PubMed

BMC Cancer. 2023 Aug 23;23(1):789. doi: 10.1186/s12885-023-11239-w.ABSTRACTThis study aimed to evaluate the potential of exosomes from cancer cells to predict chemoresistance in pancreatic cancer (PC) and explore the molecular mechanisms through RNA-sequencing and mass spectrometry. We sought to understand the connection between the exosomal Medium-chain acyl-CoA dehydrogenase (ACADM) level and the reaction to gemcitabine in vivo and in patients with PC. We employed loss-of-function, gain-of-function, metabolome mass spectrometry, and xenograft models to investigate the effect of exosomal ACADM in chemoresistance in PC. Our results showed that the molecules involved in lipid metabolism in exosomes vary between PC cells with different gemcitabine sensitivity. Exosomal ACADM (Exo-ACADM) was strongly correlated with gemcitabine sensitivity in vivo, which can be used as a predictor for postoperative gemcitabine chemosensitivity in pancreatic patients. Moreover, ACADM was found to regulate the gemcitabine response by affecting ferroptosis through Glutathione peroxidase 4 (GPX4) and mevalonate pathways. It was also observed that ACADM increased the consumption of unsaturated fatty acids and decreased intracellular lipid peroxides and reactive oxygen species (ROS) levels. In conclusion, this research suggests that Exo-ACADM may be a viable biomarker for predicting the responsiveness of patients to chemotherapy.PMID:37612627 | DOI:10.1186/s12885-023-11239-w

Sci Rep. 2023 Aug 23;13(1):13752. doi: 10.1038/s41598-023-39737-8.ABSTRACTIntegration of the omics data, including metabolomics and proteomics, provides a unique opportunity to search for new associations within metabolic disorders, including Alzheimer's disease. Using metabolomics, we have previously profiled oxylipins, endocannabinoids, bile acids, and steroids in 293 CSF and 202 matched plasma samples from AD cases and healthy controls and identified both central and peripheral markers of AD pathology within inflammation-regulating cytochrome p450/soluble epoxide hydrolase pathway. Additionally, using proteomics, we have identified five cerebrospinal fluid protein panels, involved in the regulation of energy metabolism, vasculature, myelin/oligodendrocyte, glia/inflammation, and synapses/neurons, affected in AD, and reflective of AD-related changes in the brain. In the current manuscript, using metabolomics-proteomics data integration, we describe new associations between peripheral and central lipid mediators, with the above-described CSF protein panels. Particularly strong associations were observed between cytochrome p450/soluble epoxide hydrolase metabolites, bile acids, and proteins involved in glycolysis, blood coagulation, and vascular inflammation and the regulators of extracellular matrix. Those metabolic associations were not observed at the gene-co-expression level in the central nervous system. In summary, this manuscript provides new information regarding Alzheimer's disease, linking both central and peripheral metabolism, and illustrates the necessity for the "omics" data integration to uncover associations beyond gene co-expression.PMID:37612324 | DOI:10.1038/s41598-023-39737-8

Chin Med J (Engl). 2023 Aug 23. doi: 10.1097/CM9.0000000000002816. Online ahead of print.ABSTRACTBACKGROUND: Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 (CTNNB1), the most frequently altered proto-oncogene in hepatic neoplasms.METHODS: Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 (β-cateninΔ(ex3)/+), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-cateninΔ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro. Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus (HBV); β-cateninlox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer.RESULTS: MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV; β-cateninlox(ex3)/+ mice, which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer.CONCLUSION: MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.PMID:37612257 | DOI:10.1097/CM9.0000000000002816

J Biol Chem. 2023 Aug 21:105186. doi: 10.1016/j.jbc.2023.105186. Online ahead of print.ABSTRACTLoss of protein kinase Cδ (PKCδ) activity renders cells resistant to DNA damaging agents, including irradiation, however the mechanism(s) underlying resistance is poorly understood. Here we have asked if metabolic reprogramming by PKCδ contributes to radioprotection. Analysis of global metabolomics showed that depletion of PKCδ affects metabolic pathways that control energy production, and antioxidant, nucleotide, and amino acid biosynthesis. Increased NADPH and nucleotide production in PKCδ depleted cells is associated with upregulation of the pentose phosphate pathway (PPP) as evidenced by increased activation of G6PD and an increase in the nucleotide precursor, 5-phosphoribosyl-1-pyrophosphate. Stable isotope tracing with U-[13C6] glucose showed reduced utilization of glucose for glycolysis in PKCδ depleted cells, and no increase in U-[13C6] glucose incorporation into purines or pyrimidines. In contrast, isotope tracing with [13C5, 15N2] glutamine showed increased utilization of glutamine for synthesis of nucleotides, glutathione and TCA intermediates, and increased incorporation of labelled glutamine into pyruvate and lactate. Using a glycolytic rate assay, we confirmed that anaerobic glycolysis is increased in PKCδ depleted cells; this was accompanied by a reduction in oxidative phosphorylation, as assayed using a mitochondrial stress assay. Importantly, pretreatment of cells with specific inhibitors of the PPP or glutaminase prior to irradiation reversed radioprotection in PKCδ depleted cells, indicating that these cells have acquired co-dependency on the PPP and glutamine for survival. Our studies demonstrate that metabolic reprogramming to increase utilization of glutamine and nucleotide synthesis contributes to radioprotection in the context of PKCδ inhibition.PMID:37611829 | DOI:10.1016/j.jbc.2023.105186

Cell Rep. 2023 Aug 18:112997. doi: 10.1016/j.celrep.2023.112997. Online ahead of print.ABSTRACTColorectal cancer (CRC) is driven by genomic alterations in concert with dietary influences, with the gut microbiome implicated as an effector in disease development and progression. While meta-analyses have provided mechanistic insight into patients with CRC, study heterogeneity has limited causal associations. Using multi-omics studies on genetically controlled cohorts of mice, we identify diet as the major driver of microbial and metabolomic differences, with reductions in α diversity and widespread changes in cecal metabolites seen in high-fat diet (HFD)-fed mice. In addition, non-classic amino acid conjugation of the bile acid cholic acid (AA-CA) increased with HFD. We show that AA-CAs impact intestinal stem cell growth and demonstrate that Ileibacterium valens and Ruminococcus gnavus are able to synthesize these AA-CAs. This multi-omics dataset implicates diet-induced shifts in the microbiome and the metabolome in disease progression and has potential utility in future diagnostic and therapeutic developments.PMID:37611587 | DOI:10.1016/j.celrep.2023.112997

Ecotoxicol Environ Saf. 2023 Aug 21;263:115393. doi: 10.1016/j.ecoenv.2023.115393. Online ahead of print.ABSTRACTChildren are disproportionately represented among those who suffer asthma, which is a kind of chronic airway inflammation. Asthma symptoms might worsen when exposed to the air pollutant particulate matter 2.5 (PM2.5). However, it is becoming more prevalent among older adults, with more asthma-related deaths occurring in this pollution than in any other age group, and symptoms caused by asthma can reduce the quality of life of the elderly, whose asthma is underdiagnosed due to physiological factors. Therefore, in an effort to discover a therapy for older asthma during exposure to air pollution, we sought to ascertain the effects of pre-exposure (PA) and persistent exposure (PAP) to PM2.5 in aged asthma rats. In this study, we exposed aged rats to PM2.5 at different times (PA and PAP) and established an ovalbumin-mediated allergic asthma model. The basic process of elderly asthma caused by PM2.5 exposure was investigated by lung function detection, enzyme-linked immunosorbent assay (ELISA), histopathology, cytology, cytokine microarray, untargeted metabolomics, and gut microbiota analysis. Our findings demonstrated that in the PA and PAP groups, exposure to PM2.5 reduced lung function and exacerbated lung tissue damage, with varying degrees of effect on immunoglobulin levels, the findings of a cytological analysis, cytokines, and chemokines. The PA and PAP rats had higher amounts of polycyclic aromatic hydrocarbons (PAHs), such as naphthalene, 2-methylNaphthalene, 1-methylNaphthalene and flourene. Moreover, exposure to PM2.5 at different times showed different effects on plasma metabolism and gut microbiota. Bioinformatics analysis showed a strong correlation between PAHs, cytokines, and gut microbiota, and PAHs may cause metabolic disorders through the gut microbiota. These findings point to a possible mechanism for the development of asthma in older people exposure to PM2.5 that may be related to past interactions between PAHs, cytokines, gut microbiota, and plasma metabolites.PMID:37611479 | DOI:10.1016/j.ecoenv.2023.115393

Phytomedicine. 2023 Aug 16;120:155037. doi: 10.1016/j.phymed.2023.155037. Online ahead of print.ABSTRACTBACKGROUND: Pudilan Xiaoyan Oral Liquid (PDL) is a famous traditional Chinese prescription recorded in the Chinese Pharmacopeia, which is widely used to treat inflammatory diseases of the respiratory tract in children and adults. However, the endogenous changes in children and adults with PDL in the treatment of acute pharyngitis remain unclear.PURPOSE: The differential regulatory roles of PDL in endogenous metabolism and gut microbes in young and adult rats were investigated with a view to providing a preclinical data reference for PDL in medication for children.METHODS: An acute pharyngitis model was established, and serum levels of inflammatory factors and histopathology were measured. This study simulated the growth and development of children in young rats and explored the endogenous metabolic characteristics and intestinal microbial composition after the intervention of PDL by using serum metabolomic technique and 16S rRNA high-throughput sequencing technique.RESULTS: The results showed that PDL had therapeutic effects on young and adult rats with acute pharyngitis. Sixteen biomarkers were identified by metabolomics in the serum of young rats and 23 in adult rats. PDL can also affect intestinal microbial diversity and community richness in young and adult rats. Alloprevotella, Allobaculum, Alistipes, Bifidobacterium, and Enterorhabdus were prominent bacteria in young rats. Bacteria from the phylum Firmicutes of the adult rats changed more significantly under the treatment of PDL. In young rats, amino acid metabolism was the primary regulatory mode of PDL, whereas, in adult rats, glycerophospholipid metabolism was studied.CONCLUSION: The regulation of PDL on the serum metabolite group and intestinal microflora in young rats was different from that in adult rats, indicating the necessity of an independent study on children's medication. PDL may also exert therapeutic effects on young and adult rats by regulating gut microbial homeostasis. The results support the clinical application of PDL.PMID:37611464 | DOI:10.1016/j.phymed.2023.155037

Comput Biol Med. 2023 Aug 10;165:107329. doi: 10.1016/j.compbiomed.2023.107329. Online ahead of print.ABSTRACTScreening potential drug-drug interactions, drug-gene interactions, contraindications, and other factors is crucial in clinical practice. However, implementing these screening concepts in real-world settings poses challenges. This work proposes an approach towards precision medicine that combines genetic and nongenetic factors to facilitate clinical decision-making. The approach focuses on raising the performance of four potential interaction screenings in the prescribing process, including drug-drug interactions, drug-gene interactions, drug-herb interactions, drug-social lifestyle interactions, and two potential considerations for patients with liver or renal impairment. The work describes the design of a curated knowledge-based model called the knowledge model for potential interaction and consideration screening, the screening logic for both the detection module and inference module, and the personalized prescribing report. Three case studies have demonstrated the proof-of-concept and effectiveness of this approach. The proposed approach aims to reduce decision-making processes for healthcare professionals, reduce medication-related harm, and enhance treatment effectiveness. Additionally, the recommendation with a semantic network is suggested to assist in risk-benefit analysis when health professionals plan therapeutic interventions with new medicines that have insufficient evidence to establish explicit recommendations. This approach offers a promising solution to implementing precision medicine in clinical practice.PMID:37611418 | DOI:10.1016/j.compbiomed.2023.107329

J Hazard Mater. 2023 Aug 19;460:132344. doi: 10.1016/j.jhazmat.2023.132344. Online ahead of print.ABSTRACTAlgal-bacterial symbiosis systems have emerged as sustainable methods for the treatment of new pollutants and the recovery of resources. However, the bio-refinery of biomass derived from microalgae is inefficient and expensive. In order to simultaneously degrade antibiotic and recover resources efficiently, two algal-bacterial symbiosis systems were constructed using Pseudomonas aeruginosa (alginate overproduction) and Bacillus subtilis (poly-γ-glutamic acid overproduction) with amoxicillin-degrading-microalga Prototheca zopfii W1. The optimal conditions for W1 to degrade amoxicillin are 35 °C, pH 7, and 180 rpm. In the presence of 5-50 mg/L of amoxicillin, W1-P. aeruginosa and W1-B. subtilis exhibit higher amoxicillin degradation and produce more extracellular polymers than W1 or bacteria alone. The metabolomic analysis demonstrates that the algal-bacterial symbiosis enhances the tolerance of W1 to amoxicillin by altering carbohydrate metabolism and promotes the production of biopolymers by upregulating the precursors synthesis. Moreover, the removal of amoxicillin (10 mg/L) from livestock effluent by W1-P. aeruginosa and W1-B. subtilis is greater than 90 % in 3 days, and the maximum yields of alginate and poly-γ-glutamate are 446.1 and 254.3 mg/g dry cell weight, respectively. These outcomes provide theoretical support for the application of algal-bacterial symbiosis systems to treatment of amoxicillin wastewater and efficient production of biopolymers.PMID:37611392 | DOI:10.1016/j.jhazmat.2023.132344

PLoS One. 2023 Aug 23;18(8):e0289272. doi: 10.1371/journal.pone.0289272. eCollection 2023.ABSTRACTQuercus mongolica is a common landscape, afforestation, and construction timber species in northern China with high ecological, economic, and ornamental value. Leaf senescence is a complex process that has important implications for plant growth and development. To explore changes of metabolites during the ageing of Quercus mongolica leaves, we investigated physiological responses and metabolite composition in ageing leaves harvested from 15-20-year-old Quercus mongolica. Leaf samples of Q. mongolica were collected when they were still green (at maturity) (stage 1), during early senescence (stage 2), and during late senescence (stage 3). These leaves were then subjected to physiological index and metabolome sequencing analyses. The physiological analysis showed that the leaves of Q. mongolica changed from green to yellow during senescence, which induced significant accumulation of soluble sugar and significant reductions in the concentration of soluble protein and chlorophyll. Peroxidase and catalase were the main antioxidant enzymes mitigating leaf senescence. Metabolomic analysis identified 797 metabolites during leaf senescence. Compared to stage 1, 70 differential metabolites were screened in stage 2 and 72 were screened in stage 3. Differential metabolites in the two senescent stages were principally enriched in amino acid metabolism, lipid metabolism and secondary metabolite biosynthesis. The contents of N-oleoylethanolamine and N, N-dimethylglycine were significantly increased only in stage 2, while the contents of trifolin, astragalin, valine, isoleucine, leucine, and citric acid were significantly increased only in stage 3. Histidine, homoserine, tryptophan, tyrosine, phenylalanine, proline, norleucine, N-glycyl-L-leucine, linoleic acid, linolenic acid, gallic acid, 3-indoleacrylic acid, 3-amino-2-naphthoic acid, 3-hydroxy-3-methylpentane-1,5-dioic acid, 2,3,4-trihydroxybenzoic acid, trifolin, astragalin, DL-2-aminoadipic acid, pinoresinol dimethyl ether, dimethylmatairesinol, and lysophosphatidylcholine increased during both stage 2 and stage 3. Increasing contents of these metabolites may constitute the main mechanism by which Q. mongolica leaves adapt to senescence.PMID:37611226 | DOI:10.1371/journal.pone.0289272

Hum Cell. 2023 Aug 23. doi: 10.1007/s13577-023-00967-7. Online ahead of print.ABSTRACTThe identification and development of therapeutic targets in cancer stem cells that lead to tumor development, recurrence, metastasis, and drug resistance is an important goal in cancer research. The hepatocellular carcinoma cell line Li-7 contains functionally different types of cells. Cells with tumor-forming activity are enriched in cancer stem cell-like CD13+CD166- cells and this cell population gradually decreases during culture in conventional culture medium (RPMI1640 containing 10% fetal bovine serum). When Li-7 cells are cultured in mTeSR1, a medium developed for human pluripotent stem cells, CD13+CD166- cells, and their tumorigenicity is maintained. Here, we sought to identify the mechanisms of tumorigenicity in this sub-population. We compared gene expression profiles of CD13+CD166- cells with other cell sub-populations and identified nine overexpressed genes (ENPP2, SCGN, FGFR4, MCOLN3, KCNJ16, SMIM22, SMIM24, SERPINH1, and TMPRSS2) in CD13+CD166- cells. After transfer from mTeSR1 to RPMI1640 containing 10% fetal bovine serum, the expression of these nine genes decreased in Li-7 cells and they lost tumorigenicity. In contrast, when these genes of Li-7 cells were forcibly expressed in cultures using RPMI1640 containing 10% fetal bovine serum, Li-7 cells maintained tumorigenicity. A metabolome analysis using capillary electrophoresis-mass spectrometry showed that two metabolic pathways, "Alanine, aspartate and glutamate metabolism" and "Arginine biosynthesis" were activated in cancer stem-cell-like cells. Our analyses here showed potential therapeutic target genes and metabolites for treatment of cancer stem cells in hepatocellular carcinoma.PMID:37610679 | DOI:10.1007/s13577-023-00967-7

Curr Nutr Rep. 2023 Aug 23. doi: 10.1007/s13668-023-00491-y. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: Existing dietary and lifestyle interventions and recommendations, to improve the risk factors of obesity and type 2 diabetes with the target to mitigate this double global epidemic, have produced inconsistent results due to interpersonal variabilities in response to these conventional approaches, and inaccuracies in dietary assessment methods. Precision nutrition, an emerging strategy, tailors an individual's key characteristics such as diet, phenotype, genotype, metabolic biomarkers, and gut microbiome for personalized dietary recommendations to optimize dietary response and health. Precision nutrition is suggested to be an alternative and potentially more effective strategy to improve dietary intake and prevention of obesity and chronic diseases. The purpose of this narrative review is to synthesize the current research and examine the state of the science regarding the effect of precision nutrition in improving the risk factors of obesity and type 2 diabetes.RECENT FINDINGS: The results of the research review indicate to a large extent significant evidence supporting the effectiveness of precision nutrition in improving the risk factors of obesity and type 2 diabetes. Deeper insights and further rigorous research into the diet-phenotype-genotype and interactions of other components of precision nutrition may enable this innovative approach to be adapted in health care and public health to the special needs of individuals. Precision nutrition provides the strategy to make individualized dietary recommendations by integrating genetic, phenotypic, nutritional, lifestyle, medical, social, and other pertinent characteristics about individuals, as a means to address the challenges of generalized dietary recommendations. The evidence presented in this review shows that precision nutrition markedly improves risk factors of obesity and type 2 diabetes, particularly behavior change.PMID:37610590 | DOI:10.1007/s13668-023-00491-y

Bioinformatics. 2023 Aug 23:btad523. doi: 10.1093/bioinformatics/btad523. Online ahead of print.ABSTRACTMOTIVATION: The method of GWAS and metabolomics combined provide an quantitative approach to pinpoint metabolic pathways and genes linked to specific diseases; however, such analyses require both genomics and metabolomics datasets from the same individuals/samples. In most cases, this approach is not feasible due to high costs, lack of technical infrastructure, unavailability of samples, and other factors. Therefore, an unmet need exists for a bioinformatics tool that can identify gene loci-associated polymorphic variants for metabolite alterations seen in disease states using standalone metabolomics.RESULTS: Here, we developed a bioinformatics tool, metGWAS 1.0, that integrates independent GWAS data from the GWAS database and standalone metabolomics data using a network-based systems biology approach to identify novel disease/trait-specific metabolite-gene associations. The tool was evaluated using standalone metabolomics datasets extracted from two metabolomics-GWAS case studies. It discovered both the observed and novel gene loci with known single nucleotide polymorphisms when compared to the original studies.AVAILABILITY AND IMPLEMENTATION: The developed metGWAS 1.0 framework is implemented in an R pipeline and available at: https://github.com/saifurbd28/metGWAS-1.0.PMID:37610350 | DOI:10.1093/bioinformatics/btad523

mSystems. 2023 Aug 23:e0066123. doi: 10.1128/msystems.00661-23. Online ahead of print.ABSTRACTDespite multiple vaccine doses early in life, a substantial proportion of infants do not mount protective responses. In this study, we followed a cohort of children over the first 2 years of life, collecting microbiome and metabolome data longitudinally to investigate correlates of lower and higher responses to primary vaccinations. We found that the stool and nasopharyngeal microbiome developed with age, though demonstrated divergent timing and patterns in maturation. When measured at child age 2 months, evenness of genera in the stool microbiome correlated with lower vaccine responses, upregulated metabolome genes that encode for lipid A biosynthesis and oxidative phosphorylation correlated with higher vaccine responses, and abundance of phenylpyruvic acid in serum correlated with lower vaccine responses, measured 10 months later. Antibiotic exposure was associated with low vaccine response, and microbiome/metabolome features at child age 2 months, before childhood vaccinations commenced, correlated with variations in vaccine responses measured at child age 1 year. These results indicate that there may be potential to intervene before first childhood vaccinations to improve later protection. IMPORTANCE We show that simultaneous study of stool and nasopharyngeal microbiome reveals divergent timing and patterns of maturation, suggesting that local mucosal factors may influence microbiome composition in the gut and respiratory system. Antibiotic exposure in early life as occurs commonly, may have an adverse effect on vaccine responsiveness. Abundance of gut and/or nasopharyngeal bacteria with the machinery to produce lipopolysaccharide-a toll-like receptor 4 agonist-may positively affect future vaccine protection, potentially by acting as a natural adjuvant. The increased levels of serum phenylpyruvic acid in infants with lower vaccine-induced antibody levels suggest an increased abundance of hydrogen peroxide, leading to more oxidative stress in low vaccine-responding infants.PMID:37610205 | DOI:10.1128/msystems.00661-23

J Asthma. 2023 Aug 23:1-15. doi: 10.1080/02770903.2023.2251062. Online ahead of print.ABSTRACTOBJECTIVE: Asthma, a common disease among children and adolescents, poses a great health risk when ignored; therefore, a thorough follow-up to prevent exacerbations is emphasized. The aim of the present study is to investigate asthma exacerbation in children during the Coronavirus disease 2019 (COVID-19) era.Data Sources: This narrative review has been done by searching the PubMed and Embase databases using Asthma, COVID-19, Pandemic, and Symptom flare up as keywords.Study Selections: Studies related to asthma exacerbation in COVID-19 pandemic were included.RESULTS: Based on studies, controlled or mild to moderate asthma has not been considered a risk factor for COVID-19 severity and has not affected hospitalization, intensive care unit (ICU) admission, and mortality. Surprisingly, emergent and non-emergent visits and asthmatic attacks decreased during the pandemic. The three main reasons for decreased incidence and exacerbation of asthma episodes in the COVID-19 era included reduced exposure to environmental allergens, increasing the acceptance of treatment by pediatrics and caregivers, and decreased risk of other respiratory viral infections. Based on the available studies, COVID-19 vaccination had no serious side effects, except in cases of uncontrolled severe asthma, and can be injected in these children. Also, there was no conclusive evidence of asthma exacerbation after the injection of COVID-19 vaccines.CONCLUSION: Further studies are recommended to follow the pattern of asthma in the post-pandemic situation and to become prepared for similar future conditions.PMID:37610180 | DOI:10.1080/02770903.2023.2251062

Nat Prod Res. 2023 Aug 23:1-5. doi: 10.1080/14786419.2023.2248648. Online ahead of print.ABSTRACTAntimicrobial potential of Citrus medica var. sarcodactylis (Siebold ex Hoola van Nooten) Swingle and Limonia acidissima L. fruits and leaves extracts CMF, CML, LAF and LAL, respectively were evaluated. Gas chromatography-mass spectrometry (GC-MS) analysis for lipoidal matters revealed a high percentage of non-oxygenated compounds. Phytol was the major in LAL. Palmitic and linoleic acid were the major in CML and LAL, respectively. Rutin and P-hydroxy benzoic acid were the main compounds identified by High-performance liquid chromatography (HPLC) analysis. The antibacterial and antifungal activities of the plants extract were determined by the well diffusion method. Antimicrobial investigation for different successive fractions of active methanol extracts of CML, LAL, LAF and CMF showed the highest activity (CML), whereas the petroleum ether (CML PE) and MeOH (CML) fractions exhibit a significant antifungal activity against Candida albicans minimum inhibitory concentration (MIC) 12 and 15 µg/mL, respectively. The antifungal activity prevailed by C. medica leaves may be attributed to its polyphenolics (rutin, chlorogenic and rosmarinic acid) in addition to phenylated hydrocarbon.PMID:37610160 | DOI:10.1080/14786419.2023.2248648

Gut Microbes. 2023 Dec;15(2):2246184. doi: 10.1080/19490976.2023.2246184.ABSTRACTOpioid crisis is an ongoing epidemic since the past several decades in the United States. Opioid use-associated microbial dysbiosis is emerging as a key regulator of intestinal homeostasis and behavioral responses to opioid. However, the mechanistic insight into the role of microbial community in modulating host response is unavailable. To uncover the role of opioid-induced dysbiosis in disrupting intestinal homeostasis we utilized whole genome sequencing, untargeted metabolomics, and mRNA sequencing to identify changes in microbiome, metabolome, and host transcriptome respectively. Morphine treatment resulted in significant expansion of Parasuterella excrementihominis, Burkholderiales bacterium 1_1_47, Enterococcus faecalis, Enterorhabdus caecimuris and depletion of Lactobacillus johnsonii. These changes correlated with alterations in lipid metabolites and flavonoids. Significant alteration in microbial metabolism (metabolism of lipids, amino acids, vitamins and cofactors) and increased expression of virulence factors and biosynthesis of lipopolysaccharides (LPS) and lipoteichoic acid (LTA) were observed in microbiome of morphine-treated animals. In concurrence with changes in microbiome and metabolome extensive changes in innate and adaptive immune response, lipid metabolism, and gut barrier dysfunction were observed in the host transcriptome. Microbiome depleted mice displayed lower levels of inflammation, immune response and tissue destruction compared to mice harboring a dysbiotic microbiome in response to morphine treatment, thus establishing dysbiotic microbiome as mediator of morphine gut pathophysiology. Integrative analysis of multi-omics data highlighted the associations between Parasutterella excrementihominis, Burkholderiales bacterium 1_1_47, Enterococcus faecalis, Enterorhabdus caecimuris and altered levels of riboflavin, flavonoids, and lipid metabolites including phosphocholines, carnitines, bile acids, and ethanolamines with host gene expression changes involved in inflammation and barrier integrity of intestine. Omic analysis also highlighted the role of probiotic bacteria Lactobacillus johnsonii, metabolites flavonoids and riboflavin that were depleted with morphine as important factors for intestinal homeostasis. This study presents for the first time ever an interactive view of morphine-induced changes in microbial metabolism, strain level gut microbiome analysis and comprehensive view of changes in gut transcriptome. We also identified areas of potential therapeutic interventions to limit microbial dysbiosis and present a unique resource to the opioid research community.PMID:37610102 | DOI:10.1080/19490976.2023.2246184

Anal Chem. 2023 Aug 23. doi: 10.1021/acs.analchem.3c02583. Online ahead of print.ABSTRACTPeak alignment is a crucial step in liquid chromatography-mass spectrometry (LC-MS)-based large-scale untargeted metabolomics workflows, as it enables the integration of metabolite peaks across multiple samples, which is essential for accurate data interpretation. Slight differences or fluctuations in chromatographic separation conditions, however, can cause the chromatographic retention time (RT) shift between consecutive analyses, ultimately affecting the accuracy of peak alignment between samples. Here, we introduce a novel RT shift correction method based on the retention index (RI) and apply it to peak alignment. We synthesized a series of N-acyl glycine (C2-C23) homologues via the amidation reaction between glycine with normal saturated fatty acids (C2-C23) as calibrants able to respond proficiently in both mass spectrometric positive- and negative-ion modes. Using these calibrants, we established an N-acyl glycine RI system. This RI system is capable of covering a broad chromatographic space and addressing chromatographic RT shift caused by variations in flow rate, gradient elution, instrument systems, and LC separation columns. Moreover, based on the RI system, we developed a peak shift correction model to enhance peak alignment accuracy. Applying the model resulted in a significant improvement in the accuracy of peak alignment from 15.5 to 80.9% across long-term data spanning a period of 157 days. To facilitate practical application, we developed a Python-based program, which is freely available at https://github.com/WHU-Fenglab/RI-based-CPSC.PMID:37609864 | DOI:10.1021/acs.analchem.3c02583

J Allergy Clin Immunol Glob. 2023 Aug;2(3):100115. doi: 10.1016/j.jacig.2023.100115. Epub 2023 May 5.ABSTRACTBACKGROUND: Asthma exacerbations are highly prevalent in children, but only a few studies have examined the biologic mechanisms underlying exacerbations in this population.OBJECTIVE: High-resolution metabolomics analyses were performed to understand the differences in metabolites in children with exacerbating asthma who were hospitalized in a pediatric intensive care unit for status asthmaticus. We hypothesized that compared with a similar population of stable outpatients with asthma, children with exacerbating asthma would have differing metabolite abundance patterns with distinct clustering profiles.METHODS: A total of 98 children aged 6 through 17 years with exacerbating asthma (n = 69) and stable asthma (n = 29) underwent clinical characterization procedures and submitted plasma samples for metabolomic analyses. High-confidence metabolites were retained and utilized for pathway enrichment analyses to identify the most relevant metabolic pathways that discriminated between groups.RESULTS: In all, 118 and 131 high-confidence metabolites were identified in positive and negative ionization mode, respectively. A total of 103 unique metabolites differed significantly between children with exacerbating asthma and children with stable asthma. In all, 8 significantly enriched pathways that were largely associated with alterations in arginine, phenylalanine, and glycine metabolism were identified. However, other metabolites and pathways of interest were also identified.CONCLUSION: Metabolomic analyses identified multiple perturbed metabolites and pathways that discriminated children with exacerbating asthma who were hospitalized for status asthmaticus. These results highlight the complex biology of inflammation in children with exacerbating asthma and argue for additional studies of the metabolic determinants of asthma exacerbations in children because many of the identified metabolites of interest may be amenable to targeted interventions.PMID:37609569 | PMC:PMC10443927 | DOI:10.1016/j.jacig.2023.100115

Front Plant Sci. 2023 Aug 7;14:1261685. doi: 10.3389/fpls.2023.1261685. eCollection 2023.NO ABSTRACTPMID:37609522 | PMC:PMC10441578 | DOI:10.3389/fpls.2023.1261685