Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Metabolic consequences of various fruit-based diets in a generalist insect species

Tue, 06/06/2023 - 12:00
Elife. 2023 Jun 6;12:e84370. doi: 10.7554/eLife.84370.ABSTRACTMost phytophagous insect species exhibit a limited diet breadth and specialize on a few or a single host plant. In contrast, some species display a remarkably large diet breadth, with host plants spanning several families and many species. It is unclear, however, whether this phylogenetic generalism is supported by a generic metabolic use of common host chemical compounds ('metabolic generalism') or alternatively by distinct uses of diet-specific compounds ('multi-host metabolic specialism')? Here, we simultaneously investigated the metabolomes of fruit diets and of individuals of a generalist phytophagous species, Drosophila suzukii, that developed on them. The direct comparison of metabolomes of diets and consumers enabled us to disentangle the metabolic fate of common and rarer dietary compounds. We showed that the consumption of biochemically dissimilar diets resulted in a canalized, generic response from generalist individuals, consistent with the metabolic generalism hypothesis. We also showed that many diet-specific metabolites, such as those related to the particular color, odor, or taste of diets, were not metabolized, and rather accumulated in consumer individuals, even when probably detrimental to fitness. As a result, while individuals were mostly similar across diets, the detection of their particular diet was straightforward. Our study thus supports the view that dietary generalism may emerge from a passive, opportunistic use of various resources, contrary to more widespread views of an active role of adaptation in this process. Such a passive stance towards dietary chemicals, probably costly in the short term, might favor the later evolution of new diet specializations.PMID:37278030 | DOI:10.7554/eLife.84370

Therapeutic effects of columbianadin from Angelicae Pubescentis radix on the progression of collagen-induced rheumatoid aarthritis by regulating inflammation and oxidative stress

Mon, 05/06/2023 - 12:00
J Ethnopharmacol. 2023 Jun 3:116727. doi: 10.1016/j.jep.2023.116727. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Angelicae pubescentis radix (APR) has a long history in the treatment of rheumatoid arthritis (RA) in China. It has the effects of dispelling wind to eliminate dampness, removing arthralgia and stopping pain in the Chinese Pharmacopeia, but its mechanisms was remained unclear. Columbianadin (CBN), one of the main bioactive compounds of APR, was reported that it has many pharmacological effects including anti-inflammatory and immunosuppression. However, little study has been investigated therapeutic effect of CBN on RA.AIM OF THE STUDY: A comprehensive strategy via incorporating pharmacodynamics, microbiomics, metabolomics, and multiple molecular biological methods was adopted to evaluated the therapeutic effects of CBN on collagen-induced arthritis (CIA) mice and explored the potential mechanisms.MATERIALS AND METHODS: A variety of pharmacodynamic methods were used to evaluate the therapeutic effect of CBN on CIA mice. The microbial and metabolic characteristics of CBN anti-RA were obtained by metabolomics and 16S rRNA sequencing technology. The potential mechanism of CBN anti-RA was predicted through bioinformatics network analysis, and verified by a variety of molecular biology methods.RESULTS: CBN effectively improve symptoms of rheumatoid arthritis in CIA mice, including paw swelling and arthritic scores. The inflammatory factors and oxidative stress markers were effectively regulated by the treatment of CBN. The fecal microbial communities and serum and urine metabolic compositions were significantly altered in CIA mice, CBN ameliorated the CIA-associated gut microbiota dysbiosis, and regulated the disturbance of serum and urine metabolome and reversed the changes of key CIA and gut microbiota-related metabolites. The acute toxicity test, results showed that the LD50 of CBN is greater than 2000 mg kg-1, which confirmed the security of CBN.CONCLUSIONS: CBN exert anti-RA effects from four perspectives: inhibiting inflammatory response, regulating oxidative stress, and improving changes in gut microbiota and metabolites. The JAK1/STAT3, NF-κB and Keap1/Nrf2 pathway may be an important mechanism for CBN's inflammatory response and oxidative stress activity. CBN could be considered as a potential anti-RA drug for further study.PMID:37277080 | DOI:10.1016/j.jep.2023.116727

The effects of environmental Microplastic on wharf roach (Ligia exotica): A Multi-Omics approach

Mon, 05/06/2023 - 12:00
Chemosphere. 2023 Jun 3:139122. doi: 10.1016/j.chemosphere.2023.139122. Online ahead of print.ABSTRACTThis is the first report to evaluate the potential effects of microplastics (MPs) on wild wharf roaches (Ligia exotica) in a shoreline habitant. L. exotica is an important plastic detritus consumer in coastal area. A survey was conducted from May to June in the years 2019 and 2020 in two South Korean nearshore sites: Nae-do (as MPs-uncontaminated) and Maemul-do (as MPs-contaminated). MPs (>20 μm in size) were detected highly in gastrointestinal tracts of the L. exotica from Maemul-do, at an average level of 50.56 particles/individual. They were detected in much lower levels in the L. exotica from Nae-do. at an average rate of 1.00 particles/individual. The polymer type and shape were dominated by expanded polystyrene (EPS, 93%) and fragment (99.9%) in L. exotica from Maemul-do. Especially, Hexabromocyclododecanes, brominated flame retardants added to EPS, have been detected highly in L. exotica from Maemul-do (630.86 ± 587.21 ng/g l. w.) than those of Nae-do (detection limit: 10.5 ng/g l. w). Genome-wide transcriptome profiling revealed altered expression of genes associated with fatty acid metabolic processes, the innate-immune response-activating system and vesicle cytoskeletal trafficking in L. exotica from Maemul-do. The activation of the p53 signaling pathway (which is related to proteasome, ER regulation and cell morphogenesis) is likely to be involved in the EPS-uptake of wild L. exotica. Four neurosteroids were also detected in head tissue, and cortisol and progesterone concentrations differed significantly in L. exotica from Maemul-do. Our findings also suggest that resident plastic detritus consumer might be a useful indicator organism for evaluating pollution and potential effects of environmental microplastics.PMID:37276999 | DOI:10.1016/j.chemosphere.2023.139122

Metabolomic profiling of an ultra-processed dietary pattern in a domiciled randomized controlled crossover feeding trial

Mon, 05/06/2023 - 12:00
J Nutr. 2023 Jun 3:S0022-3166(23)72408-5. doi: 10.1016/j.tjnut.2023.06.003. Online ahead of print.ABSTRACTBACKGROUND: Objective markers of ultra-processed foods (UPF) may improve assessment of UPF intake and provide insight into how UPF influence health.OBJECTIVE: To identify metabolites that differed between dietary patterns (DPs) high in or void of UPF according to Nova classification.METHODS: In a randomized, crossover, controlled feeding trial (ClinicalTrials.govNCT03407053), 20 domiciled healthy participants (mean ± SD: Age 31 ± 7 years, BMI 22 ± 11.6 kg/m2) consumed ad libitum a UPF-DP (80% UPF) and an unprocessed DP (UN-DP; 0% UPF) for two weeks each. Metabolites were measured using liquid chromatography with tandem mass spectrometry in EDTA plasma, collected at week 2, and 24-hr and spot urine, collected at week 1 and 2, of each DP. Linear mixed models, adjusted for energy intake, were used to identify metabolites that differed between DPs.RESULTS: After multiple comparisons correction, 257 out of 993 plasma and 606 out of 1279 24-hr urine metabolites differed between UPF-DP and UN-DP. Overall, 21 known and 9 unknown metabolites differed between DPs across all timepoints and biospecimen types. Six metabolites were higher (4-Hydroxy-L-glutamic acid, N-Acetylaminooctanoic acid, 2-Methoxyhydroquinone sulfate, 4-Ethylphenylsulfate, 4-Vinylphenol sulfate, and Acesulfame) and 14 were lower following the UPF-DP; pimelic acid, was lower in plasma but higher in urine following the UPF-DP.CONCLUSIONS: Consuming a DP high in, compared to one void of, UPF has a measurable impact on the short-term human metabolome. Observed differential metabolites could serve as candidate biomarkers of UPF intake or metabolic response in larger samples with varying UPF DPs.CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03407053 and NCT03878108.PMID:37276937 | DOI:10.1016/j.tjnut.2023.06.003

Targeting HMG-CoA synthase 2 suppresses tamoxifen-resistant breast cancer growth by augmenting mitochondrial oxidative stress-mediated cell death

Mon, 05/06/2023 - 12:00
Life Sci. 2023 Jun 3:121827. doi: 10.1016/j.lfs.2023.121827. Online ahead of print.ABSTRACTAIMS: In this study, we aimed to investigate previously unrecognized lipid metabolic perturbations in tamoxifen-resistant breast cancer (BC) by conducting comprehensive metabolomics and transcriptomics analysis. We identified the role of 3-hydroxy-3-methylglutary-coenzyme-A-synthase 2 (HMGCS2), a key enzyme responsible for ketogenesis, in tamoxifen-resistant BC growth.MAIN METHODS: Comprehensive metabolomics (CE-TOFMS, LC-TOFMS) and transcriptiomics analysis were performed to characterize metabolic pathways in tamoxifen-resistant BC cells. The upregulation of HMGCS2 were verified thorugh immunohistochemistry (IHC) in clinical samples obtained from patients with recurrent BC. HMGCS2 inhibitor was discovered through surface plasmon resonance analysis, enzyme assay, and additional molecular docking studies. The effect of HMGCS2 suppression on tumor growth was studied thorugh BC xenograft model, and intratumoral lipid metabolites were analyzed via MALDI-TOFMS imaging.KEY FINDINGS: We revealed that the level of HMGCS2 was highly elevated in both tamoxifen-resistant T47D sublines (T47D/TR) and clinical refractory tumor specimens from patients with ER+ breast cancer, who had been treated with adjuvant tamoxifen. Suppression of HMGCS2 in T47D/TR resulted in the accumulation of mitochondrial reactive oxygen species (mtROS) and apoptotic cell death. Further, we identified alphitolic acid, a triterpenoid natural product, as a novel HMGCS2-specific inhibitor that elevated mtROS levels and drastically retarded the growth of T47D/TR in in vitro and in vivo experiments.SIGNIFICANCE: Enhanced ketogenesis with upregulation of HMGCS2 is a potential metabolic vulnerability of tamoxifen-resistant BC that offers a new therapeutic opportunity for treating patients with ER+ BC that are refractory to tamoxifen treatment.PMID:37276910 | DOI:10.1016/j.lfs.2023.121827

Metabolomics analysis of the potential mechanism of Yi-Guan-Jian decoction to reverse bone loss in glucocorticoid-induced osteoporosis

Mon, 05/06/2023 - 12:00
J Orthop Surg Res. 2023 Jun 5;18(1):409. doi: 10.1186/s13018-023-03778-6.ABSTRACTBACKGROUND: Glucocorticoid-induced osteoporosis (GIOP) is a disease in which long-term use of glucocorticoid causes bone loss, deterioration of bone microstructure and fracture. Currently, clinical drugs targeting this disease have certain side effects. There is still a need to find effective drugs with fewer side effects. The theory of traditional Chinese medicine suggests that YGJ has therapeutic effect on GIOP, but it has not been explained. Therefore, this study aims to explore the protective effect of YGJ on GIOP mouse models and elucidate the underlying mechanism through LC-MS-based metabolomics analysis.METHODS: The general condition of 8 week age male C57BL/6J mice was recorded after 8 weeks of treatment with dexamethasone (DEX) and YGJ. Bone-related parameters and bone morphology were determined by Micro-CT. HE staining was used to observe the pathological changes of bone tissue. Serum levels of bone metabolism markers were detected by ELISA. Liver metabolomics analysis was conducted to search for the significant markers of anti-GIOP of YGJ and the metabolic pathway affecting it.RESULTS: After treatment, YGJ significantly reversed the weight loss caused by DEX; increase the number of bone trabecular in ROI region, significantly improve the bone-related parameters of GIOP mice, and increase the levels of alkaline phosphatase and osteocalcin. In the study of metabolic mechanism, YGJ reversed 24 potential markers in GIOP mice. These included cortisol, 3-hydroxybutyric acid, taurine, esculin and uric acid, which are closely associated with osteoporosis. Topological analysis results showed that YGJ had the most significant effect on taurine and hypotaurine metabolism, with - log10 (P) > 2.0 and Impact > 0.4.CONCLUSIONS: Yi-Guan-Jian decoction can increase bone density and improve bone microstructure by regulating the levels of alkaline phosphatase and osteocalcin and reverse bone loss in GIOP mouse model. The underlying metabolic mechanism may be related to taurine and hypotaurine metabolic pathway.PMID:37277810 | DOI:10.1186/s13018-023-03778-6

Integrated fecal microbiota and metabolomics analysis of the orlistat intervention effect on polycystic ovary syndrome rats induced by letrozole combined with a high-fat diet

Mon, 05/06/2023 - 12:00
J Ovarian Res. 2023 Jun 5;16(1):109. doi: 10.1186/s13048-023-01193-3.ABSTRACTBACKGROUND: This study aimed to compare the characteristics of the gut microbiota and their metabolite profiles between polycystic ovary syndrome (PCOS) and orlistat-treated PCOS rats (ORL-PCOS), which could help to better understand the underlying mechanism of the effect of orlistat on PCOS.METHODS: PCOS rat models were established using letrozole combined with a high-fat diet. Ten rats were randomly selected as a PCOS control group (PCOS). The other three groups (n = 10/group) were additionally supplemented with different doses of orlistat (low, medium, high). Then, fecal samples of the PCOS and ORL-PCOS groups were analysed by 16S rRNA gene sequencing and untargeted metabolomics. Blood samples were collected to detect serum sex hormones and lipids.RESULTS: The results showed that orlistat attenuated the body weight gain, decreased the levels of T, LH, the LH/FSH ratio, TC, TG and LDL-C; increased the level of E2; and improved estrous cycle disorder in PCOS rats. The bacterial richness and diversity of the gut microbiota in the ORL-PCOS group were higher than those in the PCOS group. The ratio of Firmicutes to Bacteroidetes was decreased with orlistat treatment. Moreover, orlistat treatment led to a significant decrease in the relative abundance of Ruminococcaceae and Lactobacillaceae, and increases in the abundances of Muribaculaceae and Bacteroidaceae. Metabolic analysis identified 216 differential fecal metabolites in total and 6 enriched KEGG pathways between the two groups, including steroid hormone biosynthesis, neuroactive ligand-receptor interaction and vitamin digestion and absorption. Steroid hormone biosynthesis was the pathway with the most significant enrichment. The correlations between the gut microbiota and differential metabolites were calculated, which may provide a basis for understanding the composition and function of microbial communities.CONCLUSIONS: Our data suggested that orlistat exerts a PCOS treatment effect, which may be mediated by modifying the structure and composition of the gut microbiota, as well as the metabolite profiles of PCOS rats.PMID:37277785 | DOI:10.1186/s13048-023-01193-3

Sex-specific metabolic profiling to explain the increased CVD risk in women with migraine: a narrative review

Mon, 05/06/2023 - 12:00
J Headache Pain. 2023 Jun 6;24(1):64. doi: 10.1186/s10194-023-01601-5.ABSTRACTBACKGROUND: Migraine is a disabling neurological disorder whose diagnosis is based on clinical criteria. A shortcoming of these criteria is that they do not fully capture the underlying neurobiological factors and sex-specific complications in migraine such as cardio- and cerebrovascular disease. Biomarker research can help to improve disease characterization and identify pathophysiological mechanism underlying these comorbidities.OBJECTIVE: In this narrative review we searched for sex-specific metabolomics research to identify markers that may explain the migraine-cardiovascular disease (CVD) relationship.DISCUSSION: Large-scale plasma metabolome analyses revealed alterations in migraine. Sex-specific findings showed a less CVD-protective HDL metabolism as well as the ApoA1 lipoprotein, especially for women with migraine. To explore other possible pathophysiological pathways, we expanded our review to include inflammatory markers, endothelial and vascular markers and sex hormones. Biological sex differences may affect the pathophysiology of migraine and its complications.CONCLUSIONS: There is no general large dyslipidemia profile in migraine patients, in line with findings that the increased risk of CVD in migraine patients seems not to be due to (large artery) atherosclerosis. Sex-specific associations are indicative towards a less CVD-protective lipoprotein profile in women with migraine. Future studies into the pathophysiology of CVD and migraine need to take sex specific factors into account. By establishing the overlapping pathophysiological mechanism of migraine and CVD, and unraveling the associated effects these diseases exert on each other, better preventative measures can be identified.PMID:37277733 | DOI:10.1186/s10194-023-01601-5

Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine

Mon, 05/06/2023 - 12:00
Nat Genet. 2023 Jun 5. doi: 10.1038/s41588-023-01409-8. Online ahead of print.ABSTRACTThe kidneys operate at the interface of plasma and urine by clearing molecular waste products while retaining valuable solutes. Genetic studies of paired plasma and urine metabolomes may identify underlying processes. We conducted genome-wide studies of 1,916 plasma and urine metabolites and detected 1,299 significant associations. Associations with 40% of implicated metabolites would have been missed by studying plasma alone. We detected urine-specific findings that provide information about metabolite reabsorption in the kidney, such as aquaporin (AQP)-7-mediated glycerol transport, and different metabolomic footprints of kidney-expressed proteins in plasma and urine that are consistent with their localization and function, including the transporters NaDC3 (SLC13A3) and ASBT (SLC10A2). Shared genetic determinants of 7,073 metabolite-disease combinations represent a resource to better understand metabolic diseases and revealed connections of dipeptidase 1 with circulating digestive enzymes and with hypertension. Extending genetic studies of the metabolome beyond plasma yields unique insights into processes at the interface of body compartments.PMID:37277652 | DOI:10.1038/s41588-023-01409-8

Metabolomics identifies the intestinal geography of microbial metabolite production

Mon, 05/06/2023 - 12:00
Nat Metab. 2023 Jun 5. doi: 10.1038/s42255-023-00805-y. Online ahead of print.NO ABSTRACTPMID:37277611 | DOI:10.1038/s42255-023-00805-y

Baicalein Attenuates Neuroinflammation in LPS-Treated BV-2 Cells by Inhibiting Glycolysis via STAT3/c-Myc Pathway

Mon, 05/06/2023 - 12:00
Neurochem Res. 2023 Jun 5. doi: 10.1007/s11064-023-03961-5. Online ahead of print.ABSTRACTMore and more evidence shows that metabolic reprogramming is closely related to the occurrence of AD. The metabolic conversion of oxidative phosphorylation into glycolysis will aggravate microglia-mediated inflammation. It has been demonstrated that baicalein could inhibit neuroinflammation in LPS-treated BV-2 microglial cells, but whether the anti-neuroinflammatory mechanisms of baicalein were related to glycolysis is unclear. Our results depicted that baicalein significantly inhibited the levels of nitric oxide (NO), interleukin-6 (IL-6), prostaglandin 2 (PGE2) and tumor necrosis factor (TNF-α) in LPS-treated BV-2 cells. 1H-NMR metabolomics analysis showed that baicalein decreased the levels of lactic acid and pyruvate, and significantly regulated glycolytic pathway. Further study revealed that baicalein significantly inhibited the activities of glycolysis-related enzymes including hexokinase (HK), 6-phosphate kinase (6-PFK), pyruvate kinase (PK), lactate dehydrogenase (LDH), and inhibited STAT3 phosphorylation and c-Myc expression. By using of STAT3 activator RO8191, we found that baicalein suppressed the increase of STAT3 phosphorylation and c-Myc expression triggered by RO8191, and inhibited the increased levels of 6-PFK, PK and LDH caused by RO8191. In conclusion, these results suggested that baicalein attenuated the neuroinflammation in LPS-treated BV-2 cells by inhibiting glycolysis through STAT3/c-Myc pathway.PMID:37277556 | DOI:10.1007/s11064-023-03961-5

Sexual differentiation in human malaria parasites is regulated by competition between phospholipid metabolism and histone methylation

Mon, 05/06/2023 - 12:00
Nat Microbiol. 2023 Jun 5. doi: 10.1038/s41564-023-01396-w. Online ahead of print.ABSTRACTFor Plasmodium falciparum, the most widespread and virulent malaria parasite that infects humans, persistence depends on continuous asexual replication in red blood cells, while transmission to their mosquito vector requires asexual blood-stage parasites to differentiate into non-replicating gametocytes. This decision is controlled by stochastic derepression of a heterochromatin-silenced locus encoding AP2-G, the master transcription factor of sexual differentiation. The frequency of ap2-g derepression was shown to be responsive to extracellular phospholipid precursors but the mechanism linking these metabolites to epigenetic regulation of ap2-g was unknown. Through a combination of molecular genetics, metabolomics and chromatin profiling, we show that this response is mediated by metabolic competition for the methyl donor S-adenosylmethionine between histone methyltransferases and phosphoethanolamine methyltransferase, a critical enzyme in the parasite's pathway for de novo phosphatidylcholine synthesis. When phosphatidylcholine precursors are scarce, increased consumption of SAM for de novo phosphatidylcholine synthesis impairs maintenance of the histone methylation responsible for silencing ap2-g, increasing the frequency of derepression and sexual differentiation. This provides a key mechanistic link that explains how LysoPC and choline availability can alter the chromatin status of the ap2-g locus controlling sexual differentiation.PMID:37277533 | DOI:10.1038/s41564-023-01396-w

'Multi-omics' data integration: applications in probiotics studies

Mon, 05/06/2023 - 12:00
NPJ Sci Food. 2023 Jun 5;7(1):25. doi: 10.1038/s41538-023-00199-x.ABSTRACTThe concept of probiotics is witnessing increasing attention due to its benefits in influencing the host microbiome and the modulation of host immunity through the strengthening of the gut barrier and stimulation of antibodies. These benefits, combined with the need for improved nutraceuticals, have resulted in the extensive characterization of probiotics leading to an outburst of data generated using several 'omics' technologies. The recent development in system biology approaches to microbial science is paving the way for integrating data generated from different omics techniques for understanding the flow of molecular information from one 'omics' level to the other with clear information on regulatory features and phenotypes. The limitations and tendencies of a 'single omics' application to ignore the influence of other molecular processes justify the need for 'multi-omics' application in probiotics selections and understanding its action on the host. Different omics techniques, including genomics, transcriptomics, proteomics, metabolomics and lipidomics, used for studying probiotics and their influence on the host and the microbiome are discussed in this review. Furthermore, the rationale for 'multi-omics' and multi-omics data integration platforms supporting probiotics and microbiome analyses was also elucidated. This review showed that multi-omics application is useful in selecting probiotics and understanding their functions on the host microbiome. Hence, recommend a multi-omics approach for holistically understanding probiotics and the microbiome.PMID:37277356 | DOI:10.1038/s41538-023-00199-x

Remembering Ad de Jong

Mon, 05/06/2023 - 12:00
Mol Cell Proteomics. 2023 Jun 3;22(6):100568. doi: 10.1016/j.mcpro.2023.100568. Online ahead of print.NO ABSTRACTPMID:37276839 | DOI:10.1016/j.mcpro.2023.100568

A comprehensive view of metabolic responses to CYP98 perturbation in ancestral plants

Mon, 05/06/2023 - 12:00
Plant Physiol Biochem. 2023 May 23;201:107793. doi: 10.1016/j.plaphy.2023.107793. Online ahead of print.ABSTRACTCytochrome P450 monooxygenase 98 (CYP98) is a critical rate-limiting enzyme of the phenylpropanoid pathway. One of the end-product of the phenylpropanoid pathway is a lignin monomer, although the occurrence of lignin in bryophytes is controversial. Here we investigated the functions of PpCYP98 in Physcomitrium patens by transcriptome and metabolome analyses. We identified 5266 differentially expressed genes (DEGs) and 68 differentially abundant secondary metabolites between wild-type and ΔPpCYP98 gametophores. Of the identified metabolites, 23 phenolic acids were identified, with only one showing upregulation. Among the phenolic acids, 4-coumaroyl tartaric acid and chlorogenic acid showed significant decreases. Declines were also observed in coniferylaldehyde and coniferin, precursor substances and downstream products of the lignin monomer coniferyl alcohol, respectively. Thus, the pre-lignin synthesis pathway already exists in bryophytes, and PpCYP98 plays vital roles in this pathway. Besides, most flavonoids show significant reductions, including eriodyctiol, dihydroquecetin, and dihydromyricetin, whereas naringenin chalone and dihydrokaempferol were increased after PpCYP98 knockout. Therefore, the synthesis of flavonoids shares the core pathway with phenylpropanoids and mainly starts from caffeoyl-CoA, that is the compound of divergence between the two pathways in moss. PpCYP98 showed systemic effects on metabolisms, including carbohydrate, fatty acid, and hormonal signaling transductions, suggesting that PpCYP98 might indirectly regulate carbon influx allocation. Our results demonstrated roles of PpCYP98 were essential for the development of the early landing plant.PMID:37276808 | DOI:10.1016/j.plaphy.2023.107793

Nervonic acid improves liver inflammation in a mouse model of Parkinson's disease by inhibiting proinflammatory signaling pathways and regulating metabolic pathways

Mon, 05/06/2023 - 12:00
Phytomedicine. 2023 Jun 1;117:154911. doi: 10.1016/j.phymed.2023.154911. Online ahead of print.ABSTRACTBACKGROUND: Nervonic acid (NA) - a type of bioactive fatty acid that is found in natural sources - can inhibit inflammatory reactions and regulate immune system balance. Therefore, the use of NA for the treatment of neurodegenerative diseases has received considerable attention. Our previous study found that NA inhibited inflammatory responses in the brain of Parkinson's disease (PD) mouse models. In addition to the brain, PD is also associated with visceral organ dysfunction, especially impaired liver function. Thus, studying the role of NA in PD-mediated inflammation of the liver is particularly important.METHODS: A combined transcriptome and metabolomic approach was utilized to investigate the anti-inflammatory effects of NA on the liver of PD mice. Inflammatory signaling molecules and metabolic pathway-related genes were examined in the liver using real-time PCR and western blotting.RESULTS: Liver transcriptome analysis revealed that NA exerted anti-inflammatory effects by controlling several pro-inflammatory signaling pathways, such as the down-regulation of the tumor necrosis factor and nuclear factor kappa B signaling pathways, both of which were essential in the development of inflammatory disease. In addition, liver metabolomic results revealed that metabolites related to steroid hormone biosynthesis, arachidonic acid metabolism, and linoleic acid metabolism were up-regulated and those related to valine, leucine, and isoleucine degradation pathways were down-regulated in NA treatment groups compared with the PD model. The integration of metabolomic and transcriptomic results showed NA significantly exerted its anti-inflammatory function by regulating the transcription and metabolic pathways of multiple genes. Particularly, linoleic acid metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis were the crucial pathways of the anti-inflammatory action of NA. Key genes in these metabolic pathways and key molecules in inflammatory signaling pathways were also verified, which were consistent with transcriptomic results.CONCLUSION: These findings provide novel insights into the liver protective effects of NA against PD mice. This study also showed that NA could be a useful dietary element for improving and treating PD-induced liver inflammation.PMID:37276724 | DOI:10.1016/j.phymed.2023.154911

Responses of gut microbiomes to commercial polyester polymer biodegradation in Tenebrio molitor Larvae

Mon, 05/06/2023 - 12:00
J Hazard Mater. 2023 Jun 2;457:131759. doi: 10.1016/j.jhazmat.2023.131759. Online ahead of print.ABSTRACTPolyethylene terephthalate (PET) is a mass-produced fossil-based plastic polymer that contributes to catastrophic levels of plastic pollution. Here we demonstrated that Tenebrio molitor (mealworms) was capable of rapidly biodegrading two commercial PET resins (microplastics) with respective weight-average molecular weight (Mw) of 39.33 and 29.43 kDa and crystallinity of 22.8 ± 3.06% and 18 ± 2.25%, resulting in an average mass reduction of 71.03% and 73.28% after passage of their digestive tract, and respective decrease by 9.22% and 11.36% in Mw of residual PET polymer in egested frass. Sequencing of 16 S rRNA gene amplicons of gut microbial communities showed that dominant bacterial genera were enriched and associated with PET degradation. Also, PICRUSt prediction exhibited that oxidases (monooxygenases and dioxygenases), hydrolases (cutinase, carboxylesterase and chitinase), and PET metabolic enzymes, and chemotaxis related functions were up-regulated in the PET-fed larvae. Additionally, metabolite analyses revealed that PET uptake caused alterations of stress response and plastic degradation related pathways, and lipid metabolism pathways in the T. molitor larvae could be reprogrammed when the larvae fed on PET. This study provides new insights into gut microbial community adaptation to PET diet under nutritional stress (especially nitrogen deficiency) and its contribution to PET degradation.PMID:37276692 | DOI:10.1016/j.jhazmat.2023.131759

Identification of nutritional biomarkers through highly sensitive and chemoselective metabolomics

Mon, 05/06/2023 - 12:00
Food Chem. 2023 Jun 1;425:136481. doi: 10.1016/j.foodchem.2023.136481. Online ahead of print.ABSTRACTThe importance of a healthy diet for humans is known for decades. The elucidation of key molecules responsible for the beneficial and adverse dietary effects is slowly developing as the tools are missing. Carbonyl-containing metabolites are a common bioproducts through conversion of diet by the microbiome. In here, we have utilized our recently developed mass spectrometric methodology based on chemoselective conjugation of carbonyl-metabolites. The method has been applied for urine sample analysis from a dietary (poly)phenol intervention study (N = 78 individuals) for the first time. We have identified a series of carbonyl-metabolites of dietary origin and the chemical structure was validated for 30 metabolites. Our sensitive analysis led to the discovery of four unknown dietary markers with high sensitivity and selectivity (AUC > 0.91). Our chemical metabolomics method has been successfully applied for large-scale analysis and provides the basis for targeted metabolomics to identify unknown nutritional and disease-related biomarkers.PMID:37276670 | DOI:10.1016/j.foodchem.2023.136481

UHPLC-Q-Orbitrap HR-MS-Based Metabolomics for Profiling the Sida rhombifolia Metabolites with Different Plant Organs and Cultivation Ages

Mon, 05/06/2023 - 12:00
Chem Biodivers. 2023 Jun 5:e202201042. doi: 10.1002/cbdv.202201042. Online ahead of print.ABSTRACTPlant organs and cultivation ages can result in different compositions and concentration levels of plant metabolites. The metabolite profile of plants can be determined using liquid chromatography. This study determined the metabolite profiles of leaves, stems, and roots of Sida rhombifolia at different cultivation ages at 3, 4, and 5 months post-planting (MPP) using liquid chromatography-mass spectrometry/mass spectrometry (LC/MS/MS). The results identified that 41 metabolites in S. rhombifolia extract for all plant organs and cultivation ages. We successfully identified approximately 36 (leaves), 22 (stems), and 18 (roots) compounds in all extract. Using principal component analysis (PCA) with peak area as the variable, we clustered all sample extracts based on plant organs and cultivation ages. As a result of PCA, S. rhombifolia extracts were grouped according to plant organs and cultivation ages. In conclusion, a clear difference in the composition and concentration levels of metabolites was observed in the leaves, stems, and roots of S. rhombifolia harvested at 3-, 4-, and 5-MPP.PMID:37276379 | DOI:10.1002/cbdv.202201042

Directed Evolution of a G-Quadruplex Peroxidase DNAzyme and Application in Proteomic DNAzyme-Aptamer Proximity Labeling

Mon, 05/06/2023 - 12:00
J Am Chem Soc. 2023 Jun 5. doi: 10.1021/jacs.3c02625. Online ahead of print.ABSTRACTDNAzymes have been limited in application by their low catalytic rates. Here, we evolved a new peroxidase DNAzyme mSBDZ-X-3 through a directed evolution method based on the capture of self-biotinylated DNA catalyzed by its intrinsic peroxidase activity. The mSBDX-X-3 DNAzyme has a parallel G-quadruplex structure and has more favorable catalytic properties than all previously reported peroxidase DNAzyme variants. We applied mSBDZ-X-3 in an aptamer-coupled proximity-based labeling proteomic assay to determine the proteins that bind to cell surface cancer biomarkers EpCAM and nucleolin. Confocal microscopy, western blot analysis, and LC-MS/MS showed that the hybrid DNAzyme aptamer-coupled proximity assay-labeled proteins associated with EpCAM and nucleolin within 6-12 min in fixed cancer cells. The labeled proteins were identified by mass spectrometry. This study provides a highly efficient peroxidase DNAzyme, a methodology for selection of such variants, and a method for its application in spatial proteomics using entirely nucleic acid-based tooling.PMID:37276197 | DOI:10.1021/jacs.3c02625

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