curcumin encapsulated into different lupin protein isolate-based carriers was evaluated by coupling an in vitro gastrointestinal digestion (INFOGEST) with an in vitro co-culture absorption model, Caco-2/HT29-MTX, consisting of both absorptive and mucus producing cells. A targeted ultrahigh-performance quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) method was applied to monitor the fate of curcumin post digestion and absorption, specifically analyzing the apical, cellular, and basolateral fractions. Lupin protein nanoparticles, obtained by desolvation, protected curcumin from degradation better than oil in water (O/W) emulsions stabilized with lupin protein isolate. A recovery of 70 % of initial curcumin was found in the whole digesta of nanoparticles, whereas the emulsion systems displayed ≤35 % recovery. Interestingly, unlike in the case of emulsions, where curcumin was found in the micellar phase, most of the curcumin in the digesta of nanoparticles was recovered in the insoluble phase, highlighting the influence of the matrix structure in ensuring bioaccessibility of bioactive components. Regardless of the treatment, curcumin was not detected in the basolateral compartment, after absorption and transport through the in vitro cell monolayer model. However, a noteworthy proportion of curcumin, 54 % for protein nanoparticles and ≤ 24 % for emulsions, was retrieved within the cell monolayer. Non-targeted metabolomics analysis revealed the presence of a range of curcumin metabolites in the basolateral fraction and showed distinct profiles depending on the type (structure) of the delivery systems. The study highlights the critical need for thorough research into the behavior of bioactive compounds within the gut and emphasizes the necessity for future studies aimed at gaining a deeper understanding of the impact of the food matrix. Such insights are vital for enhancing and optimizing the delivery of bioactive compounds from complex food sources.PMID:39667234 | DOI:10.1016/j.foodchem.2024.142384

Plant J. 2024 Dec 12. doi: 10.1111/tpj.17169. Online ahead of print.ABSTRACTExtreme dryness is lethal for nearly all plants, excluding the so-called resurrection plants, which evolved vegetative desiccation tolerance (VDT) by recruiting genes common in most plants. To better understand the evolution of VDT, we generated chromosome-level assemblies and improved genome annotations of two Selaginella species with contrasting abilities to survive desiccation. We identified genomic features and critical mechanisms associated with VDT through sister-group comparative genomics integrating multi-omics data. Our findings indicate that Selaginella evolved VDT through the expansion of some stress protection-related gene families and the contraction of senescence-related genes. Comparative analyses revealed that desiccation-tolerant Selaginella species employ a combination of constitutive and inducible protection mechanisms to survive desiccation. We show that transcriptional priming of stress tolerance-related genes and accumulation of flavonoids in unstressed plants are hallmarks of VDT in Selaginella. During water loss, the resurrection Selaginella induces phospholipids and glutathione metabolism, responses that are missing in the desiccation-sensitive species. Additionally, gene regulatory network analyses indicate the suppression of growth processes as a major component of VDT. This study presents novel perspectives on how gene dosage impacts crucial protective mechanisms and the regulation of central processes to survive extreme dehydration.PMID:39666518 | DOI:10.1111/tpj.17169

JAMA Netw Open. 2024 Dec 2;7(12):e2450467. doi: 10.1001/jamanetworkopen.2024.50467.ABSTRACTIMPORTANCE: Gestational diabetes (GD) is linked to health risks for the birthing parent and infant. The outcomes of GD on human milk composition are mostly unknown.OBJECTIVE: To determine associations between GD, the human milk metabolome, and infant growth and body composition.DESIGN, SETTING, AND PARTICIPANTS: Cohort study using data from the Mothers and Infants Linked for Healthy Growth and the Maternal Milk, Metabolism, and the Microbiome studies at the University of Oklahoma and University of Minnesota, large prospective US cohorts with a high proportion of exclusive breastfeeding. Participants were mother-infant dyads recruited between October 2014 and August 2019 who planned to exclusively breastfeed for 3 or more months. Data were analyzed from July 2022 to August 2024.EXPOSURE: GD diagnosed via oral glucose tolerance test.MAIN OUTCOMES AND MEASURES: The milk metabolome was assessed by untargeted liquid chromatography-gas chromatography-mass spectrometry at 1 month post partum. Infant growth (weight for length z score, length for age z score, and rapid weight gain) and body composition (percentage body fat and fat-free mass index) from 0 to 6 months were assessed. Linear regression analyses tested associations between GD and milk metabolites, with adjustment for covariates and potential confounders.RESULTS: Among 348 dyads (53 with GD), 27 (51%) of the GD-exposed infants were female and 157 (53%) of nonexposed infants were male; 10 (19%) were Asian, 2 (4%) were Black or African American, and 37 (70%) were White. The mean (SD) age was higher in the GD group (with GD, 34.0 [4.3] years; without GD, 30.7 [4.1] years). In adjusted models, GD was associated with differential levels of 9 metabolites of 458 tested (FDR<0.05); 3 were higher (2-hydroxybutyric acid, 3-methylphenylacetic acid, and pregnanolone sulfate) and 6 were lower in women with GD (4-cresyl sulfate, cresol, glycine, P-cresol sulfate, phenylacetic acid, and stearoylcarnitine). Phenylacetic acid was associated with length for age z score (β = 0.27; SE, 0.13; 95% CI, 0.02 to 0.16), 2-hydroxybutryic acid with percentage body fat (β = -1.50; SE, 0.66; 95% CI, -2.79 to -4.82), and stearoylcarnitine with greater odds of rapid weight gain (odds ratio, 1.66; 95% CI, 1.23 to 2.25). GD was associated with greater length for age z scores (β = 0.48; SE, 0.22; 95% CI, 0.04 to 0.91).CONCLUSIONS AND RELEVANCE: In this observational cohort study, GD was associated with altered concentrations of several human milk metabolites. The associations between these metabolites and infant growth suggest that milk compositional differences in mothers with GD may beneficially moderate the growth and body composition of their infants.PMID:39666338 | DOI:10.1001/jamanetworkopen.2024.50467

J Food Drug Anal. 2022 Sep 15;30(3):402-416. doi: 10.38212/2224-6614.3425.ABSTRACTTraditional Chinese medicine (TCM) has been applied to improve human health for millennia. In the TCM system, "medicinal property" ( yao xing; hot and cold properties) is a core concept used to describe the influences of medicinal materials on human physiological conditions, and metabolites are believed to be one of the major ingredients of TCMs that affect their medicinal property. However, due to a lack of comprehensive analyses of TCM metabolomes, information about the relationships between TCM metabolite composition and medicinal property remains limited. In this pilot study, a mass spectral molecular networking-based platform was established and applied to systematically profile the metabolome of 24 TCMs with various medicinal properties. The molecular networks were built based on the liquid chromatography-tandem mass spectrometry (LC-MS/MS) data from 50% EtOH extracts of 24 TCMs. The results showed that various classes of metabolites were clustered in the molecular networks, and the potential medicinal property-associated molecular families were filtered by screening the medicinal property and the diversity of TCM sources. For example, some specific types of flavonoids were identified in the representative cold-property (han xing) molecular families. In contrast, due to the limited sample size, the representative and universal hot-property (re xing) molecular family has not been well revealed. In summary, this study provides methodology and information on the potential relationships between the metabolite composition and the concept of medicinal property in TCM. Furthermore, the results can serve as a foundation for mass spectral molecular networking-based analysis of TCM metabolomes, facilitating TCM research and development.PMID:39666294 | DOI:10.38212/2224-6614.3425

Insights Imaging. 2024 Dec 12;15(1):299. doi: 10.1186/s13244-024-01876-5.ABSTRACTOBJECTIVES: Radical prostatectomy (RP) is a common intervention in patients with localized prostate cancer (PCa), with nerve-sparing RP recommended to reduce adverse effects on patient quality of life. Accurate pre-operative detection of extraprostatic extension (EPE) remains challenging, often leading to the application of suboptimal treatment. The aim of this study was to enhance pre-operative EPE detection through multimodal data integration using explainable machine learning (ML).METHODS: Patients with newly diagnosed PCa who underwent [68Ga]Ga-PSMA-11 PET/MRI and subsequent RP were recruited retrospectively from two time ranges for training, cross-validation, and independent validation. The presence of EPE was measured from post-surgical histopathology and predicted using ML and pre-operative parameters, including PET/MRI-derived features, blood-based markers, histology-derived parameters, and demographic parameters. ML models were subsequently compared with conventional PET/MRI-based image readings.RESULTS: The study involved 107 patients, 59 (55%) of whom were affected by EPE according to postoperative findings for the initial training and cross-validation. The ML models demonstrated superior diagnostic performance over conventional PET/MRI image readings, with the explainable boosting machine model achieving an AUC of 0.88 (95% CI 0.87-0.89) during cross-validation and an AUC of 0.88 (95% CI 0.75-0.97) during independent validation. The ML approach integrating invasive features demonstrated better predictive capabilities for EPE compared to visual clinical read-outs (Cross-validation AUC 0.88 versus 0.71, p = 0.02).CONCLUSION: ML based on routinely acquired clinical data can significantly improve the pre-operative detection of EPE in PCa patients, potentially enabling more accurate clinical staging and decision-making, thereby improving patient outcomes.CRITICAL RELEVANCE STATEMENT: This study demonstrates that integrating multimodal data with machine learning significantly improves the pre-operative detection of extraprostatic extension in prostate cancer patients, outperforming conventional imaging methods and potentially leading to more accurate clinical staging and better treatment decisions.KEY POINTS: Extraprostatic extension is an important indicator guiding treatment approaches. Current assessment of extraprostatic extension is difficult and lacks accuracy. Machine learning improves detection of extraprostatic extension using PSMA-PET/MRI and histopathology.PMID:39666257 | DOI:10.1186/s13244-024-01876-5

J Gastroenterol. 2024 Dec 12. doi: 10.1007/s00535-024-02197-6. Online ahead of print.ABSTRACTBACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a formidable health challenge due to its detection at a late stage and a lack of reliable biomarkers for early detection. Although levels of carbohydrate antigen 19-9 are often used in conjunction with imaging-based tests to aid in the diagnosis of PDAC, there is still a need for more sensitive and specific biomarkers for early detection of PDAC.METHODS: We obtained serum samples from 88 subjects (patients with PDAC (n = 58) and controls (n = 30)). We carried out a multi-omics analysis to measure cytokines and related proteins using proximity extension technology and lipidomics and metabolomics using tandem mass spectrometry. Statistical analysis was carried out to find molecular alterations in patients with PDAC and a machine learning model was used to derive a molecular signature of PDAC.RESULTS: We quantified 1,462 circulatory proteins along with 873 lipids and 1,001 metabolites. A total of 505 proteins, 186 metabolites and 33 lipids including bone marrow stromal antigen 2 (BST2), keratin 18 (KRT18), and cholesteryl ester(20:5) were found to be significantly altered in patients. We identified different levels of sphingosine, sphinganine, urobilinogen and lactose indicating that glycosphingolipid and galactose metabolisms were significantly altered in patients compared to controls. In addition, elevated levels of diacylglycerols and decreased cholesteryl esters were observed in patients. Using a machine learning model, we identified a signature of 38 biomarkers for PDAC, composed of 21 proteins, 4 lipids, and 13 metabolites.CONCLUSIONS: Overall, this study identified several proteins, metabolites and lipids involved in various pathways including cholesterol and lipid metabolism to be changing in patients. In addition, we discovered a multi-analyte signature that could be further tested for detection of PDAC.PMID:39666045 | DOI:10.1007/s00535-024-02197-6