PubMed

Nat Med. 2023 Jan 9. doi: 10.1038/s41591-022-02097-3. Online ahead of print.ABSTRACTInnovative pro-regenerative treatment strategies for progressive multiple sclerosis (PMS), combining neuroprotection and immunomodulation, represent an unmet need. Neural precursor cells (NPCs) transplanted in animal models of multiple sclerosis have shown preclinical efficacy by promoting neuroprotection and remyelination by releasing molecules sustaining trophic support and neural plasticity. Here we present the results of STEMS, a prospective, therapeutic exploratory, non-randomized, open-label, single-dose-finding phase 1 clinical trial ( NCT03269071 , EudraCT 2016-002020-86), performed at San Raffaele Hospital in Milan, Italy, evaluating the feasibility, safety and tolerability of intrathecally transplanted human fetal NPCs (hfNPCs) in 12 patients with PMS (with evidence of disease progression, Expanded Disability Status Scale ≥6.5, age 18-55 years, disease duration 2-20 years, without any alternative approved therapy). The safety primary outcome was reached, with no severe adverse reactions related to hfNPCs at 2-year follow-up, clearly demonstrating that hfNPC therapy in PMS is feasible, safe and tolerable. Exploratory secondary analyses showed a lower rate of brain atrophy in patients receiving the highest dosage of hfNPCs and increased cerebrospinal fluid levels of anti-inflammatory and neuroprotective molecules. Although preliminary, these results support the rationale and value of future clinical studies with the highest dose of hfNPCs in a larger cohort of patients.PMID:36624312 | DOI:10.1038/s41591-022-02097-3

Commun Med (Lond). 2023 Jan 9;3(1):5. doi: 10.1038/s43856-022-00231-3.ABSTRACTBACKGROUND: Type 2 diabetes is a common disease around the world and its major complications are diabetic retinopathy (DR) and diabetic kidney disease (DKD). Persons with type 2 diabetes with complications, especially who have both DR and DKD, have poorer prognoses than those without complications. Therefore, prevention and early identification of the complications of type 2 diabetes are necessary to improve the prognosis of persons with type 2 diabetes. The aim of this study is to identify factors associated with the development of multiple complications of type 2 diabetes.METHODS: We profiled serum metabolites of persons with type 2 diabetes with both DR and DKD (N = 141) and without complications (N = 159) using a comprehensive non-targeted metabolomics approach with mass spectrometry. Based on the serum metabolite profiles, case-control comparisons and metabolite set enrichment analysis (MSEA) were performed.RESULTS: Here we show that five metabolites (cyclohexylamine, P = 4.5 × 10-6; 1,2-distearoyl-glycero-3-phosphocholine, P = 7.3 × 10-6; piperidine, P = 4.8 × 10-4; N-acetylneuraminic acid, P = 5.1 × 10-4; stearoyl ethanolamide, P = 6.8 × 10-4) are significantly increased in those with the complications. MSEA identifies fatty acid biosynthesis as the type 2 diabetes complications-associated biological pathway (P = 0.0020).CONCLUSIONS: Our metabolome analysis identifies the serum metabolite features of the persons with type 2 diabetes with multiple complications, which could potentially be used as biomarkers.PMID:36624208 | DOI:10.1038/s43856-022-00231-3

Annu Rev Food Sci Technol. 2022 Jan 9. doi: 10.1146/annurev-food-060822-113022. Online ahead of print.ABSTRACTDespite the almost universal acceptance of the phrase "you are what you eat," investment in understanding diet-based nutrition to address human health has been dwarfed compared to that for medicine-based interventions. Moreover, traditional breeding has focused on yield to the detriment of nutritional quality, meaning that although caloric content has remained high, the incidence of nutritional deficiencies and accompanying diseases (so-called hidden hunger) has risen dramatically. We review how genome sequencing coupled with metabolomics can facilitate the screening of genebank collections in the search for superior alleles related to the nutritional quality of crops. We argue that the first examples are very promising, suggesting that this approach could benefit broader ranges of crops and compounds with known relevance for human health. We argue that this represents an approach complementary to metabolic engineering by transgenesis or gene editing that could be used to reverse some of the losses incurred through a recent focus on breeding for yield, although we caution that ensuring such approaches are not (re)introducing antinutrients is also necessary. Furthermore, deploying effective postharvest processing technologies to increase the density of nutrients in the food matrix and improve palatability remains an attractive alternative. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 14 is March 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.PMID:36623924 | DOI:10.1146/annurev-food-060822-113022

Drug Metab Dispos. 2023 Jan 9:DMD-AR-2022-000975. doi: 10.1124/dmd.122.000975. Online ahead of print.ABSTRACTTestosterone exhibits high variability in pharmacokinetics and glucuronidation after oral administration. While testosterone metabolism has been studied for decades, the impact of UGT2B17 gene deletion and the role of gut bacterial β-glucuronidases on its disposition are not well characterized. We first performed an exploratory study to investigate the effect of UGT2B17 gene deletion on the global liver proteome, which revealed significant increases in proteins from multiple biological pathways. The most upregulated liver proteins were aldoketoreductases (AKR1D1, AKR1C4, AKR7A3, AKR1A1, 7-dehydrocholesterol reductase (DHCR7)) and alcohol or aldehyde dehydrogenases (ADH6, ADH1C, ALDH1A1, ALDH9A1, and ALDH5A). In vitro assays revealed that AKR1D1 and AKR1C4 inactivate testosterone to 5β-dihydrotestosterone (5β-DHT) and 3α, 5β-tetrahydrotestosterone (3α, 5β-THT), respectively. These metabolites also appeared in human hepatocytes treated with testosterone and in human serum collected after oral testosterone dosing in men. Second, we evaluated the fate of testosterone glucuronide (TG) secreted into the intestinal lumen and its potential reactivation into testosterone. Incubation of TG with purified gut microbial β-glucuronidase (GUS) enzymes and with human fecal extracts confirmed testosterone reactivation by gut bacterial enzymes. Our exploratory study suggests that testosterone is metabolized by AKRs to 5β-DHT and 3α, 5β-THT in individuals harboring a UGT2B17 deletion, and these metabolites are then eliminated through glucuronidation by another UGT isoforms, UGT2B7. Both testosterone metabolic switching and variable testosterone activation by gut microbial enzymes are important mechanisms for explaining disposition of orally administered testosterone, and appear essential to unraveling the molecular mechanisms underlying UGT2B17-associated pathophysiological conditions. Significance Statement We investigated the association of UGT2B17 gene deletion and the role of gut bacterial β-glucuronidases on testosterone disposition in vitro. The experiment revealed upregulation of AKR1D1 and AKR1C4 and their role to inactivate testosterone to 5β-dihydrotestosterone and 3α, 5β-tetrahydrotestosterone, respectively. Key gut bacterial species responsible for testosterone glucuronide activation were identified. These data are important for explaining disposition of exogenously administered testosterone and appear essential to unraveling the molecular mechanisms underlying UGT2B17-associated pathophysiological conditions.PMID:36623880 | DOI:10.1124/dmd.122.000975

FEMS Microbiol Ecol. 2023 Jan 9:fiad002. doi: 10.1093/femsec/fiad002. Online ahead of print.ABSTRACTFructooligosaccharides (FOS), Ad-fructooligosaccharides (Ad-FOS), resistant maltodextrin (RMD), and maltooligosaccharides (MOS) are commercially available prebiotic oligosaccharides. In this study, the effects of prebiotics on the human gut microbial ecosystem were evaluated using an in vitro gut model. FOS and Ad-FOS showed tolerance to digestion, whereas RMD and MOS showed moderate digestion by digestive enzymes. In in vitro fecal fermentation, Bifidobacterium spp. increased in the following order: FOS, Ad-FOS, MOS, and RMD, whereas Bacteroides spp. increased in RMD medium. Bacteroides xylanisolvens exhibited cross-feeding by enabling the growth of other beneficial bacteria during co-culture in RMD medium. In metabolome analysis, total short-chain fatty acids (SCFAs) were highly produced in the following order: RMD, FOS, MOS, and Ad-FOS; acetate in the order of FOS, MOS/RMD, and Ad-FOS; butyrate in the order of RMD, MOS, FOS, and Ad-FOS; and propionate only in RMD. In addition, the conversion of betaine to trimethylamine was rarely affected in the following order: MOS, RMD, FOS, and Ad-FOS. Lastly, the four oligosaccharides inhibited the adhesion of pathogenic Escherichia coli to human epithelial cells to a similar extent. The comparative analysis results obtained in this study will provide comprehensive information of these substances to manufacturers and customers.PMID:36623850 | DOI:10.1093/femsec/fiad002

Environ Pollut. 2023 Jan 6:120993. doi: 10.1016/j.envpol.2022.120993. Online ahead of print.ABSTRACTComplex legacy contamination from human use is a major issue for estuaries globally. In particular, contamination of water and sediments with bioavailable metals/metalloids, in addition to other industrial contaminants, such as hydrocarbons. Yet, understanding of complex toxicity and local adaptation in field exposed, non-model, invertebrate communities is limited. Herein, we apply multi-omics (metabolomics, lipidomics, proteomics) coupled to traditional sediment quality analyses, to better characterise molecular and cellular responses necessary for application to monitoring, as an eco-surveillance tool. Using these approaches, we characterise functional phenotypes of a sediment associated invertebrate (sipunculid), from an estuary exposed to complex legacy contamination (metals: Zn, Hg, Cd, Pb, Cu, As; and polycyclic aromatic hydrocarbons, PAHs). We sampled individuals at a range of exposure sites, highly (NTB5), moderately (NTB13), and lesser-influenced reference sites. Size differences were observed in sampled individuals between sites, with smaller individuals collected from NTB13. Analysis of environmental variables that correlated with change in the metabolite data revealed that the metabolism of smaller individuals at medium exposure NTB13 was highly differentiated by sediment concentrations of Hg, despite higher concentrations at more exposed NTB5. Functional phenotypes of these smaller individuals were characterised by sulphur and aromatic amino acid metabolism, increases in oxidised intermediates, upregulation of protein responses to oxidative stress, and melanin synthesis, and saturation of membrane and storage of lipids; in addition to the metabolism of naphthalene (PAH). Such widespread change was not observed in the metabolite and lipid profiles of larger individuals at high exposure NTB5, suggesting possible differences in effects between sites may also be associated with size (developmental stage, or age) and/or PAH exposure. This study serves to further understanding of differing modes of toxicity and local adaptation to multiple contaminants, and drivers of functional change in a complex estuary environment.PMID:36623788 | DOI:10.1016/j.envpol.2022.120993

Environ Toxicol Pharmacol. 2023 Jan 6:104063. doi: 10.1016/j.etap.2023.104063. Online ahead of print.ABSTRACTIn this study, a non-target metabolomic approach was used to investigate changes in the metabolome of juvenile meagre (Argyrosomus regius) exposed to venlafaxine (20µg/L). A total of 24, 22 and 8 endogenous metabolites tentatively identified in liver, brain and plasma, respectively, were significantly changed in venlafaxine exposed meagre, showing tissue-dependent variations in the metabolic profile. The amino acids tryptophan, tyrosine and phenylalanine, which are related to the synthesis, availability, and expression of neurotransmitters (e.g., serotonin, dopamine, epinephrine), showed to be dysregulated by venlafaxine exposure. A high impact was observed in fish brain metabolome that showed a trend of up-regulation for most of the tentatively identified metabolites. In conclusion, the identification of possible biomarkers of exposure in fish metabolome to environmental stressors such as venlafaxine is crucial to assess early signal changes at molecular level, enabling the prevention of deleterious effects at the organism and population levels.PMID:36623700 | DOI:10.1016/j.etap.2023.104063

Chemosphere. 2023 Jan 6:137752. doi: 10.1016/j.chemosphere.2023.137752. Online ahead of print.ABSTRACTTo evaluate the maximum possible hazard of veterinary antimicrobial mixtures at doses accessible to humans, Sprague-Dawley male rats were orally dosed with a mixture of 26 commonly used veterinary antimicrobials for 90 consecutive days. The daily dosage of each component was 100 times (G1), 10 times (G2) and, 1 time (G3) of acceptable daily intake (ADI) in China. Hematology analysis and biochemical analysis found significant changes of several parameters, suggesting liver damage. Histopathological examination further indicated that mixtures of veterinary drugs at three levels caused obvious hepatotoxicity, and the severity of damage increased with dosage. LC-MS-based metabolomics analysis was carried out to detect metabolite changes in liver tissue. In G1, G2, and G3, 208, 165, and 195 differential accumulated metabolites (DAMs) compared with the Ctrl group were filtered, respectively. Similarly, RNA-seq helped us to filter a total of 183, 118, and 38 differentially expressed genes (DEGs) in G1, G2, and G3 compared with the Ctrl group, respectively. By integrating with the transcriptomic and metabolomic data, we revealed that mineral absorption, ascorbate and aldarate metabolism may be the major pathways affected by the veterinary antimicrobial mixtures in our study. This study provided useful data for the risk assessment of multiple chemicals.PMID:36623596 | DOI:10.1016/j.chemosphere.2023.137752

Am J Trop Med Hyg. 2023 Jan 9:tpmd201608. doi: 10.4269/ajtmh.20-1608. Online ahead of print.ABSTRACTScrub typhus is an acute febrile, mite-borne disease endemic to the Asia-Pacific region. In South Korea, it is a seasonal disease that occurs frequently in the autumn, and its incidence has increased steadily. In this study, we used a liquid chromatography and flow injection analysis-tandem mass spectrometry-based targeted urine metabolomics approach to evaluate the host response to Orientia tsutsugamushi infection. Balb/c mice were infected with O. tsutsugamushi Boryong, and their urine metabolite profile was examined. Metabolites that differed significantly between the experimental groups were identified using the Kruskal-Wallis test. Sixty-five differential metabolites were identified. The principal metabolite classes were acylcarnitines, glycerophospholipids, biogenic amines, and amino acids. An ingenuity pathway analysis revealed that several toxic (cardiotoxic, hepatotoxic, and nephrotoxic) metabolites are induced by scrub typhus infection. This is the first report of urinary metabolite biomarkers of scrub typhus infection and it enhances our understanding of the metabolic pathways involved.PMID:36623483 | DOI:10.4269/ajtmh.20-1608

Food Chem. 2023 Jan 5;410:135413. doi: 10.1016/j.foodchem.2023.135413. Online ahead of print.ABSTRACTThe gut microbiota plays an evolutionarily conserved role in host metabolism, which is influenced by diet. Here, we investigated differences in shaping the gut microbiota and regulating metabolism in cow milk-based infant formula, goat milk-based infant formula, and mix milk-based infant formula compared with pasteurized human milk. 16S rRNA results showed that goat milk-based infant formula selectively increased the relative abundance of Blautia, Roseburia, Alistites and Muribaculum in the gut compared to other infant formulas. Metabolomics identification indicated that goat milk-based infant formula mainly emphasized bile acid biosynthesis, arachidonic acid metabolism and steroid biosynthesis metabolic pathways. Metabolites associated with these metabolic pathways were positively associated with increased microorganisms in goat milk-based infant formula, particularly Alistipes. Furthermore, we found a deficiency of Akkermansia abundance in three infant formula-fed compared to pasteurizedhuman milk-fed. This study presents new insights into the improvement and application of goat milk-based infant formulas in terms of intestinal microecology.PMID:36623461 | DOI:10.1016/j.foodchem.2023.135413

Food Chem. 2022 Dec 23;409:135297. doi: 10.1016/j.foodchem.2022.135297. Online ahead of print.ABSTRACTSegment drying is a common internal physiological disorder in citrus fruit, and vesicles get granulated or collapsed. This study aimed to probe whether and how the phenylpropanoid metabolism changes in vesicles during collapse of blood orange (Citrus sinensis cv. Tarocco). Vesicle collapse led to a decrease in the content of nutrients and flavonoids, while an increase in lignin content. This disorder was further associated with the increasing enzyme activities and gene expression levels of both the general phenylpropanoid pathway and branch pathway of lignin synthesis, while decreasing enzyme activities and gene expression levels of branch pathway of flavonoids synthesis. Targeted metabolomics analysis of 14 metabolites of the lignin pathway revealed that lignin precursors were accumulated in collapsed vesicles. We provide solid evidence that phenylpropanoid metabolism could be activated, and, intriguingly, metabolic flux may be shuttled to lignin precursors synthesis rather than flavonoids synthesis in vesicles during collapse of blood orange.PMID:36623356 | DOI:10.1016/j.foodchem.2022.135297

Autophagy. 2023 Jan 9. doi: 10.1080/15548627.2023.2165323. Online ahead of print.ABSTRACTFerroptosis is a type of iron-dependent regulated cell death characterized by unrestricted lipid peroxidation and membrane damage. Although GPX4 (glutathione peroxidase 4) plays a master role in blocking ferroptosis by eliminating phospholipid hydroperoxides, the regulation of GPX4 remains poorly understood. Here, we report an unexpected role for copper in promoting ferroptotic cell death, but not cuproptosis, by inducing macroautophagic/autophagic degradation of GPX4. Copper chelators reduce ferroptosis sensitivity but do not inhibit other types of cell death, such as apoptosis, necroptosis, and alkaliptosis. Conversely, exogenous copper increases GPX4 ubiquitination and the formation of GPX4 aggregates by directly binding to GPX4 protein cysteines C107 and C148. TAX1BP1 (Tax1 binding protein 1) then acts as an autophagic receptor for GPX4 degradation and subsequent ferroptosis in response to copper stress. Consequently, copper enhances ferroptosis-mediated tumor suppression in a mouse model of pancreatic cancer tumor, whereas copper chelators attenuate experimental acute pancreatitis associated with ferroptosis. Taken together, these findings provide new insights into the link between metal stress and autophagy-dependent cell death.PMID:36622894 | DOI:10.1080/15548627.2023.2165323

mSphere. 2023 Jan 9:e0051722. doi: 10.1128/msphere.00517-22. Online ahead of print.ABSTRACTIn the marine environment, surface-associated bacteria often produce an array of antimicrobial secondary metabolites, which have predominantly been perceived as competition molecules. However, they may also affect other hallmarks of surface-associated living, such as motility and biofilm formation. Here, we investigate the ecological significance of an antibiotic secondary metabolite, tropodithietic acid (TDA), in the producing bacterium, Phaeobacter piscinae S26. We constructed a markerless in-frame deletion mutant deficient in TDA biosynthesis, S26ΔtdaB. Molecular networking demonstrated that other chemical sulfur-containing features, likely related to TDA, were also altered in the secondary metabolome. We found several changes in the physiology of the TDA-deficient mutant, ΔtdaB, compared to the wild type. Growth of the two strains was similar; however, ΔtdaB cells were shorter and more motile. Transcriptome and proteome profiling revealed an increase in gene expression and protein abundance related to a type IV secretion system, and to a prophage, and a gene transfer agent in ΔtdaB. All these systems may contribute to horizontal gene transfer (HGT), which may facilitate adaptation to novel niches. We speculate that once a TDA-producing population has been established in a new niche, the accumulation of TDA acts as a signal of successful colonization, prompting a switch to a sessile lifestyle. This would lead to a decrease in motility and the rate of HGT, while filamentous cells could form the base of a biofilm. In addition, the antibiotic properties of TDA may inhibit invading competing microorganisms. This points to a role of TDA in coordinating colonization and adaptation. IMPORTANCE Despite the broad clinical usage of microbial secondary metabolites with antibiotic activity, little is known about their role in natural microbiomes. Here, we studied the effect of production of the antibiotic tropodithietic acid (TDA) on the producing strain, Phaeobacter piscinae S26, a member of the Roseobacter group. We show that TDA affects several phenotypes of the producing strain, including motility, cell morphology, metal metabolism, and three horizontal gene transfer systems: a prophage, a type IV secretion system, and a gene transfer agent. Together, this indicates that TDA participates in coordinating the colonization process of the producer. TDA is thus an example of a multifunctional secondary metabolite that can mediate complex interactions in microbial communities. This work broadens our understanding of the ecological role that secondary metabolites have in microbial community dynamics.PMID:36622251 | DOI:10.1128/msphere.00517-22

J Proteome Res. 2023 Jan 9. doi: 10.1021/acs.jproteome.2c00610. Online ahead of print.ABSTRACTThe pmartR (https://github.com/pmartR/pmartR) package was designed for the quality control (QC) and analysis of mass spectrometry data, tailored to specific characteristics of proteomic (isobaric or labeled), metabolomic, and lipidomic data sets. Since its initial release, the tool has been expanded to address the needs of its growing userbase and now includes QC and statistics for nuclear magnetic resonance metabolomic data, and leverages the DESeq2, edgeR, and limma-voom R packages for transcriptomic data analyses. These improvements have made progress toward a unified omics processing pipeline for ease of reporting and streamlined statistical purposes. The package's statistics and visualization capabilities have also been expanded by adding support for paired data and by integrating pmartR with the trelliscopejs R package for the quick creation of trellis displays (https://github.com/hafen/trelliscopejs). Here, we present relevant examples of each of these enhancements to pmartR and highlight how each new feature benefits the omics community.PMID:36622218 | DOI:10.1021/acs.jproteome.2c00610

Plant Physiol Biochem. 2023 Jan 4;195:101-113. doi: 10.1016/j.plaphy.2022.12.028. Online ahead of print.ABSTRACTThe color and fragrance of rose flowers affect their commercial value. However, several rose varieties with new floral colors developed by the bud mutation method lost their fragrance during the breeding process, raising the question: Is there a relationship between floral color and aroma traits? Rose cultivar 'Yellow Island' (YI) with intensely aroma and yellow petals, while its bud mutant 'Past Feeling' (PF) with light aroma and pink petals mixing some yellow, two cultivars were used to explore this question using multiomics approaches. We investigated the genomic polymorphisms between PF and YI by whole-genome resequencing. 71 differentially abundant metabolites and 155 related differentially expressed genes identified in petals between PF and YI. From this, we constructed a model of metabolic changes affecting floral color and fragrance integrating shikimate, terpenoid, carotenoid, and green leaf volatile metabolites and predicted the associated key genes and transcription factors. This study provides a reference for understanding the molecular mechanism of variation in rose floral color and aroma traits.PMID:36621304 | DOI:10.1016/j.plaphy.2022.12.028

Curr Opin Biotechnol. 2023 Jan 6;79:102876. doi: 10.1016/j.copbio.2022.102876. Online ahead of print.ABSTRACTClustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) gene editing has become a powerful tool in genome manipulation for crop improvement. Advances in omics technologies, including genomics, transcriptomics, and metabolomics, allow the identification of causal genes that can be used to improve crops. However, the functional validation of these genetic components remains a challenge due to the lack of efficient protocols for crop engineering. Hairy roots gene editing using CRISPR/Cas, coupled with omics analyses, provide a platform for rapid, precise, and cost-effective functional analysis of genes. Here, we describe common requirements for efficient crop genome editing, focused on the transformation of recalcitrant legumes, and highlight the great opportunities that gene editing in hairy roots offers for future crop improvement.PMID:36621223 | DOI:10.1016/j.copbio.2022.102876

Front Psychiatry. 2022 Dec 21;13:998709. doi: 10.3389/fpsyt.2022.998709. eCollection 2022.ABSTRACTINTRODUCTION: Schizophrenia (SZ) is a severe chronic mental disorder with increased risk of hepatitis B virus (HBV) infection, which is incurable currently and induces various negative emotions and psychological pressures in patients to exacerbate mental disorders. To facilitate the therapeutic design for SZ patients complicated with HBV infection (SZ + HBV), it is helpful to first elucidate the metabolic perturbations in SZ + HBV patients.METHODS: In this study, metabolic profiles of the serum samples from four groups of participants comprising healthy controls (HC, n = 72), HBV infection (n = 52), SZ patients (n = 37), and SZ + HBV (n = 41) patients were investigated using a high-resolution 1H NMR-based metabolomics approach.RESULTS AND DISCUSSION: Distinguishable metabolic profiles were found in the four groups. In comparison with HC, HBV infection induced increased levels of citrate and succinate to perturbate the tricarboxylic acid cycle and succinate-related pathways. Similar to SZ cases, SZ + HBV patients exhibited decreased glucose but increased citrate, pyruvate, and lactate, suggesting the occurrence of disturbance in glucose metabolism. Moreover, in comparison with HC, several serum amino acid levels in SZ + HBV patients were significantly altered. Our findings suggest that Warburg effect, energy metabolism disorders, neurotransmitter metabolism abnormalities, mitochondrial dysfunction and several disturbed pathways in relation to tyrosine and choline appear to play specific and central roles in the pathophysiology of SZ + HBV. Apart from replicating metabolic alterations induced by SZ and HBV separately (e.g., in energy metabolism and Warburg effect), the specific metabolic abnormalities in the SZ + HBV group (e.g., several tyrosine- and choline-related pathways) highlighted the existence of a synergistic action between SZ and HBV pathologies. Current study revealed the metabolic alterations specific to the interaction between SZ and HBV pathologies, and may open important perspectives for designing precise therapies for SZ + HBV patients beyond the simple combination of two individual treatments.PMID:36620683 | PMC:PMC9810819 | DOI:10.3389/fpsyt.2022.998709

Front Oncol. 2022 Dec 22;12:1069635. doi: 10.3389/fonc.2022.1069635. eCollection 2022.ABSTRACTUsing circulating molecular biomarkers to screen for cancer and other debilitating disorders in a high-throughput and low-cost fashion is becoming increasingly attractive in medicine. One major limitation of investigating protein biomarkers in body fluids is that only one-fourth of the entire proteome can be routinely detected in these fluids. In contrast, Human Leukocyte Antigen (HLA) presents peptides from the entire proteome on the cell surface. While peptide-HLA complexes are predominantly membrane-bound, a fraction of HLA molecules is released into body fluids which is referred to as soluble HLAs (sHLAs). As such peptides bound by sHLA molecules represent the entire proteome of their cells/tissues of origin and more importantly, recent advances in mass spectrometry-based technologies have allowed for accurate determination of these peptides. In this perspective, we discuss the current understanding of sHLA-peptide complexes in the context of cancer, and their potential as a novel, relatively untapped repertoire for cancer biomarkers. We also review the currently available tools to detect and quantify these circulating biomarkers, and we discuss the challenges and future perspectives of implementing sHLA biomarkers in a clinical setting.PMID:36620582 | PMC:PMC9815702 | DOI:10.3389/fonc.2022.1069635

Front Physiol. 2022 Dec 23;13:1072893. doi: 10.3389/fphys.2022.1072893. eCollection 2022.ABSTRACTApriona swainsoni is a vital forest pest prevalent in China. The larvae of A. swainsoni live solely in the branches of trees and rely entirely on the xylem for nutrition. However, there is still a lack of in-depth research on the gut microbiota's use of almost nitrogen-free wood components to provide bio-organic macromolecular components needed for their growth. Thus, in this study, the metagenome, metaproteome, and metabolome of the A. swainsoni larvae in four gut segments (foregut; midgut; anterior hindgut; posterior hindgut) were analyzed by the multi-omics combined technology, to explore the metabolic utilization mechanism of the corresponding gut microbiota of A. swainsoni. Firstly, we found that the metagenome of different gut segments was not significantly different in general, but there were different combinations of dominant bacteria and genes in different gut segments, and the metaproteome and metabolome of four gut segments were significantly different in general. Secondly, the multi-omics results showed that there were significant gradient differences in the contents of cellulose and hemicellulose in different segments of A. swainsoni, and the expression of corresponding metabolic proteins was the highest in the midgut, suggesting the metabolic characteristics of these lignocellulose components in A. swainsoni gut segments. Finally, we found that the C/N ratio of woody food was significantly lower than that of frass, and metagenomic results showed that nitrogen fixation genes mainly existed in the foregut and two hindgut segments. The expression of the key nitrogen fixing gene nifH occurred in two hindgut parts, indicating the feature of nitrogen fixation of A. swainsoni. In conclusion, our results provide direct evidence that the larvae of A. swainsoni can adapt to the relatively harsh niche conditions through the highly organized gut microbiome in four gut segments, and may play a major role in their growth.PMID:36620205 | PMC:PMC9816477 | DOI:10.3389/fphys.2022.1072893

Front Microbiol. 2022 Dec 22;13:1085113. doi: 10.3389/fmicb.2022.1085113. eCollection 2022.ABSTRACTEngineered nanomaterials can provide eco-friendly alternatives for crop disease management. Chitosan based nanoparticles has shown beneficial applications in sustainable agricultural practices and effective healthcare. Previously we demonstrated that Thymol loaded chitosan nanoparticles (TCNPs) showed bactericidal activity against Xanthomonas campestris pv campestris (Xcc), a bacterium that causes black rot disease in brassica crops. Despite the progress in assessing the antibacterial action of TCNPs, the knowledge about the molecular response of Xcc when exposed to TCNPs is yet to be explored. In the present study, we combined physiological, spectroscopic and untargeted metabolomics studies to investigate the response mechanisms in Xcc induced by TCNPs. Cell proliferation and membrane potential assays of Xcc cells exposed to sub-lethal concentration of TCNPs showed that TCNPs affects the cell proliferation rate and damages the cell membrane altering the membrane potential. FTIR spectroscopy in conjunction with untargeted metabolite profiling using mass spectrometry of TCNPs treated Xcc cells revealed alterations in amino acids, lipids, nucleotides, fatty acids and antioxidant metabolites. Mass spectroscopy analysis revealed a 10-25% increase in nucleic acid, fatty acids and antioxidant metabolites and a 20% increase in lipid metabolites while a decrease of 10-20% in amino acids and carbohydrates was seen in in TCNP treated Xcc cells. Overall, our results demonstrate that the major metabolic perturbations induced by TCNPs in Xcc are associated with membrane damage and oxidative stress, thus providing information on the mechanism of TCNPs mediated cytotoxicity. This will aid towards the development of nano- based agrochemicals as an alternative to chemical pesticides in future.PMID:36620059 | PMC:PMC9815552 | DOI:10.3389/fmicb.2022.1085113