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

ApoJ/Clusterin concentrations are determinants of cerebrospinal fluid cholesterol efflux capacity and reduced levels are associated with Alzheimer's disease

Mon, 26/12/2022 - 12:00
Alzheimers Res Ther. 2022 Dec 26;14(1):194. doi: 10.1186/s13195-022-01119-z.ABSTRACTBACKGROUND: Alzheimer's disease (AD) shares risk factors with cardiovascular disease (CVD) and dysregulated cholesterol metabolism is a mechanism common to both diseases. Cholesterol efflux capacity (CEC) is an ex vivo metric of plasma high-density lipoprotein (HDL) function and inversely predicts incident CVD independently of other risk factors. Cholesterol pools in the central nervous system (CNS) are largely separate from those in blood, and CNS cholesterol excess may promote neurodegeneration. CEC of cerebrospinal fluid (CSF) may be a useful measure of CNS cholesterol trafficking. We hypothesized that subjects with AD and mild cognitive impairment (MCI) would have reduced CSF CEC compared with Cognitively Normal (CN) and that CSF apolipoproteins apoA-I, apoJ, and apoE might have associations with CSF CEC.METHODS: We retrieved CSF and same-day ethylenediaminetetraacetic acid (EDTA) plasma from 108 subjects (40 AD; 18 MCI; and 50 CN) from the Center for Neurodegenerative Disease Research biobank at the Perelman School of Medicine, University of Pennsylvania. For CSF CEC assays, we used N9 mouse microglial cells and SH-SY5Y human neuroblastoma cells, and the corresponding plasma assay used J774 cells. Cells were labeled with [3H]-cholesterol for 24 h, had ABCA1 expression upregulated for 6 h, were exposed to 33 μl of CSF, and then were incubated for 2.5 h. CEC was quantified as percent [3H]-cholesterol counts in medium of total counts medium+cells, normalized to a pool sample. ApoA-I, ApoJ, ApoE, and cholesterol were also measured in CSF.RESULTS: We found that CSF CEC was significantly lower in MCI compared with controls and was poorly correlated with plasma CEC. CSF levels of ApoJ/Clusterin were also significantly lower in MCI and were significantly associated with CSF CEC. While CSF ApoA-I was also associated with CSF CEC, CSF ApoE had no association with CSF CEC. CSF CEC is significantly and positively associated with CSF Aβ. Taken together, ApoJ/Clusterin may be an important determinant of CSF CEC, which in turn could mitigate risk of MCI and AD risk by promoting cellular efflux of cholesterol or other lipids. In contrast, CSF ApoE does not appear to play a role in determining CSF CEC.PMID:36572909 | PMC:PMC9791777 | DOI:10.1186/s13195-022-01119-z

Divergent impacts on the gut microbiome and host metabolism induced by traditional Chinese Medicine with Cold or Hot properties in mice

Mon, 26/12/2022 - 12:00
Chin Med. 2022 Dec 26;17(1):144. doi: 10.1186/s13020-022-00697-2.ABSTRACTBACKGROUND: Traditional Chinese Medicine (TCM) has been practiced and developed in China over thousands of years under the guidance of a series of complicated traditional theories. Herbs within TCM usually are classified according to their different properties ranging from cold, cool, warm to hot, which are simplified as Cold and Hot properties. TCM with either Cold or Hot properties are used in various formulae designed for the purpose of restoring the balance of patients. Emerging evidence has highlighted that an altered gut microbiota or host metabolism are critically involved in affecting the healing properties of TCM. However, at present the exact influences and crosstalk on the gut microbiota and host metabolism remain poorly understood.METHODS: In the present study, the divergent impacts of six TCMs with either Cold or Hot properties on gut microbiome and host metabolism during short- or long-term intervention in mice were investigated. Six typical TCMs with Hot or Cold properties including Cinnamomi Cortex (rougui, RG), Zingiberis Rhizoma (ganjiang, GJ), Aconiti Lateralis Radix Praeparata (fuzi, FZ), Rhei Radix et Rhizoma (dahuang, DH), Scutellariae Radix (huangqin, HQ), and Copitdis Rhizoma (huanglian, HL) were selected and orally administered to male C57BL/6J mice for a short- or a long-term (7 or 35 days). At the end of experiments, serum and cecal contents were collected for metabolomic and gut microbiome analyses using gas chromatography-tandem mass spectrometry (GC-MS) or 16S ribosomal deoxyribonucleic acid (16S rDNA) sequencing.RESULTS: The results revealed that the gut microbiome underwent divergent changes both in its composition and functions after short-term intervention with TCM possessing either Cold or Hot properties. Interestingly, the number of changed genus and bacteria pathways was reduced in Hot_LT, but was increased in Cold_LT, especially in the HL group. Increased α diversity and a reduced F/B ratio revealed the changes in Hot_ST, but a reduced Shannon index and increased altered bacteria function was evident in Cold_LT. The serum metabolic profile showed that the influence of TCM on host metabolism was gradually reduced over time. Glycolipid metabolism related pathways were specifically regulated by Hot_ST, but also surprisingly by Cold_LT. Reduced lactic acid in Cold_ST, increased tryptophan concentrations and decreased proline and threonine concentrations in Cold_LT perhaps highlighting the difference between the two natures influence on serum metabolism. These metabolites were closely correlated with altered gut microbiota shown by further correlation analyses.CONCLUSION: The results indicated that TCM properties could be, at least partially characterized by an alteration in the gut microbiota and metabolic profile, implying that the divergent responses of gut microbiome and host metabolism are involved in different responses to TCM.PMID:36572936 | DOI:10.1186/s13020-022-00697-2

LC-MS/MS based metabolomics and proteomics reveal candidate biomarkers and molecular mechanism of early IgA nephropathy

Mon, 26/12/2022 - 12:00
Clin Proteomics. 2022 Dec 27;19(1):51. doi: 10.1186/s12014-022-09387-5.ABSTRACTBACKGROUND: Immunoglobulin A nephropathy (IgAN), a globally common primary chronic glomerulopathy, is one of the leading causes of end-stage renal disease. However, the underlying mechanisms of IgAN have yet to be demonstrated. There were no adequate and reliable plasma biomarkers for clinical diagnosis, especially at the early stage. In the present study, integrative proteomics and metabolomics were aimed at exploring the mechanism of IgAN and identifying potential biomarkers.METHODS: Plasma from IgAN and healthy individuals were collected and analyzed in a randomized controlled manner. Data-independent acquisition quantification proteomics and mass spectrometry based untargeted metabolomics techniques were used to profile the differentially expressed proteins (DEPs) and differentially abundant metabolites (DAMs) between two groups and identify potential biomarkers for IgAN from health at the early stage. Disease-related pathways were screened out by clustering and function enrichment analyses of DEPs and DAMs. And the potential biomarkers for IgAN were identified through the machine learning approach. Additionally, an independent cohort was used to validate the priority candidates by enzyme-linked immunosorbent assay (ELISA).RESULTS: Proteomic and metabolomic analyses of IgAN plasma showed that the complement and the immune system were activated, while the energy and amino acid metabolism were disordered in the IgAN patients. PRKAR2A, IL6ST, SOS1, and palmitoleic acid have been identified as potential biomarkers. Based on the AUC value for the training and test sets, the classification performance was 0.994 and 0.977, respectively. The AUC of the external validation of the four biomarkers was 0.91.CONCLUSION: In this study, we combined proteomics and metabolomics techniques to analyze the plasma of IgAN patients and healthy individuals, constructing a biomarker panel, which could provide new insights and provide potential novel molecular diagnoses for IgAN.PMID:36572849 | DOI:10.1186/s12014-022-09387-5

Integrated metabolomics and transcriptomics analysis of roots of Bupleurum chinense and B. scorzonerifolium, two sources of medicinal Chaihu

Mon, 26/12/2022 - 12:00
Sci Rep. 2022 Dec 26;12(1):22335. doi: 10.1038/s41598-022-27019-8.ABSTRACTRadix Bupleuri (Chaihu in Chinese) is a traditional Chinese medicine commonly used to treat colds and fevers. The root metabolome and transcriptome of two cultivars of B. chinense (BCYC and BCZC) and one of B. scorzonerifolium (BSHC) were determined and analyzed. Compared with BSHC, 135 and 194 differential metabolites were identified in BCYC and BCZC, respectively, which were mainly fatty acyls, organooxygen metabolites. A total of 163 differential metabolites were obtained between BCYC and BCZC, including phenolic acids and lipids. Compared with BSHC, 6557 and 5621 differential expression genes (DEGs) were found in BCYC and BSHC, respectively, which were annotated into biosynthesis of unsaturated fatty acid and fatty acid metabolism. A total of 4,880 DEGs existed between the two cultivars of B. chinense. The abundance of flavonoids in B. scorzonerifolium was higher than that of B. chinense, with the latter having higher saikosaponin A and saikosaponin D than the former. Pinobanksin was the most major flavonoid which differ between the two cultivars of B. chinense. The expression of chalcone synthase gene was dramatically differential, which had a positive correlation with the biosynthesis of pinobanksin. The present study laid a foundation for further research on biosynthesis of flavonoids and terpenoids of Bupleurum L.PMID:36572795 | DOI:10.1038/s41598-022-27019-8

Perioral secretions enable complex social signaling in African mole-rats (genus Fukomys)

Mon, 26/12/2022 - 12:00
Sci Rep. 2022 Dec 26;12(1):22366. doi: 10.1038/s41598-022-26351-3.ABSTRACTSubterranean common mole-rats of the genus Fukomys (family Bathyergidae) live in large, cooperatively-breeding families. Odor cues have been hypothesized to play an important role in mediating social behaviors in the underground ecotope, but only little is known about the role of olfactory signaling in burrowing mammals. Here we characterize the so far neglected perioral glands of Fukomys and other African mole-rats as an important source of olfactory social information. Histology demonstrates these structures to be derived sebaceous glands that are developed regardless of sex and reproductive status. However, gland activity is higher in Fukomys males, leading to sexually dimorphic patterns of stain and clotting of the facial pelage. Behavioral assays revealed that conspecifics prefer male but not female perioral swabs over scent samples from the back fur and that male sebum causes similar attraction as anogenital scent, a known source of social information in Fukomys. Finally, we assessed volatile compounds in the perioral sebum of the giant mole-rat (Fukomys mechowii) via GCxGC-MS-based metabolomic profiling. Volatiles display pronounced sex-specific signatures but also allow to differentiate between intrasexual reproductive status groups. These different lines of evidence suggest that mole-rat perioral glands provide complex odor signals which play a crucial role in social communication.PMID:36572727 | DOI:10.1038/s41598-022-26351-3

Mixed heavy metal stress induces global iron starvation response

Mon, 26/12/2022 - 12:00
ISME J. 2022 Dec 26. doi: 10.1038/s41396-022-01351-3. Online ahead of print.ABSTRACTMultiple heavy metal contamination is an increasingly common global problem. Heavy metals have the potential to disrupt microbially mediated biogeochemical cycling. However, systems-level studies on the effects of combinations of heavy metals on bacteria are lacking. For this study, we focused on the Oak Ridge Reservation (ORR; Oak Ridge, TN, USA) subsurface which is contaminated with several heavy metals and high concentrations of nitrate. Using a native Bacillus cereus isolate that represents a dominant species at this site, we assessed the combined impact of eight metal contaminants, all at site-relevant concentrations, on cell processes through an integrated multi-omics approach that included discovery proteomics, targeted metabolomics, and targeted gene-expression profiling. The combination of eight metals impacted cell physiology in a manner that could not have been predicted from summing phenotypic responses to the individual metals. Exposure to the metal mixture elicited a global iron starvation response not observed during individual metal exposures. This disruption of iron homeostasis resulted in decreased activity of the iron-cofactor-containing nitrate and nitrite reductases, both of which are important in biological nitrate removal at the site. We propose that the combinatorial effects of simultaneous exposure to multiple heavy metals is an underappreciated yet significant form of cell stress in the environment with the potential to disrupt global nutrient cycles and to impede bioremediation efforts at mixed waste sites. Our work underscores the need to shift from single- to multi-metal studies for assessing and predicting the impacts of complex contaminants on microbial systems.PMID:36572723 | DOI:10.1038/s41396-022-01351-3

Comprehensive investigation of pathway enrichment methods for functional interpretation of LC-MS global metabolomics data

Mon, 26/12/2022 - 12:00
Brief Bioinform. 2022 Dec 26:bbac553. doi: 10.1093/bib/bbac553. Online ahead of print.ABSTRACTBACKGROUND: Global or untargeted metabolomics is widely used to comprehensively investigate metabolic profiles under various pathophysiological conditions such as inflammations, infections, responses to exposures or interactions with microbial communities. However, biological interpretation of global metabolomics data remains a daunting task. Recent years have seen growing applications of pathway enrichment analysis based on putative annotations of liquid chromatography coupled with mass spectrometry (LC-MS) peaks for functional interpretation of LC-MS-based global metabolomics data. However, due to intricate peak-metabolite and metabolite-pathway relationships, considerable variations are observed among results obtained using different approaches. There is an urgent need to benchmark these approaches to inform the best practices.RESULTS: We have conducted a benchmark study of common peak annotation approaches and pathway enrichment methods in current metabolomics studies. Representative approaches, including three peak annotation methods and four enrichment methods, were selected and benchmarked under different scenarios. Based on the results, we have provided a set of recommendations regarding peak annotation, ranking metrics and feature selection. The overall better performance was obtained for the mummichog approach. We have observed that a ~30% annotation rate is sufficient to achieve high recall (~90% based on mummichog), and using semi-annotated data improves functional interpretation. Based on the current platforms and enrichment methods, we further propose an identifiability index to indicate the possibility of a pathway being reliably identified. Finally, we evaluated all methods using 11 COVID-19 and 8 inflammatory bowel diseases (IBD) global metabolomics datasets.PMID:36572652 | DOI:10.1093/bib/bbac553

Advancing metabolic networks and mapping updated urinary metabolic fingerprints after exposure to typical carcinogenic heterocyclic aromatic amines

Mon, 26/12/2022 - 12:00
Environ Pollut. 2022 Dec 23:120936. doi: 10.1016/j.envpol.2022.120936. Online ahead of print.ABSTRACTHeterocyclic aromatic amines (HAAs) were not only present in cooked foods and cigarette smoke, but also measured in airborne particles and diesel-exhaust particles. Typical HAAs have been reported to induce carcinogenicity and metabolic disturbances, but how these hazardous compounds interfere with metabolic networks by regulating metabolic pathways and fingerprinting signature metabolites as biomarkers remains ambiguous. We developed an advanced strategy that adopts chemical isotope labeling ultrahigh-performance liquid chromatography coupled to quadrupole-Orbitrap high-resolution mass spectrometry for urinary nontargeted metabolomics analysis to gain new insight into in vivo physiological responses stimulated by exposure to typical HAAs. Rats were orally administered with a single dose of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) or 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx) (1 and 10 mg/kg bw) and their D3-isotopic compounds, respectively, and urine samples were then continuously collected within 36 h. Metabolomics data were acquired and processed by classical multivariate statistical analysis, while urinary metabolites were further identified and characterized according to mass spectrometric fragmentation rules, time- and dose-dependent profiles, and calibration of synthesized standards. We monitored 23 and 37 urinary metabolites as the biotransformation products of PhIP and MeIQx, respectively, and first identified demethylated metabolites of PhIP, tentatively named 2-amino-6-phenylimidazo [4,5-b]pyridine, and dihydroxylation products of classical HAAs as short-term biomarkers of exposure to further unravel the metabolic networks. In addition, our findings revealed that both HAAs significantly disturb histidine metabolism, arginine and proline metabolism, tryptophan metabolism, pyrimidine metabolism, tricarboxylic acid cycle, etc. Furthermore, we found that histamine, methionine, alanine, and 4-guanidinobutanoic acid could be considered potential characteristic biomarkers for the oncogenicity or carcinogenicity of both PhIP and MeIQx and screened their specific key pivotal metabolites. The current metabolomics approach is applicable in mapping updated urinary metabolic fingerprints and identifying potential specific biomarkers for HAAs-induced early tumorigenesis.PMID:36572270 | DOI:10.1016/j.envpol.2022.120936

Metabolic reprograming of cancer as a therapeutic target

Mon, 26/12/2022 - 12:00
Biochim Biophys Acta Gen Subj. 2022 Dec 23:130301. doi: 10.1016/j.bbagen.2022.130301. Online ahead of print.ABSTRACTOur understanding of metabolic reprogramming in cancer has tremendously improved along with the technical progression of metabolomic analysis. Metabolic changes in cancer cells proved much more complicated than the classical Warburg effect. Previous studies have approached metabolic changes as therapeutic and/or chemopreventive targets. Recently, several clinical trials have reported anti-cancer agents associated with metabolism. However, whether cancer cells are dependent on metabolic reprogramming or favor suitable conditions remains nebulous. Both scenarios are possibly intertwined. Identification of downstream molecules and the understanding of mechanisms underlying reprogrammed metabolism can improve the effectiveness of cancer therapy. Here, we review several examples of the metabolic reprogramming of cancer cells and the therapies targeting the metabolism-related molecules as well as discuss practical approaches to improve the next generation of cancer therapies focused on the metabolic reprogramming of cancer.PMID:36572257 | DOI:10.1016/j.bbagen.2022.130301

Plasma non-targeted metabolomics analysis of Yili horses raced on tracks with different surface hardness

Mon, 26/12/2022 - 12:00
J Equine Vet Sci. 2022 Dec 23:104197. doi: 10.1016/j.jevs.2022.104197. Online ahead of print.ABSTRACTIn this study, the plasma non-targeted metabolomics of Yili horses were characterized before and after exercise on tracks that differed in surface hardness to better understand exercise-related biochemical changes. Blood samples were obtained from eight trained Yili horses before and immediately after exercise. Samples were used for metabolomic analysis by ultra-performance liquid chromatography-Q-EXACTIVE mass spectrometry. In total, 938 significantly different metabolites involving sugar, lipid, and amino acid metabolism were detected in the plasma, with significant increases in glucose, glucoheptanoic acid, lactic acid, malic acid, and methylmalonic acid and significant decreases in creatinine, D-tryptophan, carnitine, and citric acid after exercise. Among these metabolites, acetylcarnitine, tuliposide, vitamin C, and methylmalonic acid showed regular changes in concentration after exercise on tracks that differed in surface hardness, providing new insights into equine exercise physiology. The findings indicated the potential of vitamin C and methylmalonic acid as novel biomarkers of equine locomotor injury.PMID:36572130 | DOI:10.1016/j.jevs.2022.104197

Fasted Sprint Interval Training Results in Some Beneficial Skeletal Muscle Metabolic, but Similar Metabolomic and Performance Adaptations Compared With Carbohydrate-Fed Training in Recreationally Active Male

Mon, 26/12/2022 - 12:00
Int J Sport Nutr Exerc Metab. 2022 Dec 26:1-11. doi: 10.1123/ijsnem.2022-0142. Online ahead of print.ABSTRACTEndurance training in fasted conditions (FAST) induces favorable skeletal muscle metabolic adaptations compared with carbohydrate feeding (CHO), manifesting in improved exercise performance over time. Sprint interval training (SIT) is a potent metabolic stimulus, however nutritional strategies to optimize adaptations to SIT are poorly characterized. Here we investigated the efficacy of FAST versus CHO SIT (4-6 × 30-s Wingate sprints interspersed with 4-min rest) on muscle metabolic, serum metabolome and exercise performance adaptations in a double-blind parallel group design in recreationally active males. Following acute SIT, we observed exercise-induced increases in pan-acetylation and several genes associated with mitochondrial biogenesis, fatty acid oxidation, and NAD+-biosynthesis, along with favorable regulation of PDK4 (p = .004), NAMPT (p = .0013), and NNMT (p = .001) in FAST. Following 3 weeks of SIT, NRF2 (p = .029) was favorably regulated in FAST, with augmented pan-acetylation in CHO but not FAST (p = .033). SIT induced increases in maximal citrate synthase activity were evident with no effect of nutrition, while 3-hydroxyacyl-CoA dehydrogenase activity did not change. Despite no difference in the overall serum metabolome, training-induced changes in C3:1 (p = .013) and C4:1 (p = .010) which increased in FAST, and C16:1 (p = .046) and glutamine (p = .021) which increased in CHO, were different between groups. Training-induced increases in anaerobic (p = .898) and aerobic power (p = .249) were not influenced by nutrition. These findings suggest some beneficial muscle metabolic adaptations are evident in FAST versus CHO SIT following acute exercise and 3 weeks of SIT. However, this stimulus did not manifest in differential exercise performance adaptations.PMID:36572038 | DOI:10.1123/ijsnem.2022-0142

A novel approach to Lactiplantibacillus plantarum: From probiotic properties to the omics insights

Mon, 26/12/2022 - 12:00
Microbiol Res. 2022 Dec 22;268:127289. doi: 10.1016/j.micres.2022.127289. Online ahead of print.ABSTRACTLactiplantibacillus plantarum (previously known as Lactobacillus plantarum) strains are one of the lactic acid bacteria (LAB) commonly used in fermentation and their probiotic and functional properties along with their health-promoting roles come to the fore. Food-derived L. plantarum strains have shown good resistance and adhesion in the gastrointestinal tract (GI) and excellent antioxidant and antimicrobial properties. Furthermore, many strains of L. plantarum can produce bacteriocins with interesting antimicrobial activity. This probiotic properties of L. plantarum and existing in different niches give a great potential to have beneficial effects on health. It is also has been shown that L. plantarum can regulate the intestinal microbiota composition in a good way. Recently, omics approaches such as metabolomics, secretomics, proteomics, transcriptomics and genomics try to understand the roles and mechanisms of L. plantarum that are related to its functional characteristics. This review provides an overview of the probiotic properties, including the specific interactions between microbiota and host, and omics insights of L. plantarum.PMID:36571922 | DOI:10.1016/j.micres.2022.127289

Myofibrillar protein-chlorogenic acid complexes ameliorate glucose metabolism via modulating gut microbiota in a type 2 diabetic rat model

Mon, 26/12/2022 - 12:00
Food Chem. 2022 Dec 12;409:135195. doi: 10.1016/j.foodchem.2022.135195. Online ahead of print.ABSTRACTGrowing evidence suggests that polyphenols could mitigate type 2 diabetes mellitus (T2DM). The glucose-regulatory effects of protein-bound polyphenols, however, have been rarely studied. In this study, macrogenomic and metabolomic analyses were applied to investigate the modulation of myofibrillar protein-chlorogenic acid (MP-CGA) complexes on T2DM rats from the gut microbiota perspective. Results showed that MP-CGA improved hyperglycemia and hyperlipidemia, decreased intestinal inflammation, and reduced intestinal barrier injury. MP-CGA reconstructed gut microbiota in T2DM rats, elevating the abundance of probiotics Bacteroides, Akkermansia, and Parabacteroides while suppressing opportunistic pathogens Enterococcus and Staphylococcus. MP-CGA significantly elevated the concentrations of intestinal metabolites like butyric acid that positively regulate T2DM and reduced the secondary bile acids contents. Therefore, MP-CGA modulated the gut microbiota and related metabolites to maintain stable blood glucose in T2DM rats, providing new insights into the application of protein-polyphenol complexes in foods.PMID:36571901 | DOI:10.1016/j.foodchem.2022.135195

Repeated use of 3,4-methylenedioxymethamphetamine is associated with the resilience in mice after chronic social defeat stress: A role of gut-microbiota-brain axis

Mon, 26/12/2022 - 12:00
Psychiatry Res. 2022 Dec 21;320:115020. doi: 10.1016/j.psychres.2022.115020. Online ahead of print.ABSTRACT3,4-Methylenedioxymethamphetamine (MDMA), the most widely used illicit compound worldwide, is the most attractive therapeutic drug for post-traumatic stress disorder (PTSD). Recent observational studies of US adults demonstrated that lifetime MDMA use was associated with lower risk of depression. Here, we examined whether repeated administration of MDMA can affect resilience versus susceptibility in mice exposed to chronic social defeat stress (CSDS). CSDS produced splenomegaly, anhedonia-like phenotype, and higher plasma levels of interleukin-6 (IL-6) in the saline-treated mice. In contrast, CSDS did not cause these changes in the MDMA-treated mice. Analysis of gut microbiome found several microbes altered between saline + CSDS group and MDMA + CSDS group. Untargeted metabolomics analysis showed that plasma levels of N-epsilon-methyl-L-lysine in the saline + CSDS group were significantly higher than those in the control and MDMA + CSDS groups. Interestingly, there were positive correlations between plasma IL-6 levels and the abundance of several microbes (or plasma N-epsilon-methyl-L-lysine) in the three groups. Furthermore, there were also positive correlations between the abundance of several microbes and N-epsilon-methyl-L-lysine in the three groups. In conclusion, these data suggest that repeated administration of MDMA might contribute to stress resilience in mice subjected to CSDS through gut-microbiota-brain axis.PMID:36571897 | DOI:10.1016/j.psychres.2022.115020

Magnetic field-driven biochemical landscape of browning abatement in goat milk using spatial-omics uncovers

Mon, 26/12/2022 - 12:00
Food Chem. 2022 Dec 22;408:135276. doi: 10.1016/j.foodchem.2022.135276. Online ahead of print.ABSTRACTInfluence of magnetic field (MF) treatment on the glycation of goat milk proteins is yet to be elucidated. Proteomic and metabolomic analyses of brown goat milk samples with and without MF treatment were performed. Assessed glycation degree and structural modification of proteins explained that MF treatment dramatically down-regulated the glycation of brown goat milk protein, possibly due to the aggregation behavior induced by MF treatment, which consumed additional glycation sites as well as altered their accessibility and preference. Integrated datasets uncovered that the energy metabolism-related biological events including carbohydrate metabolism, glycerophospholipid metabolism, TCA cycle may mainly account for the browning abatement mechanism of MF. In addition, MF treatment enhanced both the quality and flavor of brown goat milk. This study suggests the feasibility of MF treatment to reduce glycation in brown goat milk for producing high-quality dairy ingredients and products.PMID:36571880 | DOI:10.1016/j.foodchem.2022.135276

H<sub>2</sub>-induced transient upregulation of phospholipids with suppression of energy metabolism

Mon, 26/12/2022 - 12:00
Med Gas Res. 2023 Jul-Sep;13(3):133-141. doi: 10.4103/2045-9912.344973.ABSTRACTMolecular hydrogen (H2) is an antioxidant and anti-inflammatory agent; however, the molecular mechanisms underlying its biological effects are largely unknown. Similar to other gaseous molecules such as inhalation anesthetics, H2 is more soluble in lipids than in water. A recent study demonstrated that H2 reduces radical polymerization-induced cellular damage by suppressing fatty acid peroxidation and membrane permeability. Thus, we sought to examine the effects of short exposure to H2 on lipid composition and associated physiological changes in SH-SY5Y neuroblastoma cells. We analyzed cells by liquid chromatography-high-resolution mass spectrometry to define changes in lipid components. Lipid class analysis of cells exposed to H2 for 1 hour revealed transient increases in glycerophospholipids including phosphatidylethanolamine, phosphatidylinositol, and cardiolipin. Metabolomic analysis also showed that H2 exposure for 1 hour transiently suppressed overall energy metabolism accompanied by a decrease in glutathione. We further observed alterations to endosomal morphology by staining with specific antibodies. Endosomal transport of cholera toxin B to recycling endosomes localized around the Golgi body was delayed in H2-exposed cells. We speculate that H2-induced modification of lipid composition depresses energy production and endosomal transport concomitant with enhancement of oxidative stress, which transiently stimulates stress response pathways to protect cells.PMID:36571379 | DOI:10.4103/2045-9912.344973

Comprehensive physiological, transcriptomic, and metabolomic analyses reveal the synergistic mechanism of <em>Bacillus pumilus</em> G5 combined with silicon alleviate oxidative stress in drought-stressed <em>Glycyrrhiza uralensis</em> Fisch

Mon, 26/12/2022 - 12:00
Front Plant Sci. 2022 Dec 8;13:1033915. doi: 10.3389/fpls.2022.1033915. eCollection 2022.ABSTRACTGlycyrrhiza uralensis Fisch. is often cultivated in arid, semi-arid, and salt-affected regions that suffer from drought stress, which leads to the accumulation of reactive oxygen species (ROS), thus causing oxidative stress. Plant growth-promoting bacteria (PGPB) and silicon (Si) have been widely reported to be beneficial in improving the tolerance of plants to drought stress by maintaining plant ROS homeostasis. Herein, combining physiological, transcriptomic, and metabolomic analyses, we investigated the response of the antioxidant system of G. uralensis seedlings under drought stress to Bacillus pumilus (G5) and/or Si treatment. The results showed that drought stress caused the overproduction of ROS, accompanied by the low efficiency of antioxidants [i.e., superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), the ascorbate (AsA)-glutathione (GSH) pool, total carotenoids, and total flavonoids]. Inversely, supplementation with G5 and/or Si enhanced the antioxidant defense system in drought-stressed G. uralensis seedlings, and the complex regulation of the combination of G5 and Si differed from that of G5 or Si alone. The combination of G5 and Si enhanced the antioxidant enzyme system, accelerated the AsA-GSH cycle, and triggered the carotenoid and flavonoid metabolism, which acted in combination via different pathways to eliminate the excess ROS induced by drought stress, thereby alleviating oxidative stress. These findings provide new insights into the comparative and synergistic roles of PGPB and Si in the antioxidant system of plants exposed to drought and a guide for the application of PGPB combined with Si to modulate the tolerance of plants to stress.PMID:36570944 | PMC:PMC9773211 | DOI:10.3389/fpls.2022.1033915

Integrated transcriptome and metabolome analysis reveals the anthocyanin biosynthesis mechanisms in blueberry (<em>Vaccinium corymbosum</em> L.) leaves under different light qualities

Mon, 26/12/2022 - 12:00
Front Plant Sci. 2022 Dec 8;13:1073332. doi: 10.3389/fpls.2022.1073332. eCollection 2022.ABSTRACTINTRODUCTION: Blueberry (Vaccinium corymbosum L.) is a popular fruit with an abundance of anthocyanins in its leaves and fruits. Light is one of the pivotal environmental elements that affects plant growth and development, but the regulatory mechanism between light quality and anthocyanin formation is poorly understood.METHODS: An integrated transcriptome and metabolome analysis was performed to investigate the effects of white (control), blue (B), red (R), and red/blue (60R/40B) light on blueberry growth and reveal the potential pathway controlling anthocyanin biosynthesis in blueberry leaves.RESULTS: The anthocyanin content was significantly improved by the blue and red/blue light when compared with white light, whereas there was a significant reduction in the photosynthesis under the blue light, showing an inverse trend to that of anthocyanin accumulation. Transcriptomic analysis resulted in the assembly of 134,709 unigenes. Of these, 22 were differentially expressed genes (DEGs) that participate in the anthocyanin biosynthesis pathway, with the majority being significantly up-regulated under the blue light. Most of the photosynthesis-related genes that were down-regulated were expressed during anthocyanin accumulation. Targeted metabolome profiling identified 44 metabolites associated with anthocyanin biosynthesis. The contents of most of these metabolites were higher under blue light than the other light conditions, which was consistent with the transcriptome results. The integrated transcriptome and metabolome analysis suggested that, under blue light, leucoanthocyanidin dioxygenase (LDOX), O-methyltransferase (OMT), and UDP-glucose flavonoid glucosyltransferase (UFGT) were the most significantly expressed, and they promoted the synthesis of cyanidin (Cy), malvidin (Mv), and pelargonidin (Pg) anthocyanidins, respectively. The expression levels of dihydroflavonol 4-reductase (DFR) and OMT, as well as the accumulation of delphinidin (Dp), peonidin (Pn), and petunidin (Pt), were significantly increased by the red/blue light.DISCUSSION: The blue and red/blue lights promoted anthocyanin biosynthesis via inducing the expression of key structural genes and accumulation of metabolites involved in anthocyanin synthesis pathway. Moreover, there was a possible feedback regulating correlation between anthocyanin biosynthesis and photosynthesis under different light qualities in blueberry leaves. This study would provide a theoretical basis for elucidating the underlying regulatory mechanism of anthocyanin biosynthesis of V. corymbosum.PMID:36570935 | PMC:PMC9772006 | DOI:10.3389/fpls.2022.1073332

Editorial: Host plant resistance mechanisms against fungal pathogens

Mon, 26/12/2022 - 12:00
Front Plant Sci. 2022 Dec 8;13:1103046. doi: 10.3389/fpls.2022.1103046. eCollection 2022.NO ABSTRACTPMID:36570920 | PMC:PMC9773977 | DOI:10.3389/fpls.2022.1103046

Antioxidant processes involving epicatechin decreased symptoms of pine wilt disease

Mon, 26/12/2022 - 12:00
Front Plant Sci. 2022 Dec 9;13:1015970. doi: 10.3389/fpls.2022.1015970. eCollection 2022.ABSTRACTSince the pine wood nematode (PWN, Bursaphelenchus xylophilus) invasion of Northeast China, both symptomatic and asymptomatic PWN carriers have been found. Asymptomatic PWN carriers, which are more dangerous than symptomatic carriers, constitute a source of infection in the following spring. The simultaneous presence of symptomatic and asymptomatic PWN carriers indicates that Pinus koraiensis has different tolerance levels to PWN. In this study, validity of susceptibility testing discovered differential types of P. koraiensis including Latent Reservoirs, Low Susceptibles, High Susceptibles and Bell Ringers. Among those types, the Low Susceptibles and Latent Reservoirs were asymptomatic PWN carriers, and Latent Reservoirs were the most dangerous. Transcriptome and metabolomic data showed that 5 genes (3 ans and 2 anr gene) involved in the epicatechin (EC) synthesis pathway were significantly upregulated, which increased the content of EC antioxidants in Latent Reservoirs. Hydrogen peroxide (H2O2) staining and content determination showed that the hypersensitive response (HR) and H2O2, which functions as a signaling molecule in systemic acquired resistance, decreased in Latent Reservoirs. However, low contents of EC and high contents of H2O2 were found in the High Susceptibles of P. koraiensis. RT-PCR results showed that the expression of ans and anr was upregulated together only in Latent Reservoirs. These results show that the susceptibility of P. koraiensis to PWN differed among different individuals, although no resistant individuals were found. Latent Reservoirs, in which more PWNs resided without visible symptoms via prolonged incubation period, inhibited the symptoms caused by H2O2 because of increased contents of the EC antioxidants.PMID:36570913 | PMC:PMC9780601 | DOI:10.3389/fpls.2022.1015970

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