PubMed

PLoS One. 2024 Oct 17;19(10):e0310014. doi: 10.1371/journal.pone.0310014. eCollection 2024.ABSTRACTIntervertebral disc degeneration (IVDD) is a prevalent orthopedic condition with lower back pain as the predominant clinical presentation that challenges clinical treatment with few therapeutic options. Duhuo Jisheng Decoction (DHJSD) has been proven effective in the therapy of IVDD, but the precise underlying mechanisms remain not fully elucidated. The current study was designed to test our hypothesis that DHJSD may systematically correct the phenotypic disruption of the gut microbiota and changes in the serum metabolome linked to IVDD. Analysis of the active ingredients of DHJSD by ultra high performance liquid chromatography. An integrated metagenomic and metabonomic approach was used to analyze feces and blood samples from normal and IVDD rats. Compared to the control group, fiber ring pinning on the caudal 3 to caudal 5 segments of the rats caused IVDD and significantly altered the compositions of the intestinal microbiota and serum metabolites. Integrated analysis revealed commonly-altered metabolic pathways shared by both intestinal microbiota and serum metabolome of the IVDD rats. DHJSD inhibited the degenerative process and restored the compositions of the perturbed gut microbiota, particularly the relative abundance of commensal microbes of the Prevotellaceae family. DHJSD also corrected the altered metabolic pathways involved in the metabolism of glycine, serine, threonine, valine, the citric acid cycle, and biosynthesis of leucine and isoleucine. DHJSD inhibited the disc degeneration process by an integrated metagenomic and metabonomic mechanism to restore the microbiome profile and normalize the metabonomic pathways.PMID:39418241 | DOI:10.1371/journal.pone.0310014

Crit Care Med. 2024 Nov 1;52(11):e536-e544. doi: 10.1097/CCM.0000000000006391. Epub 2024 Aug 23.ABSTRACTOBJECTIVE: To investigate the metabolomic profiles associated with different immune activation states in sepsis patients.DESIGN: Subgroup analysis of the PROVIDE (a Personalized Randomized trial of Validation and restoration of Immune Dysfunction in severe infections and Sepsis) prospective clinical study.SETTING: Results of the PROVIDE study showed that patients with sepsis may be classified into three states of immune activation: 1) macrophage-activation-like syndrome (MALS) characterized by hyperinflammation, sepsis-induced immunoparalysis, and 3) unclassified or intermediate patients without severe immune dysregulation.PATIENTS OR SUBJECTS: Two hundred ten patients from 14 clinical sites in Greece meeting the Sepsis-3 definitions with lung infection, acute cholangitis, or primary bacteremia.INTERVENTIONS: During our comparison, we did not perform any intervention.MEASUREMENTS AND MAIN RESULTS: Untargeted metabolomics analysis was performed on plasma samples from 210 patients (a total of 1394 products). Differential abundance analysis identified 221 significantly different metabolites across the immune states. Metabolites were enriched in pathways related to ubiquinone biosynthesis, tyrosine metabolism, and tryptophan metabolism when comparing MALS to immunoparalysis and unclassified patients. When comparing MALS to unclassified, 312 significantly different metabolites were found, and pathway analysis indicated enrichment in multiple pathways. Comparing immunoparalysis to unclassified patients revealed only two differentially regulated metabolites.CONCLUSIONS: Findings suggest distinct metabolic dysregulation patterns associated with different immune dysfunctions in sepsis: the strongest metabolic dysregulation is associated with MALS.PMID:39418210 | DOI:10.1097/CCM.0000000000006391

JAMA Netw Open. 2024 Oct 1;7(10):e2440047. doi: 10.1001/jamanetworkopen.2024.40047.ABSTRACTIMPORTANCE: Associations of body mass index (BMI) with survival in pancreatic ductal adenocarcinoma (PDA) have substantial variability in literature, potentially due to heterogeneous patient populations and retrospective analyses. Additionally, BMI may inadequately describe body composition (ie, morphomics; including subcutaneous and visceral fats, muscle, and fascia), which might have independent biological roles and associations with survival.OBJECTIVE: To study the associations of BMI and morphomics with survival and metabolomics in metastatic PDA.DESIGN, SETTING, AND PARTICIPANTS: This cohort study prospectively collected patient data, imaging, and serum on the phase 3 trial (Avenger500), which investigated the efficacy and safety of 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) versus modified FOLFIRINOX plus devimistat. The randomized trial accrued 528 patients with chemotherapy-naive, metastatic PDA from Europe, Israel, Korea, and the US between 2018 and 2020. In the present study, per-protocol patients with L1 to L4, T10 to T12 vertebral levels were evaluated. Data analysis occurred from January 2023 to April 2024.EXPOSURE: Patient data were collected by clinical staff. Morphomics were analyzed from baseline imaging. Metabolites were extracted from baseline serum.MAIN OUTCOME AND MEASURES: A multifaceted statistical approach evaluated associations of BMI and morphomics with progression-free survival (PFS) and overall survival (OS). Associations of morphomics with metabolites were also studied.RESULTS: Of the 528 initial patients, 476 (median [IQR] age, 63 [56-68] years; 280 male [58.8%]; median [IQR] BMI, 25.0 [22.1-25.9]) were evaluable for the present study. BMI (obese [≥30] compared with normal [18.5-24.9]) was not associated with OS (hazard ratio [HR], 0.90; 95% CI, 0.67-1.22; P for trend = .33). More subcutaneous fat was associated with longer OS (HR, 0.62; 95% CI, 0.41-0.94; P for trend = .02). Higher visceral fat density was associated with shorter PFS (HR, 1.74; 95% CI, 1.23-2.48; P for trend = .002) and OS (HR, 1.50; 95% CI, 1.12-2.00; P for trend = .008). A higher muscle-to-fascia ratio was associated with longer PFS (HR, 0.58; 95% CI, 0.40-0.84; P for trend = .005) and OS (HR, 0.56; 95% CI, 0.41-0.75; P for trend = 1.7 × 10-4). Subcutaneous fat was positively associated with long-chain fatty acid metabolism including pristanic acid, decanoylcarnitine, decenoylcarnitine, and octanoylcarnitine. Muscle-to-fascia was positively associated with metabolites including acetylcarnosine (β = 0.34; 95% CI, 0.21-0.47; P = 1.27 × 10-6).CONCLUSIONS AND RELEVANCE: In cohort study of patients with metastatic PDA, BMI was not associated with survival. Higher visceral fat density, subcutaneous fat area, and muscle-to-fascia ratio were associated with survival independent of BMI. The latter 2 were associated with higher levels of animal product metabolism. These findings could represent novel focuses for prognostication and intervention to improve survival of patients with PDA.PMID:39418020 | DOI:10.1001/jamanetworkopen.2024.40047

J Appl Physiol (1985). 2024 Oct 17. doi: 10.1152/japplphysiol.00629.2024. Online ahead of print.ABSTRACTThere are known sex differences in cardiorespiratory fitness (CRF). Little is known about the impact of pubertal blockade with a gonadotropin releasing hormone agonist (GnRHa) followed by hormone therapy on CRF for transgender adolescents. We aimed to (1) determine the effect of GnRHa monotherapy on CRF and mitochondrial function and associations with metabolomic profiles, and (2) evaluate for changes after 1 and 12 months of testosterone therapy among transgender adolescents . Participants assigned female at birth (n=19, baseline age 15.0+1.0 years) from two groups: GnRHa+ (n=8) and GnRHa- (n=11) were examined at baseline and 1- and 12-months post-testosterone therapy in a longitudinal observational study to assess cardiorespiratory fitness, mitochondrial respiration and metabolic profile. Fasted morning labs including assessment of metabolomics and peripheral blood mononuclear cell mitochondrial respiration and degree of mitochondrial coupling (respiratory control ratio, RCR). A graded cycle ergometer test was performed. Baseline differences were evaluated between groups. Changes were compared with mixed linear regression models evaluating time (baseline, 1 and 12 months), group (GnRHa treatment yes/no), and their interaction. At baseline GnRHa+ individuals had higher relative VO2peak (30.1+4.83 vs. 25.24+4.47 ml/kg/min, p=0.042) than GnRHa- individuals. In regression models, GnRHa+ individuals had a significant increase in peak watts (p=0.011) and total exercise time (p=0.005)after 12 months of testosterone (p=0.012), but not GnRHa- individuals. GnRHa+ individuals have significantly higher RCR under carbohydrate (p=0.0007) and lipid (p=0.0002) conditions than GnRHa+ individuals. Pretreatment with GnRHa positively influences peak CRF and mitochondrial respiration in adolescent transgender males undergoing testosterone therapy.PMID:39417821 | DOI:10.1152/japplphysiol.00629.2024

Elife. 2024 Oct 17;13:RP94558. doi: 10.7554/eLife.94558.ABSTRACTThe exchange of metabolites (i.e., metabolic interactions) between bacteria in the rhizosphere determines various plant-associated functions. Systematically understanding the metabolic interactions in the rhizosphere, as well as in other types of microbial communities, would open the door to the optimization of specific predefined functions of interest, and therefore to the harnessing of the functionality of various types of microbiomes. However, mechanistic knowledge regarding the gathering and interpretation of these interactions is limited. Here, we present a framework utilizing genomics and constraint-based modeling approaches, aiming to interpret the hierarchical trophic interactions in the soil environment. 243 genome scale metabolic models of bacteria associated with a specific disease-suppressive vs disease-conducive apple rhizospheres were drafted based on genome-resolved metagenomes, comprising an in silico native microbial community. Iteratively simulating microbial community members' growth in a metabolomics-based apple root-like environment produced novel data on potential trophic successions, used to form a network of communal trophic dependencies. Network-based analyses have characterized interactions associated with beneficial vs non-beneficial microbiome functioning, pinpointing specific compounds and microbial species as potential disease supporting and suppressing agents. This framework provides a means for capturing trophic interactions and formulating a range of testable hypotheses regarding the metabolic capabilities of microbial communities within their natural environment. Essentially, it can be applied to different environments and biological landscapes, elucidating the conditions for the targeted manipulation of various microbiomes, and the execution of countless predefined functions.PMID:39417540 | DOI:10.7554/eLife.94558

Crit Rev Anal Chem. 2024 Oct 17:1-18. doi: 10.1080/10408347.2024.2407615. Online ahead of print.ABSTRACTCamellia oil is a high-value edible seed oil, recommended by the Food and Agriculture Organization (FAO). It is essential to develop accurate and rapid analytical methods to authenticate camellia oil due to its susceptibility to adulteration. Recently, hyphenated chromatography-mass spectrometry, especially high-resolution mass spectrometry using chemometrics, has become a promising platform for the identification of camellia oil. Based on the compositional analysis, the fatty acid, sterol, phenol, and tocopherol profiles (or fingerprints) were utilized as predictor variables for assessing authenticity. The review systematically summarizes the workflow of chromatography-mass spectrometry technologies and comprehensively investigates recent metabolomic applications combined with chemometrics for camellia oil authentication. Metabolomics has significantly improved our understanding of camellia oil composition at the molecular level, contributing to its identification and full characterization. Hence, its integration with standard analytical methods is essential to enhance the tools available for public and private laboratories to assess camellia oil authenticity. Integrating metabolomics with artificial intelligence is expected to accelerate drug discovery by identifying new metabolic pathways and biomarkers, promising to revolutionize medicine.PMID:39417299 | DOI:10.1080/10408347.2024.2407615

J Gerontol A Biol Sci Med Sci. 2024 Oct 17:glae237. doi: 10.1093/gerona/glae237. Online ahead of print.ABSTRACTSarcopenia is recognized as a complex and multifactorial disorder that includes nutritional deficiency, inactivity, proinflammatory status, hormonal changes, neurological degeneration, and metabolic disturbances. Its' pathogenesis is not fully understood. Therefore, identifying specific biomarkers of sarcopenia will help us understand its pathophysiology. The most frequently reported blood-derived biomarkers of sarcopenia are growth factors, neuromuscular junctions, endocrine systems, mitochondrial dysfunction, inflammation-mediated and redox processes, muscle protein turnover, blood metabolomics, and behavior-mediated biomarkers. Here, we address the implications of sarcopenia biomarkers based on our research experience with KFACS cohort data. It includes free testosterone, myostatin, fibroblast growth factor 21 (FGF-21), growth differentiation factor 15 (GDF-15), procollagen type III N-terminal peptide (P3NP), creatinine-based biomarkers, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), brain-derived neurotrophic factor (BDNF), metabolites (proline, alanine, tryptophan), and multi-biomarker risk score. We attempted to explain the paradoxical findings of myostatin and FGF-21 levels in relation to sarcopenia. GDF-15 levels were associated with sarcopenia prevalence but not its incidence. Plasma P3NP and BDNF levels may be biomarkers of muscle quality rather than quantity. Lower erythrocyte EPA and DHA levels were associated with slow gait speed, and erythrocyte EPA levels were associated with low handgrip strength. We developed a multi-biomarker risk score for sarcopenia and found that its accuracy in diagnosing sarcopenia was higher than that of any single biomarker.PMID:39417263 | DOI:10.1093/gerona/glae237

Food Funct. 2024 Oct 17. doi: 10.1039/d4fo03633f. Online ahead of print.ABSTRACTInsufficient selenium intake can lead to serious health problems. However, most research on the functional properties of selenium-enriched probiotics has focused on sub-health conditions or disease models, with limited studies involving healthy subjects. Additionally, previous research has primarily explored the direct effects of selenium itself, neglecting its influence on gut microbiota and metabolism. This study aimed to explore whether long-term intake of Pichia kudriavzevii enriched with selenium affected gut microbiota and host metabolism in mice and to identify microbiota and metabolites related to beneficial outcomes. Results demonstrated that selenium-enriched P. kudriavzevii (SeY) exhibited non-toxic properties, did not cause colon or liver damage, enhanced antioxidant capacity, and reduced inflammation in a selenium dose-dependent manner. Additionally, SeY supplementation significantly altered the gut microbiota. High-dose SeY (HSeY) elevated the abundance of beneficial bacteria such as Lactobacillus and suppressed harmful bacteria such as Eubacterium nodatum group, Prevotellaceae_NK3B31_group, and unclassified_f__Lachnospiraceae. Low-dose SeY (LSeY) increased the abundance of Faecalibaculum. The strain without enriched selenium exhibited higher levels of Akkermansia compared to selenium-enriched strains. Both strains, with or without enriched selenium, stimulated the production of short-chain fatty acids. Non-targeted metabolomics analysis revealed that HSeY treatment regulated various metabolic pathways, such as tryptophan metabolism, tyrosine metabolism, and arginine biosynthesis. LSeY treatment modulated tyrosine metabolism, secondary bile acid metabolism, bile secretion, and primary bile acid metabolism. P. kudriavzevii regulated the metabolism of purine, arginine, proline, and tryptophan. Our study highlights the promise of SeY supplementation in regulating host metabolism and the gut microbiota, offering insights into its implications for promoting health.PMID:39417221 | DOI:10.1039/d4fo03633f

Front Microbiol. 2024 Oct 2;15:1463911. doi: 10.3389/fmicb.2024.1463911. eCollection 2024.ABSTRACTStreptomyces sp. VB1, an actinomycete isolated from marine sediments in Valparaíso Bay, Chile, synthesizes antimicrobial and antiproliferative compounds. This study presents comprehensive metabolomics and comparative genomics analyses of strain VB1. LC-HRMS dereplication and Molecular Networking analysis of crude extracts identified antibiotics such as globomycin and daunorubicin, along with known and potentially novel members of the arylomycin family. These compounds exhibit activity against a range of clinically relevant bacterial and cancer cell lines. Phylogenomic analysis underscores the uniqueness of strain VB1, suggesting it represents a novel taxon. Such uniqueness is further supported by its Biosynthetic Novelty Index (BiNI) and BiG-SCAPE analysis of Gene Cluster Families (GCFs). Notably, two Biosynthetic Gene Clusters (BGCs) were found to be unique to VB1 compared to closely related strains: BGC #15, which encodes potentially novel anthracycline compounds with cancer cell growth inhibition properties, and BGC #28, which features a non-canonical configuration combining arylomycin, globomycin, and siamycin BGCs. This supercluster, the first described to consist of more than two adjacent and functional BGCs, co-produces at least three antimicrobial compounds from different antibiotic families. These findings highlight Streptomyces sp. VB1's potential for discovering new bioactive molecules, positioning it as a promising candidate for further research.PMID:39417076 | PMC:PMC11479970 | DOI:10.3389/fmicb.2024.1463911

Toxicol Res (Camb). 2024 Oct 15;13(5):tfae169. doi: 10.1093/toxres/tfae169. eCollection 2024 Oct.ABSTRACTHuman exposure to mycotoxins through food involve a mixture of compounds, which can be harmful to human health. The Fusarium fungal species are known to produce zearalenone (ZEN), a non-steroidal estrogenic mycotoxin, and its metabolite alpha-zearalenol (α-ZEL), both of which possess endocrine-disruptive properties. Given their potential harm to human health through food exposure, investigating the combined effects of ZEN and α-ZEL becomes crucial. Hence, the combined impact of ZEN and α-ZEL study hold significant importance. This in vitro study delves into the critical area, examining their combined impact on the proliferation and metabolic profile of endometrial cancer Ishikawa cells via sulforhodamine, clonogenic, proliferating cell nuclear antigen (PCNA) and liquid chromatography-high resolution mass spectrometry (LC-HRMS) based untargeted metabolomics. Low concentrations of ZEN (25 nm), α-ZEL (10 nm), or a combination of both were observed to significantly enhance cell proliferation of Ishikawa cells, as evidenced by PCNA immunostaining, immunoblotting as well and clonogenic assays. The metabolomics revealed the perturbations in glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and phenylalanine, tyrosine, tryptophan biosynthesis provides valuable insights into potential mechanism by which these mycotoxins may facilitate cell proliferation. However, further investigations are warranted to comprehensively understand the implications of these findings and their possible implications for human health.PMID:39417035 | PMC:PMC11474235 | DOI:10.1093/toxres/tfae169

Biotechnol Notes. 2023 Dec 31;5:1-7. doi: 10.1016/j.biotno.2023.12.006. eCollection 2024.ABSTRACTFungal endophytes are valuable sources of bioactive compounds with diverse applications. The exploration of these compounds not only contributes to our understanding of ecological interactions but also holds promise for the development of novel products with agricultural, medicinal, and industrial significance. Continued exploration of fungal endophyte diversity and understanding the ecological roles of bioactive compounds present opportunities for new discoveries and applications. Omics techniques, which include genomics, transcriptomics, proteomics, and metabolomics, contribute to the discovery of novel bioactive compounds produced by fungal endophytes with their potential applications. The omics techniques play a critical role in unraveling the complex interactions between fungal endophytes and their host plants, providing valuable insights into the molecular mechanisms and potential applications of these relationships. This review provides an overview of how omics techniques contribute to the study of fungal endophytes.PMID:39416692 | PMC:PMC11446381 | DOI:10.1016/j.biotno.2023.12.006

bioRxiv [Preprint]. 2024 Oct 11:2024.10.07.617124. doi: 10.1101/2024.10.07.617124.ABSTRACTChronic infections drive a CD8 T cell program termed T cell exhaustion, characterized by reduced effector functions. While cell-intrinsic mechanisms underlying CD8 T cell exhaustion have been extensively studied, the impact of the metabolic environment in which exhausted CD8 T cells (Tex) operate remains less clear. Using untargeted metabolomics and the murine lymphocytic choriomeningitis virus infection model we investigated systemic metabolite changes early and late following acute versus chronic viral infections. We identified distinct short-term and persistent metabolite shifts, with the most significant differences occurring transiently during the acute phase of the sustained infection. This included nutrient changes that were independent of viral loads and partially associated with CD8 T cell-induced anorexia and lipolysis. One remarkable observation was the elevation of medium- and long-chain fatty acid (FA) and acylcarnitines during the early phase after chronic infection. During this time, virus-specific CD8 T cells from chronically infected mice exhibited increased lipid accumulation and uptake compared to their counterparts from acute infection, particularly stem-like Tex (Tex STEM ), a subset that generates effector-like Tex INT which directly limit viral replication. Notably, only Tex STEM increased oxidative metabolism and ATP production upon FA exposure. Consistently, short-term reintroduction of FA during late chronic infection exclusively improved Tex STEM mitochondrial fitness, percentages and numbers. This treatment, however, also reduced Tex INT , resulting in compromised viral control. Our study offers a valuable resource for investigating the role of specific metabolites in regulating immune responses during acute and chronic viral infections and highlights the potential of long-chain FA to influence Tex STEM and viral control during a protracted infection.SIGNIFICANCE: This study examines systemic metabolite changes during acute and chronic viral infections. Notably, we identified an early, transient nutrient shift in chronic infection, marked by an increase in medium- and long-chain fatty acid related species. Concomitantly, a virus-specific stem-like T cell population, essential for maintaining other T cells, displayed high lipid avidity and was capable of metabolizing exogenous fatty acids. Administering fatty acids late in chronic infection, when endogenous lipid levels had normalized, expanded this stem-like T cell population and enhanced their mitochondrial fitness. These findings highlight the potential role of fatty acids in regulating stem-like T cells in chronic settings and offer a valuable resource for studying other metabolic signatures in both acute and persistent infections.PMID:39416134 | PMC:PMC11483027 | DOI:10.1101/2024.10.07.617124

bioRxiv [Preprint]. 2024 Oct 10:2024.10.07.617109. doi: 10.1101/2024.10.07.617109.ABSTRACTDespite extensive efforts, extracting information on medication exposure from clinical records remains challenging. To complement this approach, we developed the tandem mass spectrometry (MS/MS) based GNPS Drug Library. This resource integrates MS/MS data for drugs and their metabolites/analogs with controlled vocabularies on exposure sources, pharmacologic classes, therapeutic indications, and mechanisms of action. It enables direct analysis of drug exposure and metabolism from untargeted metabolomics data independent of clinical records. Our library facilitates stratification of individuals in clinical studies based on the empirically detected medications, exemplified by drug-dependent microbiota-derived N -acyl lipid changes in a human immunodeficiency virus cohort. The GNPS Drug Library holds potential for broader applications in drug discovery and precision medicine.PMID:39416075 | PMC:PMC11482764 | DOI:10.1101/2024.10.07.617109

Comput Struct Biotechnol J. 2024 Sep 17;23:3454-3466. doi: 10.1016/j.csbj.2024.09.010. eCollection 2024 Dec.ABSTRACTThe advent of the genomics era enabled the generation of high-throughput data and computational methods that serve as powerful hypothesis-generating tools to understand the genomic and gene functional basis of plant stress resilience. The proliferation of experimental and analytical methods used in biology has resulted in a situation where plentiful data exists, but the volume and heterogeneity of this data has made analysis a significant challenge. Current advanced deep-learning models have displayed an unprecedented level of comprehension and problem-solving ability, and have been used to predict gene structure, function and expression based on DNA or protein sequence, and prominently also their use in high-throughput phenomics in agriculture. However, the application of deep-learning models to understand gene regulatory and signalling behaviour is still in its infancy. We discuss in this review the availability of data resources and bioinformatic tools, and several applications of these advanced ML/AI models in the context of plant stress response, and demonstrate the use of a publicly available LLM (ChatGPT) to derive a knowledge graph of various experimental and computational methods used in the study of plant stress. We hope this will stimulate further interest in collaboration between computer scientists, computational biologists and plant scientists to distil the deluge of genomic, transcriptomic, proteomic, metabolomic and phenomic data into meaningful knowledge that can be used for the benefit of humanity.PMID:39415960 | PMC:PMC11480249 | DOI:10.1016/j.csbj.2024.09.010

Front Pharmacol. 2024 Oct 2;15:1452921. doi: 10.3389/fphar.2024.1452921. eCollection 2024.ABSTRACTThe gut microbiota may help mitigate bone loss linked to postmenopausal osteoporosis by affecting the immune and inflammatory responses and the gut-bone axis. Dihydromyricetin (DMY), a natural flavonoid, has some anti-inflammatory and antioxidant properties. This study aimed to investigate the mechanisms underlying the amelioration of bone loss in ovariectomized (OVX) mice treated with various doses of DMY. Eight-week-old C57/BL6 mice underwent ovariectomy and received varying DMY doses over 8 weeks. Thereafter, femoral bone microarchitecture, serum biomarker levels, and colon samples were analyzed to assess bone metabolism and inflammatory and hormonal responses. Fecal samples were subjected to 16S rDNA sequencing, and short-chain fatty acids were quantified. An untargeted metabolomics approach was applied to both serum and fecal samples to investigate alterations in the intestinal microbiota and metabolic profiles following DMY treatment in the OVX mice. The results show high-dose DMY has anti-osteoporotic effects. Compared to the OVX group, the DMY-treated group showed enhanced bone mineral density and reduced inflammation and colonic damage levels. The DMY treatment altered the gut microbiota composition, including the relative abundances at both the phylum and genus levels. In addition, DMY treatment increased the production of acetate and propionate. Metabolomic analysis revealed differential regulation of 37 and 70 metabolites in the serum and feces samples, respectively, in the DMY-treated group compared to those in the OVX group, affecting the serotonergic signaling, arachidonic acid metabolism, and unsaturated fatty acid biosynthesis pathways. In conclusion, these findings indicate that DMY can ameliorate bone loss in OVX mice via the gut-bone axis.PMID:39415843 | PMC:PMC11479887 | DOI:10.3389/fphar.2024.1452921

Microb Biotechnol. 2024 Oct;17(10):e70026. doi: 10.1111/1751-7915.70026.ABSTRACTFusarium wilt is one of the major constraints on global watermelon production, and Fusarium oxysporum f. sp. niveum (Fon) is the causative agent of Fusarium wilt in watermelon and results in severe yield and quality losses worldwide. The enhancement of antifungal activity from antagonistic bacteria against Fon is highly practical for managing Fusarium wilt in watermelon. The aim of this study was to maximize the antifungal activity of Bacillus velezensis LZN01 by optimizing fermentation conditions and analysing its regulatory mechanism via transcriptome sequencing. The culture and fermentation conditions for strain LZN01 were optimized by single-factor and response surface experiments. The optimum culture conditions for this strain were as follows: the addition of D-fructose at 35 g/L and NH4Cl at 5 g/L in LB medium, pH 7, and incubation at 30°C for 72 h. The fungal inhibition rate for strain LZN01 reached 71.1%. The improvement of inhibition rate for strain LZN01 in optimization fermentation was supported by transcriptomic analysis; a total of 491 genes were upregulated, while 736 genes were downregulated. Transcriptome analysis revealed that some differentially expressed genes involved in carbon and nitrogen metabolism, oxidation-reduction, fatty acid and secondary metabolism; This optimization process could potentially lead to significant alterations in the production levels and types of antimicrobial compounds by the strain. Metabolomics and UPLC/Q-Exactive Orbitrap MS analysis revealed that the production yields of antimicrobial compounds, such as surfactin, fengycin, shikimic acid, and myriocin, increased or were detected in the cell-free supernatant (CFS) after the fermentation optimization process. Our results indicate that fermentation optimization enhances the antifungal activity of the LZN01 strain by influencing the expression of genes responsible for the synthesis of antimicrobial compounds.PMID:39415743 | DOI:10.1111/1751-7915.70026

Curr Pharm Des. 2024 Oct 16. doi: 10.2174/0113816128333694240928161703. Online ahead of print.ABSTRACTDiabetic nephropathy (DN) is increasing worldwide in parallel with type 2 diabetes mellitus. Identifying diagnostic biomarkers for DN at an early stage is crucial due to the considerable societal and economic burden associated with diabetes mellitus (DM) and its risk factors. In the past, early indicators of microvascular problems, such as microalbuminuria (MA), have been used to predict the possibility of developing advanced chronic kidney disease (CKD). However, because of the incapacity of MA to appropriately estimate DN, particularly, non-albuminuric DN, additional markers have been suggested for recognizing the early renal abnormalities and structural lesions, even before MA. This study aims to assess the existing and future biomarkers used to diagnose or predict early DN. This review provides comprehensive insight into diagnostic approaches for early detection of CKD, addressing the following areas: (i) markers of glomerular damage, (ii) markers of tubular damage, (iii) oxidative stress biomarkers, (iv) inflammatory biomarkers and (v) futuristic biomarkers such as micro-ribonucleic acids (miRNAs), proteomics, metabolomics and genomics and gut microbiota. Early detection of DN may lead to improvement in clinical management and quality of life, emphasizing the importance of identifying a specific and reliable predictive biomarker. Emerging serum and urinary biomarkers offer promise for early DN diagnosis, potentially reducing prevalence and preventing progression to end-stage renal disease (ESRD). Further advancements in miRNAs, proteomics, metabolomics genomics and gut microbiota offer prospects for even earlier and more precise DN diagnosis.PMID:39415582 | DOI:10.2174/0113816128333694240928161703

Magn Reson Chem. 2024 Oct 16. doi: 10.1002/mrc.5488. Online ahead of print.ABSTRACTDiffusion-ordered NMR spectroscopy (DOSY) is a powerful tool to analyse mixtures. Spatially encoded (SPEN) DOSY enables recording a full DOSY dataset in just one scan by performing spatial parallelisation of the gradient dimension. The simplest and most widely used approach to processing DOSY data is to fit each peak in the spectrum with a single or multiple exponential decay. However, when there is peak overlap, and/or when the diffusion decays of the contributing components are too similar, this method has limitations. Multivariate analysis of DOSY data, which is an attractive alternative, consists of decomposing the experimental data, into compound-specific diffusion decays and 1D NMR spectra. Multivariate analysis has been very successfully used for conventional DOSY data, but its use for SPEN DOSY data has only recently been reported. Here, we present a comparison, for SPEN DOSY data, of two widely used algorithms, SCORE and OUTSCORE, that aim at unmixing the spectra of overlapped species through a least square fit or a cross-talk minimisation, respectively. Data processing was performed with the General NMR Analysis Toolbox (GNAT), with custom-written code elements that now expands the capabilities, and makes it possible to import and process SPEN DOSY data. This comparison is demonstrated on three different two-component mixtures, each with different characteristics in terms of signal overlap, diffusion coefficient similarity, and component concentration.PMID:39415466 | DOI:10.1002/mrc.5488

Am J Epidemiol. 2024 Oct 16:kwae400. doi: 10.1093/aje/kwae400. Online ahead of print.ABSTRACTOur study aimed to investigate the impact of tea and coffee consumption and related metabolomic signatures on dynamic transitions from diabetes-free status to incident type 2 diabetes (T2D), and subsequently to T2D-related complications and death. We included 438,970 participants in the UK Biobank who were free of diabetes and diabetes complications at baseline. Of these, 212,146 individuals had information on all metabolic biomarkers. We identified tea- and coffee-related metabolomic signatures using elastic net regression models. We examined associations of tea and coffee intake and related metabolomic signatures with the onset and progression of T2D using multi-state regression models. We observed that tea and coffee consumption and related metabolomic signatures were inversely associated with the risk of five T2D transitions. For example, HRs (95% CIs) per SD increase of the tea-related metabolomic signature were 0.87 (0.85, 0.89), 0.97 (0.95, 0.99), 0.91 (0.90, 0.92), 0.92 (0.91, 0.94), and 0.91 (0.90, 0.92) for transitions from diabetes-free state to incident T2D, from diabetes-free state to total death, from incident T2D to T2D complications, from incident T2D to death, and from T2D complications to death. These findings highlight the benefit of tea and coffee intake in reducing the risk of occurrence and progression of T2D.PMID:39415441 | DOI:10.1093/aje/kwae400

Biofactors. 2024 Oct 16. doi: 10.1002/biof.2132. Online ahead of print.ABSTRACTMitochondrial dysfunction may precipitate intestinal dysfunction, while inflammatory bowel disease manifests as a chronic inflammatory ailment affecting the gastrointestinal tract. This condition disrupts the barrier function of the intestinal epithelium and alters metabolic products. Increasing mitochondrial adenosine triphosphate (ATP) synthesis in intestinal epithelial cells presents a promising avenue for colitis treatments. Nevertheless, the impact of cedrol on ATP and the intestinal barrier remains unexplored. Hence, this study is dedicated to examining the cedrol's protective effect on an inflammatory cocktail (IC)-induced intestinal epithelial barrier dysfunction in Caco-2 cells. The finding reveals that cedrol enhances ATP content and the transepithelial electrical resistance value in the intestinal epithelial barrier. Moreover, cedrol mitigates the IC-induced decrease in the messenger ribonucleic acid (mRNA) expression of tight junction proteins (ZO-1, Occludin, and Claudin-1), thereby ameliorating intestinal epithelial barrier dysfunction. Furthermore, nuclear magnetic resonance (NMR)-based metabolomic analysis indicated that IC-exposed Caco-2 cells are restored by cedrol treatments. Notably, cedrol elevates metabolites such as amino acids, thereby enhancing the intestinal barrier. In conclusion, cedrol alleviates IC-induced intestinal epithelial barrier dysfunction by promoting ATP-dependent proliferation of Caco-2 cells and bolstering amino acid levels to sustain tight junction messenger ribonucleic acid expression.PMID:39415440 | DOI:10.1002/biof.2132