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MSphere Jul 2024Ticks, like other obligatory blood-feeding arthropods, rely on endosymbiotic bacteria to supplement their diet with B vitamins lacking in blood. It has been suggested...
UNLABELLED
Ticks, like other obligatory blood-feeding arthropods, rely on endosymbiotic bacteria to supplement their diet with B vitamins lacking in blood. It has been suggested that additional metabolites such as L-proline may be involved in this nutritional symbiosis, but this has yet to be tested. Here, we studied the metabolite-based interaction between the brown dog tick (Acari: Ixodidae) and its like endosymbionts (CLE). We measured amino acid titers and tested the effect of B vitamins and L-proline supplementation on the fitness of CLE-suppressed female ticks, displaying low titers of CLE. We found higher titers of L-proline in the symbiont-hosting organs of unfed ticks and in engorged blood-fed whole ticks. Supplementation of B vitamins increased the hatching rate of CLE-suppressed ticks; this effect appears to be stronger when L-proline is added. Our results indicate that L-proline is produced by CLE, and we suggest that CLE is essential in states of high metabolic demand that affects tick reproductive fitness, such as oogenesis and embryonic development. These findings demonstrate the broader effect of nutritional symbionts on their hosts and may potentially contribute to the control of ticks and tick-borne diseases.
IMPORTANCE
-like endosymbionts (CLE) are essential to the brown dog tick for feeding and reproduction. This symbiosis is based on the supplementation of B vitamins lacking in the blood diet. The involvement of additional metabolites has been suggested, but no experimental evidence is available as yet to confirm a metabolic interaction. Here, we show that B vitamins and L-proline, both of which contribute to tick reproductive fitness, are produced by CLE. These findings demonstrate the importance of symbiont-derived metabolites for the host's persistence and shed light on the complex bacteria-host metabolic interaction, which can be channeled to manipulate and control tick populations.
PubMed: 38953331
DOI: 10.1128/msphere.00693-23 -
Natural Product Research Jul 2024The pantropical are traditionally used for the prevention and treatment of various illnesses, diseases, and cancers. While most earlier studies on the species have...
The pantropical are traditionally used for the prevention and treatment of various illnesses, diseases, and cancers. While most earlier studies on the species have focused on the phytochemistry of the leaf and stem extracts, recent studies have indicated that its fruit may contain bioactive compounds of medical interest. In this study, we investigated the cytotoxicity of extracts from the fruit of against colorectal cancer cell lines and revealed its phytochemical profile high-resolution tandem mass spectrometry analysis. Following a 24-h treatment with the fruit extract, cytoplasm shrinkage and nucleus condensation were observed in the colorectal cancer cell lines HCT116 and HT29, indicating the induction of programmed cell death. Phytochemically, 71 putative metabolites were identified. Some of these metabolites have been reported to inhibit cancers to varying degrees, further supporting the correlation of the putative metabolites with the cytotoxicity against colorectal cancer cells demonstrated in this study.
PubMed: 38953123
DOI: 10.1080/14786419.2024.2370521 -
Frontiers in Pharmacology 2024Ezetimibe, which lowers cholesterol by blocking the intestinal cholesterol transporter Niemann-Pick C1 like 1, is reported to reduce hepatic steatosis in humans and...
BACKGROUND
Ezetimibe, which lowers cholesterol by blocking the intestinal cholesterol transporter Niemann-Pick C1 like 1, is reported to reduce hepatic steatosis in humans and animals. Here, we demonstrate the changes in hepatic metabolites and lipids and explain the underlying mechanism of ezetimibe in hepatic steatosis.
METHODS
We fed Otsuka Long-Evans Tokushima Fatty (OLETF) rats a high-fat diet (60 kcal % fat) with or vehicle (control) or ezetimibe (10 mg kg) via stomach gavage for 12 weeks and performed comprehensive metabolomic and lipidomic profiling of liver tissue. We used rat liver tissues, HepG2 hepatoma cell lines, and siRNA to explore the underlying mechanism.
RESULTS
In OLETF rats on a high-fat diet, ezetimibe showed improvements in metabolic parameters and reduction in hepatic fat accumulation. The comprehensive metabolomic and lipidomic profiling revealed significant changes in phospholipids, particularly phosphatidylcholines (PC), and alterations in the fatty acyl-chain composition in hepatic PCs. Further analyses involving gene expression and triglyceride assessments in rat liver tissues, HepG2 hepatoma cell lines, and siRNA experiments unveiled that ezetimibe's mechanism involves the upregulation of key phospholipid biosynthesis genes, CTP:phosphocholine cytidylyltransferase alpha and phosphatidylethanolamine N-methyl-transferase, and the phospholipid remodeling gene lysophosphatidylcholine acyltransferase 3.
CONCLUSION
This study demonstrate that ezetimibe improves metabolic parameters and reduces hepatic fat accumulation by influencing the composition and levels of phospholipids, specifically phosphatidylcholines, and by upregulating genes related to phospholipid biosynthesis and remodeling. These findings provide valuable insights into the molecular pathways through which ezetimibe mitigates hepatic fat accumulation, emphasizing the role of phospholipid metabolism.
PubMed: 38953111
DOI: 10.3389/fphar.2024.1406493 -
Data in Brief Aug 2024Despite epidemiological indications, utility of metformin in liver cancer remains debated and the understanding of the mechanism underlying its anti-cancer effects...
Despite epidemiological indications, utility of metformin in liver cancer remains debated and the understanding of the mechanism underlying its anti-cancer effects remains incomplete. Particularly, whether it operates via similar mechanism under glucose-sufficient and glucose- deficient environments or whether these effects are reversible remains unexplored. This metabolomic dataset was collected from liver cancer (HepG2) cells treated with metformin or placebo over a period of 3 h to 48 h as well as from cells recovering after metformin withdrawal. Cells were exposed to placebo or 2.5 mM metformin with or without glucose (5 mM) supplementation. The cells were harvested at 3, 6, 12, 24, and 48 h post-treatment. Cells were also harvested after 24 h of treatment under one of these conditions followed by reversal of glucose and/or metformin exposure status for 48 h. Metabolites from six biological replicates of each experimental group were extracted using chilled monophasic metabolite extraction solvent (Water: Acetonitrile: Isopropanol= 2:3:3) containing homovanillic acid as an internal standard. Samples were derivatized using MOX reagent followed by MSTFA. Untargeted metabolomic profiling of derivatized samples were performed using an Agilent 7890B gas chromatograph coupled to a 5977B single quadrupole mass spectrometer. Analytes were injected through a splitless liner and separated on a HP-5MS ultra-inert column using ultrapure helium as the carrier gas. Peak alignment, annotation, and integration were done using Agilent MassHunter Quantitative analysis software. Multivariate analysis was performed using MetaboAnalyst 5.0. These experiments were performed to unravel the longitudinal evolution of cellular metabolome in response to metformin treatment, its glucose dependence, as well as to examine the reversibility of these changes. The dataset can help to identify glucose-independent pathways involved in anti-cancer effect of metformin. The dataset can be used to design experiments to develop novel therapeutic combinations synergistically acting with metformin to cripple the metabolic fitness of cancer cells. It can also help to develop experiments to test the effect of metformin withdrawal in liver cancer.
PubMed: 38952952
DOI: 10.1016/j.dib.2024.110562 -
Frontiers in Neuroscience 2024Evidence has demonstrated that exoskeleton robots can improve intestinal function in patients with spinal cord injury (SCI). However, the underlying mechanisms remain...
Evidence has demonstrated that exoskeleton robots can improve intestinal function in patients with spinal cord injury (SCI). However, the underlying mechanisms remain unelucidated. This study investigated the effects of exoskeleton-assisted walking (EAW) on intestinal function and intestinal flora structure in T2-L1 motor complete paraplegia patients. The results showed that five participants in the EAW group and three in the conventional group reported improvements in at least one bowel management index, including an increased frequency of bowel evacuations, less time spent on bowel management per day, and less external assistance (manual digital stimulation, medication, and enema usage). After 8 weeks of training, the amount of glycerol used in the EAW group decreased significantly (0.05). The EAW group showed an increasing trend in the neurogenic bowel dysfunction (NBD) score after 8 weeks of training, while the conventional group showed a worsening trend. Patients who received the EAW intervention exhibited a decreased abundance of and , while , , and were upregulated. In addition, there were decreases in the abundances of , , , , , , and . In contrast, , , , , , , and showed upregulation among the top 15 genera. The abundance of was significantly higher in the EAW group than in the conventional group, and increased significantly in EAW individuals at 8 weeks. This study suggests that EAW can improve intestinal function of SCI patients in a limited way, and may be associated with changes in the abundance of intestinal flora, especially an increase in beneficial bacteria. In the future, we need to further understand the changes in microbial groups caused by EAW training and all related impact mechanisms, especially intestinal flora metabolites. : https://www.chictr.org.cn/.
PubMed: 38952922
DOI: 10.3389/fnins.2024.1395671 -
Frontiers in Plant Science 2024Arsenate, a metalloid, acting as an analog to phosphate, has a tendency to accumulate more readily in plant species, leading to adverse effects.
INTRODUCTION
Arsenate, a metalloid, acting as an analog to phosphate, has a tendency to accumulate more readily in plant species, leading to adverse effects.
METHODS
In the current study, sunflower seedlings were exposed to 25, 50 and 100 ppm of the arsenic.
RESULTS
Likewise, a notable reduction (p<0.05) was observed in the relative growth rate (RGR) by 4-folds and net assimilation rate (NAR) by 75% of when subjected to arsenic (As) stress. Nevertheless, the presence of , a plant growth-promoting rhizobacterium with As tolerance, yielded an escalation in the growth of within As-contaminated media. facilitated the conversion of As into a form accessible to plants, thereby, increasing its uptake and subsequent accumulation in plant tissues. encouraged the enzymatic antioxidant systems (Superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX) and catalase (CAT)) and non-enzymatic antioxidants (flavonoids, phenolics, and glutathione) in seedlings following substantial As accumulation. The strain also induced the host plant to produce osmolytes like proline and sugars, mitigating water loss and maintaining cellular osmotic balance under As-induced stress. rectified imbalances in lignin content, reduced high malonaldehyde (MDA) levels, and minimized electrolyte leakage, thus counteracting the toxic impacts of the metal.
CONCLUSION
The strain exhibited the capability to concurrently encourage plant growth and remediate Ascontaminated growth media through 2-folds rate of biotransformation and bio-mobilization.
PubMed: 38952849
DOI: 10.3389/fpls.2024.1391348 -
Frontiers in Plant Science 2024is a traditional Chinese herb that has gained much attention for its production of Huperzine A (HupA). HupA has shown promise on treating Alzheimer's disease (AD)....
INTRODUCTION
is a traditional Chinese herb that has gained much attention for its production of Huperzine A (HupA). HupA has shown promise on treating Alzheimer's disease (AD). However, the biosynthetic pathway and molecular mechanism of HupA in are still not well understood.
METHODS
Integrated transcriptome and metabolome analysis was performed to reveal the molecular mechanisms related to HupA biosynthesis and antioxidant activity in .
RESULTS
HT ( thallus) exhibits higher antioxidant activity and lower cytotoxicity than WH (wild ). Through hierarchical clustering analysis and qRT-PCR verification, 7 important enzyme genes and 13 transcription factors (TFs) related to HupA biosynthesis were detected. Among them, the average |logFC| value of (Cytochrome P450) and (Copper amine oxidase) was the largest. Metabolomic analysis identified 12 metabolites involved in the HupA biosynthesis and 29 metabolites related to antioxidant activity. KEGG co-enrichment analysis revealed that tropane, piperidine and pyridine alkaloid biosynthesis were involved in the HupA biosynthesis pathway. Furthermore, the phenylpropanoid, phenylalanine, and flavonoid biosynthesis pathway were found to regulate the antioxidant activity of . The study also identified seven important genes related to the regulation of antioxidant activity, including (primary-amine oxidase). Based on the above joint analysis, the biosynthetic pathway of HupA and potential mechanisms of antioxidant in was constructed.
DISCUSSION
Through differential transcriptome and metabolome analysis, DEGs and DAMs involved in HupA biosynthesis and antioxidant-related were identified, and the potential metabolic pathway related to HupA biosynthesis and antioxidant in were constructed. This study would provide valuable insights into the HupA biosynthesis mechanism and the thallus medicinal value.
PubMed: 38952843
DOI: 10.3389/fpls.2024.1411471 -
BioRxiv : the Preprint Server For... May 2024COVID-19 significantly decreases amino acids, fatty acids, and most eicosanoidsSARS-CoV-2 preferentially localizes to central lung tissueMetabolic disturbance is highest...
COVID-19 significantly decreases amino acids, fatty acids, and most eicosanoidsSARS-CoV-2 preferentially localizes to central lung tissueMetabolic disturbance is highest in peripheral tissue, not central like viral loadSpatial metabolomics allows detection of metabolites not altered overallSARS-CoV-2, the virus responsible for COVID-19, is a highly contagious virus that can lead to hospitalization and death. COVID-19 is characterized by its involvement in the lungs, particularly the lower lobes. To improve patient outcomes and treatment options, a better understanding of how SARS-CoV-2 impacts the body, particularly the lower respiratory system, is required. In this study, we sought to understand the spatial impact of COVID-19 on the lungs of mice infected with mouse-adapted SARS2-N501Y . Overall, infection caused a decrease in fatty acids, amino acids, and most eicosanoids. When analyzed by segment, viral loads were highest in central lung tissue, while metabolic disturbance was highest in peripheral tissue. Infected peripheral lung tissue was characterized by lower levels of fatty acids and amino acids when compared to central lung tissue. This study highlights the spatial impacts of SARS-CoV-2 and helps explain why peripheral lung tissue is most damaged by COVID-19.
PubMed: 38952797
DOI: 10.1101/2024.05.22.595414 -
MedRxiv : the Preprint Server For... Jun 2024The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown.
BACKGROUND
The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown.
OBJECTIVE
To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multi-ethnic cohorts and responses to OIT.
METHODS
Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N=384), a Costa Rican cohort of children with asthma (N=1040), and a peanut OIT trial (N=20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterwards). Generalized linear regression modeling and pathway enrichment analysis identified metabolites associated with food allergy and OIT outcomes.
RESULTS
Compared with unaffected children, those with food allergy were more likely to have metabolomic profiles with altered histidines and increased bile acids. Eicosanoids (e.g., arachidonic acid derivatives) (q=2.4×10 ) and linoleic acid derivatives (q=3.8×10 ) pathways decreased over time on OIT. Comparing SU versus TD revealed differing concentrations of bile acids (q=4.1×10 ), eicosanoids (q=7.9×10 ), and histidine pathways (q=0.015). In particular, the bile acid lithocholate (4.97[1.93,16.14], p=0.0027), the eicosanoid leukotriene B4 (3.21[1.38,8.38], p=0.01), and the histidine metabolite urocanic acid (22.13[3.98,194.67], p=0.0015) were higher in SU.
CONCLUSIONS
We observed distinct profiles of bile acids, histidines, and eicosanoids that vary among patients with food allergy, over time on OIT and between SU and TD. Participants with SU had higher levels of metabolites such as lithocholate and urocanic acid, which have immunomodulatory roles in key T-cell subsets, suggesting potential mechanisms of tolerance in immunotherapy.
KEY MESSAGES
- Compared with unaffected controls, children with food allergy demonstrated higher levels of bile acids and distinct histidine/urocanic acid profiles, suggesting a potential role of these metabolites in food allergy. - In participants receiving oral immunotherapy for food allergy, those who were able to maintain tolerance-even after stopping therapyhad lower overall levels of bile acid and histidine metabolites, with the exception of lithocholic acid and urocanic acid, two metabolites that have roles in T cell differentiation that may increase the likelihood of remission in immunotherapy.
CAPSULE SUMMARY
This is the first study of plasma metabolomic profiles of responses to OIT in individuals with IgE-mediated food allergy. Identification of immunomodulatory metabolites in allergic tolerance may help identify mechanisms of tolerance and guide future therapeutic development.
PubMed: 38952781
DOI: 10.1101/2024.05.31.24308233 -
Vavilovskii Zhurnal Genetiki I Selektsii Jun 2024Beneficial endophytic bacteria can suppress the development of insect pests through direct antagonism, with the help of metabolites, or indirectly by the induction of...
Beneficial endophytic bacteria can suppress the development of insect pests through direct antagonism, with the help of metabolites, or indirectly by the induction of systemic resistance through the regulation of hormonal signaling pathways. Lipopeptides are bacterial metabolites that exhibit direct antagonistic activity against many organisms, including insects. Also, lipopeptides are able to trigger induced systemic resistance (ISR) in plants against harmful organisms, but the physiological mechanisms of their action are just beginning to be studied. In this work, we studied ten strains of bacteria isolated from the tissues of wheat and potatoes. Sequencing of the 16S rRNA gene showed that all isolates belong to the genus Bacillus and to two species, B. subtilis and B. velezensis. The genes for lipopeptide synthetase - surfactin synthetase (Bs_srf ), iturin synthetase (Bs_ituA, Bs_ituB) and fengycin synthetase (Bs_fenD) - were identified in all bacterial isolates using PCR. All strains had high aphicidal activity against the Greenbug aphid (Schizaphis graminum Rond.) due to the synthesis of lipopeptides, which was proven using lipopeptide-rich fractions (LRFs) isolated from the strains. Endophytic lipopeptide-synthesizing strains of Bacillus spp. indirectly affected the viability of aphids, the endurance of plants against aphids and triggered ISR in plants, which manifested itself in the regulation of oxidative metabolism and the accumulation of transcripts of the Pr1, Pr2, Pr3, Pr6 and Pr9 genes due to the synthesis of lipopeptides, which was proven using LRF isolated from three strains: B. subtilis 26D, B. subtilis 11VM, and B. thuringiensis B-6066. We have for the first time demonstrated the aphicidal effect of fengycin and the ability of the fengycin-synthesizing strains and isolates, B. subtilis Ttl2, Bacillus sp. Stl7 and B. thuringiensis B-6066, to regulate components of the pro-/antioxidant system of aphid-infested plants. In addition, this work is the first to demonstrate an elicitor role of fengycin in triggering a systemic resistance to S. graminum in wheat plants. We have discovered new promising strains and isolates of endophytes of the genus Bacillus, which may be included in the composition of new biocontrol agents against aphids. One of the criteria for searching for new bacteria active against phloem-feeding insects can be the presence of lipopeptide synthetase genes in the bacterial genome.
PubMed: 38952706
DOI: 10.18699/vjgb-24-32