PubMed

Phytomedicine. 2023 Sep 9;120:155056. doi: 10.1016/j.phymed.2023.155056. Online ahead of print.ABSTRACTBACKGROUND: Increasing evidence suggests that repairing the damaged intestinal epithelial barrier and restoring its function is the key to solving the problem of prolonged ulcerative colitis. Previous studies have shown that paeonol (pae) can alleviate colitis by down-regulating inflammatory pathways. In addition, pae also has a certain effect on regulating intestinal flora. However, it remains unclear whether pae can play a role in repairing the intestinal barrier and whether there is a relationship between the therapeutic effect and the gut microbiota.PURPOSES: The aim of this study is to investigate the effect of pae on intestinal barrier repair in UC mice and how the gut microbiota plays a part in it.STUDY DESIGN AND METHODS: The therapeutic effect of pae was evaluated in a 3% DSS-induced UC mouse model. The role of pae in repairing the intestinal barrier was evaluated by detecting colonic cupped cells by Alcian blue staining, the expression of colonic epithelial tight junction protein by immunofluorescence and western blot, and the proportion of IL-22+ILC3 cells in the lamina propria lymphocytes by flow cytometry. Subsequently, 16S rRNA sequencing was used to observe the changes in intestinal flora, GC-MS was used to detect the level of SCFAs, and qPCR was used to identify the abundance of Clostridium butyricum in the intestine to evaluate the effect of pae on the gut microbiota. The antibiotic-mediated depletion of the gut flora was then used to verify that pae depends on C. butyricum to play a healing role. Finally, non-targeted metabolomics was employed to investigate the potential pathways of pae regulating C. butyricum.RESULTS: Pae could improve intestinal microecological imbalance and promote the production of short-chain fatty acids (SCFAs). Most importantly, we identified C. butyricum as a key bacterium responsible for the intestinal barrier repair effect of pae in UC mice. Eradication of intestinal flora by antibiotics abolished the repair of the intestinal barrier and the promotion of SCFAs production by pae, while C. butyricum colonization could restore the therapeutic effects of pae in UC mice, which further confirmed that C. butyricum was indeed the "driver bacterium" of pae in UC treatment. Untargeted metabolomics showed that pae regulated some amino acid metabolism and 2-Oxocarboxylic acid metabolism in C. butyricum.CONCLUSIONS: Our study showed that the restoration of the impaired intestinal barrier by pae to alleviate colitis is associated with increased C. butyricum and SCFAs production, which may be a promising strategy for the treatment of UC.PMID:37703619 | DOI:10.1016/j.phymed.2023.155056

Skelet Muscle. 2023 Sep 13;13(1):16. doi: 10.1186/s13395-023-00325-z.ABSTRACTBACKGROUND: Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy without an effective treatment, caused by mutations in the DMD gene, leading to the absence of dystrophin. DMD results in muscle weakness, loss of ambulation, and death at an early age. Metabolomics studies in mdx mice, the most used model for DMD, reveal changes in metabolites associated with muscle degeneration and aging. In DMD, the tongue muscles exhibit unique behavior, initially showing partial protection against inflammation but later experiencing fibrosis and loss of muscle fibers. Certain metabolites and proteins, like TNF-α and TGF-β, are potential biomarkers for dystrophic muscle characterization.METHODS: To investigate disease progression and aging, we utilized young (1 month old) and old (21-25 months old) mdx and wild-type tongue muscles. Metabolite changes were analyzed using 1H nuclear magnetic resonance, while TNF-α and TGF-β were assessed using Western blotting to examine inflammation and fibrosis. Morphometric analysis was conducted to assess the extent of myofiber damage between groups.RESULTS: The histological analysis of the mid-belly tongue showed no differences between groups. No differences were found between the concentrations of metabolites from wild-type or mdx whole tongues of the same age. The metabolites alanine, methionine, and 3-methylhistidine were higher, and taurine and glycerol were lower in young tongues in both wild type and mdx (p < 0.001). The metabolites glycine (p < 0.001) and glutamic acid (p = 0.0018) were different only in the mdx groups, being higher in young mdx mice. Acetic acid, phosphocreatine, isoleucine, succinic acid, creatine, and the proteins TNF-α and TGF-β had no difference in the analysis between groups (p > 0.05).CONCLUSIONS: Surprisingly, histological, metabolite, and protein analysis reveal that the tongue of old mdx remains partially spared from the severe myonecrosis observed in other muscles. The metabolites alanine, methionine, 3-methylhistidine, taurine, and glycerol may be effective for specific assessments, although their use for disease progression monitoring should be cautious due to age-related changes in the tongue muscle. Acetic acid, phosphocreatine, isoleucine, succinate, creatine, TNF-α, and TGF-β do not vary with aging and remain constant in spared muscles, suggesting their potential as specific biomarkers for DMD progression independent of aging.PMID:37705069 | DOI:10.1186/s13395-023-00325-z

Metabolomics. 2023 Sep 13;19(9):83. doi: 10.1007/s11306-023-02044-4.ABSTRACTINTRODUCTION: Ischemia-reperfusion injury (IRI) induces several perturbations that alter immediate kidney graft function after transplantation and may affect long-term graft outcomes. Given the IRI-dependent metabolic disturbances previously reported, we hypothesized that proximal transporters handling endo/exogenous substrates may be victims of such lesions.OBJECTIVES: This study aimed to determine the impact of hypoxia/reoxygenation on the human proximal transport system through two semi-targeted omics analyses.METHODS: Human proximal tubular cells were cultured in hypoxia (6 or 24 h), each followed by 2, 24 or 48-h reoxygenation. We investigated the transcriptomic modulation of transporters. Using semi-targeted LC-MS/MS profiling, we characterized the extra/intracellular metabolome. Statistical modelling was used to identify significant metabolic variations.RESULTS: The expression profile of transporters was impacted during hypoxia (y + LAT1 and OCTN2), reoxygenation (MRP2, PEPT1/2, rBAT, and OATP4C1), or in both conditions (P-gp and GLUT1). The P-gp and GLUT1 transcripts increased (FC (fold change) = 2.93 and 4.11, respectively) after 2-h reoxygenation preceded by 24-h hypoxia. We observed a downregulation (FC = 0.42) of y+LAT1 after 24-h hypoxia, and of PEPT2 after 24-h hypoxia followed by 2-h reoxygenation (FC = 0.40). Metabolomics showed that hypoxia altered the energetic pathways. However, intracellular metabolic homeostasis and cellular exchanges were promptly restored after reoxygenation.CONCLUSION: This study provides insight into the transcriptomic response of the tubular transporters to hypoxia/reoxygenation. No correlation was found between the expression of transporters and the metabolic variations observed. Given the complexity of studying the global tubular transport systems, we propose that further studies focus on targeted transporters.PMID:37704888 | DOI:10.1007/s11306-023-02044-4

Sci Rep. 2023 Sep 13;13(1):15138. doi: 10.1038/s41598-023-42312-w.ABSTRACTDrug induced liver injury (DILI) is a kind of liver dysfunction which caused by drugs, and gut microbiota could affect liver injury. However, the relationship between gut microbiota and its metabolites in DILI patients is not clear. The total gut microbiota DNA was extracted from 28 DILI patient and 28 healthy control volunteers (HC) and 16S rDNA gene were amplified. Next, differentially metabolites were screened. Finally, the correlations between the diagnostic strains and differentially metabolites were studied.The richness and uniformity of the bacterial communities decreased in DILI patients, and the structure of gut microbiota changed obviously. Enterococcus and Veillonella which belong to Firmicutes increased in DILI, and Blautia and Ralstonia which belong to Firmicutes, Dialister which belongs to Proteobacteria increased in HC. In addition, these diagnostic OTUs of DILI were associated with the DILI damage mechanism. On the other hands, there were 66 differentially metabolites between DILI and HC samples, and these metabolites were mainly enriched in pyrimidine metabolism and steroid hormone biosynthesis pathways. Furthermore, the collinear network map of the key microbiota-metabolites were constructed and the results indicated that Cortodoxone, Prostaglandin I1, Bioyclo Prostaglandin E2 and Anacardic acid were positively correlated with Blautia and Ralstonia, and negatively correlated with Veillonella.This study analyzed the changes of DILI from the perspective of gut microbiota and metabolites. Key strains and differentially metabolites of DILI were screened and the correlations between them were studied. This study further illustrated the mechanism of DILI.PMID:37704684 | DOI:10.1038/s41598-023-42312-w

Sci Rep. 2023 Sep 13;13(1):15124. doi: 10.1038/s41598-023-40999-5.ABSTRACTThe mechanisms driving SARS-CoV-2 susceptibility remain poorly understood, especially the factors determining why unvaccinated individuals remain uninfected despite high-risk exposures. To understand lipid and metabolite profiles related with COVID-19 susceptibility and disease progression. We collected samples from an exceptional group of unvaccinated healthcare workers heavily exposed to SARS-CoV-2 but not infected ('non-susceptible') and subjects who became infected during the follow-up ('susceptible'), including non-hospitalized and hospitalized patients with different disease severity providing samples at early disease stages. Then, we analyzed their plasma metabolomic profiles using mass spectrometry coupled with liquid and gas chromatography. We show specific lipids profiles and metabolites that could explain SARS-CoV-2 susceptibility and COVID-19 severity. More importantly, non-susceptible individuals show a unique lipidomic pattern characterized by the upregulation of most lipids, especially ceramides and sphingomyelin, which could be interpreted as markers of low susceptibility to SARS-CoV-2 infection. This study strengthens the findings of other researchers about the importance of studying lipid profiles as relevant markers of SARS-CoV-2 pathogenesis.PMID:37704651 | DOI:10.1038/s41598-023-40999-5

Vaccine. 2023 Sep 11:S0264-410X(23)01085-X. doi: 10.1016/j.vaccine.2023.09.017. Online ahead of print.ABSTRACTPorcine epidemic diarrhea virus (PEDV) is a main cause of severe enteric disease in piglets, leading to millions of dollars lost annually in the global pig industry. Parenteral vaccination is limited in generating sufficient mucosal immunity, which is crucial for early defense against PEDV. Here, we orally administered ginseng stem-leaf saponins (GSLS) to mice before parenteral vaccination and found that GSLS significantly enhanced the phagocytosis of dendritic cells, promoted the activities of CD4+ T cells and increased PEDV-specific IgA antibodies in the intestinal mucosa. Transcriptomic results showed that the altered genes following GSLS treatment were mostly related to the immune response and metabolism. In addition, integrated analysis of the transcriptome and metabolome revealed that the mechanism by which GSLS enhances mucosal immunity may be associated with progesterone-related pathways. Further studies are needed to explore the detailed molecular mechanisms.PMID:37704497 | DOI:10.1016/j.vaccine.2023.09.017

Diabetes Care. 2023 Sep 13:dc230645. doi: 10.2337/dc23-0645. Online ahead of print.ABSTRACTOBJECTIVE: Insulin remains the only glucose-lowering treatment modality recommended for totally pancreatectomized patients. We investigated the effects of the sodium-glucose cotransporter 2 inhibitor empagliflozin on fasting and postprandial glucose concentrations in pancreatectomized patients and matched healthy control participants.RESEARCH DESIGN AND METHODS: In a randomized, double-blind, placebo-controlled crossover study, 10 pancreatectomized patients and 10 matched control participants underwent two 3-h liquid mixed meal tests preceded by two doses of 25 mg empagliflozin (administered the night before and in the morning of the meal test) or placebo, respectively. Basal insulin was administered as usual, but bolus insulin was omitted before the meal test during experimental days.RESULTS: Compared with placebo, empagliflozin lowered fasting plasma glucose (5.0 ± 0.4 vs. 7.9 ± 0.9 mmol/L [mean ± SEM], P = 0.007) and postprandial plasma glucose excursions as assessed by baseline-subtracted area under the curve (1,080 [733; 1,231] vs. 1,169 [1,036; 1,417] pmol/L × min [median (25th and 75th percentiles)], P = 0.014) in the pancreatectomized patients. In the control participants, empagliflozin lowered fasting plasma glucose compared with placebo (5.1 ± 0.1 vs. 5.5 ± 0.1 mmol/L, P = 0.008) without affecting postprandial glucose excursions significantly. The pancreatomy group exhibited greater postprandial glucagon excursions compared with the control group on both experimental days (P ≤ 0.015); no within-group differences between days were observed.CONCLUSIONS: Empagliflozin administered the day before and immediately before a standardized liquid mixed meal test normalized fasting hyperglycemia and improved postprandial glucose tolerance in pancreatectomized patients.PMID:37703527 | DOI:10.2337/dc23-0645

PLoS One. 2023 Sep 13;18(9):e0289841. doi: 10.1371/journal.pone.0289841. eCollection 2023.ABSTRACTBACKGROUND: The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine.HYPOTHESIS: Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers.METHODS: We measured the efficiency of glucuronidation in three groups of children, ASD (n = 66), ADHD (n = 46) and healthy controls (CTR, n = 37). The children were recruited from the clinics of Rutgers-NJ Medical School. A urine specimen was collected from each child. Multiple mass spectrometric analyses including the complete metabolome were determined and used to derive values for the efficiency of glucuronidation for 12 varied glucuronidation pathways including those for BPA and MEHP.RESULTS: (1) Both fold differences and metabolome analyses showed that the three groups of children were metabolically different from each other. (2) Of the 12 pathways examined, only the BPA and DEHP pathways discriminated between the three groups. (3) Glucuronidation efficiencies for BPA were reduced by 11% for ASD (p = 0.020) and 17% for ADHD (p<0.001) compared to controls. DEHP showed similar, but not significant trends.CONCLUSION: ASD and ADHD are clinically and metabolically different but share a reduction in the efficiency of detoxification for both BPA and DEHP with the reductions for BPA being statistically significant.PMID:37703261 | DOI:10.1371/journal.pone.0289841

Cell Rep. 2023 Sep 12;42(9):113120. doi: 10.1016/j.celrep.2023.113120. Online ahead of print.ABSTRACTFacioscapulohumeral muscular dystrophy (FSHD) is one of the most common neuromuscular disorders and has no cure. Due to an unknown molecular mechanism, FSHD displays overlapping manifestations with the neurodegenerative disease amyotrophic lateral sclerosis (ALS). FSHD is caused by aberrant gain of expression of the transcription factor double homeobox 4 (DUX4), which triggers a pro-apoptotic transcriptional program resulting in inhibition of myogenic differentiation and muscle wasting. Regulation of DUX4 activity is poorly known. We identify Matrin 3 (MATR3), whose mutation causes ALS and dominant distal myopathy, as a cellular factor controlling DUX4 expression and activity. MATR3 binds to the DUX4 DNA-binding domain and blocks DUX4-mediated gene expression, rescuing cell viability and myogenic differentiation of FSHD muscle cells, without affecting healthy muscle cells. Finally, we characterize a shorter MATR3 fragment that is necessary and sufficient to directly block DUX4-induced toxicity to the same extent as the full-length protein. Collectively, our data suggest MATR3 as a candidate for developing a treatment for FSHD.PMID:37703175 | DOI:10.1016/j.celrep.2023.113120

Plant Mol Biol. 2023 Sep 13. doi: 10.1007/s11103-023-01377-x. Online ahead of print.ABSTRACTSeed storage compound deposition is influenced by both maternal and filial tissues. Within this framework, we analyzed strategies that operate during the development and filling of soybean embryos, using in vitro culture systems combined with metabolomics and proteomics approaches. The carbon:nitrogen ratio (C:N) of the maternal supply and the hormone abscisic acid (ABA) are specific and interacting signals inducing differential metabolic reprogrammings linked to changes in the accumulation of storage macromolecules like proteins or oils. Differences in the abundance of sugars, amino acids, enzymes, transporters, transcription factors, and proteins involved in signaling were detected. Embryos adapted to the nutritional status by enhancing the metabolism of both carbon and nitrogen under lower C:N ratio condition or only carbon under higher C:N ratio condition. ABA turned off multiple pathways especially in high availability of amino acids, prioritizing the storage compounds biosynthesis. Common responses induced by ABA involved increased sucrose uptake (to increase the sink force) and oleosin (oil body structural component) accumulation. In turn, ABA differentially promoted protein degradation under lower nitrogen supply in order to sustain the metabolic demands. Further, the operation of a citrate shuttle was suggested by transcript quantification and enzymatic activity measurements. The results obtained are useful to help define biotechnological tools and technological approaches to improve oil and protein yields, with direct impact on human and animal nutrition as well as in green chemistry.PMID:37702897 | DOI:10.1007/s11103-023-01377-x

Environ Health Perspect. 2023 Sep;131(9):97006. doi: 10.1289/EHP12125. Epub 2023 Sep 13.ABSTRACTBACKGROUND: Parabens, found in everyday items from personal care products to foods, are chemicals with endocrine-disrupting activity, which has been shown to influence reproductive function.OBJECTIVES: This study investigated whether urinary concentrations of methylparaben, propylparaben, or butylparaben were associated with the urinary metabolome during the periconceptional period, a critical window for female reproductive function. Changes to the periconceptional urinary metabolome could provide insights into the mechanisms by which parabens could impact fertility.METHODS: Urinary paraben concentrations were measured in paired pre- and postconception urine samples from 42 participants in the Early Pregnancy Study, a prospective cohort of 221 women attempting to conceive. We performed untargeted and targeted metabolomics analyses using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry. We used principal component analysis, orthogonal partial least-squares discriminant analysis, and permutation testing, coupled with univariate statistical analyses, to find metabolites associated with paraben concentration at the two time points. Potential confounders were identified with a directed acyclic graph and used to adjust results with multivariable linear regression. Metabolites were identified using fragmentation data.RESULTS: Seven metabolites were associated with paraben concentration (variable importance to projection score >1, false discovery rate-corrected q-value<0.1). We identified four diet-related metabolites to the Metabolomics Standards Initiative (MSI) certainty of identification level 2, including metabolites from smoke flavoring, grapes, and olive oil. One metabolite was identified to the class level only (MSI level 3). Two metabolites were unidentified (MSI level 4). After adjustment, three metabolites remained associated with methylparaben and propylparaben, two of which were diet-related. No metabolomic markers of endocrine disruption were associated with paraben concentrations.DISCUSSION: This study identified novel relationships between urinary paraben concentrations and diet-related metabolites but not with metabolites on endocrine-disrupting pathways, as hypothesized. It demonstrates the feasibility of integrating untargeted metabolomics data with environmental exposure information and epidemiological adjustment for confounders. The findings underscore a potentially important connection between diet and paraben exposure, with applications to nutritional epidemiology and dietary exposure assessment. https://doi.org/10.1289/EHP12125.PMID:37702489 | DOI:10.1289/EHP12125

Curr Drug Res Rev. 2023 Sep 12. doi: 10.2174/2589977516666230912120412. Online ahead of print.ABSTRACTBACKGROUND: Cancer is amongst the most dreadful ailments of modern times, and its impact continuously worsens global health systems. Early diagnosis and suitable therapeutic agents are the prime keys to managing this disease. Metabolomics deals with the complete profiling of cells and physiological phenomena in their organelles, thus helping in keen knowledge of the pathological status of the disease. It has been proven to be one of the best strategies in the early screening of cancer.OBJECTIVE: This review has covered the recent updates on the promising role of metabolomics in the identification of significant biochemical markers in cancer-prone individuals that could lead to the identification of cancer in the early stages.METHODS: The literature was collected through various databases, like Scopus, PubMed, and Google Scholar, with stress laid on the last ten years' publications.CONCLUSION: It was assessed in this review that early recognition of cancerous growth could be achieved via complete metabolic profiling in association with transcriptomics and proteomics. The outcomes are rooted in various clinical studies that anticipated various biomarkers like tryptophan, phenylalanine, lactates, and different metabolic pathways associated with the Warburg effect. This metabolite imaging has been a fundamental step for the target acquisition, evaluation of predictive cancer biomarkers for early detection, and outlooks into cancer therapy along with critical evaluation. Significant efforts should be made to make this technique most reliable and easy.PMID:37702236 | DOI:10.2174/2589977516666230912120412

Curr Pharm Biotechnol. 2023 Sep 12. doi: 10.2174/1389201025666230912123849. Online ahead of print.ABSTRACTBACKGROUND: Antibiotic resistance is a serious public health problem as it causes previously manageable diseases to become deadly infections that can cause serious disability or even death. Scientists are creating novel approaches and procedures that are essential for the treatment of infections and limiting the improper use of antibiotics in an effort to counter this rising risk.OBJECTIVE: With a focus on the numerous postbiotic metabolites formed from the beneficial gut microorganisms, their potential antimicrobial actions, and recent associated advancements in the food and medical areas, this review presents an overview of the emerging ways to prevent antibiotic resistance.RESULTS: Presently, scientific literature confirms that plant-derived antimicrobials, RNA therapy, fecal microbiota transplantation, vaccines, nanoantibiotics, haemofiltration, predatory bacteria, immunotherapeutics, quorum-sensing inhibitors, phage therapies, and probiotics can be considered natural and efficient antibiotic alternative candidates. The investigations on appropriate probiotic strains have led to the characterization of specific metabolic byproducts of probiotics named postbiotics. Based on preclinical and clinical studies, postbiotics with their unique characteristics in terms of clinical (safe origin, without the potential spread of antibiotic resistance genes, unique and multiple antimicrobial action mechanisms), technological (stability and feasibility of large-scale production), and economic (low production costs) aspects can be used as a novel alternative agent or adjuvant for the common antibiotics utilized in the production of animal-based foods.CONCLUSION: Postbiotic constituents may be a new approach for utilization in the pharmaceutical and food sectors for developing therapeutic treatments. Further metabolomics investigations are required to describe novel postbiotics and clinical trials are also required to define the sufficient dose and optimum administration frequency of postbiotics.PMID:37702234 | DOI:10.2174/1389201025666230912123849

Front Genet. 2023 Aug 28;14:1234263. doi: 10.3389/fgene.2023.1234263. eCollection 2023.ABSTRACTIntroduction: Cervical cancer remains a significant global health burden, and Doxorubicin is a crucial therapeutic agent against this disease. However, the precise molecular mechanisms responsible for its therapeutic effects are not fully understood. Methods: In this study, we employed a multi-omics approach that combined transcriptomic and metabolomic analyses with cellular and in vivo experiments. The goal was to comprehensively investigate the molecular landscape associated with Doxorubicin treatment in cervical cancer. Results: Our unbiased differential gene expression analysis revealed distinct alterations in gene expression patterns following Doxorubicin treatment. Notably, the ANKRD18B gene exhibited a prominent role in the response to Doxorubicin. Simultaneously, our metabolomic analysis demonstrated significant perturbations in metabolite profiles, with a particular focus on L-Ornithine. The correlation between ANKRD18B gene expression and L-Ornithine levels indicated a tightly controlled gene-metabolite network. These results were further confirmed through rigorous cellular and in vivo experiments, which showed reductions in subcutaneous tumor size and significant changes in ANKRD18B, L-Ornithine, and Doxorubicin concentration. Discussion: The findings of this study underscore the intricate interplay between transcriptomic and metabolomic changes in response to Doxorubicin treatment. These insights could have implications for the development of more effective therapeutic strategies for cervical cancer. The identification of ANKRD18B and L-Ornithine as key components in this process lays the groundwork for future research aiming to unravel the complex molecular networks that underlie Doxorubicin's therapeutic mechanism. While this study provides a solid foundation, it also highlights the necessity for further investigation to fully grasp these interactions and their potential implications for cervical cancer treatment.PMID:37701623 | PMC:PMC10494242 | DOI:10.3389/fgene.2023.1234263

Hortic Res. 2023 Aug 1;10(9):uhad152. doi: 10.1093/hr/uhad152. eCollection 2023 Sep.ABSTRACTThe development of tree peony annual shoots is characterized by "withering", which is related to whether there are bud points in the leaf axillaries of annual shoots. However, the mechanism of "withering" in tree peony is still unclear. In this study, Paeonia ostii 'Fengdan' and P. suffruticosa 'Luoyanghong' were used to investigate dynamic changes of annual shoots through anatomy, physiology, transcriptome, and metabolome. The results demonstrated that the developmental dynamics of annual shoots of the two cultivars were comparable. The withering degree of P. suffruticosa 'Luoyanghong' was higher than that of P. ostii 'Fengdan', and their upper internodes of annual flowering shoots had a lower degree of lignin deposition, cellulose, C/N ratio, showing no obvious sclerenchyma, than the bottom ones and the whole internodes of vegetative shoot, which resulted in the "withering" of upper internodes. A total of 36 phytohormone metabolites were detected, of which 33 and 31 were detected in P. ostii 'Fengdan' and P. suffruticosa 'Luoyanghong', respectively. In addition, 302 and 240 differentially expressed genes related to lignin biosynthesis, carbon and nitrogen metabolism, plant hormone signal transduction, and zeatin biosynthesis were screened from the two cultivars. Furtherly, 36 structural genes and 40 transcription factors associated with the development of annual shoots were highly co-expressed, and eight hub genes involved in this developmental process were identified. Consequently, this study explained the developmental dynamic on the varied annual shoots through multi-omics, providing a theoretical foundation for germplasm innovation and the mechanized harvesting of tree peony annual shoots.PMID:37701456 | PMC:PMC10493643 | DOI:10.1093/hr/uhad152

Conserv Physiol. 2023 Jun 10;11(1):coad040. doi: 10.1093/conphys/coad040. eCollection 2023.ABSTRACTFreshwater mussels (order Unionida) play a key role in freshwater systems as ecosystem engineers and indicators of aquatic ecosystem health. The fauna is globally imperilled due to a diversity of suspected factors; however, causes for many population declines and mortality events remain unconfirmed due partly to limited health assessment tools. Mussel-monitoring activities often rely on population-level measurements, such as abundance and age structure, which reflect delayed responses to environmental conditions. Measures of organismal health would enable preemptive detection of declining condition before population-level effects manifest. Metabolomic analysis can identify shifts in biochemical pathways in response to stressors and changing environmental conditions; however, interpretation of the results requires information on inherent variability of metabolite concentrations in mussel populations. We targeted metabolites in the haemolymph of two common mussels, Lampsilis cardium and Lampsilis siliquoidea, from three Indiana streams (USA) using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectroscopy. The influence of species, stream and sex on metabolite variability was examined with distance-based redundancy analysis. Metabolite variability was most influenced by species, followed by site and sex. Inter- and intraspecies metabolite variability among sexes was less distinct than differences among locations. We further categorized metabolites by occurrence and variability in mussel populations. Metabolites with high occurrence (Categories 1 and 2) included those indicative of energy status (catabolism versus anabolism; arginine, proline, carnitine, nicotinic acid, pantothenic acid), oxidative stress (proline, glutamine, glutamate) and protein metabolism (thymidine, cytidine, inosine). Metabolites with lower occurrence (Category 3) are constituents of assorted metabolic pathways and can be important biomarkers with additional temporal sampling to characterize their variability. These data provide a reference for future temporal (before/after) monitoring and for studies of stressor-metabolite linkages in freshwater mussels.PMID:37701372 | PMC:PMC10494281 | DOI:10.1093/conphys/coad040

Front Microbiol. 2023 Aug 28;14:1247251. doi: 10.3389/fmicb.2023.1247251. eCollection 2023.ABSTRACTYak (Bos grunniens) is an important economic animal species on the Qinghai-Tibet Plateau. Yaks grazed in the cold season often suffer from nutritional stress, resulting in low production performance. This situation can be improved by properly feeding the grazing yaks in the cold season; however, there is still little information about the effect of different feeding levels on the intestinal microflora and metabolites of yaks. Therefore, this study aimed to explore the effect of feeding different doses of concentrate supplements on rumen bacterial communities and metabolites in grazing yaks during the cold season. Feed concentrate supplementation significantly improved the production performance and rumen fermentation status of grazing yaks during the cold season, and switched the type of ruminal fermentation from acetic acid fermentation to propionic acid fermentation. Ruminal fermentation parameters and ruminal bacterial abundance correlated strongly. At the phylum level, the abundance of Firmicutes increased with increasing concentrate supplementation, while the opposite was true for Bacteroidota. At the genus level, the abundance of Christensenellaceae_R-7_group, NK4A214_group, Ruminococcus, norank_f__Eubacterium_coprostanoligenes_group, norank_f__norank_o__ Clostridia_UCG-014, Lachnospiraceae_NK3A20_group, Acetitomaculum, and Family_XIII_AD3011_group increased with increasing concentrate supplementation, while the abundance of Rikenellaceae_RC9_gut_ group decreased. Dietary concentrate supplementation altered the concentration and metabolic mode of metabolites in the rumen, significantly affecting the concentration of metabolites involved in amino acid and derivative metabolism (e.g., L-aspartic acid, L-glutamate, and L-histidine), purine metabolism (e.g., guanine, guanosine, and hypoxanthine), and glycerophospholipid metabolism (e.g., phosphatidate, phosphatidylcholine, and phosphocholine), and other metabolic pathways. The strong correlation between yak rumen microorganisms and metabolites provided a more comprehensive understanding of microbial community composition and function. This study showed significant changes in the composition and abundance of bacteria and metabolites in the rumen of cool season grazing yaks fed with concentrate supplements. Changes in ruminal fermentation parameters and metabolite concentration also showed a strong correlation with ruminal bacterial communities. These findings will be helpful to formulate supplementary feeding strategies for grazing yaks in the cold season from the perspective of intestinal microorganisms.PMID:37700865 | PMC:PMC10494446 | DOI:10.3389/fmicb.2023.1247251

J Clin Biochem Nutr. 2023 Sep;73(2):161-171. doi: 10.3164/jcbn.22-110. Epub 2023 Sep 1.ABSTRACTMetabolic differences between colorectal cancer (CRC) and NI (NI) play an important role in early diagnoses and in-time treatments. We investigated the metabolic alterations between CRC patients and NI, and identified some potential biomarkers, and these biomarkers might be used as indicators for diagnosis of CRC. In this study, there were 79 NI, 50 CRC I patients, 52 CRC II patients, 56 CRC III patients, and 52 CRC IV patients. MS-MS was used to measure the metabolic alterations. Univariate and multivariate data analysis and metabolic pathway analysis were applied to analyze metabolic data and determine differential metabolites. These indicators revealed that amino acid and fatty acids could separate these groups. Several metabolites indicated an excellent variables capability in the separation of CRC patients and NI. Ornithine, arginine, octadecanoyl carnitine, palmitoyl carnitine, adipoyl carnitine, and butyryl carnitine/propanoyl carnitine were selected to distinguish the CRC patients and NI. And methionine and propanoyl carnitine, were directly linked to different stages of CRC. Receiver operating characteristics curves and variables importance in projection both represented an excellent performance of these metabolites. In conclusion, we assessed the difference between CRC patients and NI, which supports guidelines for an early diagnosis and effective treatment.PMID:37700848 | PMC:PMC10493213 | DOI:10.3164/jcbn.22-110

Sci Rep. 2023 Sep 12;13(1):15036. doi: 10.1038/s41598-023-41835-6.ABSTRACTPancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival. To explore an uncharted function of K-Ras proto-oncogene, K-Ras was activated in mesenchymal stem cells (MSCs) and the effects of MSC conditioned medium (CM) on PDAC were examined. Overexpression of K-Ras elevated PI3K signaling in MSCs, and K-Ras/PI3K-activated MSC-derived CM reduced the proliferation and migration of tumor cells, as well as the growth of ex vivo freshly isolated human PDAC cultures. CM's anti-tumor capability was additive with Gemcitabine, a commonly used chemotherapeutic drug in the treatment of PDAC. The systemic administration of CM in a mouse model suppressed the colonization of PDAC in the lung. MSC CM was enriched with Moesin (MSN), which acted as an extracellular tumor-suppressing protein by interacting with CD44. Tumor-suppressive CM was also generated by PKA-activated peripheral blood mononuclear cells. Collectively, this study demonstrated that MSC CM can be engineered to act as a tumor-suppressive agent by activating K-Ras and PI3K, and the MSN-CD44 regulatory axis is in part responsible for this potential unconventional option in the treatment of PDAC.PMID:37699930 | PMC:PMC10497626 | DOI:10.1038/s41598-023-41835-6

Sci Total Environ. 2023 Sep 10:166973. doi: 10.1016/j.scitotenv.2023.166973. Online ahead of print.ABSTRACTA challenge in bee protection is to assess the risks of pesticide-pathogen interactions. Lotmaria passim, a ubiquitous unicellular parasite in honey bees, is considered harmful under specific conditions. Imidacloprid causes unpredictable side effects. Research indicates that both L. passim and imidacloprid may affect the physiology, behavior, immunity, microbiome and lifespan of honey bees. We designed cage experiments to test whether the infection of L. passim is affected by a sublethal dose of imidacloprid. Workers collected at the time of emergence were exposed to L. passim and 2.5 μg/L imidacloprid in the coexposure treatment group. First, samples of bees were taken from cages since they were 5 days old and 3 days postinfection, i.e., after finishing an artificial 24 h L. passim infection. Additional bees were collected every two additional days. In addition, bees frozen at the time of emergence and collected from the unexposed group were analyzed. Abdomens were analyzed using qPCR to determine parasite load, while corresponding selected heads were subjected to a label-free proteomic analysis. Our results show that bees are free of L. passim at the time of emergence. Furthermore, imidacloprid considerably increased the prevalence as well as parasite loads in individual bees. This means that imidacloprid facilitates infection, enabling faster parasite spread in a colony and potentially to surrounding colonies. The proteomic analysis of bee heads showed that imidacloprid neutralized the increased transferrin 1 expression by L. passim. Importantly, this promising marker has been previously observed to be upregulated by infections, including gut parasites. This study contributes to understanding the side effects of imidacloprid and demonstrates that a single xenobiotic/pesticide compound can interact with the gut parasite. Our methodology can be used to assess the effects of different compounds on L. passim.PMID:37699488 | DOI:10.1016/j.scitotenv.2023.166973