PubMed

Radiat Res. 2022 Nov 1;198(5):488-507. doi: 10.1667/RADE-21-00174.1.ABSTRACTThe intestinal compensatory proliferative potential is a key influencing factor for susceptibility to radiation-induced intestinal injury. Studies indicated that the carnitine palmitoyltransferase 1 (CPT1) mediated fatty acid β-oxidation (FAO) plays a crucial role in promoting the survival and proliferation of tumor cells. Here, we aimed to explore the effect of 60Co gamma rays on CPT1 mediated FAO in the radiation-induced intestinal injury models, and investigate the role of CPT1 mediated FAO in the survival and proliferation of intestinal cells after irradiation. We detected the changed of FAO in the plasma and small intestine of Sprague Dawley (SD) rats at 24 h after 60Co gamma irradiation (0, 5 and 10 Gy), using target metabolomics, qRT-PCR, immunohistochemistry (IHC), western blot (WB) and related enzymatic activity kits. We then analyzed the FAO changes in radiation-induced intestinal injury models regardless of ex vivo (mice enteroids), or in vitro (normal human intestinal epithelial cell lines, HIEC-6). HIEC-6 cells were transduced with lentivirus vector GV392 and treated with puromycin for obtaining CPT1 stable knockout cell lines, named CPT1 KO. CPT1 enzymatic activities of HIEC-6 cells and mice enteroids were also inhibited by pharmaceutical inhibitor ST1326 and Etomoxir (ETO), to study the function of CPT1 in the survival and proliferation of HIEC-6 cells after 60Co gamma irradiation. We found that CPT1 mediated FAO was altered in the small intestine of the SD rats after irradiation, especially, the expression level and enzymatic activity of CPT1 were significantly increased. Similarly, the expression levels of CPT1 were also remarkably enhanced in mice enteroids and HIEC-6 cells after irradiation. CPT1 inhibition decreased the proliferation of the HIEC-6 cells and mice enteroids after irradiation partially by reducing the extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways activation, CPT1 inhibition also reduced the proliferation of mice enteroids after irradiation partially by down-regulating the Wnt/β-catenin signaling activity. In conclusion, our study indicated that CPT1 plays a crucial role in promoting intestinal epithelial cell proliferation after irradiation.PMID:36351324 | DOI:10.1667/RADE-21-00174.1

Environ Sci Technol. 2022 Nov 9. doi: 10.1021/acs.est.2c05828. Online ahead of print.ABSTRACTTo promote the sustainable and safe application of nanotechnology employing engineered nanoparticles (NPs) in agroecosystems, it is crucial to pay more attention to the NP-mediated biological response process and environmental impact assessment simultaneously. Herein, 50 mg kg-1 La2O3 NPs were added to soils without and with earthworms for cherry radish growth for 50 days to investigate the response changes of metabolites in radish above- and below-ground organs and rhizosphere bacterial communities. We found that La2O3 NP exposure, especially with earthworms, notably increased the La bioavailability and uptake by taproots and eventually increased radish leaf sucrose content and plant biomass. The La2O3 NP exposure significantly altered metabolite profiles in taproot flesh and peel tissues, and particularly La2O3 NP exposure combined with earthworms was more conducive to La2O3 NPs to promote radish taproot peel to synthesize more secondary antioxidant metabolites. Moreover, compared with the control, the La2O3 NP exposure resulted in weaker and fewer correlations between rhizosphere bacteria and taproot metabolites, but this was recovered somewhat after the inoculation of earthworms. Altogether, our results provide novel insights into the soil-fauna-driven biological and biochemical impact of La2O3 NP exposure on edible root crops and the long-term environmental risks to the rhizosphere microbiota in agroecosystems.PMID:36351052 | DOI:10.1021/acs.est.2c05828

Environ Sci Technol. 2022 Nov 9. doi: 10.1021/acs.est.2c06260. Online ahead of print.ABSTRACTBiodegradation of polystyrene (PS) in mealworms (Tenebrio molitor lavae) has been identified with commercial PS foams. However, there is currently limited understanding of the influence of molecular weight (MW) on insect-mediated plastic biodegradation and the corresponding responses of mealworms. In this study, we provided the results of PS biodegradation, gut microbiome, and metabolome by feeding mealworms with high-purity PS microplastics with a wide variety of MW. Over 24 days, mealworms (50 individuals) fed with 0.20 g of PS showed decreasing removal of 74.1 ± 1.7, 64.1 ± 1.6, 64.4 ± 4.0, 73.5 ± 0.9, 60.6 ± 2.6, and 39.7 ± 4.3% for PS polymers with respective weight-average molecular weights (Mw) of 6.70, 29.17, 88.63, 192.9, 612.2, and 1346 kDa. The mealworms degraded most PS polymers via broad depolymerization but ultrahigh-MW PS via limited-extent depolymerization. The gut microbiome was strongly associated with biodegradation, but that with low- and medium-MW PS was significantly distinct from that with ultrahigh-MW PS. Metabolomic analysis indicated that PS biodegradation reprogrammed the metabolome and caused intestinal dysbiosis depending on MW. Our findings demonstrate that mealworms alter their gut microbiome and intestinal metabolic pathways in response to in vivo biodegradation of PS polymers of various MWs.PMID:36350780 | DOI:10.1021/acs.est.2c06260

J Agric Food Chem. 2022 Nov 9. doi: 10.1021/acs.jafc.2c04715. Online ahead of print.ABSTRACTMetabolomic studies on root uptake and transformation of bioactive compounds, like cereal benzoxazinoids (BXs) in non-BX producing plants, are very limited. Therefore, a targeted mass-spectrometry-based metabolomics study was performed to elucidate the root uptake of BXs in white clover (Trifolium repens L.) and the impact of absorbed BXs on intrinsic clover secondary metabolites. Clover plants grew in a medium containing 100 μM of individual BXs (five aglycone and one glycoside BXs) for 3 weeks. Subsequently, plant tissues were analyzed by liquid chromatography-tandem mass spectrometry to quantify the BXs and clover secondary metabolite concentrations. All BXs were taken up by clover roots and translocated to the shoots. Upon uptake of 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA), 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), 2-hydroxy-1,4-benzoxazin-3-one (HBOA), and 2-β-d-glucopyranosyloxy-1,4-benzoxazin-3-one (HBOA-glc), the parent compounds and a range of transformation products were seen in the roots and shoots. The individual BX concentrations ranged from not detected (nd) to 469 μg/g of dry weight (dw) and from nd to 170 μg/g of dw in the roots and shoots, respectively. The root uptake of BXs altered the composition of intrinsic clover secondary metabolites. In particular, the concentration of flavonoids and the hormone abscisic acid increased substantially in comparison to control plants.PMID:36350751 | DOI:10.1021/acs.jafc.2c04715

Curr Opin Rheumatol. 2022 Nov 10. doi: 10.1097/BOR.0000000000000919. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: To review recent studies using 'Omics' approaches (genomics, proteomics, metabolomics, single cell analyses) in patient populations and animal models of osteoarthritis (OA), with the goal of identifying disease-modifying mechanisms that could serve as therapeutic and diagnostic targets.RECENT FINDINGS: The number of genes, pathways and molecules with potential roles in OA pathogenesis has grown substantially over the last 18 months. Studies have expanded from their traditional focus on cartilage and gene expression to other joint tissues, proteins and metabolites. Single cell approaches provide unprecedented resolution and exciting insights into the heterogeneity of cellular activities in OA. Functional validation and investigation of underlying mechanisms in animal models of OA, in particular genetically engineered mice, link Omics findings to pathophysiology and potential therapeutic applications.SUMMARY: Although great progress has been made in the use of Omics approaches to OA, in both animal models and patient samples, much work remains to be done. In addition to filling gaps in data sets not yet existing, integration of data from the various approaches, mechanistic investigations, and linkage of Omics data to patient stratification remain significant challenges.PMID:36350386 | DOI:10.1097/BOR.0000000000000919

Genet Med. 2022 Nov 8:S1098-3600(22)00970-4. doi: 10.1016/j.gim.2022.10.002. Online ahead of print.ABSTRACTPURPOSE: For patients with inherited metabolic disorders (IMDs), any diagnostic delay should be avoided because early initiation of personalized treatment could prevent irreversible health damage. To improve diagnostic interpretation of genetic data, gene function tests can be valuable assets. For IMDs, variant-transcending functional tests are readily available through (un)targeted metabolomics assays. To support the application of metabolomics for this purpose, we developed a gene-based guide to select functional tests to either confirm or exclude an IMD diagnosis.METHODS: Using information from a diagnostic IMD exome panel, Kyoto Encyclopedia of Genes and Genomes, and Inborn Errors of Metabolism Knowledgebase, we compiled a guide for metabolomics-based gene function tests. From our practical experience with this guide, we retrospectively selected illustrative cases for whom combined metabolomic/genomic testing improved diagnostic success and evaluated the effect hereof on clinical management.RESULTS: The guide contains 2047 metabolism-associated genes for which a validated or putative variant-transcending gene function test is available. We present 16 patients for whom metabolomic testing either confirmed or ruled out the presence of a second pathogenic variant, validated or ruled out pathogenicity of variants of uncertain significance, or identified a diagnosis initially missed by genetic analysis.CONCLUSION: Metabolomics-based gene function tests provide additional value in the diagnostic trajectory of patients with suspected IMD by enhancing and accelerating diagnostic success.PMID:36350326 | DOI:10.1016/j.gim.2022.10.002

J Agric Food Chem. 2022 Nov 9. doi: 10.1021/acs.jafc.2c05156. Online ahead of print.ABSTRACTCitrus canker, caused by the bacterium Xanthomonas citri subsp. citri (X. citri), is a plant disease affecting Citrus crops worldwide. However, little is known about defense compounds in Citrus. Here, we conducted a mass spectrometry-based metabolomic approach to obtain an overview of the chemical responses of Citrus leaves to X. citri infection. To facilitate result interpretation, the multivariate analyses were combined with molecular networking to identify biomarkers. Metabolite variations among untreated and X. citri-inoculated Citrus samples under greenhouse conditions highlighted induced defense biomarkers. Notably, the plant tryptophan metabolism pathway was activated, leading to the accumulation of N-methylated tryptamine derivatives. This finding was subsequently confirmed in symptomatic leaves in the field. Several tryptamine derivatives showed inhibitory effects in vitro against X. citri. This approach has enabled the identification of new chemically related biomarker groups and their dynamics in the response of Citrus leaves to Xanthomonas infection.PMID:36350271 | DOI:10.1021/acs.jafc.2c05156

J Sep Sci. 2022 Nov 9. doi: 10.1002/jssc.202200311. Online ahead of print.ABSTRACTAbrus mollis Hance is a traditional Chinese medicine that is widely used to treat acute and chronic hepatitis, steatosis and fibrosis This article is protected by copyright. All rights reserved.PMID:36349515 | DOI:10.1002/jssc.202200311

J Sci Food Agric. 2022 Nov 8. doi: 10.1002/jsfa.12321. Online ahead of print.ABSTRACTBACKGROUND: Fermented capsicum (i.e., pickled pepper) is one of the most popular fermented vegetables. However, the effect of inoculated microbial fermentation on pickled pepper was not yet fully understood.RESULTS: Cyberlindnera rhodanensis J52 with a rich ester flavour and P. pentosaceus AL with a strong inhibitory effect on foodborne pathogenic bacteria were selected to prepare single- and double-strain fermented capsicum under low salt (<10 g L-1 NaCl) conditions. The inhibition zone of P. pentosaceus AL against Escherichia coli was up to 44 mm in diameter. Biochemical indicator analyses found that co-fermentation of P. pentosaceus AL and C. rhodanensis J52 changed the contents of vitamin C and short-chain fatty acids. Analysis of microbial diversity and volatile metabolome showed that 125 microbial species and 72 volatile compounds were detected, and P. pentosaceus was the dominant bacterium that inhibited the growth of other bacteria, while C. rhodanensis was the fungus that contributed the most to flavour. Correlation analysis between microorganisms and flavour compounds showed 725 correlations, and 124 microbial species may have participated in the formation of 69 compounds. Furthermore, 10 and 29 correlations were detected between P. pentosaceus AL or C. rhodanensis J52 and flavour compounds, respectively. Among them, 3-methyl-1-butanol acetate is speculated to be the main substance affecting the flavour of fermented capsicum by inoculation with C. rhodanensis J52.CONCLUSION: The inoculation of P. pentosaceus and C. rhodanensis had a significant impact on the microbial community and volatile compounds of fermented capsicum and helped to improve its organoleptic qualities. This article is protected by copyright. All rights reserved.PMID:36349455 | DOI:10.1002/jsfa.12321

Oral Dis. 2022 Nov 8. doi: 10.1111/odi.14432. Online ahead of print.ABSTRACTOBJECTIVE: Tumor cells can acquire a large amount of energy and structural components by reprogramming energy metabolism; moreover, metabolic profiles slightly differ according to cancer type. This study compared and assessed the metabolic profile of head and neck squamous cell carcinoma (HNSCC) and normal tissues, which were collected from patients without cancer.SUBJECTS AND METHODS: Overall, 23 patients with HNSCC and 6 patients without cancer were included in the analysis. Metabolomic profiles were analyzed using capillary electrophoresis-mass spectrometry. Gene expression was evaluated using real-time reverse transcription-polymerase chain reaction.RESULTS: Glycolysis, the pentose phosphate pathway, tricarboxylic acid cycle, and glutamine metabolism were upregulated in HNSCC tissues based on gene expression analysis. HNSCC could then have enhanced energy production and structural component. The levels of lactate, succinate, glutathione, 2-hydroxyglutarate, and S-adenosylmethionine, considered as oncometabolites, increased and these had accumulated in HNSCC tissues.CONCLUSIONS: The level of metabolites and the expression of enzymes differ between HNSCC and normal tissues. Reprogramming metabolism in HNSCC provides an energy source as well as structural components, creating a system that offers rapid proliferation, progression, and is less likely to be eliminated.PMID:36349421 | DOI:10.1111/odi.14432

Drug Des Devel Ther. 2022 Nov 2;16:3805-3816. doi: 10.2147/DDDT.S379335. eCollection 2022.ABSTRACTPURPOSE: The prevalence of hyperlipidemia and related illnesses is on its rise, and atorvastatin is the frequently used hypolipidemic agent. However, there is still uncertainty about the mechanisms, especially the relationship between the lipid-lowering effect, intestinal microbiome, and metabolic profiles. We aim to intensively explain the mechanism of the hypolipidemic effect of atorvastatin through multi-omics perspective of intestinal microbiome and metabolomics.METHODS: Multi-omics methods play an increasingly important role in the analysis of intestinal triggers and evaluation of metabolic disorders such as obesity, hyperlipidemia, and diabetes. Therefore, we were prompted to explore intestinal triggers, underlying biomarkers, and potential intervention targets of atorvastatin in the treatment of dyslipidemia through multi-omics. To achieve this, SPF Wistar rats were fed a high-fat diet or normal diet for 8 weeks. Atorvastatin was then administered to high-fat diet-fed rats.RESULTS: By altering intestinal microbiome, a high-fat diet can affect feces and plasma metabolic profiles. Treatment with atorvastatin possibly increases the abundance of Bacteroides, thereby improving "propanoate metabolism" and "glycine, serine and threonine metabolism" in feces and plasma, and contributing to blood lipid reduction.CONCLUSION: Our study elucidated the intestinal triggers and metabolites of high-fat diet-induced dyslipidemia from the perspective of intestinal microbiome and metabolomics. It equally identified potential intervention targets of atorvastatin. This further explains the mechanism of the hypolipidemic effect of atorvastatin from a multi-omics perspective.PMID:36349306 | PMC:PMC9637332 | DOI:10.2147/DDDT.S379335

FASEB Bioadv. 2022 Sep 17;4(11):709-723. doi: 10.1096/fba.2022-00073. eCollection 2022 Nov.ABSTRACTIn solid organs, cells of the same "type" can vary in their molecular phenotype. The basis of this state variation is being revealed by characterizing cell features including the expression pattern of mRNAs and the internal distribution of proteins. Here, the variability of metabolic state between cells is probed by enzyme activity profiling. We study individual cells of types that can be identified during the post-mitotic phase of oogenesis in Xenopus laevis. Whole-cell homogenates of isolated oocytes are used for kinetic analysis of enzymes, with a focus on the initial reaction rate. For each oocyte type studied, the activity signatures of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and malate dehydrogenase 1 (MDH1) vary more between the homogenates of single oocytes than between repeat samplings of control homogenates. Unexpectedly, the activity signatures of GAPDH and MDH1 strongly co-vary between oocytes of each type and change in strength of correlation during oogenesis. Therefore, variability of the kinetic behavior of these housekeeping enzymes between "identical" cells is physiologically programmed. Based on these findings, we propose that single-cell profiling of enzyme kinetics will improve understanding of how metabolic state heterogeneity is related to heterogeneity revealed by omics methods including proteomics, epigenomics, and metabolomics.PMID:36349298 | PMC:PMC9635011 | DOI:10.1096/fba.2022-00073

Food Sci Nutr. 2022 Jul 15;10(11):3814-3827. doi: 10.1002/fsn3.2978. eCollection 2022 Nov.ABSTRACTAging is closely related to altered gut function and its microbiome composition. To elucidate the mechanisms involved in the preventive effect of special high-docosahexaenoic acid tuna oil (HDTO) on senescence, the effects of different doses of HDTO on the gut microbiome and metabolome of d-galactose-induced aging mice were studied. Deferribacteres and Tenericutes and uridine might be used as indicator bacteria and characteristic metabolites to identify aging, respectively. HDTO markedly improved the impaired memory and antioxidant abilities induced by d-galactose. At the phylum level, the abundance of Firmicutes and Tenericutes was significantly increased upon d-galactose induction, while that of Bacteroidetes, Proteobacteria, and Deferribacteres was significantly decreased. At the genus level, the variation mainly presented as an increase in the abundance of the Firmicutes genera Ligilactobacillus, Lactobacillus, and Erysipelothrix, the decrease in the abundance of the Bacteroidetes genera Bacteroides and Alistipes, the Firmicutes genus Dielma, and the Deferribacteres genus Mucispirillum. HDTO supplementation reversed the alterations in the intestinal flora by promoting the proliferation of beneficial flora during the aging process; the metabolic pathways, such as glycine-serine-threonine metabolism, valine-leucine-isoleucine biosynthesis, and some metabolic pathways involved in uridine, were also partially restored. Furthermore, the correlation analysis illustrated an obvious correlation between gut microbiota, its metabolites, and aging-related indices. Moreover, it is worth noting that the metabolic regulation by dietary intervention varied with different HDTO doses and did not present a simple additive effect; indeed, each dose showed a unique modulation mechanism.PMID:36348794 | PMC:PMC9632196 | DOI:10.1002/fsn3.2978

Food Sci Nutr. 2022 Aug 24;10(11):3993-4002. doi: 10.1002/fsn3.2995. eCollection 2022 Nov.ABSTRACTAspergillus section Flavi constitutes several species of opportunistic fungi, notable among them are A. flavus and A. parasiticus, capable of surviving harsh conditions and colonizing a wide range of agricultural products pre- and postharvest. Physical and chemical control methods are widely applied in order to mitigate the invasion of A. flavus in crops. However, physical control is not suitable for large scale and chemical control often leads to environmental pollution, whereas biological control offers a safer, environmentally friendly, and economical alternative. The present study aimed to investigate the antagonism of several non-aflatoxigenic A. flavus strains against the aflatoxigenic ones in vitro (semisynthetic peanut growth medium; MPA) in terms of colony growth rate and AFB1 inhibition. Different peanut concentrations were used to obtain the optimum peanut concentration in the formulated growth medium. A dual culture assay was performed to assess the antagonism of nonaflatoxigenic strains against the aflatoxigenic ones. Results revealed that 9% MPA exhibited the highest growth and AFB1 inhibition by nonaflatoxigenic strains. It was also found that different nonaflatoxigenic strains exhibited different antagonism against the aflatoxigenic ones which ranged from 11.09 ± 0.65% to 14.06 ± 0.14% for growth inhibition, and 53.97 ± 2.46% to 72.64 ± 4.54% for AFB1 inhibition. This variability could be due to the difference in antagonistic metabolites produced by different nonaflatoxigenic strains assessed in the present study. Metabolomics study to ascertain the specific metabolites that conferred the growth and aflatoxin inhibition is ongoing.PMID:36348788 | PMC:PMC9632215 | DOI:10.1002/fsn3.2995

BMC Genomics. 2022 Nov 9;23(1):739. doi: 10.1186/s12864-022-08947-1.ABSTRACTHere we respond to Zhou (BMC Genomics 21:734, 2020) "Combined Transcriptome and Metabolome analysis of Pitaya fruit unveiled the mechanisms underlying peel and pulp color formation" published in BMC Genomics. Given the evolutionary conserved anthocyanin biosynthesis pathway in betalain-pigmented species, we are open to the idea that species with both anthocyanins and betalains might exist. However, in absence of LC-MS/MS spectra, apparent lack of biological replicates, and no comparison to authentic standards, the findings of Zhou (BMC Genomics 21:734, 2020) are not a strong basis to propose the presence of anthocyanins in betalain-pigmented pitaya. In addition, our re-analysis of the datasets indicates the misidentification of important genes and the omission of key flavonoid and anthocyanin synthesis genes ANS and DFR. Finally, our re-analysis of the RNA-Seq dataset reveals no correlation between anthocyanin biosynthesis gene expression and pigment status.PMID:36348495 | DOI:10.1186/s12864-022-08947-1

Exp Hematol Oncol. 2022 Nov 8;11(1):88. doi: 10.1186/s40164-022-00334-6.ABSTRACTBACKGROUND: Accumulating evidence implicates that gut fungi are associated with the pathogenesis of colorectal cancer (CRC). Our previous study has revealed that Candida tropicalis (C. tropicalis) promotes colorectal tumorigenesis by enhancing immunosuppressive function of myeloid-derived suppressor cells (MDSCs) and increasing accumulation of MDSCs, but the underlying mechanisms remain unestablished.METHODS: Bone marrow-derived MDSCs were stimulated with C. tropicalis. RNA-sequencing analysis was performed to screen the differentially expressed genes. Quantitative real-time PCR and western blot were used to measure the expression of related proteins. Co-culture assay of MDSCs and CD8+ T cells was used to determine the immunosuppressive ability of MDSCs. Metabolomic analysis was conducted to detect metabolic reprogramming of MDSCs. Aerobic glycolysis of MDSCs was assessed by extracellular acidification rate (ECAR), glucose consumption and lactate production. A CAC mouse model was induced by AOM and DSS to determine the therapeutic action of TEPP-46. IHC and immunofluorescence were performed to examine the expression of PKM2, PKM2 (p-Y105) and iNOS in human CRC-infiltrated MDSCs.RESULTS: C. tropicalis facilitates immunosuppressive function of MDSCs by increasing the expression of iNOS, COX2 and NOX2, production of nitric oxide (NO) and reactive oxygen species (ROS). Mechanistically, C. tropicalis facilitates the immunosuppressive function of MDSCs through the C-type lectin receptors Dectin-3 and Syk. C. tropicalis-enhanced immunosuppressive function of MDSCs is further dependent on aerobic glycolysis. On the one hand, NO produced by MDSCs enhanced aerobic glycolysis in a positive feedback manner. On the other hand, C. tropicalis promotes p-Syk binding to PKM2, which results in PKM2 Tyr105 phosphorylation and PKM2 nuclear translocation in MDSCs. Nuclear PKM2 interacts with HIF-1α and subsequently upregulates the expression of HIF-1α target genes encoding glycolytic enzymes, GLUT1, HK2, PKM2, LDHA and PDK1, which are required for the C. tropicalis-induced aerobic glycolysis of MDSCs. Blockade of PKM2 nuclear translocation attenuates C. tropicalis-mediated colorectal tumorigenesis. The high expression of PKM2, PKM2 (p-Y105) and iNOS in CRC-infiltrated MDSCs correlates with the development of human CRC.CONCLUSION: C. tropicalis enhances immunosuppressive function of MDSCs via Syk-PKM2-HIF-1α-glycolysis signaling axis, which drives CRC. Therefore, we identify the Syk-PKM2-HIF-1α-glycolysis signaling axis as a potential therapeutic target for CRC.PMID:36348389 | DOI:10.1186/s40164-022-00334-6

J Neurovirol. 2022 Nov 8. doi: 10.1007/s13365-022-01102-2. Online ahead of print.ABSTRACTThis study sought to identify neuroimaging and immunological factors associated with substance use and that contribute to neurocognitive impairment (NCI) in people with HIV (PWH). We performed cross-sectional immunological phenotyping, neuroimaging, and neurocognitive testing on virally suppressed PWH in four substance groups: cocaine only users (COC), marijuana only users (MJ), dual users (Dual), and Non-users. Participants completed substance use assessments, multimodal MRI brain scan, neuropsychological testing, and blood and CSF sampling. We employed a two-stage analysis of 305 possible biomarkers of cognitive function associated with substance use. Feature reduction (Kruskal Wallis p-value < 0.05) identified 53 biomarkers associated with substance use (22 MRI and 31 immunological) for model inclusion along with clinical and demographic variables. We employed eXtreme Gradient Boosting (XGBoost) with these markers to predict cognitive function (global T-score). SHapley Additive exPlanations (SHAP) values were calculated to rank features for impact on model output and NCI. Participants were 110 PWH with sustained HIV viral suppression (33 MJ, 12 COC, 22 Dual, and 43 Non-users). The ten highest ranking biomarkers for predicting global T-score were 4 neuroimaging biomarkers including functional connectivity, gray matter volume, and white matter integrity; 5 soluble biomarkers (plasma glycine, alanine, lyso-phosphatidylcholine (lysoPC) aC17.0, hydroxy-sphingomyelin (SM.OH) C14.1, and phosphatidylcholinediacyl (PC aa) C28.1); and 1 clinical variable (nadir CD4 count). The results of our machine learning model suggest that substance use may indirectly contribute to NCI in PWH through both metabolomic and neuropathological mechanisms.PMID:36348233 | DOI:10.1007/s13365-022-01102-2

Cell Mol Life Sci. 2022 Nov 8;79(12):585. doi: 10.1007/s00018-022-04614-6.ABSTRACTAlzheimer's disease (AD) is the most common neurodegenerative disorders presenting with the pathological hallmarks of amyloid plaques and tau tangles. Over the past few years, great efforts have been made to explore reliable biomarkers of AD. High-throughput omics are a technology driven by multiple levels of unbiased data to detect the complex etiology of AD, and it provides us with new opportunities to better understand the pathophysiology of AD and thereby identify potential biomarkers. Through revealing the interaction networks between different molecular levels, the ultimate goal of multi-omics is to improve the diagnosis and treatment of AD. In this review, based on the current AD pathology and the current status of AD diagnostic biomarkers, we summarize how genomics, transcriptomics, proteomics and metabolomics are all conducing to the discovery of reliable AD biomarkers that could be developed and used in clinical AD management.PMID:36348101 | DOI:10.1007/s00018-022-04614-6

Plant Cell Rep. 2022 Nov 8. doi: 10.1007/s00299-022-02947-x. Online ahead of print.ABSTRACTInoculation of wheat seedling with Bacillus sp. wp-6 changed amino acid metabolism and flavonoid synthesis and promoted plant growth. Plant growth-promoting rhizobacteria (PGPR), which can reduce the use of agrochemicals, is vital for the development of sustainable agriculture. In this study, proteomics and metabolomics analyses were performed to investigate the effects of inoculation with a PGPR, Bacillus sp. wp-6, on wheat (Triticum aestivum L.) seedling growth. The results showed that inoculation with Bacillus sp. wp-6 increased shoot and root fresh weights by 19% and 18%, respectively, after 40 days. The expression levels of alpha-linolenic acid metabolism-related proteins and metabolites (lipoxygenase 2, allene oxide synthase 2, jasmonic acid, 17-hydroxylinolenic acid) and flavonoid biosynthesis-related proteins and metabolites (chalcone synthase 2 and PHC 4'-O-glucoside) were up-regulated. In addition, the expression levels of amino acid metabolism-related proteins (NADH-dependent glutamate synthase, bifunctional aspartokinase/homoserine, anthranilate synthase alpha subunit 1, and 3-phosphoshikimate 1-carboxyvinyltransferase) and metabolites (L-aspartate, L-arginine, and S-glutathionyl-L-cysteine) were also significantly up-regulated. Among them, NADH-dependent glutamate synthase and bifunctional aspartokinase/homoserine could act as regulators of nitrogen metabolism. Overall, inoculation of wheat with Bacillus sp. wp-6 altered alpha-linolenic acid metabolism, amino acid metabolism, and flavonoid synthesis and promoted wheat seedling growth. This study will deepen our understanding of the mechanism by which Bacillus sp. wp-6 promotes wheat growth using proteomics and metabolomics.PMID:36348065 | DOI:10.1007/s00299-022-02947-x

Sci Rep. 2022 Nov 8;12(1):19026. doi: 10.1038/s41598-022-23750-4.ABSTRACTKruppel like factor 15 (KLF15), a transcriptional factor belonging to the Kruppel-like factor (KLF) family of genes, has recently been reported as a tumor suppressor gene in breast cancer. However, the specific mechanisms by which KLF15 inhibits BrCa have not been elucidated. Here we investigated the role and mechanism of KLF15 in triple-negative breast cancer (TNBC). KLF15 expression and methylation were detected by RT-qPCR, RT-PCR and methylation-specific PCR in breast cancer cell lines and tissues. The effects of KLF15 on TNBC cell functions were examined via various cellular function assays. The specific anti-tumor mechanisms of KLF15 were further investigated by RNA sequence, RT-qPCR, Western blotting, luciferase assay, ChIP, and bioinformatics analysis. As the results showed that KLF15 is significantly downregulated in breast cancer cell lines and tissues, which promoter methylation of KLF15 partially contributes to. Exogenous expression of KLF15 induced apoptosis and G2/M phase cell cycle arrest, suppressed cell proliferation, metastasis and in vivo tumorigenesis of TNBC cells. Mechanism studies revealed that KLF15 targeted and downregulated C-C motif chemokine ligand 2 (CCL2) and CCL7. Moreover, transcriptome and metabolome analysis revealed that KLF15 is involved in key anti-tumor regulatory and metabolic pathways in TNBC. In conclusion, KLF15 suppresses cell growth and metastasis in TNBC by downregulating CCL2 and CCL7. KLF15 may be a prognostic biomarker in TNBC.PMID:36347994 | DOI:10.1038/s41598-022-23750-4