PubMed

Rev Med Virol. 2023 Oct 30:e2485. doi: 10.1002/rmv.2485. Online ahead of print.ABSTRACTHepatitis B virus (HBV)-associated liver cancer is the third most prevalent cancer-related cause of death worldwide. Different studies have been done on the histomolecular analysis of HBV induced-liver cancer including epigenetics which are dynamic molecular mechanisms to control gene expression without altering the host deoxyribonucleic acid, genomics characterise the integration of the viral genome with host genome, proteomics characterise how gene modifies and results overexpression of proteins, glycoproteomics discover different glyco-biomarker candidates and show glycosylation in malignant hepatocytes, metabolomics characterise how HBV impairs a variety of metabolic functions during hepatocyte immortalisation, exosomes characterise immortalised liver cells in terms of their differentiation and proliferation, and autophagy plays a role in the development of hepatocarcinogenesis linked to HBV infection.PMID:37902197 | DOI:10.1002/rmv.2485

CNS Neurosci Ther. 2023 Oct 30. doi: 10.1111/cns.14494. Online ahead of print.ABSTRACTAIM: As the main type of stroke, the incidence of cerebral venous thrombosis (CVT) has been rising. However, the comprehensive mechanisms behind it remain unclear. Thus, the multi-omics study is required to investigate the mechanism after CVT and elucidate the characteristic pathology of venous stroke and arterial stroke.METHODS: Adult rats were subjected to CVT and MCAO models. Whole-transcriptome sequencing (RNA-seq) and untargeted metabolomics analysis were performed to construct the transcriptome and metabolism profiles of rat brains after CVT and also MCAO. The difference analysis, functional annotation, and enrichment analysis were also performed.RESULTS: Through RNA-seq analysis, differentially expressed genes (DEGs) were screened. 174 CVT specific genes including Il1a, Ccl9, Cxxl6, Tnfrsf14, etc., were detected. The hemoglobin genes, including both Hba and Hbb, were significantly downregulated after CVT, compared both to the MCAO and Sham groups. Metabolism analysis showed that CVT had higher heterogeneity of metabolism compared to MCAO. Metabolites including N-stearoyltyrosine, 5-methoxy-3-indoleaceate, Afegostat, pipecolic acid, etc. were specially regulated in CVT. Through the immune infiltration analysis, it was found that CVT had a higher immune response, with the abundance of certain types of immune cells increased, especially T helper cells. It was important to find the prevalence of the activation of inflammatory chemokine, cytokine, NOD-like pathway, and neutrophil extracellular trap.CONCLUSION: We explored and analyzed the gene expression and metabolomic characteristics of CVT, revealed the specific inflammatory reaction mechanism of CVT and found the markers in transcriptome and metabolism levels. It points out the direction for CVT early diagnosis and treatment.PMID:37902195 | DOI:10.1111/cns.14494

Circulation. 2023 Oct 30. doi: 10.1161/CIR.0000000000001185. Online ahead of print.ABSTRACTCardiometabolic risk is increasing in prevalence across the life span with disproportionate ramifications for youth at socioeconomic disadvantage. Established risk factors and associated disease progression are harder to reverse as they become entrenched over time; if current trends are unchecked, the consequences for individual and societal wellness will become untenable. Interrelated root causes of ectopic adiposity and insulin resistance are understood but identified late in the trajectory of systemic metabolic dysregulation when traditional cardiometabolic risk factors cross current diagnostic thresholds of disease. Thus, children at cardiometabolic risk are often exposed to suboptimal metabolism over years before they present with clinical symptoms, at which point life-long reliance on pharmacotherapy may only mitigate but not reverse the risk. Leading-edge indicators are needed to detect the earliest departure from healthy metabolism, so that targeted, primordial, and primary prevention of cardiometabolic risk is possible. Better understanding of biomarkers that reflect the earliest transitions to dysmetabolism, beginning in utero, ideally biomarkers that are also mechanistic/causal and modifiable, is critically needed. This scientific statement explores emerging biomarkers of cardiometabolic risk across rapidly evolving and interrelated "omic" fields of research (the epigenome, microbiome, metabolome, lipidome, and inflammasome). Connections in each domain to mitochondrial function are identified that may mediate the favorable responses of each of the omic biomarkers featured to a heart-healthy lifestyle, notably to nutritional interventions. Fuller implementation of evidence-based nutrition must address environmental and socioeconomic disparities that can either facilitate or impede response to therapy.PMID:37902008 | DOI:10.1161/CIR.0000000000001185

Biomed Rep. 2023 Oct 6;19(6):90. doi: 10.3892/br.2023.1672. eCollection 2023 Dec.ABSTRACTHuman induced pluripotent stem (iPS) cells initiate hepatocyte differentiation in a medium without glucose and supplemented with galactose, oncostatin M and small molecules [hepatocyte differentiation inducer (HDI)]. To clarify the metabolic differences between iPS cells in HDI and ReproFF (undifferentiated state), a metabolome analysis was performed. iPS cells were cultured in a medium without glucose and supplemented with galactose, as well as 1 mM of calcium lactate, sodium lactate or lactic acid. After 7 days of culture, the cells were subjected to reverse transcription-quantitative PCR analysis. The galactose-1-phosphate concentration was significantly higher in cells cultured in HDI than in those cultured with ReproFF. The lactate concentration in the HDI group was significantly lower than that in the ReproFF group. The expression levels of α-feto protein and albumin were significantly higher in the groups cultured with calcium lactate, sodium lactate and lactic acid as compared with ReproFF. It was suggested that lactate promoted the survival of iPS cells cultured in a medium without glucose and supplemented with galactose. Under these conditions, iPS cells begin to differentiate into a hepatocyte lineage. Lactate may be applied to produce hepatocytes from iPS cells more efficiently.PMID:37901872 | PMC:PMC10603376 | DOI:10.3892/br.2023.1672

Front Microbiol. 2023 Oct 11;14:1251065. doi: 10.3389/fmicb.2023.1251065. eCollection 2023.ABSTRACTINTRODUCTION: SARS-CoV-2 subverts host cell processes to facilitate rapid replication and dissemination, and this leads to pathological inflammation.METHODS: We used niclosamide (NIC), a poorly soluble anti-helminth drug identified initially for repurposed treatment of COVID-19, which activates the cells' autophagic and lipophagic processes as a chemical probe to determine if it can modulate the host cell's total lipid profile that would otherwise be either amplified or reduced during SARS-CoV-2 infection.RESULTS: Through parallel lipidomic and transcriptomic analyses we observed massive reorganization of lipid profiles of SARS-CoV-2 infected Vero E6 cells, especially with triglycerides, which were elevated early during virus replication, but decreased thereafter, as well as plasmalogens, which were elevated at later timepoints during virus replication, but were also elevated under normal cell growth. These findings suggested a complex interplay of lipid profile reorganization involving plasmalogen metabolism. We also observed that NIC treatment of both low and high viral loads does not affect virus entry. Instead, NIC treatment reduced the abundance of plasmalogens, diacylglycerides, and ceramides, which we found elevated during virus infection in the absence of NIC, resulting in a significant reduction in the production of infectious virions. Unexpectedly, at higher viral loads, NIC treatment also resulted in elevated triglyceride levels, and induced significant changes in phospholipid metabolism.DISCUSSION: We posit that future screens of approved or new partner drugs should prioritize compounds that effectively counter SARS-CoV-2 subversion of lipid metabolism, thereby reducing virus replication, egress, and the subsequent regulation of key lipid mediators of pathological inflammation.PMID:37901834 | PMC:PMC10603251 | DOI:10.3389/fmicb.2023.1251065

Front Microbiol. 2023 Oct 12;14:1233460. doi: 10.3389/fmicb.2023.1233460. eCollection 2023.ABSTRACTElderly subjects with more than 20 natural teeth have a higher healthy life expectancy than those with few or no teeth. The oral microbiome and its metabolome are associated with oral health, and they are also associated with systemic health via the oral-gut axis. Here, we analyzed the oral and gut microbiome and metabolome profiles of elderly subjects with more than 26 natural teeth. Salivary samples collected as mouth-rinsed water and fecal samples were obtained from 22 healthy individuals, 10 elderly individuals with more than 26 natural teeth and 24 subjects with periodontal disease. The oral microbiome and metabolome profiles of elderly individuals resembled those of subjects with periodontal disease, with the metabolome showing a more substantial differential abundance of components. Despite the distinct oral metabolome profiles, there was no differential abundance of components in the gut microbiome and metabolomes, except for enrichment of short-chain fatty acids in elderly subjects. Finally, to investigate the relationship between the oral and gut microbiome and metabolome, we analyzed bacterial coexistence in the oral cavity and gut and analyzed the correlation of metabolite levels between the oral cavity and gut. However, there were few associations between oral and gut for bacteria and metabolites in either elderly or healthy subjects. Overall, these results indicate distinct oral microbiome and metabolome profiles, as well as the lack of an oral-gut axis in elderly subjects with a high number of natural teeth.PMID:37901820 | PMC:PMC10600518 | DOI:10.3389/fmicb.2023.1233460

Front Microbiol. 2023 Oct 12;14:1260909. doi: 10.3389/fmicb.2023.1260909. eCollection 2023.ABSTRACTRalstonia insidiosa can survive in a wide range of aqueous environments, including food processing areas, and is harmful to humans. It can induce Listeria monocytogenes to form suspended aggregates, resulting from the co-aggregation of two bacteria, which allows for more persistent survival and increases the risk of L. monocytogenes contamination. In our study, different groups of aggregates were analyzed and compared using Illumina RNA sequencing technology. These included R. insidiosa under normal and barren nutrient conditions and in the presence or absence of L. monocytogenes as a way to screen for differentially expressed genes (DEGs) in the process of aggregate formation. In addition, sterile supernatants of R. insidiosa were analyzed under different nutrient conditions using metabolomics to investigate the effect of nutrient-poor conditions on metabolite production by R. insidiosa. We also undertook a combined analysis of transcriptome and metabolome data to further investigate the induction effect of R. insidiosa on L. monocytogenes in a barren environment. The results of the functional annotation analysis on the surface of DEGs and qPCR showed that under nutrient-poor conditions, the acdx, puuE, and acs genes of R. insidiosa were significantly upregulated in biosynthetic processes such as carbon metabolism, metabolic pathways, and biosynthesis of secondary metabolites, with Log2FC reaching 4.39, 3.96, and 3.95 respectively. In contrast, the Log2FC of cydA, cyoB, and rpsJ in oxidative phosphorylation and ribosomal pathways reached 3.74, 3.87, and 4.25, respectively. Thirty-one key components were identified while screening for differential metabolites, which mainly included amino acids and their metabolites, enriched to the pathways of biosynthesis of amino acids, phenylalanine metabolism, and methionine metabolism. Of these, aminomalonic acid and Proximicin B were the special components of R. insidiosa that were metabolized under nutrient-poor conditions.PMID:37901811 | PMC:PMC10601645 | DOI:10.3389/fmicb.2023.1260909

Front Microbiol. 2023 Oct 12;14:1252498. doi: 10.3389/fmicb.2023.1252498. eCollection 2023.ABSTRACTMicrobial communities are key players in groundwater ecosystems. In this dark environment, heterotrophic microbes rely on biomass produced by the activity of lithoautotrophs or on the degradation of organic matter seeping from the surface. Most studies on bacterial diversity in groundwater habitats are based on 16S gene sequencing and full genome reconstructions showing potential metabolic pathways used in these habitats. However, molecular-based studies do not allow for the assessment of population dynamics over time or the assimilation of specific compounds and their biochemical transformation by microbial communities. Therefore, in this study, we combined DNA-, phospholipid fatty acid-, and metabolomic-stable isotope probing to target and identify heterotrophic bacteria in the groundwater setting of the Hainich Critical Zone Exploratory (CZE), focusing on 2 aquifers with different physico-chemical conditions (oxic and anoxic). We incubated groundwater from 4 different wells using either 13C-labeled veratric acid (a lignin-derived compound) (single labeling) or a combination of 13CO2 and D-labeled veratric acid (dual labeling). Our results show that heterotrophic activities dominate all groundwater sites. We identified bacteria with the potential to break down veratric acid (Sphingobium or Microbacterium). We observed differences in heterotrophic activities between the oxic and anoxic aquifers, indicating local adaptations of bacterial populations. The dual labeling experiments suggested that the serine pathway is an important carbon assimilation pathway and that organic matter was an important source of hydrogen in the newly produced lipids. These experiments also yielded different labeled taxa compared to the single labeling experiments, showing that there exists a complex interaction network in the groundwater habitats.PMID:37901809 | PMC:PMC10602745 | DOI:10.3389/fmicb.2023.1252498

World J Gastroenterol. 2023 Sep 28;29(36):5211-5225. doi: 10.3748/wjg.v29.i36.5211.ABSTRACTInflammatory bowel disease (IBD) is a complex disease with variability in genetic, environmental, and lifestyle factors affecting disease presentation and course. Precision medicine has the potential to play a crucial role in managing IBD by tailoring treatment plans based on the heterogeneity of clinical and temporal variability of patients. Precision medicine is a population-based approach to managing IBD by integrating environmental, genomic, epigenomic, transcriptomic, proteomic, and metabolomic factors. It is a recent and rapidly developing medicine. The widespread adoption of precision medicine worldwide has the potential to result in the early detection of diseases, optimal utilization of healthcare resources, enhanced patient outcomes, and, ultimately, improved quality of life for individuals with IBD. Though precision medicine is promising in terms of better quality of patient care, inadequacies exist in the ongoing research. There is discordance in study conduct, and data collection, utilization, interpretation, and analysis. This review aims to describe the current literature on precision medicine, its multiomics approach, and future directions for its application in IBD.PMID:37901450 | PMC:PMC10600960 | DOI:10.3748/wjg.v29.i36.5211

Front Oncol. 2023 Oct 12;13:1143163. doi: 10.3389/fonc.2023.1143163. eCollection 2023.ABSTRACTTriple-negative breast cancer (TNBC) presents significant challenges to female health owing to the lack of therapeutic targets and its poor prognosis. In recent years, in the field of molecular pathology, there has been a growing focus on the role of intra-tumoral microbial communities and metabolic alterations in tumor cells. However, the precise mechanism through which microbiota and their metabolites influence TNBC remains unclear and warrants further investigation. In this study, we analyzed the microbial community composition in various subtypes of breast cancer through 16S rRNA MiSeq sequencing of formalin-fixed, paraffin-embedded (FFPE) tissue samples. Notably, Turicibacter, a microbe associated with cancer response, exhibited a significantly higher abundance in TNBC. Similarly, mass spectrometry-based metabolomic analysis revealed substantial differences in specific metabolites, such as nutriacholic, pregnanetriol, and cortol. Furthermore, we observed significant correlations between the intra-tumoral microbiome, clinicopathological characteristics, and human epidermal growth factor receptor-2 expression(HER2). Three microbial taxa (Cytophagaceae, Conexibacteraceae, and Flavobacteriaceae) were associated with tumor-infiltrating lymphocytes(TILs), which are indicative of antitumor immunity. This study creatively utilized FFPE tissue samples to assess intra-tumoral microbial communities and their related metabolic correlations, presenting avenues for the identification of novel diagnostic biomarkers, the development of therapeutic strategies, and the early clinical diagnosis of TNBC.PMID:37901331 | PMC:PMC10602718 | DOI:10.3389/fonc.2023.1143163

Front Vet Sci. 2023 Oct 12;10:1257488. doi: 10.3389/fvets.2023.1257488. eCollection 2023.ABSTRACTMycobacterium avium subsp. paratuberculosis (MAP) causes bovine paratuberculosis (PTB). PTB is responsible for significant economic losses in dairy herds around the word. PTB control programs that rely on testing and culling of test-positive cows have been developed. Current diagnostics, such as ELISA for detecting MAP antibodies in serum samples and PCR detecting MAP DNA in feces, have inadequate sensitivity for detecting subclinical animals. Innovative "omics" technologies such as next-generation sequencing (NGS) technology-based RNA-sequencing (RNA-Seq), proteomics and metabolomics can be used to find host biomarkers. The discovered biomarkers (RNA, microRNAs, proteins, metabolites) can then be used to develop new and more sensitive approaches for PTB diagnosis. Traditional approaches for measuring host antibodies and biomarkers, such as ELISAs, northern blotting, quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR), cDNA microarrays, and mass spectrometry are time-consuming, expensive, and sometimes exhibit poor sensitivity. With the rapid development of nanotechnology, low-cost monitoring devices for measuring antibodies against MAP proteins in point-of-care (POC) settings have been developed. Lateral flow assays (LFAs), in particular, are thought to be appropriate for the on-site detection of antibodies to MAP antigens and/or host biomarkers. This review aims to summarize LFAs that have recently been developed to accurately detect antibodies against MAP antigens, as well as the benefits that host biomarkers linked with MAP infection give to PTB diagnosis. The identification of these novel biomarkers could be the basis for the development of new LFAs. The dairy industry and producers are likely to benefit from reliable and rapid technologies capable of detecting MAP infection in situ to establish a quick and sensitive PTB diagnosis.PMID:37901111 | PMC:PMC10601461 | DOI:10.3389/fvets.2023.1257488

Brain Commun. 2023 Oct 18;5(5):fcad272. doi: 10.1093/braincomms/fcad272. eCollection 2023.ABSTRACTIdiopathic intracranial hypertension, a disease classically occurring in women with obesity, is characterized by raised intracranial pressure. Weight loss leads to the reduction in intracranial pressure. Additionally, pharmacological glucagon-like peptide-1 agonism reduces cerebrospinal fluid secretion and intracranial pressure. The potential mechanisms by which weight loss reduces intracranial pressure are unknown and were the focus of this study. Meal stimulation tests (fasted plasma sample, then samples at 15, 30, 60, 90 and 120 min following a standardized meal) were conducted pre- and post-bariatric surgery [early (2 weeks) and late (12 months)] in patients with active idiopathic intracranial hypertension. Dynamic changes in gut neuropeptides (glucagon-like peptide-1, gastric inhibitory polypeptide and ghrelin) and metabolites (untargeted ultra-high performance liquid chromatography-mass spectrometry) were evaluated. We determined the relationship between gut neuropeptides, metabolites and intracranial pressure. Eighteen idiopathic intracranial hypertension patients were included [Roux-en-Y gastric bypass (RYGB) n = 7, gastric banding n = 6 or sleeve gastrectomy n = 5]. At 2 weeks post-bariatric surgery, despite similar weight loss, RYGB had a 2-fold (50%) greater reduction in intracranial pressure compared to sleeve. Increased meal-stimulated glucagon-like peptide-1 secretion was observed after RYGB (+600%) compared to sleeve (+319%). There was no change in gastric inhibitory polypeptide and ghrelin. Dynamic changes in meal-stimulated metabolites after bariatric surgery consistently identified changes in lipid metabolites, predominantly ceramides, glycerophospholipids and lysoglycerophospholipids, which correlated with intracranial pressure. A greater number of differential lipid metabolites were observed in the RYGB cohort at 2 weeks, and these also correlated with intracranial pressure. In idiopathic intracranial hypertension, we identified novel changes in lipid metabolites and meal-stimulated glucagon-like peptide-1 levels following bariatric surgery which were associated with changes in intracranial pressure. RYGB was most effective at reducing intracranial pressure despite analogous weight loss to gastric sleeve at 2 weeks post-surgery and was associated with more pronounced changes in these metabolite pathways. We suggest that these novel perturbations in lipid metabolism and glucagon-like peptide-1 secretion are mechanistically important in driving a reduction in intracranial pressure following weight loss in patients with idiopathic intracranial hypertension. Therapeutic targeting of these pathways, for example with glucagon-like peptide-1 agonist infusion, could represent a therapeutic strategy.PMID:37901040 | PMC:PMC10608960 | DOI:10.1093/braincomms/fcad272

World J Stem Cells. 2023 Sep 26;15(9):908-930. doi: 10.4252/wjsc.v15.i9.908.ABSTRACTBACKGROUND: Acute lung injury (ALI) and its final severe stage, acute respiratory distress syndrome, are associated with high morbidity and mortality rates in patients due to the lack of effective specific treatments. Gut microbiota homeostasis, including that in ALI, is important for human health. Evidence suggests that the gut microbiota improves lung injury through the lung-gut axis. Human umbilical cord mesenchymal cells (HUC-MSCs) have attractive prospects for ALI treatment. This study hypothesized that HUC-MSCs improve ALI via the lung-gut microflora.AIM: To explore the effects of HUC-MSCs on lipopolysaccharide (LPS)-induced ALI in mice and the involvement of the lung-gut axis in this process.METHODS: C57BL/6 mice were randomly divided into four groups (18 rats per group): Sham, sham + HUC-MSCs, LPS, and LPS + HUC-MSCs. ALI was induced in mice by intraperitoneal injections of LPS (10 mg/kg). After 6 h, mice were intervened with 0.5 mL phosphate buffered saline (PBS) containing 1 × 106 HUC-MSCs by intraperitoneal injections. For the negative control, 100 mL 0.9% NaCl and 0.5 mL PBS were used. Bronchoalveolar lavage fluid (BALF) was obtained from anesthetized mice, and their blood, lungs, ileum, and feces were obtained by an aseptic technique following CO2 euthanasia. Wright's staining, enzyme-linked immunosorbent assay, hematoxylin-eosin staining, Evans blue dye leakage assay, immunohistochemistry, fluorescence in situ hybridization, western blot, 16S rDNA sequencing, and non-targeted metabolomics were used to observe the effect of HUC-MSCs on ALI mice, and the involvement of the lung-gut axis in this process was explored. One-way analysis of variance with post-hoc Tukey's test, independent-sample Student's t-test, Wilcoxon rank-sum test, and Pearson correlation analysis were used for statistical analyses.RESULTS: HUC-MSCs were observed to improve pulmonary edema and lung and ileal injury, and decrease mononuclear cell and neutrophil counts, protein concentrations in BALF and inflammatory cytokine levels in the serum, lung, and ileum of ALI mice. Especially, HUC-MSCs decreased Evans blue concentration and Toll-like receptor 4, myeloid differentiation factor 88, p-nuclear factor kappa-B (NF-κB)/NF-κB, and p-inhibitor α of NF-κB (p-IκBα)/IκBα expression levels in the lung, and raised the pulmonary vascular endothelial-cadherin, zonula occludens-1 (ZO-1), and occludin levels and ileal ZO-1, claudin-1, and occludin expression levels. HUC-MSCs improved gut and BALF microbial homeostases. The number of pathogenic bacteria decreased in the BALF of ALI mice treated with HUC-MSCs. Concurrently, the abundances of Oscillospira and Coprococcus in the feces of HUS-MSC-treated ALI mice were significantly increased. In addition, Lactobacillus, Bacteroides, and unidentified_Rikenellaceae genera appeared in both feces and BALF. Moreover, this study performed metabolomic analysis on the lung tissue and identified five upregulated metabolites and 11 downregulated metabolites in the LPS + MSC group compared to the LPS group, which were related to the purine metabolism and the taste transduction signaling pathways. Therefore, an intrinsic link between lung metabolite levels and BALF flora homeostasis was established.CONCLUSION: This study suggests that HUM-MSCs attenuate ALI by redefining the gut and lung microbiota.PMID:37900940 | PMC:PMC10600741 | DOI:10.4252/wjsc.v15.i9.908

World J Stem Cells. 2023 Sep 26;15(9):876-896. doi: 10.4252/wjsc.v15.i9.876.ABSTRACTBACKGROUND: Mesenchymal stem cells (MSCs) have been used in liver transplantation and have certain effects in alleviating liver ischemia-reperfusion injury (IRI) and regulating immune rejection. However, some studies have indicated that the effects of MSCs are not very significant. Therefore, approaches that enable MSCs to exert significant and stable therapeutic effects are worth further study.AIM: To enhance the therapeutic potential of human menstrual blood-derived stromal cells (MenSCs) in the mouse liver ischemia-reperfusion (I/R) model via interferon-γ (IFN-γ) priming.METHODS: Apoptosis was analyzed by flow cytometry to evaluate the safety of IFN-γ priming, and indoleamine 2,3-dioxygenase (IDO) levels were measured by quantitative real-time reverse transcription polymerase chain reaction, western blotting, and ELISA to evaluate the efficacy of IFN-γ priming. In vivo, the liver I/R model was established in male C57/BL mice, hematoxylin and eosin and TUNEL staining was performed and serum liver enzyme levels were measured to assess the degree of liver injury, and regulatory T cell (Treg) numbers in spleens were determined by flow cytometry to assess immune tolerance potential. Metabolomics analysis was conducted to elucidate the potential mechanism underlying the regulatory effects of primed MenSCs. In vitro, we established a hypoxia/reoxygenation (H/R) model and analyzed apoptosis by flow cytometry to investigate the mechanism through which primed MenSCs inhibit apoptosis. Transmission electron microscopy, western blotting, and immunofluorescence were used to analyze autophagy levels.RESULTS: IFN-γ-primed MenSCs secreted higher levels of IDO, attenuated liver injury, and increased Treg numbers in the mouse spleens to greater degrees than untreated MenSCs. Metabolomics and autophagy analyses proved that primed MenSCs more strongly induced autophagy in the mouse livers. In the H/R model, autophagy inhibitors increased the level of H/R-induced apoptosis, indicating that autophagy exerted protective effects. In addition, primed MenSCs decreased the level of H/R-induced apoptosis via IDO and autophagy. Further rescue experiments proved that IDO enhanced the protective autophagy by inhibiting the mammalian target of rapamycin (mTOR) pathway and activating the AMPK pathway.CONCLUSION: IFN-γ-primed MenSCs exerted better therapeutic effects in the liver I/R model by secreting higher IDO levels. MenSCs and IDO activated the AMPK-mTOR-autophagy axis to reduce IRI, and IDO increased Treg numbers in the spleen and enhanced the MenSC-mediated induction of immune tolerance. Our study suggests that IFN-γ-primed MenSCs may be a novel and superior MSC product for liver transplantation in the future.PMID:37900937 | PMC:PMC10600742 | DOI:10.4252/wjsc.v15.i9.876

LC GC Eur. 2023 Jun;36(Suppl):7-10.ABSTRACTMeasuring chemical exposure is extremely challenging due to the range and number of anthropogenic molecules encountered in our daily lives, as well as their complex transformations throughout the body. To broadly characterize how chemical exposures influence human health, a combination of genomic, transcriptomic, proteomic, endogenous metabolomic, and xenobiotic measurements must be performed. However, while genomic, transcriptomic, and proteomic analyses have rapidly progressed over the last two decades, advancements in instrumentation and computations for nontargeted xenobiotic and endogenous small molecule measurements are still greatly needed.PMID:37900911 | PMC:PMC10611144

Front Plant Sci. 2023 Oct 12;14:1271490. doi: 10.3389/fpls.2023.1271490. eCollection 2023.ABSTRACTINTRODUCTION: The utilization of biochar (BC) as a soil amendment in agriculture has gained significant traction among many farmers and researchers, primarily due to its eco-friendly role in boosting crop output. However, the performance of specific metabolites (e.g., zeatin, melatonin, sucrose, and phenyllactic acid) in the various tissues of sugarcane plant (leaf, stem, and root) and rhizosphere soil-deemed plant growth and stress regulators in a long-term BC-amended field remains poorly understood. Additionally, literature on the shift in soil attributes and crop growth triggered by the strong response of these bioactive compounds to longterm BC utilization remains undocumented.METHODS: Metabolome integrated with highthroughput sequencing analyses were conducted to identify and quantify the performance of plant growth and stress-regulating metabolites in a long-term BC-amended field. Additionally, we investigated how the response of these compounds to BC-treated soil influences crop traits and soil biochemical properties.RESULTS: We also identified and quantified the performance of pathogenic bacteria and unraveled the association between these compounds and potential plant growth-promoting bacteria. The BC-supplemented soil significantly boosted the crop traits, including brix, sucrose content, and chlorophyll, as well as soil nutrients, such as soil total nitrogen (TN), ammonium (NH4 +-N), and nitrate (NO3 --N). We also noticed that metabolite-deemed plant growth and stress regulators, including melatonin and phenyllactic acid, were enriched considerably in the stem and root tissues of the BC-amended soil. Zeatin in the leaf, stem, and root tissues exhibited the same trend, followed by sucrose in the leaf tissue of the BC-treated soil, implying that the strong response of these compounds to BC utilization contributed to the promotion of crop traits and soil quality. Pathogenic bacteria belonging to Proteobacteria and Acidobacteria were suppressed under the BC-supplemented soil, especially in the root tissue and rhizosphere soil, whereas plant growth-regulating bacteria, mainly Bradyrhizobium, responded strongly and positively to several metabolites.DISCUSSION: Our finding provides valuable information for agronomists, farmers, and environmentalists to make informed decisions about crop production, land use, and soil management practices. Proper soil assessment and understanding of the interaction between the attributes of soil, BC, and metabolites are essential for promoting sustainable agriculture practices and land conservation.PMID:37900767 | PMC:PMC10600501 | DOI:10.3389/fpls.2023.1271490

Front Plant Sci. 2023 Oct 13;14:1285456. doi: 10.3389/fpls.2023.1285456. eCollection 2023.ABSTRACTEriobotrya is an evergreen fruit tree native to South-West China and adjacent countries. There are more than 26 loquat species known in this genus, while E. japonica is the only species yet domesticated to produce fresh fruits from late spring to early summer. Fruits of cultivated loquat are usually orange colored, in contrast to the red color of fruits of wild E. henryi (EH). However, the mechanisms of fruit pigment formation during loquat evolution are yet to be elucidated. To understand these, targeted carotenoid and anthocyanin metabolomics as well as transcriptomics analyses were carried out in this study. The results showed that β-carotene, violaxanthin palmitate and rubixanthin laurate, totally accounted for over 60% of the colored carotenoids, were the major carotenoids in peel of the orange colored 'Jiefangzhong' (JFZ) fruits. Total carotenoids content in JFZ is about 10 times to that of EH, and the expression levels of PSY, ZDS and ZEP in JFZ were 10.69 to 23.26 folds to that in EH at ripen stage. Cyanidin-3-O-galactoside and pelargonidin-3-O-galactoside were the predominant anthocyanins enriched in EH peel. On the contrary, both of them were almost undetectable in JFZ, and the transcript levels of F3H, F3'H, ANS, CHS and CHI in EH were 4.39 to 73.12 folds higher than that in JFZ during fruit pigmentation. In summary, abundant carotenoid deposition in JFZ peel is well correlated with the strong expression of PSY, ZDS and ZEP, while the accumulation of anthocyanin metabolites in EH peel is tightly associated with the notably upregulated expressions of F3H, F3'H, ANS, CHS and CHI. This study was the first to demonstrate the metabolic background of how fruit pigmentations evolved from wild to cultivated loquat species, and provided gene targets for further breeding of more colorful loquat fruits via manipulation of carotenoids and anthocyanin biosynthesis.PMID:37900735 | PMC:PMC10611460 | DOI:10.3389/fpls.2023.1285456

Front Cell Infect Microbiol. 2023 Oct 13;13:1267192. doi: 10.3389/fcimb.2023.1267192. eCollection 2023.ABSTRACTBACKGROUND: There is no direct evidence of gut microbiota disturbance in children with gastroesophageal reflux disease (GERD). This study aimed to provide direct evidence and a comprehensive understanding of gut microbiota disturbance in children with GERD through combined metagenomic and metabolomic analysis.METHODS: 30 children with GERD and 30 healthy controls (HCs) were continuously enrolled, and the demographic and clinical characteristics of the subjects were collected. First, 16S rRNA sequencing was used to evaluate differences in the gut microbiota between children with GERD and HC group, and 10 children with GERD and 10 children in the HC group were selected for metagenomic analysis. Nontargeted metabolomic analysis was performed using liquid chromatography/mass spectrometry (LC/MS), and metagenomic and metabolomic data were analyzed together.RESULTS: There were significant differences in the gut microbiota diversity and composition between children with GERD and HCs. The dominant bacteria in children with GERD were Proteobacteria and Bacteroidota. At the species level, the top three core bacterial groups were Bacteroides stercoris, Bacteroides vulgatus and Alistipes putredinis. The main differential pathways were identified to be related to energy, amino acid, vitamin, carbohydrate and lipid metabolism. LC/MS detected 288 different metabolites in the positive and negative ion modes between children with GERD and HCs, which were mainly involved in arachidonic acid (AA), tyrosine, glutathione and caffeine metabolism.CONCLUSION: This study provides new evidence of the pathogenesis of GERD. There are significant differences in the gut microbiota, metabolites and metabolic pathways between HCs and children with GERD, and the differences in metabolites are related to specific changes in bacterial abundance. In the future, GERD may be treated by targeting specific bacteria related to AA metabolism.PMID:37900308 | PMC:PMC10613033 | DOI:10.3389/fcimb.2023.1267192

World J Clin Cases. 2023 Sep 26;11(27):6318-6326. doi: 10.12998/wjcc.v11.i27.6318.ABSTRACTIn recent years, metabolomics research has become a hot spot in the screening and treatment of cancer. It is a popular technique for the quantitative characterization of small molecular compounds in biological cells, tissues, organs or organisms. Further study of the tumor revealed that amino acid changes may occur early in the tumor. The rapid growth and metabolism required for survival result in tumors exhibiting an increased demand for amino acids. An abundant supply of amino acids is important for cancer to maintain its proliferative driving force. Changes in amino acid metabolism can be used to screen malignant tumors and improve therapeutic outcomes. Therefore, it is particularly important to study the characteristics of amino acid metabolism in colorectal cancer. This article reviews several specific amino acid metabolism characteristics in colorectal cancer.PMID:37900242 | PMC:PMC10601002 | DOI:10.12998/wjcc.v11.i27.6318

World J Hepatol. 2023 Sep 27;15(9):1043-1059. doi: 10.4254/wjh.v15.i9.1043.ABSTRACTBACKGROUND: After receiving entecavir or combined with FuzhengHuayu tablet (FZHY) treatment, some sufferers with hepatitis B virus (HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen. Serum metabolomics at baseline in these patients who were effective in treatment remain unclear.AIM: To explore baseline serum metabolites characteristics in responders.METHODS: A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited. First, all subjects were divided into training set and validation set. Second, the included patients were subdivided into entecavir responders (E-R), entecavir no-responders (E-N), FZHY + entecavir responders (F-R), and FZHY + entecavir no-responders (F-N) following the pathological histological changes after 48 wk' treatments. Then, Serum samples of all subjects before treatment were tested by high performance liquid chromatography-tandem mass spectrometry (LC-MS) high-performance LC-MS. Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis. Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression.RESULTS: As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N, results showed that 4 pathways including linoleic acid metabolism, aminoacyl-tRNA biosynthesis, cyanoamino acid metabolism, alanine, aspartate and glutamate metabolism were screened out. As for the differential metabolites, these 7 intersected metabolites including hydroxypropionic acid, tyrosine, citric acid, taurochenodeoxycholic acid, benzoic acid, 2-Furoic acid, and propionic acid were selected.CONCLUSION: Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.PMID:37900214 | PMC:PMC10600694 | DOI:10.4254/wjh.v15.i9.1043