PubMed

Microb Pathog. 2024 Oct 30:107093. doi: 10.1016/j.micpath.2024.107093. Online ahead of print.ABSTRACTBACKGROUND: Persistent lymphopenia can be regarded as an important index of acquired immune dysfunction in sepsis. Whether the specific immune factor changes in septic patients with lymphopenia and the correlation to gut microbiota and metabolites remain unclear.METHODS: This single-center prospective observation conducted lymphocyte subgroup analysis of blood samples and 16S rRNA gene amplicons sequencing and untargeted metabolomics analysis of fecal samples from 36 subjects with the persistent (≥3d) (n=21) and non-persistent lymphopenia (<3d) (n=15).RESULTS: The persistent lymphopenia showed higher the 28d mortality and 90d mortality, while significantly lower CD3+T/LY, CD3+T cells, CD3+CD4+T cells, CD3+CD8+T cells, Th1 cells, Th2 cells, CD45RA+Treg cells. The 16S rRNA results showed that Staphylococcus, Peptostreptococcus, Bulleidia, Leuconostoc were significant enriched in the persistent lymphopenia. The metabolomics analysis showed that α-Ketoisovaleric acid was increased and 7-DHCA, α-MCA, β-MCA, HCA, LCA-3S, CA, UCA and Citramalic acid were decreased in the persistent lymphopenia.CONCLUSION: In the process of interaction between host receptors and gut microbiota in patients with persistent lymphopenia sepsis, with a significant reduction in gut microbiota diversity and bile acid metabolites. That can affect various inflammatory pathways of gut immune cells, causing immune dysfunction in the body, which may be one of the main causes of death.PMID:39486555 | DOI:10.1016/j.micpath.2024.107093

J Nutr. 2024 Oct 30:S0022-3166(24)01120-9. doi: 10.1016/j.tjnut.2024.10.043. Online ahead of print.ABSTRACTDiet affects the intestinal microbiota. Increasingly, research is linking the intestinal microbiota to various human health outcomes. Consumption of traditional prebiotics (inulin, fructooligosaccharides, and galactooligosaccharides) confers health benefits through substrate utilization by select intestinal microorganisms, namely Bifidobacterium and Lactobacilli. A similar but distinct concept focused on microorganisms to support human health is through direct consumption of certain live microorganisms recognized as probiotics, which classically include Lactobacilli or Bifidobacterium strains. With advances in sequencing technologies and culturing techniques, other novel functional intestinal microorganisms are being increasingly identified and studied to determine how they may underpin human health benefits. These novel microorganisms are targeted for enrichment within the autochthonous intestinal microbiota through dietary approaches and are also gaining interest as next-generation probiotics because of their purported beneficial properties. Thus, characterizing dietary approaches that nourish select microorganisms in situ is necessary to propel biotic-focused research forward. As such, we reviewed the literature to summarize findings on dietary approaches that nourish the human intestinal microbiota and benefit health to help fill the gap in knowledge on the connections between certain microorganisms, the metabolome, and host physiology. The overall objective of this systematic review was to summarize the impact of dietary interventions with the propensity to nourish certain intestinal bacteria, affect microbial metabolite concentrations, and support gastrointestinal, metabolic, and cognitive health in healthy adults. Findings from the 17 randomized controlled studies identified in this systematic review indicated that dietary interventions providing dietary fibers, phytonutrients, or unsaturated fatty acids differentially enriched Akkermansia, Bacteroides, Clostridium, Eubacterium, Faecalibacterium, Roseburia, and Ruminococcus, with variable effects on microbial metabolites, and subsequent associations with physiological markers of gastrointestinal and metabolic health. These findings have implications for biotic-focused research on candidate prebiotic substrates as well as next-generation probiotics.PMID:39486521 | DOI:10.1016/j.tjnut.2024.10.043

Radiother Oncol. 2024 Oct 30:110608. doi: 10.1016/j.radonc.2024.110608. Online ahead of print.ABSTRACTBACKGROUND AND PURPOSE: Radiation-induced intestinal injury (RIII) compromises the clinical utility of pelvic radiotherapy (RT). We aimed to explore the protective effect and underlying mechanism of (-)-epigallocatechin-3-gallate (EGCG) on RIII.MATERIALS AND METHODS: We evaluated the protective effect of EGCG on intestine in RIII mouse model and pelvic cancer patients, while explored the underlying mechanism through (1) 16S rRNA sequencing, (2) metabolomic profiles, (3) fresh sterile fecal filtrate (SFF) transplantation, and (4) transcriptome sequencing.RESULTS: EGCG efficiently prevented RIII in mouse, as reflected by improved survival, alleviated intestinal structure damage, promoted intestinal regeneration, and ameliorated gut microbiota dysbiosis. Prophylactic EGCG intervention reduced the severity of RIII in patients receiving pelvic RT. Mechanistically, the protective effect of EGCG could be transferred to other mice by SFF transplantation. EGCG enriched gut microbiota-derived metabolite D-tagatose, and oral administration of D-tagatose reproduced the radio-protective effect of EGCG via activating AMPK.CONCLUSION: Oral EGCG may be a promising strategy for preventing RIII clinically, and warrant further investigation in prospective randomized phase III trials.PMID:39486483 | DOI:10.1016/j.radonc.2024.110608

J Pharm Biomed Anal. 2024 Oct 28;253:116553. doi: 10.1016/j.jpba.2024.116553. Online ahead of print.ABSTRACTColitis-associated colorectal cancer (CAC) is fatal and can develop spontaneously or as a complication of inflammatory bowel diseases. Although co-administration of azoxymethane/dextran sulfate sodium (AOM/DSS) is a classic method for CAC modeling, its limitations need to be addressed. Accordingly, we aimed to optimize the AOM/DSS model to study CAC extensively and further investigate its pathogenic mechanisms relative to microbiota and metabolism. We optimized the CAC model via a single or enhanced injection of AOM combined with different administration modes and varying DSS concentrations. Subsequently, the fecal-microbiota composition was examined using 16S RNA sequencing, and fecal-colon-metabolome profiles were evaluated via ultra-high performance liquid chromatography-mass spectrometry. Two interval injections of AOM combined with 1.5 % DSS-free drinking resulted in a high tumor formation rate, uniform tumor formation, and low mortality. Based on this model, we innovatively divided the pathogenesis of CAC into three stages, namely inflammation induction, proliferation initiation, and tumorigenesis, and examined the pathological characteristics in each stage. Gut microbial dysbiosis and metabolic alteration drove colorectal tumorigenesis by aggravating inflammation while promoting cell proliferation and carcinogenesis in mice. For the first time, we dynamically demonstrated the process of colon "inflammation to cancer" transformation and provided novel insights to clarify the role of amino acid metabolism in the formation of CAC.PMID:39486392 | DOI:10.1016/j.jpba.2024.116553

J Hazard Mater. 2024 Oct 29;480:136357. doi: 10.1016/j.jhazmat.2024.136357. Online ahead of print.ABSTRACTThe use of nano-chemicals in agriculture has been shown to enhance crop production through soil additions or foliar sprays. However, the accumulation pattern, translocation efficiency, mode of action of nanomaterials (NMs) via different application methods remain unclear. In this study, wheat was treated with CuO-NPs/CeO2-NPs (50 and 100 nm) for 21 days using soil and foliar application separately. Foliar spray resulted in higher accumulation and more efficient translocation of NMs compared to soil addition. Smaller NMs exhibited higher accumulation and transfer capabilities under the same application method. The accumulation of CuO-NPs was approximately 20 times greater than that of CeO2-NPs, particularly under the soil addition treatment. Scanning electron microscopy analysis demonstrated that NMs could directly enter wheat leaves via stomata during foliar application. Wheat growth was inhibited by roughly 15 % following CuO-NPs exposure, whereas no significant effects on growth were observed with CeO2-NPs. By integrating nontargeted metabolomics analysis with targeted physiological characteristics assessments, it was revealed that CuO-NPs mainly disturbed nitrogen metabolism pathways and induced oxidative damage. In contrast, CeO2-NPs enhanced carbohydrates related biological processes such as starch and sucrose metabolism, glycolysis, and TCA cycle, which are crucial for carbon metabolism. These findings suggest that the type of nanomaterial is a crucial factor to consider when evaluating their foliar or soil application in agriculture.PMID:39486329 | DOI:10.1016/j.jhazmat.2024.136357

J Hazard Mater. 2024 Oct 30;480:136370. doi: 10.1016/j.jhazmat.2024.136370. Online ahead of print.ABSTRACTTriclocarban (TCC) is a widely used antimicrobial agent and known endocrine-disrupting chemical found in various products. While its potential toxicities on endocrine-related organs have been highlighted in previous studies, the effects of TCC on non-endocrine organs, particularly the spleen, remain largely unknown. Here, we employed a novel approach combining long-term TCC exposure in a mouse model with spatial metabolomics and lipidomics to investigate the effects of TCC on the spleen. Our results showed that TCC exposure significantly altered the splenic organ weight and coefficient and induced obvious pathological alterations. Omic analysis revealed that TCC exposure disrupted the splenic homeostasis, as indicated by the upregulation of glutathione metabolism, ceramide-to-sphingomyelin signaling and biosynthesis of glycerophospholipids. Notably, the data of mass spectrometry imaging (MSI) revealed that TCC accumulated in the red pulp of the mouse spleen, while its metabolites concentrated in the white pulp. Further MSI analyses identified region-specific metabolic disruptions, including upregulated ceramide signaling in the red pulp, indicating localized inflammation, and upregulated glutathione metabolism throughout the spleen, suggesting widespread oxidative damage. Our findings provide crucial insights into the spatial distribution and biochemical impact of TCC on mice spleens, highlighting the potential risks of long-term TCC exposure to immune function.PMID:39486321 | DOI:10.1016/j.jhazmat.2024.136370

Clin Rheumatol. 2024 Nov 1. doi: 10.1007/s10067-024-07201-1. Online ahead of print.ABSTRACTRheumatoid arthritis (RA) is widespread globally, with the emergence of metabolites derived from both the host and microbes playing a pivotal role in its pathogenesis. This study aims to elucidate the relationships between serum metabolites and the immunological and clinical features of RA. Serum samples were collected from 35 RA patients and 37 healthy controls (HC). Metabolite profiling was performed using gas chromatography-mass spectrometry (GC/MS). Principal component analysis revealed a significant distinction between the RA and HC cohorts. Employing univariate statistical analysis, we identified 36 differential metabolites. Among these, 9 metabolites, including galactose and glucose, were found to be enriched, while the remaining metabolites, such as citric acid, fumaric acid, and inosine, were depleted in RA. These diverse metabolites encompassed various metabolic processes, including the biosynthesis of fatty acids, amino acids, and glucose. The enrichment of glucose and galactose in RA exhibited a substantial correlation with elevated IgG levels, as determined through correlation analysis. Conversely, the depletion of citric acid was correlated with elevated levels of C3 and CRP. Methionine, which also declined in RA patients, displayed a negative correlation with ESR. Furthermore, galactose and glucose exhibited significant positive correlations with naïve B cells, while the decreased eicosanoic acid level in RA was significantly associated with an increase in natural killer cells. Our findings suggest that the altered serum metabolite profile in RA is closely linked to disease severity and the dysregulated immune responses observed in RA patients. Key Points • Identified nine metabolites with upregulated expression and twenty-seven metabolites with downregulated expression. • Established a correlation between alterations in serum metabolite levels and inflammatory markers in RA patients. • Discovered a significant association between changes in serum metabolites and immune cell profiles in RA patients.PMID:39485556 | DOI:10.1007/s10067-024-07201-1

Bioresour Bioprocess. 2024 Nov 1;11(1):105. doi: 10.1186/s40643-024-00817-w.ABSTRACTComparative transcriptomics uncovered distinct expression patterns of genes associated with cofactor and vitamin metabolism in the high-yielding mutant strain Saccharopolyspora erythraea HL3168 E3, as compared to the wild-type NRRL 2338. An in-depth analysis was conducted on the effects of nine vitamins, and it was determined that thiamine pyrophosphate (TPP), vitamin B2, vitamin B6, vitamin B9, vitamin B12, and hemin are key enhancers in erythromycin production in E3, increasing the erythromycin titer by 7.96-12.66%. Then, the Plackett-Burman design and the path of steepest ascent were applied to further optimize the vitamin combination for maximum production efficiency, enhancing the erythromycin titer in shake flasks by 39.2%. Otherwise, targeted metabolomics and metabolic flux analysis illuminated how vitamin supplementation modulates the central carbon metabolism with notable effects on the TCA cycle and methionine synthesis to augment the provision of energy and precursors essential for erythromycin synthesis. This work highlights the capacity for precise vitamin supplementation to refine metabolic pathways, thereby boosting erythromycin production, and provides valuable directions for application on an industrial scale.PMID:39485551 | DOI:10.1186/s40643-024-00817-w

Acta Diabetol. 2024 Nov 1. doi: 10.1007/s00592-024-02336-8. Online ahead of print.ABSTRACTAIMS: Diabetic retinopathy (DR) is a severe complication of diabetes mellitus (DM), and it is challenging to diagnose DR at an early stage by conventional methods. The aim of the present work is to propose an innovative approach to monitor the process of DR from scratch.METHODS: The plasma metabolites changed with DM were obtained by time-dependent metabolomics and lipidomics; the change of retinal function was measured by b-wave amplitude and total Ops-wave amplitude in electroretinography (ERG). Multivariate statistical analysis, logistic regression and correlation analysis were employed to identify metabolic markers from metabolites for the monitoring of DR and investigate the relationship between metabolic markers and retinal function.RESULTS: The metabolic markers LPE18:0, LPC15:0, SM d14:2/26:0, SM d12:0/28:2 and MG 21:0 associated with DR can be utilized as metabolic markers to monitor the process of DR; The decrease in myo-inositol and LPC22:5 and increase in xylonic acid and TAG10:0/16:0/18:1 indicated retinal dysfunction.CONCLUSIONS: The levels of metabolic markers can be used as an indicator of the onset of DR or as a means of monitoring changes in retinal function.PMID:39485549 | DOI:10.1007/s00592-024-02336-8

J Proteome Res. 2024 Nov 1. doi: 10.1021/acs.jproteome.4c00437. Online ahead of print.ABSTRACTThe hospitalization and mortality rates of patients gradually increase following the onset and progression of liver cirrhosis (LC). We aimed to help define clinical stage and better target interventions by detecting the expression of specific metabolites in patients with different stages of LC via Q Exactive hybrid quadrupole orbitrap mass spectrometry (UPLC-Q-Exactive) technology. This noninterventional observation case-control study involved 139 patients with LC or acute-on-chronic liver failure (ACLF) in a Chinese hospital between October 2022 and April 2023. Serum specimens were analyzed for multiple metabolite levels using UPLC-Q-Exactive. Data were processed to screen for differentially accumulated metabolites (DAMs). Short time-series expression miner (STEM) analysis and enrichment analysis were performed to assess cirrhosis progression biomarkers. Following univariate and multivariate analyses, a Venn diagram indicated nine significant DAMs in common among groups. STEM analysis showed 8'-hydroxyabscisic acid, HDCA, pyruvate-3-phosphate, indospicine, eplerenone, and DEHP as significant; their levels first peaked [Child-Turcotte-Pugh (CTP) class B peaked] and then decreased with CTP grade aggravation. Significant differences among 8'-hydroxyabscisic acid, eplerenone, and DEHP were observed among LC comorbidities and between subgroups. Therefore, serum levels of six DAMs may characterize metabolomic changes, determine the severity of LC, and predict the development of ACLF.PMID:39485280 | DOI:10.1021/acs.jproteome.4c00437

Elife. 2024 Nov 1;13:RP94811. doi: 10.7554/eLife.94811.ABSTRACTThe mRNA 5'-cap structure removal by the decapping enzyme DCP2 is a critical step in gene regulation. While DCP2 is the catalytic subunit in the decapping complex, its activity is strongly enhanced by multiple factors, particularly DCP1, which is the major activator in yeast. However, the precise role of DCP1 in metazoans has yet to be fully elucidated. Moreover, in humans, the specific biological functions of the two DCP1 paralogs, DCP1a and DCP1b, remain largely unknown. To investigate the role of human DCP1, we generated cell lines that were deficient in DCP1a, DCP1b, or both to evaluate the importance of DCP1 in the decapping machinery. Our results highlight the importance of human DCP1 in decapping process and show that the EVH1 domain of DCP1 enhances the mRNA-binding affinity of DCP2. Transcriptome and metabolome analyses outline the distinct functions of DCP1a and DCP1b in human cells, regulating specific endogenous mRNA targets and biological processes. Overall, our findings provide insights into the molecular mechanism of human DCP1 in mRNA decapping and shed light on the distinct functions of its paralogs.PMID:39485278 | DOI:10.7554/eLife.94811

J Infect Dis. 2024 Nov 1:jiae533. doi: 10.1093/infdis/jiae533. Online ahead of print.ABSTRACTBACKGROUND: In the cervicovaginal environment, HPV acquisition and cervical cancer progression are linked to non-Lactobacillus dominance, of which Atopobiaceae are key taxa. We hypothesize that Atopobiaceae modulates the cervicovaginal microenvironment to promote HPV persistence and progression to cancer. However, the extent to which Atopobiaceae impact the immunometabolic microenvironment is poorly understood.METHODS: We investigated Atopobiaceae in a cohort of primarily Hispanic and non-Hispanic White women who were HPV-negative (n=20), HPV-positive (n=31) without dysplasia, diagnosed with cervical dysplasia (n=38), or newly diagnosed with invasive cervical carcinoma (n=9). Microbiome data was integrated with clinical and demographic surveys, immunoproteomics, and metabolomics data.RESULTS: Atopobiaceae identified were Fannyhessea vaginae, Fannyhessea massiliense, Fannyhessea species type 2, Lancefieldella deltae, and an unclassified species. A higher prevalence of Atopobiaceae was observed in women who were Hispanic and had higher gravidity and parity. F. species type 2 and F. vaginae were observed with infections of high-risk HPV genotypes 31 and 52. Atopobiacaeae were negatively correlated with Lactobacillus and positively correlated to Sneathia, Dialister, Anaerococcus, Prevotella, and Bifidobacterium/Gardnerella. Proinflammatory cytokines (IL-1α, IL-1β, IL-12, TNFα), immune checkpoint proteins (PD-L1, LAG3), and cancer biomarkers (CEA, MIF, TRAIL) were positively associated with Atopobiaceae-rich profiles. Pro-oncogenic metabolites, including 4-hydroxybutyrate and sphingosine, were also elevated in women colonized by Atopobiaceae.CONCLUSIONS: Our data implicate Atopobiaceae in lipid modulation, oxidative stress, inflammatory responses, and immune evasion, which may contribute to cancer. This study highlights a key family of pathogenic cervicovaginal bacteria that could be exploited to monitor HPV persistence and/or targeted to prevent HPV-mediated cancer.PMID:39485269 | DOI:10.1093/infdis/jiae533

J Agric Food Chem. 2024 Nov 1. doi: 10.1021/acs.jafc.4c08203. Online ahead of print.ABSTRACTPostbiotics have emerged as a promising alternative to probiotics. However, it remains unclear whether postbiotics can exert regulatory effects on intestinal flora and metabolism as probiotics. Thus, we investigated the effects of probiotic and postbiotic in rats with whey protein-induced food allergy, which demonstrated that postbiotic intervention effectively alleviated allergy symptoms, reduced serum immunoglobulin E (IgE) and mast cell protease-1 (mMCP-1) levels, and regulated the type helper 1 cell/2 cell (Th1/Th2) balance in both serum and spleen. Metagenomic analysis revealed that postbiotics induced more significant changes in intestinal flora. Untargeted metabolomics analysis showed that both probiotics and postbiotics significantly up-regulated various differential metabolites, which were negatively correlated with immune indices, including malvidin-3-glucoside, 3,4-dihydroxymandelic acid, nicotinamide, triterpenoids, pirbuterol, and 4-hydroxybenzoic acid. This study confirms that postbiotics can alleviate food allergies and regulate intestinal flora and metabolites, which provides a valuable reference for the use of postbiotics in mitigating allergic diseases through gut microbiota and metabolite modulation.PMID:39485064 | DOI:10.1021/acs.jafc.4c08203

Virulence. 2024 Nov 1:2422540. doi: 10.1080/21505594.2024.2422540. Online ahead of print.ABSTRACTBACKGROUND: Liver metabolites are involved in the progression of rheumatoid arthritis (RA), indicating a connection between the liver and joints. However, the impact and mechanism of Hepatitis B virus (HBV), a hepatotropic virus, on RA are still unclear.METHODS: We investigated the correlation between HBV and RA using Mendelian randomization analysis. Single-cell transcriptome analysis was conducted to investigate changes in cell subtypes in synovial tissue of HBV-RA patients. Fibroblast-like synoviocytes (FLS) were used to create a cell model, and the transcriptome was examined to identify the key downstream molecules of FMT regulated by HBx. CIA model was constructed using HBV transgenic, HBx transgenic, and TRADF1 knockout mice to investigate the impact and mechanism of HBV on CIA.RESULTS: The results of our study revealed a significant positive correlation between HBV and RA. The functional studies identified a crucial role of fibroblast-myofibroblast transition (FMT) in the progression of RA. The results suggest that HBV-encoded HBx may promote FMT in RA by upregulating TRAFD1. Furthermore, trans-ferulic acid (TFA) was identified by screening for common metabolites in the liver, joints, and peripheral blood using the metabolome and WGCNA. Interestingly, we found that TFA ameliorated HBx-induced RA by suppressing TRAFD1 expression.CONCLUSIONS: Our study demonstrates that hidden liver-joint axis, an imbalance between TFA and HBx, plays a critical role in HBV-induced RA, which could be a potential strategy for preventing RA development.PMID:39484999 | DOI:10.1080/21505594.2024.2422540

Mater Horiz. 2024 Nov 1. doi: 10.1039/d4mh01124d. Online ahead of print.ABSTRACTInfection is the most prevalent complication of fractures, particularly in open fractures, and often leads to severe consequences. The emergence of bacterial resistance has significantly exacerbated the burden of infection in clinical practice, making infection control a significant treatment challenge for infectious bone defects. The implantation of a structural stent is necessary to treat large bone defects despite the increased risk of infection. Therefore, there is a need for the development of novel antibacterial therapies. The advancement in antibacterial biomaterials and new antimicrobial drugs offers fresh perspectives on antibacterial treatment. Although antimicrobial 3D scaffolds are currently under intense research focus, relying solely on material properties or antibiotic action remains insufficient. Antimicrobial peptides (AMPs) are one of the most promising new antibacterial therapy approaches. This review discusses the underlying mechanisms behind infectious bone defects and presents research findings on antimicrobial peptides, specifically emphasizing their mechanisms and optimization strategies. We also explore the potential prospects of utilizing antimicrobial peptides in treating infectious bone defects. Furthermore, we propose that artificial intelligence (AI) algorithms can be utilized for predicting the pharmacokinetic properties of AMPs, including absorption, distribution, metabolism, and excretion, and by combining information from genomics, proteomics, metabolomics, and clinical studies with computational models driven by machine learning algorithms, scientists can gain a comprehensive understanding of AMPs' mechanisms of action, therapeutic potential, and optimizing treatment strategies tailored to individual patients, and through interdisciplinary collaborations between computer scientists, biologists, and clinicians, the full potential of AI in accelerating the discovery and development of novel AMPs will be realized. Besides, with the continuous advancements in 3D/4D/5D/6D technology and its integration into bone scaffold materials, we anticipate remarkable progress in the field of regenerative medicine. This review summarizes relevant research on the optimal future for the treatment of infectious bone defects, provides guidance for future novel treatment strategies combining multi-dimensional printing with new antimicrobial agents, and provides a novel and effective solution to the current challenges in the field of bone regeneration.PMID:39484845 | DOI:10.1039/d4mh01124d

Vet Med Int. 2024 Oct 24;2024:4125118. doi: 10.1155/2024/4125118. eCollection 2024.ABSTRACTThe livestock industry faces significant challenges, with disease outbreaks being a particularly devastating issue. These diseases can disrupt the food supply chain and the livelihoods of those involved in the sector. To address this, there is a growing need to enhance the health and well-being of livestock animals, ultimately improving their performance while minimizing their environmental impact. To tackle the considerable challenge posed by disease epidemics, multiomics approaches offer an excellent opportunity for scientists, breeders, and policymakers to gain a comprehensive understanding of animal biology, pathogens, and their genetic makeup. This understanding is crucial for enhancing the health of livestock animals. Multiomic approaches, including phenomics, genomics, epigenomics, metabolomics, proteomics, transcriptomics, microbiomics, and metaproteomics, are widely employed to assess and enhance animal health. High-throughput phenotypic data collection allows for the measurement of various fitness traits, both discrete and continuous, which, when mathematically combined, define the overall health and resilience of animals, including their ability to withstand diseases. Omics methods are routinely used to identify genes involved in host-pathogen interactions, assess fitness traits, and pinpoint animals with disease resistance. Genome-wide association studies (GWAS) help identify the genetic factors associated with health status, heat stress tolerance, disease resistance, and other health-related characteristics, including the estimation of breeding value. Furthermore, the interaction between hosts and pathogens, as observed through the assessment of host gut microbiota, plays a crucial role in shaping animal health and, consequently, their performance. Integrating and analyzing various heterogeneous datasets to gain deeper insights into biological systems is a challenging task that necessitates the use of innovative tools. Initiatives like MiBiOmics, which facilitate the visualization, analysis, integration, and exploration of multiomics data, are expected to improve prediction accuracy and identify robust biomarkers linked to animal health. In this review, we discuss the details of multiomics concerning the health and well-being of livestock animals.PMID:39484643 | PMC:PMC11527549 | DOI:10.1155/2024/4125118

Toxicol Rep. 2024 Oct 9;13:101760. doi: 10.1016/j.toxrep.2024.101760. eCollection 2024 Dec.ABSTRACTGarlic (Allium sativum) has been traditionally valued for its medicinal properties attributed to the presence of organosulfur compounds. Despite its benefits, concerns about herbal extract toxicity have arisen, necessitating safety assessment . This study was designed to evaluate the chemical analysis and safety profile of Alliin-Rich Garlic Extract (ARGE) using Drosophila melanogaster as a model organism. The ARGE was extracted from garlic cloves (Allium sativum Linn: UIH-23262) using a microwave-assisted method and characterized using UPLC-ESI-MS, 1H NMR, HPLC and IR. Its safety evaluation was determined using D. melanogaster (Harwich strain), and various assays were conducted on 1-3-day-old flies. Toxicological markers and oxidative stress were assessed to understand the impact of ARGE on the flies. Chemical profiling of ARGE using UPLC-ESI-MS, confirmed the presence of alliin (S-ally-L-cysteine-S-oxide), L-arginine, γ-glutamylmethionine, S-(2-carboxypropyl) glutathione, N-γ-glutamyl-S-(1-propenyl) cysteine, N-γ-glutamyl-S-(2-propenyl) cysteine, N-γ-glutamylphenylalanine, S-(allylthio) cysteine, γ-glutamyl-S-allylthiocysteine and eruboside B. HPLC confirmed an alliin content of 0.073 mg/g. Toxicological assessment in D. melanogaster revealed that ARGE enhanced antioxidant defenses by increasing total thiol levels and GST activity, while reducing acetylcholinesterase activity. No significant alteration was observed in catalase activity and cellular metabolic rate. Histological examination revealed no alterations in the histoarchitecture of the brain, fat body or gut of D. melanogaster. The study demonstrated the safety of ARGE in D. melanogaster, supporting its potential as a safe herbal remedy.PMID:39484636 | PMC:PMC11525231 | DOI:10.1016/j.toxrep.2024.101760

bioRxiv [Preprint]. 2024 Oct 22:2024.10.22.619724. doi: 10.1101/2024.10.22.619724.ABSTRACTMethane mitigation is regarded as a critical strategy to combat the scale of global warming. Currently, about 40% of methane emissions originate from microbial sources, which is causing strategies to suppress methanogens, either through direct toxic effects or by diverting their substrates and energy, to gain traction. Problematically, current microbial methane mitigation knowledge derives from rumen studies and lacks detailed microbiome-centered insights, limiting translation across ecosystems. Here we utilize genome-resolved metatranscriptomes and metabolomes to assess the impact of a proposed methane inhibitor, catechin, on greenhouse gas emissions for high-methane-emitting peatlands. In microcosms, catechin drastically reduced methane emissions by 72-84% compared to controls. Longitudinal sampling allowed for reconstruction of a novel catechin degradation pathway involving Actinomycetota and Clostridium, which break down catechin into smaller phenolic compounds within the first 21 days, followed by degradation of phenolic compounds by Pseudomonas_E from days 21 to 35. These genomes also co-expressed hydrogen-uptake genes, suggesting that hydrogenases may act as a hydrogen sink during catechin degradation, depriving methanogens of substrates. This was supported by decreased gene expression in hydrogenotrophic and hydrogen-dependent methylotrophic methanogens under catechin treatment. We also saw reduced gene expression from genomes inferred to be functioning syntrophically with hydrogen-utilizing methanogens. We propose that catechin metabolic redirection effectively starves hydrogen-utilizing methanogens, offering a potent avenue for curbing methane emissions across diverse environments including ruminants, landfills, and constructed or managed wetlands.PMID:39484614 | PMC:PMC11526919 | DOI:10.1101/2024.10.22.619724

bioRxiv [Preprint]. 2024 Oct 21:2024.10.17.618907. doi: 10.1101/2024.10.17.618907.ABSTRACTPURPOSE: Exposomes are critical drivers of carcinogenesis. However, how they modulate tumor behavior remains unclear. Extensive clinical data link cigarette smoke as a key exposome that promotes aggressive tumors, higher rates of metastasis, reduced response to chemoradiotherapy, and suppressed anti-tumor immunity. We sought to determine whether smoke itself can modulate aggressive tumor behavior in head and neck squamous cell carcinoma (HNSCC) through reprogramming the cellular reductive state.EXPERIMENTAL DESIGN: Using established human and murine HNSCC cell lines and syngeneic mouse models, we utilized conventional western blotting, steady state and flux metabolomics, RNA sequencing, quantitative proteomics and flow cytometry to analyze the impact of smoke exposure on HNSCC tumor biology.RESULTS: Cigarette smoke persistently activated Nrf2 target genes essential for maintenance of the cellular reductive state and survival under conditions of increased oxidative stress in HNSCC regardless of HPV status. In contrast to e-cigarette vapor, conventional cigarette smoke mobilizes cellular metabolism toward oxidative stress adaptation, resulting in development of cross-resistance to cisplatin. In parallel, smoke exposure modulates both expression of PDL1 and the secretory phenotype of HNSCC cells through activation of NF-κB resulting in an altered tumor immune microenvironment (TIME) in syngeneic mouse models and altered PBMC differentiation that includes downregulated expression of antigen presentation and costimulatory genes in myeloid cells.CONCLUSION: Cigarette smoke exposome is a potent activator of the Nrf2 pathway and is a likely primary trigger for the tripartite phenotype of aggressive HNSCC consisting of: 1) reduced chemotherapy sensitivity, 2) enhanced metastatic potential and 3) suppressed anti-tumor immunity.STATEMENT OF SIGNIFICANCE: The smoke exposome drives aggressive tumor behavior, treatment resistance and suppressed immunity through coordinated metabolic reprogramming. Successfully targeting this adaptation is critical to improving survival in smokers with head and neck cancer.PMID:39484602 | PMC:PMC11526855 | DOI:10.1101/2024.10.17.618907

bioRxiv [Preprint]. 2024 Oct 25:2024.10.22.619714. doi: 10.1101/2024.10.22.619714.ABSTRACTEpidemiological evidence suggests an association between dioxin and dioxin-like compound (DLC) exposure and human liver disease. The prototypical DLC, 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD), has been shown to induce the progression of reversible hepatic steatosis to steatohepatitis with periportal fibrosis and biliary hyperplasia in mice. Although the effects of TCDD toxicity are mediated by aryl hydrocarbon receptor (AHR) activation, the underlying mechanisms of TCDD-induced hepatotoxicity are unresolved. In the present study, male C57BL/6NCrl mice were gavaged every 4 days for 28 days with 0.03 - 30 μg/kg TCDD and evaluated for liver histopathology and gene expression as well as complementary 1-dimensional proton magnetic resonance (1D- 1 H NMR) urinary metabolic profiling. Urinary trimethylamine (TMA), trimethylamine N -oxide (TMAO), and 1-methylnicotinamide (1MN) levels were altered by TCDD at doses ≤ 3 μg/kg; other urinary metabolites, like glycolate, urocanate, and 3-hydroxyisovalerate, were only altered at doses that induced moderate to severe steatohepatitis. Bulk liver RNA-seq data suggested altered urinary metabolites correlated with hepatic differential gene expression corresponding to specific metabolic pathways. In addition to evaluating whether altered urinary metabolites were liver-dependent, published single-nuclear RNA-seq (snRNA-seq), AHR ChIP-seq, and AHR knockout gene expression datasets provide further support for hepatic cell-type and AHR-regulated dependency, respectively. Overall, TCDD-induced liver effects were preceded by and occurred with changes in urinary metabolite levels due to AHR-mediated changes in hepatic gene expression.PMID:39484576 | PMC:PMC11526911 | DOI:10.1101/2024.10.22.619714